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Substitution of disulfide bonds with a diselenide bonds in peptides and proteins is an often-used strategy to increase the stability of naturally occurring peptides and proteins. In this paper, diselenide metathesis between model diselenide dimer peptides, as well as that in diselenide(s)-substituted biologically active peptides, were analyzed. Surprisingly, depending on the tertiary structure of the peptides, we observed that the metathesis reaction occurs under physiological conditions even in the absence of reducing agents, light and heating.
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Peptídeos , Selenocisteína , Selenocisteína/química , Peptídeos/química , Peptídeos/síntese química , Compostos Organosselênicos/química , Compostos Organosselênicos/síntese químicaRESUMO
Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite the numerous studies on the inhibition of amyloid formation, the prevention and treatment of a majority of amyloid-related disorders are still challenging. In this study, we investigated the effects of various plant extracts on amyloid formation of α-synuclein. We found that the extracts from Eucalyptus gunnii are able to inhibit amyloid formation, and to disaggregate preformed fibrils, in vitro. The extract itself did not lead cell damage. In the extract, miquelianin, which is a glycosylated form of quercetin and has been detected in the plasma and the brain, was identified and assessed to have a moderate inhibitory activity, compared to the effects of ellagic acid and quercetin, which are strong inhibitors for amyloid formation. The properties of miquelianin provide insights into the mechanisms controlling the assembly of α-synuclein in the brain.
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Human seleno-epidermal growth factor (seleno-EGF), a 53-residue peptide where all six cysteine residues of the parent human EGF sequence were replaced by selenocysteines, was synthesized and the oxidative folding of a polypeptide containing three diselenide bonds was compared to that of the parent cysteine peptide. The crude high performance liquid chromatography (HPLC) profiles clearly showed that both the native EGF and its selenocysteine-analogue fold smoothly, yielding a single sharp peak, proving that even in the case of three disulfide-bonded polypeptides the disulfide-to-diselenide bond substitution is highly isomorphous, as confirmed by conformational circular dichroism measurements and particularly by the biological assays.
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Cisteína , Selenocisteína , Humanos , Selenocisteína/química , Cisteína/química , Fator de Crescimento Epidérmico/química , Peptídeos/química , Dissulfetos/química , Dobramento de ProteínaRESUMO
The structural dynamics of the chromo-shadow domain (CSD) and chromodomain (CD) of human HP1 proteins essential for heterochromatin formation were investigated at the nanosecond and nanometer scales by site-directed spin labeling electron paramagnetic resonance and pulsed double resonance spectroscopy. Distance measurements showed that the spin-labeled CSD of human HP1α and HP1γ tightly dimerizes. Unlike CD-CD interaction observed in fission yeast HP1 in an inactivated state (Canzio et al., 2013), the two CDs of HP1α and HP1γ were spatially separated from each other, dynamically mobile, and ready for a Brownian search for H3K9-tri-methyl(me3) on histones. Complex formation of the CD with H3K9me3 slowed dynamics of the domain due to a decreased diffusion constant. CSD mobility was significantly (â¼1.3-fold) lower in full-length HP1α than in HP1γ, suggesting that the immobilized conformation of human HP1α shows an auto-inactivated state. Differential properties of HP1α and HP1γ to form the inactive conformation could be relevant to its physiological role in the heterochromatin formation in a cell.
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Proteínas Cromossômicas não Histona/metabolismo , Histonas/metabolismo , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/química , Espectroscopia de Ressonância de Spin Eletrônica , Histonas/química , Humanos , Metilação , Modelos Moleculares , Domínios ProteicosRESUMO
Caveolin-1, which is an essential protein for caveola formation, was chemically synthesized. It is composed of 177 amino acid residues, is triply palmitoylated at the C-terminal region, and is inserted into the lipid bilayer to form a V-shaped structure in the middle of the polypeptide chain. The entire sequence was divided into five peptide segments, each of which was synthesized by the solid-phase method. To improve the solubility of the C-terminal region, O-acyl isopeptide structures were incorporated. After ligation by the thioester method and the introduction of the palmitoyl groups, all the protecting groups were removed and the isopeptide structures were converted into the native peptide bond. Finally, the obtained polypeptide was successfully inserted into bicelles, thus showing the success of the synthesis.
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Caveolina 1/síntese química , Caveolina 1/química , Estrutura MolecularRESUMO
Amino acids bearing 4-methylbenzyl (MBn) and 4-methoxybenzyl (MPM)-protected sialic acid were synthesized and used for the 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of a glycopeptide. The α-sialyl linkage of the MBn-protected unit was partially cleaved under the final deprotection by trifluoroacetic acid (TFA). In addition, the removal of several MBn groups were incomplete. On the other hand, the MPM-protected unit gave the desired glycopeptide without decomposition of the α-sialyl linkage. Using this unit, peptide thioesters of the tandem repeat unit of MUC1 mucin were synthesized by the N-alkylcysteine (NAC) method and used for the one-pot ligation by the thioester method. As a result, the three tandem repeats of MUC1 carrying sialyl Tn antigens were successfully synthesized.
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Glicopeptídeos/química , Fluorenos/química , Glicopeptídeos/síntese química , Ácido N-Acetilneuramínico/química , Técnicas de Síntese em Fase Sólida , Ácido Trifluoracético/químicaRESUMO
The synthesis of a peptide selenoester was efficiently carried out by the 9-fluorenylmethoxycarbonyl (Fmoc) method using N-alkylcysteine, at the C-terminus of the peptide, as the N-to-S acyl shift device. The selenoester selectively reacted with the terminal amino group of the peptide aryl thioester in the presence of N,N-diisopropylethylamine and dipyridyldisulfide, thus leaving the aryl thioester intact. Combined with silver-ion-promoted and silver-ion-free thioester activation methods, a one-pot four-segment ligation was realized. The method was successfully used to assemble the entire sequence of superoxide dismutase (SOD), which is composed of 153 amino-acid residues, in one pot. After the folding reaction, the fully active SOD was obtained.
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Ésteres/metabolismo , Compostos Organosselênicos/metabolismo , Peptídeos/metabolismo , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismo , Ésteres/química , Estrutura Molecular , Compostos Organosselênicos/química , Peptídeos/química , Compostos de Sulfidrila/química , Superóxido Dismutase/químicaRESUMO
Synthetic insulin analogues with a long lifetime are current drug targets for the therapy of diabetic patients. The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin-degrading enzyme (IDE) without impairing the hormonal function. The [C7UA ,C7UB ] variant of bovine pancreatic insulin (BPIns) was successfully prepared by using two selenocysteine peptides (i.e., the C7U analogues of A- and B-chains, respectively). In a buffer solution at pHâ 10 they spontaneously assembled under thermodynamic control to the correct insulin fold. The selenoinsulin (Se-Ins) exhibited a bioactivity comparable to that of BPIns. Interestingly, degradation of Se-Ins with IDE was significantly decelerated (τ1/2 ≈8â h vs. ≈1â h for BPIns). The lifetime enhancement could be due to both the intrinsic stability of the diselenide bond and local conformational changes induced by the substitution.
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Insulina/química , Insulina/síntese química , Sequência de Aminoácidos , Cristalografia por Raios X , Dissulfetos/química , Insulina/análogos & derivados , Modelos MolecularesRESUMO
BACKGROUND: Volume-based parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), on F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) are useful for predicting treatment response in nonsmall cell lung cancer (NSCLC). We aimed to examine intra- and inter-operator reproducibility to measure the MTV and TLG, and to estimate their dependency on the uptake time. METHODS: Fifty NSCLC patients underwent preoperative FDG-PET. After an injection of FDG, the whole body was scanned twice: at the early phase (61.4 ± 2.8 min) and delayed phase (117.7 ± 1.6 min). Two operators independently defined the tumor boundary using three different delineation methods: (1) the absolute SUV threshold method (MTVp and TLGp; p = 2.0, 2.5, 3.0, 3.5), (2) the fixed% SUVmax threshold method (MTVq% and TLGq%; q = 35, 40, 45), and (3) the adaptive region-growing method (MTVARG and TLGARG). Parameters were compared between operators and between phases. RESULTS: Both the intra- and inter-operator reproducibility were high for all parameters using any method (intra-class correlation > 0.99 each). MTV3.0 and MTV3.5 resulted in a significant increase from the early to delayed phase (P < 0.05 for both), whereas MTV2.0 and MTV2.5 neither increased nor decreased (P = n.s.). All of the MTVq% values significantly decreased over time (P < 0.01), whereas MTVARG and TLG with any delineation method increased significantly (P < 0.05). CONCLUSIONS: High reproducibility of MTV and TLG was obtained by all of the methods used. MTV2.0 and MTV2.5 were the least sensitive to uptake time, and may be good alternatives when we compare images acquired with different uptake times, although applying constant uptake time is important for volume measurement.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicólise , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carga TumoralRESUMO
Cysteinyl RGD-peptidyl cysteinyl prolyl esters, which have different configurations at the cysteine and proline residues, were synthesized by the solid-phase method and cyclized by the native chemical ligation reaction. Cyclization efficiently proceeded to give cyclic peptides, regardless of the difference in the configuration. The peptides were further derivatized to the corresponding desulfurized or methylated cyclic peptides at the Cys residues. The inhibition activity to αvß6 integrin binding was then analyzed by ELISA. The results showed that the activity varied depending on the difference in the configuration and modification of the cysteinyl prolyl ester (CPC) moiety, demonstrating the usefulness of this method in the search for a good inhibitor of the protein-protein interaction.
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This study aimed to confirm urinary protein fragments in relation to the presence of pancreatic ductal adenocarcinoma (PDAC) via a C-terminal proteomics strategy using exploratory and validation cohorts. Urinary fragments were examined by iTRAQ-labelling of tryptic peptides and concentrations of C-terminal fragments were evaluated. Only the urinary CD276 fragment showed a fold change (FC) of > 1.5 with a significant difference of P < 0.01 between healthy (H) and PDAC participants in both the exploratory (H, n = 42; PDAC, n = 39) and validation cohorts (H, n = 36; resectable PDAC, n = 28). The sensitivity and specificity of the CD276 fragment for diagnosing resectable PDAC were 75% and 89%, respectively, in the validation cohort. Postoperative urinary levels of the CD276 fragment were low as compared to those before surgery (n = 18, P < 0.01). Comprehensive C-terminus proteomics identified an increase in the urinary CD276 fragment level as a feature of patients with PDAC. The urinary CD276 fragment is a potential biomarker for detecting resectable PDAC.
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Antígenos B7 , Biomarcadores Tumorais , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Proteômica , Humanos , Neoplasias Pancreáticas/urina , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/diagnóstico , Proteômica/métodos , Feminino , Masculino , Biomarcadores Tumorais/urina , Idoso , Antígenos B7/urina , Antígenos B7/metabolismo , Pessoa de Meia-Idade , Carcinoma Ductal Pancreático/urina , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/diagnósticoRESUMO
PURPOSE: To evaluate the performance of conventional [(11)C]choline PET/CT in comparison to that of simultaneous whole-body PET/MR. METHODS: The study population comprised 32 patients with prostate cancer who underwent a single-injection dual-imaging protocol with PET/CT and subsequent PET/MR. PET/CT scans were performed applying standard clinical protocols (5 min after injection of 793 ± 69 MBq [(11)C]choline, 3 min per bed position, intravenous contrast agent). Subsequently (52 ± 15 min after injection) PET/MR was performed (4 min per bed position). PET images were reconstructed iteratively (OSEM 3D), scatter and attenuation correction of emission data and regional allocation of [(11)C]choline foci were performed using CT data for PET/CT and segmented Dixon MR, T1 and T2 sequences for PET/MR. Image quality of the respective PET scans and PET alignment with the respective morphological imaging modality were compared using a four point scale (0-3). Furthermore, number, location and conspicuity of the detected lesions were evaluated. SUVs for suspicious lesions, lung, liver, spleen, vertebral bone and muscle were compared. RESULTS: Overall 80 lesions were scored visually in 29 of the 32 patients. There was no significant difference between the two PET scans concerning number or conspicuity of the detected lesions (p not significant). PET/MR with T1 and T2 sequences performed better than PET/CT in anatomical allocation of lesions (2.87 ± 0.3 vs. 2.72 ± 0.5; p = 0.005). The quality of PET/CT images (2.97 ± 0.2) was better than that of the respective PET scan of the PET/MR (2.69 ± 0.5; p = 0.007). Overall the maximum and mean lesional SUVs exhibited high correlations between PET/CT and PET/MR (ρ = 0.87 and ρ = 0.86, respectively; both p < 0.001). CONCLUSION: Despite a substantially later imaging time-point, the performance of simultaneous PET/MR was comparable to that of PET/CT in detecting lesions with increased [(11)C]choline uptake in patients with prostate cancer. Anatomical allocation of lesions was better with simultaneous PET/MR than with PET/CT, especially in the bone and pelvis. These promising findings suggest that [(11)C]choline PET/MR might have a diagnostic benefit compared to PET/CT in patients with prostate cancer, and now needs to be further evaluated in prospective trials.
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Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Imagem Corporal Total , Idoso , Radioisótopos de Carbono , Colina , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Neoplasias da Próstata/diagnóstico , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: The purpose of this study was to evaluate whether early changes in 3'-deoxy-3'-3H-fluorothymidine (3H-FLT) uptake can reflect the antiproliferative effect of gefitinib in a human tumor xenograft, in comparison with the histopathological markers, Ki-67 and phosphorylated EGFR (phospho-EGFR). METHODS: An EGFR-dependent human tumor xenograft model (A431) was established in female BALB/c athymic mice, which were divided into three groups: one control group and two treatment groups. Mice in the treatment groups were orally administered a partial regression dose (100 mg/kg/day) or the maximum tolerated dose of gefitinib (200 mg/kg/day), once daily for 2 days. Mice in the control group were administered the vehicle (0.1% Tween 80). Tumor size was measured before and 3 days after the start of treatment. Biodistribution of 3H-FLT and 18F-FDG (%ID/g/kg) was examined 3 days after the start of the treatment. Tumor cell proliferative activity with Ki-67 was determined. Immunohistochemical staining of EGFR and measurement of phospho-EGFR were also performed. RESULTS: High expression levels of EGFR and Ki-67 were observed in the A431 tumor. After the treatment with 100 and 200 mg/kg gefitinib, the uptake levels of 3H-FLT in the tumor were significantly reduced to 67% and 61% of the control value, respectively (0.39 ± 0.09, 0.36 ± 0.06, 0.59 ± 0.11%ID/g/kg for 100 mg/kg, 200 mg/kg, and control groups, respectively; p<0.01 vs. control), but those of 18F-FDG were not. After the treatment with 100 and 200 mg/kg gefitinib, the expression levels of Ki-67 in the tumor were markedly decreased (4.6 ± 2.4%, 6.2 ± 1.8%, and 10.4 ± 5.7% for 100 mg/kg, 200 mg/kg, and control groups, respectively, p<0.01 vs. control). The expression levels of the phospho-EGFR protein also significantly decreased (29% and 21% of the control value for 100, and 200 mg/kg, respectively p<0.01 vs. control). There was no statistically significant difference in tumor size between pre- and post-treatments in each group. CONCLUSION: In our animal model, 3H-FLT uptake levels significantly decreased after the treatment with two different doses of gefitinib before a significant change in tumor size was observed. These results were confirmed by the immunohistochemical staining of Ki-67 and phospho-EGFR protein immunoassay. Thus, it was indicated that early changes in 3H-FLT uptake may reflect the antiproliferative effect of gefitinib in a mouse model of a human epidermoid cancer.
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Antineoplásicos/farmacologia , Receptores ErbB/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Quinazolinas/farmacologia , Compostos Radiofarmacêuticos/metabolismo , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Modelos Animais de Doenças , Receptores ErbB/antagonistas & inibidores , Feminino , Fluordesoxiglucose F18/metabolismo , Gefitinibe , Humanos , Camundongos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fosforilação , Quinazolinas/administração & dosagem , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The COVID-19 pandemic caused by SARS-CoV-2 remains a serious health concern worldwide due to outbreaks of SARS-CoV-2 variants that can escape vaccine-acquired immunity and infect and transmit more efficiently. Therefore, an appropriate testing method for COVID-19 is essential for effective infection control and the prevention of local outbreaks. Compared to reverse-transcription polymerase chain reaction (RT-PCR) tests, antigen tests are used for simple point-of-care testing, enabling the identification of viral infections. In this study, we tested the clinical usefulness of the FUJIFILM COVID-19 Ag test, an antigen test based on silver amplification and immunochromatographic technology. The FUJIFILM COVID-19 Ag test was shown to detect a lower viral concentration as compared to other conventional kits without significant performance loss in detecting prevalent SARS-CoV-2 variants. We tested nasopharyngeal and nasal swabs from a single patient during two different epidemic periods dominated by various SARS-CoV-2 variants. We observed that the sensitivity of the FUJIFILM COVID-19 Ag test was 95.7% and 85.7% in nasopharyngeal and nasal swabs, respectively. These results suggest that the FUJIFILM COVID-19 Ag test is highly sensitive and applicable when RT-PCR testing is unavailable. Furthermore, these results indicate that high-frequency testing using nasal swab specimens may be a valuable screening strategy.
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Ghrelin is a gastric-derived peptide that stimulates feeding, blood glucose elevation, body temperature reduction, and growth hormone (GH) secretion. Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous antagonist of the ghrelin receptor, also called growth hormone secretagogue receptor (GHSR). We studied the effects of LEAP2 administration on feeding, body weight, glycemia, body temperature, and inflammation-related genes in the liver in C57BL/6 J mice and Ghsr-knockout (Ghsr-KO) mice. We found that a single administration of LEAP2 did not abolish fasting-induced food intake in 24-h fasted C57BL/6 J mice or Ghsr-KO mice. Moreover, continuous LEAP2 administration to mice fed ad libitum for 6 days did not affect feeding, body temperature, plasma ghrelin, or blood glucose. By contrast, continuous LEAP2 administration to calorie-restricted C57BL/6 J mice and Ghsr-KO mice induced body weight loss, hypoglycemia, body temperature reduction, and upregulation of Il-6 and Il-1ß mRNAs in the liver. Our findings suggest that LEAP2 functions independently of GHSR, implying that LEAP2 affects physiology beyond the ghrelin-GHSR system.
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Peptídeos Catiônicos Antimicrobianos , Grelina , Fígado , Receptores de Grelina , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Glicemia/metabolismo , Restrição Calórica , Grelina/genética , Grelina/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Grelina/genéticaRESUMO
The ongoing coronavirus disease 2019 (COVID-19) pandemic is a major global public health concern. Although rapid point-of-care testing for detecting viral antigen is important for management of the outbreak, the current antigen tests are less sensitive than nucleic acid testing. In our current study, we produce monoclonal antibodies (mAbs) that exclusively react with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and exhibit no cross-reactivity with other human coronaviruses, including SARS-CoV. Molecular modeling suggests that the mAbs bind to epitopes present on the exterior surface of the nucleocapsid, making them suitable for detecting SARS-CoV-2 in clinical samples. We further select the optimal pair of anti-SARS-CoV-2 nucleocapsid protein (NP) mAbs using ELISA and then use this mAb pair to develop immunochromatographic assay augmented with silver amplification technology. Our mAbs recognize the variants of concern (501Y.V1-V3) that are currently in circulation. Because of their high performance, the mAbs of this study can serve as good candidates for developing antigen detection kits for COVID-19.
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Anticorpos Monoclonais/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Epitopos/imunologia , Imunoensaio/métodos , SARS-CoV-2/metabolismo , Animais , Reações Antígeno-Anticorpo , COVID-19/patologia , COVID-19/virologia , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Fosfoproteínas/genética , Fosfoproteínas/imunologia , Fosfoproteínas/metabolismo , Sistemas Automatizados de Assistência Junto ao Leito , SARS-CoV-2/isolamento & purificação , Prata/químicaRESUMO
OBJECTIVES: The aim of the present study was to determine the relations of clinical symptoms with nigrostriatal neuron loss in drug-naïve patients with Parkinson's disease (PD). We examined the severity of motor symptoms and freezing of gait (FOG), falls and overactive bladder (OAB) in PD patients and their relations with striatal dopamine transporter (DAT) binding. PATIENTS AND METHODS: Thirty-two untreated PD patients (14 men and 18 women with a mean age of 71.4⯱â¯7.2 years) were included in this study. Clinical assessments were performed by using Unified Parkinson's Disease Rating Scale (UPDRS) and overactive bladder symptom score (OABSS), and striatal dopamine transporter (DAT) binding was measured by123I-FP-CIT SPECT. RESULTS: The results showed that striatal DAT availability was significantly lower in the high UPDRS motor score group, high akinetic-rigid score group, FOG group, and OAB group than in the low UPDRS motor score group, low akinetic-rigid score group, non-FOG group, and non-OAB group. However, the results also showed that there was no significant difference in striatal DAT availability between the high tremor score group and low tremor score group or between the faller group and non-faller group. CONCLUSIONS: The severity of bradykinesia and axial symptoms and the existence of FOG and OAB in untreated PD patients are related to a decrease in striatal DAT availability. Severity of tremors and occurrence of falls are not related to a decrease in striatal DAT availability. The mechanisms underlying the clinical symptoms of PD involve not only dopaminergic pathways but also non-dopaminergic pathways.
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Encéfalo/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Doença de Parkinson/diagnóstico por imagem , Tremor/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Índice de Gravidade de Doença , Avaliação de Sintomas , Tomografia Computadorizada de Emissão de Fóton Único , Tremor/metabolismoRESUMO
Ferredoxin (Fd) is an electron carrier protein containing a [2Fe-2S] cluster. In this paper, we synthesized Se-Fd, in which four Cys residues coordinated to the cluster are substituted to selenocysteine. After the one-pot segment coupling by the thioester method, followed by deprotection and cluster loading, the desired Se-Fd was successfully obtained.
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OBJECTIVES: The aim of the present study was to determine the relationships of drooling with motor symptoms and nigrostriatal neuron loss in drug-naïve patients with Parkinson's disease (PD). We therefore examined the relationships of drooling with motor symptoms and striatal dopamine transporter (DAT) binding measured by [123-Iodine]-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenylnortropane) dopamine transporter single-photon emission computed tomography(123I-FP-CIT SPECT). PATIENTS AND METHODS: Thirty-five untreated PD patients (14 men and 21 women with a mean age of 71.9⯱â¯7.2 years) were included in this study. The patients were divided into a drooler group and non-drooler group. They underwent clinical assessments and 123I-FP-CIT SPECT imaging. Motor symptoms were assessed using Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: The results showed that UPDRS motor score (pâ¯=â¯0.002) and akinetic-rigid score (pâ¯=â¯0.008) were higher and that striatal DAT availability (pâ¯=â¯0.03) was lower in the drooler group than in the non-drooler group. However, tremor score, age, and duration of PD showed no significant differences between the drooler group and non-drooler group. CONCLUSIONS: Drooling in untreated PD is related to an increase in motor symptoms (especially bradykinesia and axial symptoms) and to reduction of striatal DAT availability.
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Corpo Estriado/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Doença de Parkinson/complicações , Sialorreia/complicações , Idoso , Idoso de 80 Anos ou mais , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Sialorreia/metabolismo , Sialorreia/patologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
INTRODUCTION: Soft-tissue sarcomas (STS) are rare types of tumors that have variable levels of tumor differentiation. F-18 fluorodeoxyglucose positron emission tomography (FDG PET) has been established as an useful tool for STS patients, and the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are reported to be useful in various cancers. We compared the diagnostic value of four PET parameters (maximum standardized uptake value [SUVmax], SUVmean, MTV, and TLG) from two acquisition timings for predicting the expression of the pathological marker of cell proliferation Ki-67, based on pathological investigation. MATERIALS AND METHODS: In this retrospective study, we investigated 20 patients (59 ± 19 years old, 18-87 years old) with pathologically confirmed STS who underwent FDG PET before surgical intervention. The patients fasted ≥ 6 h before the intravenous injection of FDG. The whole body was scanned twice; at an early phase (61.5 ± 2.6 min) and at a delayed phase (118.0 ± 2.1 min) post-injection. The SUVmax, SUVmean, MTV, and TLG of the primary lesion were measured with a tumor boundary determined by SUV ≥ 2.0. Ki-67 was measured using MIB-1 immunohistochemistry. We used Pearson's correlation coefficient to analyze the relationships between the PET parameters and Ki-67 expressions. The Kaplan-Meier analysis with the log-rank test was performed to compare overall survival between high-group and low-group at each of the four PET parameters and Ki-67 expression. RESULTS: All four PET parameters at each phase showed significant correlations with Ki-67. Among them, the Pearson's correlation coefficient (r) was largest for TLG (r = 0.76 and 0.77 at the early and delayed phases, respectively), followed by MTV (0.70 and 0.72), SUVmax (r = 0.65 and 0.66), and SUVmean (r = 0.62 and r = 0.64). From early to delayed phases, the SUVmax and SUVmean both increased in all 20 patients, whereas the MTV and TLG increased in 13/20 (65%) and 16/20 (80%) patients, respectively. None of the %increases of the PET parameters were significantly correlated with Ki-67. The overall survival was shorter for high-SUVmax, high-SUVmean, high-TLG, and high-Ki-67 groups than the other groups, although the difference did not reach statistical significance. CONCLUSION: The SUVmax, SUVmean, MTV, and TLG acquired at both 1 and 2 h after injection showed significant correlations with Ki-67. Among them, correlation coefficient with Ki-67 expression was highest for TLG, although the best parameter should be determined in a larger population. The delayed-phase FDG PET was equally useful as that of early-phase to predict tumor aggressiveness in STS.