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1.
J Nippon Med Sch ; 91(3): 277-284, 2024.
Article in English | MEDLINE | ID: mdl-38972740

ABSTRACT

BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.


Subject(s)
Ammonia , Coronary Circulation , Mucocutaneous Lymph Node Syndrome , Myocardial Perfusion Imaging , Nitrogen Radioisotopes , Positron-Emission Tomography , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/diagnostic imaging , Male , Female , Ammonia/blood , Positron-Emission Tomography/methods , Child , Child, Preschool , Myocardial Perfusion Imaging/methods , Coronary Occlusion/etiology , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/physiopathology , Coronary Aneurysm/etiology , Coronary Aneurysm/diagnostic imaging , Coronary Aneurysm/physiopathology , Adolescent , Infant , Hemodynamics
3.
Radiol Cardiothorac Imaging ; 6(3): e230298, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38814185

ABSTRACT

Purpose To investigate whether right ventricular (RV) myocardial strain ratio (RVMSR) assessed using nitrogen 13 ammonia (13N-NH3) PET can predict cardiovascular events in patients with ischemic heart disease (IHD). Materials and Methods This retrospective study included 480 consecutive patients (mean age, 66 years ± 12 [SD]; 334 males and 146 females) with IHD who underwent 13N-NH3 PET. RVMSR was defined as the ratio of RV strain during stress to that at rest. The primary end point was major adverse cardiac events (MACEs), defined as cardiac death or heart failure hospitalization. The ability of RVMSR to predict MACE was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) with 95% CIs. Results ROC curve analysis identified a sensitivity and specificity of 84% and 82%, respectively, for predicting MACE from RVMSR. Patients with reduced RVMSR (<110.2) displayed a significantly higher rate of MACE than those with a preserved RVMSR (34 of 240 vs four of 240; P < .001). Cox proportional hazards regression analysis of imaging parameters, including myocardial flow reserve, indicated that RVMSR was an independent predictor of MACE (HR, 0.94 [95% CI: 0.92, 0.97]; P < .001). Conclusion RVMSR was an independent predictor of MACE and has potential to aid in the risk stratification of patients with IHD. Keywords: Right Ventricular Myocardial Strain Ratio, Myocardial Flow Reserve, Ischemic Heart Disease, 13N-Ammonia Positron Emission Tomography Supplemental material is available for this article. © RSNA, 2024.


Subject(s)
Ammonia , Heart Ventricles , Myocardial Ischemia , Nitrogen Radioisotopes , Positron-Emission Tomography , Humans , Male , Female , Aged , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/physiopathology , Myocardial Ischemia/diagnosis , Retrospective Studies , Positron-Emission Tomography/methods , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Risk Assessment , Middle Aged , Sensitivity and Specificity
4.
J Nucl Cardiol ; 36: 101862, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608861

ABSTRACT

BACKGROUND: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. METHODS AND RESULTS: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). CONCLUSIONS: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.


Subject(s)
Ammonia , Electrocardiography , Heart Ventricles , Myocardial Infarction , Myocardial Ischemia , Myocardial Perfusion Imaging , Nitrogen Radioisotopes , Positron Emission Tomography Computed Tomography , Humans , Male , Female , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/physiopathology , Middle Aged , Positron Emission Tomography Computed Tomography/methods , Aged , Myocardial Perfusion Imaging/methods , Heart Ventricles/diagnostic imaging , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/physiopathology , Radiopharmaceuticals , Cardiac-Gated Imaging Techniques , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Reproducibility of Results
5.
J Appl Physiol (1985) ; 136(4): 949-953, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38420678

ABSTRACT

Decompression sickness (DCS) is caused by gaseous nitrogen dissolved in tissues forming bubbles during decompression. To date, no method exists to identify nitrogen within tissues, but with advances in positron-emission tomography (PET) technology, it may be possible to track gaseous radionuclides into tissues. We aimed to develop a method to track nitrogen movement in vivo and under hyperbaric pressure that could then be used to further our understanding of DCS using nitrogen-13 (13N2). A single anesthetized female Sprague-Dawley rat was exposed to 625 kPa, composed of air, isoflurane, and 13N2 for 10 min. The PET scanner recorded 13N2 during the hyperbaric exposure with energy windows of 250-750 keV. The PET showed an increase in 13N2 concentration in the lung, heart, and abdominal regions, which all reached a plateau after ∼4 min. This showed that it is possible to gain noninvasive in vivo measurements of nitrogen kinetics through the body while at hyperbaric pressures. Tissue samples showed radioactivity above background levels in the blood, brain, liver, femur, and thigh muscle when assessed using a γ counter. The method can be used to evaluate an array of challenges to our understanding of decompression physiology by quantifying nitrogen load through γ counts of 13N2, and signal intensity of the PET. Further development of the method will improve the specificity of the measured outcomes, and enable it to be used with larger mammals, including humans.NEW & NOTEWORTHY This article describes a method for the in vivo quantification and tracking of nitrogen through the mammalian body whilst exposed to hyperbaric pressure. The method has the potential to further our understanding of decompression sickness, and quantitatively evaluate the effectiveness of both the treatment and prevention of decompression sickness.


Subject(s)
Decompression Sickness , Diving , Hyperbaric Oxygenation , Nitrogen Radioisotopes , Humans , Rats , Animals , Female , Nitrogen , Decompression Sickness/diagnostic imaging , Diving/physiology , Rats, Sprague-Dawley , Decompression/adverse effects , Gases , Hyperbaric Oxygenation/methods , Positron-Emission Tomography , Mammals
6.
Acad Radiol ; 31(4): 1248-1255, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37940426

ABSTRACT

RATIONALE AND OBJECTIVES: Cardiac magnetic resonance (CMR) and gated 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) offer accurate and highly comparable global left ventricular ejection fraction (LVEF) measurements. In addition to accuracy, however, reproducibility is crucial to avoid variations in LVEF assessment potentially negatively impacting treatment decisions. We performed a head-to-head comparison of the reproducibility of LVEF measurements derived from simultaneously acquired CMR and PET-MPI using different state-of-the-art commercially available software. MATERIALS AND METHODS: 93 patients undergoing hybrid PET/MR were retrospectively included. LVEF was derived from CMR and PET-MPI at two separate core labs, using two state-of-the-art software packages for CMR (cvi42 and Medis Suite MR) and PET (QPET and CardIQ Physio). Intra- and inter-reader agreement was assessed using correlation and Bland-Altman (BA) analyses. RESULTS: While intra- and inter-reader reproducibility of LVEF was high among both modalities and all software packages (r ≥ 0.87 and ICC≥0.91, all significant at p < 0.0001), LVEF derived from PET-MPI and analyzed with QPET outperformed all other analyses (intra-reader reproducibility: r = 0.99, ICC=0.99; inter-reader reproducibility: r = 0.98, ICC=1.00; Pearson correlations significantly higher than all others at p ≤ 0.0001). BA analyses showed smaller biases for LVEF derived from PET-MPI (-0.1% and +0.9% for intra-reader, -0.4% and -0.8% for inter-reader agreement) than those derived from CMR (+0.7% and +2.8% for intra-reader, -0.9% and -2.2% for inter-reader agreement) with similar results for BA limits of agreement. CONCLUSION: Gated 13N-ammonia PET-MPI provides equivalent reproducibility of LVEF compared to CMR. It may offer a valid alternative to CMR for patients requiring LV functional assessment.


Subject(s)
Nitrogen Radioisotopes , Ventricular Function, Left , Humans , Stroke Volume , Ammonia , Reproducibility of Results , Retrospective Studies , Positron-Emission Tomography/methods , Magnetic Resonance Imaging/methods , Radiopharmaceuticals , Magnetic Resonance Spectroscopy , Perfusion
7.
Bioresour Technol ; 393: 130047, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37989421

ABSTRACT

A salt-tolerant strain, Pseudomonas mendocina A4, was isolated from brackish-water ponds showing simultaneous heterotrophic nitrification-aerobic denitrification and phosphorus removal capability. The optimal conditions for nitrogen and phosphate removal of strain A4 were pH 7-8, carbon/nitrogen ratio 10, phosphorus/nitrogen ratio 0.2, temperature 30 °C, and salinity range of 0-5 % using sodium succinate as the carbon source. The nitrogen and phosphate removal efficiencies were 96-100 % and 88-96 % within 24 h, respectively. The nitrogen and phosphate removal processes were matched with the modified Gompertz model, and the underlying mechanisms were confirmed by the activities of key metabolic enzymes. Under 10 % salinity, the immobilization technology was employed to enhance the nitrogen and phosphate removal efficiencies of strain A4, achieving 87 % and 76 %, respectively. These findings highlight the potential application of strain A4 in both freshwater and marine culture wastewater treatment.


Subject(s)
Denitrification , Nitrogen Radioisotopes , Pseudomonas mendocina , Phosphates , Pseudomonas mendocina/metabolism , Nitrogen/metabolism , Aerobiosis , Nitrification , Phosphorus , Heterotrophic Processes , Carbon , Nitrites/chemistry
8.
Neurosurg Rev ; 46(1): 160, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37393399

ABSTRACT

While magnetic resonance imaging (MRI) is the current standard imaging method for diagnosing and localizing corticotropinomas in Cushing disease, it can fail to detect adenomas in up to 40% of cases. Recently, positron emission tomography (PET) has shown promise as a diagnostic tool to detect pituitary adenomas in Cushing disease. We perform a scoping review to characterize the uses of PET in diagnosing Cushing disease, with a focus on describing the types of PET investigated and defining PET-positive disease. A scoping review was conducted following the PRISMA-ScR guidelines. Thirty-one studies fulfilled our inclusion criteria, consisting of 10 prospective studies, 8 retrospective studies, 11 case reports, and 2 illustrative cases with a total of 262 patients identified. The most commonly utilized PET modalities in prospective/retrospective studies were FDG PET (n = 5), MET PET (n = 5), 68 Ga-DOTATATE PET (n = 2), 13N-ammonia PET (n = 2), and 68 Ga-DOTA-CRH PET (n = 2). MRI positivity ranged from 13 to 100%, while PET positivity ranged from 36 to 100%. In MRI-negative disease, PET positivity ranged from 0 to 100%. Five studies reported the sensitivity and specificity of PET, which ranged from 36 to 100% and 50 to 100%, respectively. PET shows promise in detecting corticotropinomas in Cushing disease, including MRI-negative disease. MET PET has been highly investigated and has demonstrated excellent sensitivity and specificity. However, preliminary studies with FET PET and 68 Ga-DOTA-CRH PET show promise for achieving high sensitivity and specificity and warrant further investigation.


Subject(s)
Pituitary ACTH Hypersecretion , Humans , Pituitary ACTH Hypersecretion/diagnostic imaging , Nitrogen Radioisotopes , Prospective Studies , Retrospective Studies , Positron-Emission Tomography
9.
Eur J Nucl Med Mol Imaging ; 50(12): 3609-3618, 2023 10.
Article in English | MEDLINE | ID: mdl-37391545

ABSTRACT

PURPOSE: Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. METHODS: Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18). RESULTS: Compared to remote segments, healed segments showed higher stress MBF (2.71 mL*min-1*g-1 [IQR 2.18-3.08] vs. 2.20 mL*min-1*g-1 [1.75-2.68], p < 0.0001), MFR (3.78 [2.83-4.79] vs. 3.36 [2.60-4.03], p < 0.0001), and washout (rest 0.24/min [0.18-0.31] and stress 0.53/min [0.40-0.67] vs. 0.22/min [0.16-0.27] and 0.46/min [0.32-0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE. CONCLUSION: In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation. CMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement.


Subject(s)
Coronary Artery Disease , Myocardial Perfusion Imaging , Myocarditis , Humans , Nitrogen Radioisotopes , Coronary Circulation/physiology , Myocarditis/diagnostic imaging , Ammonia , Cicatrix/diagnostic imaging , Contrast Media , Gadolinium , Magnetic Resonance Imaging , Positron-Emission Tomography , Radiopharmaceuticals , Inflammation/diagnostic imaging , Perfusion , Myocardial Perfusion Imaging/methods
10.
Article in English | MEDLINE | ID: mdl-36972401

ABSTRACT

A simple and sensitive method based on liquid chromatography-atmospheric pressure chemical ionisation-tandem mass spectrometry (LC-APCI-MS/MS) was developed and validated to determine the levels of 13N-nitrosamines and N-nitrosatable substances migrated from rubber teats into artificial saliva. The migration test from rubber teats was conducted at 40 °C and for 24 h in artificial saliva, and the migrated artificial saliva solution was analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS) without further extracting steps. The sensitivity of N-nitrosamines was examined by applying atmospheric chemical ionisation and electrospray ionisation to optimise the mass spectrometric conditions, and the atmospheric chemical ionisation (APCI) mode exhibited 1.6-19 times higher sensitivity. Method validation showed acceptable linearity, precision, and accuracy, and the detection and quantification limits were 0.07-0.35 and 0.24-1.1 µg kg-1, respectively. The developed liquid chromatography-atmospheric chemical ionisation-tandem mass spectrometry method was applied to 39 domestic and imported rubber teats. From 39 samples, N-nitrosamines [N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMOR), and N-nitroso n-methyl N-phenylamine (NMPhA)] were detected in 30 samples, with N-nitrosatable substances in 17 samples give rise to NDMA, NMOR, and N-nitrosodiethylamine. However, the levels were below the specific migration limit of Korean Standards and Specifications for Food Containers, Utensils, and Packages and EC Directive 93/11/EEC.


Subject(s)
Nitrosamines , Rubber , Rubber/analysis , Rubber/chemistry , Tandem Mass Spectrometry , Nitrogen Radioisotopes , Chromatography, Liquid/methods , Saliva, Artificial/analysis , Nitrosamines/analysis , Dimethylnitrosamine
11.
Bioorg Chem ; 133: 106403, 2023 04.
Article in English | MEDLINE | ID: mdl-36801790

ABSTRACT

Our previous studies suggested that N-phenyl aromatic amides are a class of promising xanthine oxidase (XO) inhibitor chemotypes. In this effort, several series of N-phenyl aromatic amide derivatives (4a-h, 5-9, 12i-w, 13n, 13o, 13r, 13s, 13t and 13u) were designed and synthesized to carry out an extensive structure-activity relationship (SAR). The investigation provided some valuable SAR information and identified N-(3-(1H-imidazol-1-yl)-4-((2-methylbenzyl)oxy)phenyl)-1H-imidazole-4-carboxamide (12r, IC50 = 0.028 µM) as the most potent XO inhibitor with close in vitro potency to that of topiroxostat (IC50 = 0.017 µM). Molecular docking and molecular dynamics simulation rationalized the binding affinity through a series of strong interactions with the residues Glu1261, Asn768, Thr1010, Arg880, Glu802, etc. In vivo hypouricemic studies also suggested that the uric acid lowering effect of compound 12r was improved compared with the lead g25 (30.61 % vs 22.4 % reduction in uric acid levels at 1 h; 25.91 % vs 21.7 % reduction in AUC of uric acid) . Pharmacokinetic studies revealed that compound 12r presented a short t1/2 of 0.25 h after oral administration. In addition, 12r has non-cytotoxicity against normal cell HK-2. This work may provide some insights for further development of novel amide-based XO inhibitors.


Subject(s)
Nitrogen Radioisotopes , Xanthine Oxidase , Amides/pharmacology , Enzyme Inhibitors/chemistry , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Uric Acid , Xanthine Oxidase/antagonists & inhibitors
12.
Environ Sci Pollut Res Int ; 30(14): 40189-40205, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36607573

ABSTRACT

In order to solve the problems of coal spontaneous combustion, poor inerting effect of traditional nitrogen injection, and waste of resources in goaf, based on the response surface methodology and Box-Behnken combination test principle, the self-developed continuous and precise nitrogen injection and fire-fighting equipment was used to study the best possible combination of nitrogen injection position (20-90 m), nitrogen injection amount (10-70 m3/min), and air supply volume (2100-2500 m3/min), aiming to minimize the width of the oxidation zone and CO concentration in goaf. The optimal key parameters of continuous precise nitrogen injection were determined as follows: nitrogen injection position 54.17 m, nitrogen injection amount 31.04 m3/min, and air supply 2484.81 m3/min. Under this condition, the width of the oxidation zone was 29.21 ± 0.3 m and the CO concentration was 28.1 ± 4.4 ppm, which were similar to the predicted results of the model (the width of the oxidation zone was 29.41 m; CO concentration was 27.28 ppm). The reliability of the model was verified. These preliminary studies have achieved the purpose of rapid control of the fire in the whole region of the goaf and provided valuable lessons for similar nitrogen injection fire prevention and extinguishing technologies in goaf.


Subject(s)
Coal Mining , Nitrogen , Reproducibility of Results , Coal Mining/methods , Nitrogen Radioisotopes , Coal/analysis
13.
J Nucl Cardiol ; 30(4): 1474-1483, 2023 08.
Article in English | MEDLINE | ID: mdl-36600174

ABSTRACT

AIM: The current proof-of-concept study investigates the value of radiomic features from normal 13N-ammonia positron emission tomography (PET) myocardial retention images to identify patients with reduced global myocardial flow reserve (MFR). METHODS: Data from 100 patients with normal retention 13N-ammonia PET scans were divided into two groups, according to global MFR (i.e., < 2 and ≥ 2), as derived from quantitative PET analysis. We extracted radiomic features from retention images at each of five different gray-level (GL) discretization (8, 16, 32, 64, and 128 bins). Outcome independent and dependent feature selection and subsequent univariate and multivariate analyses was performed to identify image features predicting reduced global MFR. RESULTS: A total of 475 radiomic features were extracted per patient. Outcome independent and dependent feature selection resulted in a remainder of 35 features. Discretization at 16 bins (GL16) yielded the highest number of significant predictors of reduced MFR and was chosen for the final analysis. GLRLM_GLNU was the most robust parameter and at a cut-off of 948 yielded an accuracy, sensitivity, specificity, negative and positive predictive value of 67%, 74%, 58%, 64%, and 69%, respectively, to detect diffusely impaired myocardial perfusion. CONCLUSION: A single radiomic feature (GLRLM_GLNU) extracted from visually normal 13N-ammonia PET retention images independently predicts reduced global MFR with moderate accuracy. This concept could potentially be applied to other myocardial perfusion imaging modalities based purely on relative distribution patterns to allow for better detection of diffuse disease.


Subject(s)
Coronary Artery Disease , Myocardial Perfusion Imaging , Humans , Ammonia , Nitrogen Radioisotopes , Positron-Emission Tomography/methods , Radiopharmaceuticals , Perfusion , Myocardial Perfusion Imaging/methods , Coronary Artery Disease/diagnostic imaging , Coronary Circulation
14.
Insect Biochem Mol Biol ; 148: 103827, 2022 09.
Article in English | MEDLINE | ID: mdl-36007680

ABSTRACT

Peptidoglycan recognition proteins (PGRPs) detect invading bacteria to trigger or modulate immune responses in insects. While these roles are established in Drosophila, functional studies are not yet achieved at the PGRP family level in other insects. To attain this goal, we selected Manduca sexta PGRP12 and five of the nine secreted PGRPs for recombinant expression and biochemical characterization. We cloned PGRP2-5, 12 and 13 cDNAs, produced the proteins in full (PGRP2-5, 13) or in part (PGRP3s, 12e, 13N, 13C) in Sf9 cells, and tested their bindings of two muramyl pentapeptides by surface plasmon resonance, two soluble peptidoglycans by competitive ELISA, and four insoluble peptidoglycans and eight whole bacteria by a pull-down assay. Preferential binding of meso-diaminopimelic acid-peptidoglycans (DAP-PGs) was observed in all the proteins containing a peptidoglycan binding domain and, since PGRP6, 7 and 9 proteins were hardly detected in cell-free hemolymph, the reportoire of PGRPs (including PGRP1 published previously) in M. sexta hemolymph is likely adapted to mainly detect Gram-negative bacteria and certain Gram-positive bacteria with DAP-PGs located on their surface. After incubation with plasma from naïve larvae, PGRP2, 3f, 4, 5, 13f and 13N considerably stimulated prophenoloxidase activation in the absence of a bacterial elicitor. PGRP3s and 12e had much smaller effects. Inclusion of the full-length PGRPs and their regions in the plasma also led to proHP8 activation, supporting their connections to the Toll pathway, since HP8 is a Spӓtzle-1 processing enzyme in M. sexta. Together, these findings raised concerns on the common belief that the Toll-pathway is specific for Gram-positive bacteria in insects.


Subject(s)
Manduca , Animals , Carrier Proteins , Diaminopimelic Acid/metabolism , Drosophila/metabolism , Hemolymph/metabolism , Insect Proteins/metabolism , Nitrogen Radioisotopes/metabolism , Peptidoglycan/chemistry
16.
Appl Radiat Isot ; 185: 110214, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35397362

ABSTRACT

Nitrogen-13 labeled ammonia ([13N]NH3) has been used for myocardial perfusion imaging with Positron Emission Tomography for decades. Recent increases to regulatory oversight have led to stricter adherence to Good Manufacturing Practice (GMP) when producing this short half-life (9.97 min) radiopharmaceutical. This has increased production costs. Our cyclotron facility initially developed a manual GMP production method, but it was prone to human error. With increased costs in mind, we developed and validated an Arduino-based device to purifying [13N]NH3 for clinical use. Construction, programming, and GMP validation results are discussed. The automated method was found to produce equivalent quality radiopharmaceutical but was more reproducible and robust.


Subject(s)
Ammonia , Radiopharmaceuticals , Humans , Nitrogen Radioisotopes , Positron-Emission Tomography/methods
17.
Appl Radiat Isot ; 182: 110139, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35180527

ABSTRACT

The specific activity of air in the large open room housing the 800-MeV proton synchrotron of the ISIS Spallation Neutron and Muon Source has been measured. Air from several positions within the ISIS synchrotron room was sucked through a long flexible tube, and run past a shielded HPGe gamma-ray detector outside the synchrotron room. In spite of an expectation that 13N should be the largest component of the overall activity in the air, the results of the measurements are consistent with the presence in the air of 11C and 41Ar only, and suggest that the activity in the air is mostly created not in the synchrotron room itself but in the massive shielding monoliths around the neutron-producing targets, monoliths through which ventilation air is drawn into the synchrotron room. Typical specific activities of 11C and 41Ar in the air in the synchrotron room are ∼0.10 and ∼0.03 Bq cm-3 respectively, the upper limit for 13N being at most ∼0.01 Bq cm-3.


Subject(s)
Air Pollutants, Radioactive/analysis , Nitrogen Radioisotopes/analysis , Synchrotrons , Argon/analysis , Carbon Isotopes/analysis , Protons
18.
PLoS One ; 17(2): e0263521, 2022.
Article in English | MEDLINE | ID: mdl-35167589

ABSTRACT

The Monte Carlo method is employed in this study to simulate the proton irradiation of a water-gel phantom. Positron-emitting radionuclides such as 11C, 15O, and 13N are scored using the Particle and Heavy Ion Transport Code System Monte Carlo code package. Previously, it was reported that as a result of 16O(p,2p2n)13N nuclear reaction, whose threshold energy is relatively low (5.660 MeV), a 13N peak is formed near the actual Bragg peak. Considering the generated 13N peak, we obtain offset distance values between the 13N peak and the actual Bragg peak for various incident proton energies ranging from 45 to 250 MeV, with an energy interval of 5 MeV. The offset distances fluctuate between 1.0 and 2.0 mm. For example, the offset distances between the 13N peak and the Bragg peak are 2.0, 2.0, and 1.0 mm for incident proton energies of 80, 160, and 240 MeV, respectively. These slight fluctuations for different incident proton energies are due to the relatively stable energy-dependent cross-section data for the 16O(p,2p2n)13N nuclear reaction. Hence, we develop an open-source computer program that performs linear and non-linear interpolations of offset distance data against the incident proton energy, which further reduces the energy interval from 5 to 0.1 MeV. In addition, we perform spectral analysis to reconstruct the 13N Bragg peak, and the results are consistent with those predicted from Monte Carlo computations. Hence, the results are used to generate three-dimensional scatter plots of the 13N radionuclide distribution in the modeled phantom. The obtained results and the developed methodologies will facilitate future investigations into proton range monitoring for therapeutic applications.


Subject(s)
Nitrogen Radioisotopes/pharmacology , Proton Therapy/methods , Algorithms , Humans , Monte Carlo Method , Phantoms, Imaging
19.
Nucl Med Commun ; 43(5): 502-509, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35045554

ABSTRACT

BACKGROUND: Accurate scar assessment is crucial in cardiac resynchronization therapy (CRT) candidates, since its presence is a negative predictor for CRT response. Therefore, we assessed the performance of different PET parameters to detect scar in CRT candidates. METHODS: Twenty-nine CRT candidates underwent 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT), resting 13N-NH3-PET/CT and cardiac magnetic resonance (CMR) prior to CRT implantation. Segmental 18F-FDG uptake, late 13N-NH3 uptake and absolute myocardial blood flow (MBF) were evaluated for scar detection using late gadolinium enhancement (LGE) CMR as reference. A receiver operator characteristic (ROC) area under the curve (AUC) ≥0.8 indicated a good accuracy of the methods evaluated. RESULTS: Scar was present in 111 of 464 segments. None of the approaches could reliably identify segments with nontransmural scar, except for 18F-FDG uptake in the lateral wall (AUC 0.83). Segmental transmural scars could be detected with all methods (AUC ≥ 0.8), except for septal 18F-FDG uptake and MBF in the inferior wall (AUC < 0.8). Late 13N-NH3 uptake was the best parameter for transmural scar detection, independent of its location, with a sensitivity of 80% and specificity of 92% using a cutoff of 66% of the maximum tracer activity. CONCLUSIONS: Late 13N-NH3 uptake is superior to 13N-NH3 MBF and 18F-FDG in detecting transmural scar, independently of its location. However, none of the tested PET parameters was able to accurately detect nontransmural scar.


Subject(s)
Cardiac Resynchronization Therapy , Fluorodeoxyglucose F18 , Cicatrix/diagnostic imaging , Contrast Media , Gadolinium , Humans , Nitrogen Radioisotopes , Positron Emission Tomography Computed Tomography
20.
Clin Hemorheol Microcirc ; 80(2): 153-166, 2022.
Article in English | MEDLINE | ID: mdl-34958007

ABSTRACT

OBJECTIVE: This study aimed to evaluate the diagnostic and prognostic value of 13N-NH3·H2O positron emission tomography combined with computed tomography (PET/CT) for non-obstructive coronary microvascular disease (CMVD). METHODS: A retrospective analysis was conducted on 70 patients with clinically suspected non-obstructive CMVD (35 males, 35 females) between March 2017 and August 2019. The average age of the patients was 53.32±7.82 years. The patients underwent 13N-NH3·H2O PET/CT and were divided into two groups based on diagnostic criteria: a CMVD group and a non-CMVD group. They were then followed up for 180-1,095 days. Data were analyzed using an χ2 test, the logistic regression model, the multiple linear regression model, the Kaplan-Meier method, the Cox proportional hazards regression model, and a receiver operating characteristic (ROC) curve. RESULTS: (1) The incidence of cardiovascular family history and a high calcification score (11-400) was higher in the CMVD group than in the non-CMVD group (58.8% vs. 20.8% and 29.4% vs. 5.7%, respectively; P < 0.05 for all), stress myocardial blood flow (MBF) and coronary flow reserve (CFR) values were lower in the CMVD group than in the non-CMVD group (2.280±0.693 vs. 3.641±1.365 and 2.142±0.339 vs. 3.700±1.123, respectively), and calcification score was higher in the CMVD group than in the non-CMVD group (110.18±165.07 vs. 13.21±41.68, respectively; P < 0.05 for all). Gender and diabetes were risk factors for stress MBF reduction (ß= 1.287 and ß= -0.636, respectively), calcification score and hypertension were risk factors for CFR reduction (ß= -0.004 and ß= -0.654, respectively), and hypertension, family history, and calcification score were risk factors in the CMVD group (OR = 7.323, OR = 5.108, OR = 1.012, respectively; P < 0.05 for all). (2) The prognosis of patients with CFR < 2.5 was worse than that of patients with CFR≥2.5 (x2 value: 27.404, P < 0.001). The risk of adverse cardiovascular events in diabetic patients was also increased (ß= 0.328, P < 0.001). When CFR was set to 2.595, the prognostic sensitivity was 94% and the specificity was 80%. CONCLUSION: The technology of 13N-NH3·H2O PET/CT can be used for the diagnosis and prognosis of non-obstructive CMVD. Cardiovascular risk factors are related to the occurrence and prognosis of CMVD.


Subject(s)
Coronary Artery Disease , Positron Emission Tomography Computed Tomography , Coronary Artery Disease/diagnostic imaging , Coronary Circulation/physiology , Female , Humans , Male , Middle Aged , Nitrogen Radioisotopes , Positron-Emission Tomography , Prognosis , Retrospective Studies
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