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1.
Molecules ; 29(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38611763

RESUMO

Salvia miltiorrhiza seeds (SMS) are the main by-product of the production processing of Radix Salviae Miltiorrhizae. The main purposes of this work are to analyse the nutritional components in SMS, to explore the antioxidant activity of the chemical components in SMS and to evaluate the possibility of SMS as a raw material for functional foods. The contents of crude fibre, total protein, carbohydrates, total phenolics and flavonoids in SMS and the composition and relative content of fatty acids in SMS oil were determined. The results suggested that SMS has high contents of crude fibre (28.68 ± 4.66 g/100 g), total protein (26.65 ± 2.51 g/100 g), total phenolics (6.45 ± 0.55 mg of gallic acid equivalent/g) and total flavonoids (3.28 ± 0.34 mg of rutin equivalent/g), as well as a high level of α-linolenic acid (33.774 ± 4.68%) in their oil. Twenty-two secondary metabolites were identified in SMS residue, and nine compounds were isolated. The IC50 values of the total phenolic content in SMS on an ABTS radical, DPPH radical, superoxide radical and hydroxyl radical were 30.94 ± 3.68 µg/mL, 34.93 ± 4.12 µg/mL, 150.87 ± 17.64 µg/mL and 230.19 ± 24.47 µg/mL, respectively. The results indicate that SMS contain many nutrients and have high utilization value as a promising functional food.


Assuntos
Antioxidantes , Magnésio , Radioisótopos , Salvia miltiorrhiza , Antioxidantes/farmacologia , Flavonoides , Fenóis , Compostos Fitoquímicos/farmacologia , Sementes
2.
Appl Radiat Isot ; 208: 111307, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38564840

RESUMO

Early works that used thermoluminescent dosimeters (TLDs) to measure absorbed dose from alpha particles reported relatively high variation (10%) between TLDs, which is undesirable for modern dosimetry applications. This work outlines a method to increase precision for absorbed dose measured using TLDs with alpha-emitting radionuclides by applying an alpha-specific chip factor (CF) that individually characterizes the TLD sensitivity to alpha particles. Variation between TLDs was reduced from 21.8% to 6.7% for the standard TLD chips and 7.9% to 3.3% for the thin TLD chips. It has been demonstrated by this work that TLD-100 can be calibrated to precisely measure the absorbed dose to water from alpha-emitting radionuclides.


Assuntos
Dosímetros de Radiação , Dosimetria Termoluminescente , Dosimetria Termoluminescente/métodos , Radioisótopos , Radiometria/métodos , Calibragem
3.
J Environ Manage ; 357: 120851, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581894

RESUMO

Conventional liquid treatments for large-scale, low-level radioactive wastewater, such as ion exchange and waste solidification, face challenges due to the large amounts of secondary waste and high disposal costs. A new large-scale decontamination method is proposed that uses kapok fiber composites for rapid radionuclide adsorption and high volume reduction to minimize secondary waste. The composite consists of natural zeolite and kapok holocellulose, which has high water-soaking ability and low-temperature pyrolysis. The kapok composites, fabricated using a commercial wet-laid nonwoven manufacturing process, absorbs 99% of low-level radioactive cesium in 20 min, reducing the volume by 98% and the weight by 47% at 300 °C. The low-temperature pyrolysis process below 300 °C prevents cesium desorption and gasification by avoiding zeolite destruction. The mass-producible kapok composites can be used for adsorbing various radionuclides in large-scale wastewater by attaching specific adsorbents for target isotopes to the composites.


Assuntos
Resíduos Radioativos , Zeolitas , Águas Residuárias , Césio , Radioisótopos , Adsorção , Resíduos Radioativos/prevenção & controle
4.
Q J Nucl Med Mol Imaging ; 68(1): 23-31, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38587360

RESUMO

Pediatric gastrointestinal imaging plays a crucial role in evaluating and managing digestive system disorders in children. This comprehensive review dives into the nuances of pediatric gastrointestinal imaging techniques, focusing on three specific modalities: gastric emptying scintigraphy (GES), intestinal transit scintigraphy (ITS), and gastrointestinal bleeding scintigraphy. GES involves real-time monitoring of stomach emptying using radiotracers and gamma camera technology. While challenges exist in standardizing protocols due to age-specific meal compositions, GES remains pivotal in diagnosing motility disorders, gastroesophageal reflux, and abdominal pain in children. ITS, utilizing [67Ga], provides insights into gastrointestinal motility disorders such as Hirschsprung disease. It aids in whole-gut transit evaluation, guiding surgical interventions and improving long-term clinical outcomes. Gastrointestinal bleeding scintigraphy, employing [99mTc], assists in diagnosing conditions like Meckel's diverticulum and occult bleeding, offering continuous monitoring to pinpoint the bleeding site along the entire gastrointestinal tract. SPECT-CT improves the accuracy and the standards of care. Each technique's protocol details, clinical indications, and diagnostic capabilities are thoroughly discussed, highlighting the importance of these non-invasive, functional imaging modalities in pediatric gastroenterology.


Assuntos
Esvaziamento Gástrico , Radioisótopos , Humanos , Criança , Cintilografia , Hemorragia Gastrointestinal
5.
Appl Radiat Isot ; 208: 111297, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38513476

RESUMO

Proton therapy has emerged as an advantageous modality for tumor radiotherapy due to its favorable physical and biological properties. However, this therapy generates induced radioactivity through nuclear reactions between the primary beam, secondary particles, and surrounding materials. This study focuses on systematically investigating the induced radioactivity in the gantry room during pencil beam scanning, utilizing both experimental measurements and Monte Carlo simulations. Results indicate that patients are the primary source of induced radioactivity, predominantly producing radionuclides such as 11C, 13N, and 15O. Long-term irradiation primarily generates radionuclides like 22Na, 24Na, and 54Mn etc. Additionally, this study estimates the individual doses received by medical workers in the gantry room, the irradiation dose for patient escorts, and the additional dose to patients from residual radiation. Finally, the study offers recommendations to minimize unnecessary irradiation doses to medical workers, patient escorts, and patients.


Assuntos
Terapia com Prótons , Radioatividade , Humanos , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Radioisótopos , Método de Monte Carlo , Planejamento da Radioterapia Assistida por Computador/métodos
6.
Theranostics ; 14(5): 1829-1840, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505615

RESUMO

Rationale: Evaluation of alternative radionuclides for use in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is currently focusing on 161Tb, which may provide advantages by emitting additional Auger and conversion electrons. In this pilot study, we present preliminary dosimetry data for [161Tb]Tb-PSMA-617 RLT in a direct comparison with [177Lu]Lu-PSMA-617. Method: Six patients with metastatic castration-resistant prostate cancer (mCRPC) underwent treatment with [177Lu]Lu-PSMA-617 and subsequently - after inadequate response - with [161Tb]Tb-PSMA-617. Whole-body planar and SPECT imaging-based dosimetry of organs at risk (kidneys and salivary glands) and tumor lesions were calculated using IDAC for 177Lu and OLINDA/EXM for 161Tb. The therapeutic index (TI) of mean tumor-absorbed doses over relevant organs at risk was calculated. Results: Mean absorbed doses to organs at risk of PSMA-RLT were slightly higher for [161Tb]Tb-PSMA-617 compared to [177Lu]Lu-PSMA-617 (kidneys: 0.643 ± 0.247 vs. 0.545 ± 0.231 Gy/GBq, factor 1.18; parotid gland: 0.367 ± 0.198 vs. 0.329 ± 0.180 Gy/GBq, factor 1.10), but markedly higher regarding tumor lesions (6.10 ± 6.59 vs 2.59 ± 3.30 Gy/GBq, factor 2.40, p < 0.001). Consequently, the mean TI was higher for [161Tb]Tb-PSMA-617 compared to [177Lu]Lu-PSMA-617 for both, the kidneys (11.54 ± 9.74 vs. 5.28 ± 5.13, p = 0.002) and the parotid gland (16.77 ± 13.10 vs. 12.51 ± 18.09, p = 0.008). Conclusion: In this intra-individual head-to-head pilot study, [161Tb]Tb-PSMA-617 delivered higher tumor-absorbed doses and resulted in superior TI compared to [177Lu]Lu-PSMA-617. This preliminary data support 161Tb as a promising radionuclide for PSMA-RLT in mCRPC.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Projetos Piloto , Compostos Radiofarmacêuticos/uso terapêutico , Dipeptídeos/uso terapêutico , Antígeno Prostático Específico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Radioisótopos/uso terapêutico , Lutécio
7.
Appl Radiat Isot ; 207: 111235, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38430824

RESUMO

The use of radiopharmaceuticals has gained a special place in the diagnosis and treatment of cancers and evaluation of the function of different organs of the body. In this study, the absorbed dose distribution of organs after injection of 188Re-Mu-9 has been investigated using MIRD method and MCNP-4C simulation code. The 188Re-Mu-9 labeled was injected the mouse body and the amount of 188Re-labeled accumulation was evaluated after 1, 4 and 2 4 h. Having a map of the distribution of radiopharmaceutical activity in the animal body, it is possible to convert it into a human model to obtain the internal dose received by 188Re-Mu-9 injection using the MIRD calculation method and the MCNP simulation code. According to the results of the study, the animal/human model can be acceptable method for dose estimation of antibody-based radiopharmaceuticals.


Assuntos
Compostos Radiofarmacêuticos , Rênio , Humanos , Camundongos , Animais , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos , Rênio/uso terapêutico , Radiometria/métodos
8.
Acc Chem Res ; 57(6): 933-944, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501206

RESUMO

ConspectusNuclear medicine harnesses radioisotopes for the diagnosis and treatment of disease. While the isotopes 99mTc and 111In have enabled the clinical diagnosis of millions of patients over the past 3 decades, more recent clinical translation of numerous 68Ga/177Lu-based radiopharmaceuticals for diagnostic imaging and therapy underscores the clinical utility of metal-based radiopharmaceuticals in mainstream cancer treatment. In addition to such established radionuclides, advancements in radioisotope production have enabled the production of radionuclides with a broad range of half-lives and emission properties of interest for nuclear medicine. Chemical means to form kinetically inert, in vivo-compatible species that can be modified with disease-targeting vectors is imperative. This presents a challenge for radiosiotopes of elements where the aqueous chemistry is still underdeveloped and poorly understood. Here, we discuss our efforts to date in exploring the aqueous, radioactive coordination chemistry of highly Lewis acidic metal ions and how our discoveries apply to the diagnosis and treatment of cancer in preclinical models of disease. The scope of this Account includes approaches to aqueous coordination of to-date understudied highly Lewis acidic metal ions with radioisotopes of emerging interest and the modulation of well-understood coordination environments of radio-coordination complexes to induce metal-catalyzed reactivity for separation and pro-drug applications.First, we discuss the development of seven-coordinate, small-cavity macrocyclic chelator platform mpatcn/picaga as an exemplary case study, which forms robust complexes with 44Sc/47Sc isotopes. Due to the high chemical hardness and pronounced Lewis acidity of the Sc3+ ion, the displacement of ternary ligand H2O by 18/natF- can be achieved to form an inert Sc-18/natF bond. Corresponding coordination complex natSc-18F is in vivo compatible and forms a theranostic tetrad with corresponding 44Sc/47Sc, 177Lu complexes all exhibiting homologous biodistribution profiles. Another exceptionally hard, highly Lewis acidic ion with underdeveloped aqueous chemistry and emerging interest in nuclear medicine is 45Ti4+. To develop de novo approaches to the mononuclear chelation of this ion under aqueous conditions, we employed a fragment-based bidentate ligand screening approach which identified two leads. The screen successfully predicted the formation of [45Ti][Ti(TREN-CAM)], a Ti-triscatechol complex that exhibits remarkable in vivo stability. Furthermore, the fragment-based screen also identified approaches that enabled solid-phase separation of Ti4+ and Sc3+ of interest in streamlining the isotope production of 45Ti and accessing new ways to separate 44Ti/44Sc for the development of a long-lived generator system. In addition to establishing the inert chelation of Ti4+ and Sc3+, we introduce controlled, metal-induced reactivity of corresponding coordination complexes on macroscopic and radiotracer scales. Metal-mediated autolytic amide bond cleavage (MMAAC) enables the temperature-dependent release of high-molar-activity, ready-to-inject radiopharmaceuticals; cleavage is selectively triggered by coordinated trivalent Lewis acid nat/68Ga3+ or Sc3+. Following the scope of reactivity and mechanistic studies, we validated MMAAC for the synthesis of high-molar-activity radiopharmaceuticals to image molecular targets with low expression and metal-mediated prodrug hydrolysis in vivo.This Account summarizes how developing the aqueous coordination chemistry and tuning the chemical reactivity of metal ions with high Lewis acidity at the macroscopic and tracer scales directly apply to the radiopharmaceutical synthesis with clinical potential.


Assuntos
Complexos de Coordenação , Medicina Nuclear , Humanos , Compostos Radiofarmacêuticos/química , Ácidos de Lewis , Complexos de Coordenação/química , Ligantes , Distribuição Tecidual , Radioisótopos/química , Quelantes/química , Metais , Íons
9.
Sci Rep ; 14(1): 5241, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438490

RESUMO

This study assessed the radioactivity levels and associated risks in the black sand-separated products obtained from the black sand separation plant in Delta, Egypt. A total of sixteen samples were taken from hot spots during and after the separation process. These include water samples and other samples that represent monazite, rutile, zircon, granite, ilmenite, and silica products. The hot spots included the area where the ore was stored. The activity concentrations of 232 T h , 226 R a , and 40 K were determined in these samples using a p-type HPGe detector. Based on gamma spectrometric analysis, samples of rutile, zircon, and monazite had the highest amounts of radioactivity because they contained the highest NORM's activity concentrations. In addition, it indicated that the radiological hazard indices of the collected samples were higher than the average world limits for sand texture. These findings suggest that the black sand separation process reveals potential risks to human health and the environment, and therefore, appropriate measures need to be taken to mitigate these risks, especially for the safety of the workers on-site. Reducing the risk associated with those sites should be controlled by implementing the recommendations declared for the series of International Basic Safety Standards of the International Atomic Energy Agency (GSR) Part 3, as affirmed in Document No. 103 of 2007 by the International Commission on Radiological Protection (ICRP) as will be presented in the paper body.


Assuntos
Dermatite , Metais Terras Raras , Areia , Silicatos , Titânio , Zircônio , Humanos , Minerais , Radioisótopos
10.
Environ Monit Assess ; 196(3): 330, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427152

RESUMO

The Kanyakumari coast is known to be a high background natural radiation area due to the placer deposits of heavy minerals such as ilmenite, monazite, and rutile. The Kanyakumari river sediments that could be the source of the elevated amounts of natural radionuclides in the coastal sands have been studied in this paper. The activity concentrations of primordial radionuclides 226Ra, 232Th, and 40K were determined using high-purity germanium (HPGe) gamma-ray spectrometry. The mean activity concentrations of 226Ra, 232Th, and 40K were found to be 75 Bq kg-1, 565 Bq kg-1, and 360 Bq kg-1, respectively. The mean absorbed dose rate was 395 nGy h-1. Radiological hazard parameters were studied and compared with the world average values. The contribution of 232Th to the total dose rate was found to be higher than that of the two other radionuclides. The high mean ratio of 232Th/226Ra suggested an enrichment of 232Th and the occurrence of 226Ra leaching due to an oxidizing environment. Principal component analysis (PCA) was carried out for the radionuclides in order to discriminate the source of the sediments. This study provides new insights into the distribution of natural radionuclides in sediments of rivers and streams.


Assuntos
Monitoramento de Radiação , Poluentes Radioativos do Solo , Rios , Radiação de Fundo , Monitoramento Ambiental , Tório/análise , Radioisótopos/análise , Poluentes Radioativos do Solo/análise , Índia , Medição de Risco , Monitoramento de Radiação/métodos , Radioisótopos de Potássio/análise
11.
Probl Endokrinol (Mosk) ; 70(1): 13-17, 2024 Feb 27.
Artigo em Russo | MEDLINE | ID: mdl-38433537

RESUMO

Within the framework of the article, the authors analyzed the available information about the damage to the lacrimal apparatus during radionuclide therapy. In focus of article lesions of the lacrimal production system, the main and accessory lacrimal glands, as well as lacrimal drainage are considered. It was found that damage to the lacrimal apparatus is characteristic of 131I therapy for thyroid cancer, as well as for radioligand therapy using anti-PSMA antibodies labeled with 177Lu and 225Ac. 177Lu-PSMA and 225Ac-PSMA may damage the lacrimal gland with the formation of a clinically pronounced "dry eye syndrome". The pathogenesis of such lesions is associated with the accumulation of a radioisotope in the tissues of the lacrimal apparatus, while during therapy with 131I, accumulation is realized due to the expression of the sodium-iodine symporter in the nasolacrimal duct, and during therapy with 177Lu-PSMA and 225Ac-PSMA, the radiobiological effect is realized in connection with the expression PSMA by lacrimal tissue. An analysis of the available sources showed that to date there are no results of systematic studies on the problem, there is a lack of knowledge regarding the individual risks of developing these complications, methods for their prevention that have proven effectiveness have not been developed, and the treatment methods used, having relatively low efficiency, are not specialized. The authors concluded that the strengthening of interdisciplinary interaction, as well as the organization verification methodology and correct studies, can contribute to solving problems related to the study of the complications under consideration.


Assuntos
Aparelho Lacrimal , Lutécio , Radioisótopos , Actínio , Radioisótopos do Iodo
12.
J Nucl Med Technol ; 52(1): 48-51, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443109

RESUMO

The radionuclide gastric emptying study is the gold standard for the diagnosis of gastroparesis. Methods: We performed a retrospective analysis of 510 patients to evaluate how often a diagnosis of slow gastric emptying determined by gastric emptying scintigraphy (GES) changes clinical management at our institution. Results: We found evidence of gastroparesis in 100 patients. A change in management was recommended for 62% within 1 mo of the GES. Conclusion: Our results illustrate the importance of performing GES on patients with clinically suspected gastroparesis.


Assuntos
Esvaziamento Gástrico , Gastroparesia , Humanos , Gastroparesia/diagnóstico por imagem , Estudos Retrospectivos , Cintilografia , Radioisótopos
13.
Ann Med ; 56(1): 2320301, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38442298

RESUMO

Aim: This comprehensive review aims to explore the potential applications of Gastrin-releasing peptide receptor (GRPR) in the diagnosis and treatment of prostate cancer. Additionally, the study investigates the role of GRPR in prognostic assessment for individuals afflicted with prostate cancer.Methods: The review encompasses a thorough examination of existing literature and research studies related to the upregulation of GRPR in various tumor types, with a specific focus on prostate. The review also evaluates the utility of GRPR as a molecular target in prostate cancer research, comparing its significance to the well-established Prostate-specific membrane antigen (PSMA). The integration of radionuclide-targeted therapy with GRPR antagonists is explored as an innovative therapeutic approach for individuals with prostate cancer.Results: Research findings suggest that GRPR serves as a promising molecular target for visualizing low-grade prostate cancer. Furthermore, it is demonstrated to complement the detection of lesions that may be negative for PSMA. The integration of radionuclide-targeted therapy with GRPR antagonists presents a novel therapeutic paradigm, offering potential benefits for individuals undergoing treatment for prostate cancer.Conclusions: In conclusion, this review highlights the emerging role of GRPR in prostate cancer diagnosis and treatment. Moreover, the integration of radionuclide-targeted therapy with GRPR antagonists introduces an innovative therapeutic approach that holds promise for improving outcomes in individuals dealing with prostate cancer. The potential prognostic value of GRPR in assessing the disease's progression adds another dimension to its clinical significance in the realm of urology.


Assuntos
Neoplasias da Próstata , Receptores da Bombesina , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Biomarcadores , Regulação para Cima , Radioisótopos
14.
J Radiol Prot ; 44(2)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38507787

RESUMO

The manipulation of unsealed radiopharmaceuticals by healthcare workers can cause accidental personal contamination leading to occupational radiation skin dose. The UK Ionising Radiations Regulations 2017 require that potential skin doses arising from reasonably foreseeable accident scenarios are included in risk assessments. Workers must be designated as classified if these dose estimates exceed 150 mSv equivalent dose averaged over 1 cm2. Updates from the UK Health and Safety Executive recently prompted many in the UK to review the classification of workers in Nuclear Medicine. Skin dose from contamination cannot be measured, it must be estimated. Varskin+ is a code that is widely recommended for estimating skin dose. The subjective choices made by users when defining modelled scenarios in Varskin+ lead to significant variation in the calculated skin doses. At the time of writing there is no definitive calculation method and all calculations rely on theoretical models. NHS Health Boards in Scotland have adopted a standardised framework for performing skin dose estimates for risk assessments. The parametric sensitivity of Varskin+ inputs were examined and the available evidence was reviewed. Generic, reasonably forseeable, worst-case accident scenarios were decided upon for: direct skin contamination, glove contamination and needlestick injury. Standardised inputs and assumptions for each scenario were compiled in a protocol that has been adopted by the Scottish Health Boards. The protocol allows for differences in practice between departments, but standardises most inputs. While significant uncertainty remains in the estimated skin doses, this approach reduces variation and enables the comparison of estimated skin doses between departments. The framework facilitates continuous improvement as more evidence is gathered to refine the standardised assumptions. Task by task skin dose estimates were made for workers in Nuclear Medicine in Scotland and many workers were designated classified as a result.


Assuntos
Medicina Nuclear , Exposição Ocupacional , Humanos , Doses de Radiação , Radioisótopos , Pele , Compostos Radiofarmacêuticos
15.
Front Immunol ; 15: 1355388, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550578

RESUMO

Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering ß-emitting 177Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response. To determine the optimal dosage and timing of 177Lu-DOTATATE treatment, we measured CAR T cell infiltration and expansion in tumors longitudinally through positron emission tomography (PET) using a SSTR2-specific positron-emitting radiotracer,18F-NOTA-Octreotide. In animals receiving CAR T cells and a low-dose (2.5 Gy) of TRT following the administration of 177Lu-DOTATATE, we observed a rapid regression of large subcutaneous tumors, which coincided with a dramatic increase in serum proinflammatory cytokines. Tumor burden was also reduced when a higher radiation dose (6 Gy) was delivered to the tumor. However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.


Assuntos
Neoplasias , Animais , Neoplasias/tratamento farmacológico , Octreotida/uso terapêutico , Linfócitos T , Imunoterapia , Radioisótopos/uso terapêutico
16.
Open Vet J ; 14(2): 683-691, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38549576

RESUMO

Background: Canine atopic dermatitis (CAD) is caused by skin barrier dysfunction due to allergen exposure. Excessive glutamate release in the skin is associated with delayed skin barrier function recovery and epidermal thickening and lichenification. Treatment with Yokukansan (YKS), a traditional Japanese medicine, reduces dermatitis severity and scratching behavior in NC/Nga mice by decreasing epidermal glutamate levels. However, the association between canine keratinocytes and glutamate and the mechanism by which YKS inhibits glutamate release from keratinocytes remains unknown. Aim: We aimed to investigate glutamate release from canine progenitor epidermal keratinocytes (CPEKs) and the inhibitory effect of YKS on this release. We also explored the underlying mechanism of YKS to enable its application in CAD treatment. Methods: Glutamate produced from CPEKs in the medium at 24 hours was measured. The measurement conditions varied in terms of cell density and YKS concentration. CPEKs were treated with a glutamate receptor antagonist (MK-801), a glutamate transporter antagonist (THA), and a glutamate dehydrogenase inhibitor (epigallocatechin gallate; EGCG), and the inhibitory effect of YKS, YKS + THA, MK-801, and EGCG on this release was determined. MK-801 and glutamate dehydrogenase inhibitor were tested alone, and THA was tested in combination with YKS. Finally, glutamine incorporated into CPEKs at 24 hours was measured using radioisotope labeling. Results: CPEKs released glutamate in a cell density-dependent manner, inhibited by YKS in a concentration-dependent manner. Moreover, YKS reduced the intracellular uptake of radioisotope-labeled glutamine in a concentration-dependent manner. No involvement of glutamate receptor antagonism or activation of glutamate transporters was found, as suggested by previous studies. In addition, EGCG could inhibit glutamate release from CPEKs. Conclusion: Our findings indicated that glutamate release from CPEKs could be effectively inhibited by YKS, suggesting the utility of YKS in maintaining skin barrier function during CAD. In addition, CPEKs are appropriate for analyzing the mechanism of YKS. However, we found that the mechanism of action of YKS differs from that reported in previous studies, suggesting that it may have had a similar effect to EGCG in this study. Further research is warranted to understand the exact mechanism and clinical efficacy in treating CAD.


Assuntos
Medicamentos de Ervas Chinesas , Ácido Glutâmico , Glutamina , Camundongos , Animais , Cães , Ácido Glutâmico/farmacologia , Glutamina/farmacologia , Maleato de Dizocilpina/farmacologia , Glutamato Desidrogenase/farmacologia , Queratinócitos , Radioisótopos/farmacologia
17.
JAMA Health Forum ; 5(3): e240324, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38551588

RESUMO

Importance: While the Patient Protection and Affordable Care Act (ACA) helped make health insurance premiums more affordable with premium tax credits, ACA marketplace enrollees continue to face barriers to care. Objective: To investigate the effect of informational emails on plan switching and health care utilization. Design, Setting, and Participants: This randomized clinical trial was conducted during the 2021 special enrollment period in California's Affordable Care Act marketplace among households that reported receiving unemployment insurance and were enrolled in non-silver-tier plans. The trial targeted 42 470 households that became temporarily eligible for cost-sharing reduction (CSR) silver plans that covered 94% of medical costs (CSR silver 94 plans) as a result of the 2021 American Rescue Plan Act. Intervention: Households were randomized to either a no-email control group or to a treatment group receiving 2 informational emails encouraging households to switch to CSR plans. Main Outcomes and Measures: The primary outcome was the switch rate to a CSR silver plan by July 31, 2021. Secondary outcomes include various measures of health care utilization in the second half of 2021 (July 1, 2021, to December 31, 2021). Health care utilization was measured by rates of practitioner visits, emergency department visits, hospitalizations, and prescription fills. Results: Of the 42 470 households (head of household mean [SD], age, 41.4 [13.3] years; 51.7% male), 10 650 (25.1%) were in the control group and 31 820 (74.9%) were in the treatment group. The emails led to a statistically significant 3.1-percentage point (95% CI, 2.6-3.6 percentage points) increase in CSR silver 94 enrollment (a 74.8% relative increase) by July 31, 2021, and a 1.3-percentage point (95% CI, 0.2-2.4 percentage points) increase (a 2.3% relative increase) in practitioner visits by December 31, 2021. The emails had no detectable effect on prescription fills, emergency department visits, or hospitalizations. Conclusions and Relevance: The results of this randomized clinical trial provide experimental evidence that, with access to more affordable health care, individuals are more likely to visit practitioners. Trial Registration: ClinicalTrials.gov Identifier: NCT05891418.


Assuntos
Trocas de Seguro de Saúde , Patient Protection and Affordable Care Act , Radioisótopos , Masculino , Humanos , Estados Unidos , Adulto , Feminino , Seguro Saúde , Prata , Cobertura do Seguro , Custo Compartilhado de Seguro , Aceitação pelo Paciente de Cuidados de Saúde
18.
Artigo em Inglês | MEDLINE | ID: mdl-38541314

RESUMO

This article reports the results of an investigation into the activity concentration of natural radionuclides in raw building materials for underground parking lots, together with the assessment of the radiation hazard for the public related to exposure to ionizing radiations. To this purpose, high-purity germanium (HPGe) γ-ray spectrometry was employed in order to quantify the average specific activity of 226Ra, 232Th, and 40K natural radioisotopes. With the aim to assess any possible radiological health risk for the population, the absorbed γ-dose rate (D), the annual effective dose equivalent outdoor (AEDEout) and indoor (AEDEin), the activity concentration index (I), and the alpha index (Iα) were also estimated, resulting in values that were lower than the maximum recommended ones for humans. Finally, the extent of the correlations existing between the observed radioactivity and radiological parameters and of these parameters with the analyzed samples was quantified through statistical analyses, including Pearson's correlation, a principal component analysis (PCA), and a hierarchical cluster analysis (HCA). As a result, three clusters of the investigated samples were recognized based on their chemical composition and mineralogical nature. Noteworthily, this paper covers a certain gap in science since its topic does not appear in literature in this form. Thus, the authors underline the importance of this work to global knowledge in the environmental research and public health fields.


Assuntos
Monitoramento de Radiação , Radioatividade , Rádio (Elemento) , Poluentes Radioativos do Solo , Humanos , Monitoramento de Radiação/métodos , Radioisótopos/análise , Saúde Radiológica , Espectrometria gama , Materiais de Construção/análise , Tório/análise , Radioisótopos de Potássio/análise , Rádio (Elemento)/análise , Poluentes Radioativos do Solo/análise
19.
ACS Nano ; 18(12): 9114-9127, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38477305

RESUMO

Immune checkpoint blockade (ICB) therapy is promising to revolutionize cancer regimens, but the low response rate and the lack of a suitable patient stratification method have impeded universal profit to cancer patients. Noninvasive positron emission tomography (PET) imaging in the whole body, upon coupling with specific biomarkers closely related to the immune response, could provide spatiotemporal information to prescribe cancer therapy. Herein, we demonstrate that antisilencing function 1a (ASF1a) could serve as a biomarker target to delineate tumor immune microenvironments by immune PET (iPET). The iPET radiotracer (68Ga-AP1) is designed to target ASF1a in tumors and predict immune response, and the signal intensity predicts anti-PD-1 (αPD-1) therapy response in a negative correlation manner. The ICB-resistant tumors with a high level of ASF1a as revealed by iPET (ASF1aHigh-iPET) are prescribed to be treated by either the combined 177Lu-labeled AP1 and αPD-1 or the standalone α particle-emitting 225Ac-labeled AP1, both achieving enhanced therapeutic efficacy and prolonged survival time. Our study not only replenishes the iPET arsenal for immune-related response evaluation by designing a reliable biomarker and a facile radiotracer but also provides optional therapeutic strategies for ICB-resistant tumors with versatile radionuclide-labeled AP1 peptides, which is promising for real-time clinical diagnosis and individualized therapy planning simultaneously.


Assuntos
Neoplasias , Radioisótopos , Humanos , Tomografia por Emissão de Pósitrons/métodos , Biomarcadores , Peptídeos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral
20.
Indian J Cancer ; 61(Suppl 1): S1-S28, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424680

RESUMO

ABSTRACT: PET/CT and radioisotope therapy are diagnostic and therapeutic arms of Nuclear Medicine, respectively. With the emergence of better technology, PET/CT has become an accessible modality. Diagnostic tracers exploring disease-specific targets has led the clinicians to look beyond FDG PET. Moreover, with the emergence of theranostic pairs of radiopharmaceuticals, radioisotope therapy is gradually making it's way into treatment algorithm of common cancers in India. We therefore would like to discuss in detail the updates in PET/CT imaging and radionuclide therapy and generate a consensus-driven evidence based document which would guide the practitioners of Oncology.


Assuntos
Neoplasias , Medicina Nuclear , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos , Fluordesoxiglucose F18
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