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1.
Alzheimers Dement ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967283

RESUMO

INTRODUCTION: Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation is critical for connecting amyloid beta (Aß) and tau-based degenerative events and early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT-PET radiotracer, [11C]MPC-6827, in multiple established AD mouse models. METHODS: Longitudinal PET, biodistribution, autoradiography, immunohistochemistry, and behavioral studies were conducted at multiple time points in APPswe/PSEN1dE9 (APP/PS1), P301S-PS19 (P301S), 5xFAD, and age-matched control mice. RESULTS: Longitudinal [11C]MPC-6827 brain imaging showed significant increases in APP/PS1, P301S, and 5xFAD mice compared to controls. Longitudinal MT-PET correlated positively with biodistribution, autoradiography, and immunohistochemistry results and negatively with behavior data. DISCUSSION: Our study demonstrated significant longitudinal [11C]MPC-6827 PET increases in multiple AD mouse models for the first time. Strong correlations between PET and biomarker data underscored the interplay of MT destabilization, amyloid, and tau pathology in AD. These results suggest [11C]MPC-6827 PET as a promising tool for monitoring MT dysregulation early in AD progression. HIGHLIGHTS: Longitudinal positron emission tomography (PET) imaging studies using [11C]MPC-6827 in multiple established Alzheimer's disease (AD) mouse models revealed an early onset of microtubule dysregulation, with significant changes in brain radiotracer uptake evident from 2 to 4 months of age. Intra-group analysis showed a progressive increase in microtubule dysregulation with increasing AD burden, supported by significant correlations between PET imaging data and biodistribution, autoradiography, and molecular pathological markers. [11C]MPC-6827 PET imaging demonstrated its efficacy in detecting early microtubule alterations preceding observable behavioral changes in AD mouse models, suggesting its potential for early AD imaging. The inclusion of the 5xFAD mouse model further elucidated the impact of amyloid beta (Aß) toxicity on inducing tau hyperphosphorylation-mediated microtubule dysregulation, highlighting the versatility of [11C]MPC-6827 in delineating various aspects of AD pathology. Our study provides immediate clarity on high uptake of the microtubule-based radiotracer in AD brains in a longitudinal setting, which directly informs clinical utility in Aß/tau-based studies.

2.
Chirality ; 35(7): 427-434, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36843151

RESUMO

Ganirelix, a drug used in in vitro fertilization (IVF), prevents ovulation in women who are not ready to have children by inhibiting a gene that produces gonadotropin. Peptides are macromolecules that are able to preserve a predetermined shape while carrying out the structural and regulatory roles for which they were originally intended. Peptide structures can be altered in the production and storage processes. Therapeutic peptides' biological activity can be drastically altered by even small modifications in their primary and secondary structures. The molecules' secondary structures can be monitored by subjecting them to different processing or storage conditions. In our investigation, we used circular dichroism (CD) spectroscopy with two different software programs for secondary structure evaluation to look at how environmental factors like temperature and humidity affected the secondary structure of Ganirelix in an injectable formulation. The CD results revealed that the alpha-helical (regular and distorted), beta-sheet, beta-strands (regular and distorted), beta-turn, and random coil structures of temperature and humidity stressed generic drug products are comparable to reference-listed drug.


Assuntos
Hormônio Liberador de Gonadotropina , Criança , Feminino , Humanos , Temperatura , Dicroísmo Circular , Umidade , Estereoisomerismo , Hormônio Liberador de Gonadotropina/uso terapêutico
3.
Molecules ; 27(23)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36500672

RESUMO

The purpose of this research study was to develop an analytical method for the quantification of 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4] triazolo [4,3-a] pyrazine (7-nitroso impurity), which is a potential genotoxic impurity. Since sitagliptin is an anti-diabetic medication used to treat type 2 diabetes and the duration of the treatment is long-term, the content of nitroso impurity must be controlled by using suitable techniques. To quantify this impurity, a highly sensitive and reproducible ultraperformance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-MS/MS) method was developed. The analysis was performed on a Kromasil-100, with a C18 column (100 mm × 4.6 mm with a particle size of 3.5 µm) at an oven temperature of approximately 40 °C. The mobile phase was composed of 0.12% formic acid in water, with methanol as mobile phases A and B, and the flow rate was set to 0.6 mL/min. The method was validated according to the current International Council for Harmonisation (ICH) guidelines with respect to acceptable limits, specificity, reproducibility, accuracy, linearity, precision, ruggedness and robustness. This method is useful for the detection of the impurity at the lowest limit of detection (LOD), which was 0.002 ppm, and the lowest limit of quantification (LOQ), which was 0.005 ppm. This method was linear in the range of 0.005 to 0.06 ppm and the square of the correlation coefficient (R2) was determined to be > 0.99. This method could help to determine the impurity in the regular analysis of sitagliptin drug substances and drug products.


Assuntos
Diabetes Mellitus Tipo 2 , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Fosfato de Sitagliptina , Reprodutibilidade dos Testes , Cromatografia Líquida
4.
Molecules ; 27(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36432023

RESUMO

Cross contamination of ß-lactams is one of the highest risks for patients using pharmaceutical products. Penicillin and some non-penicillin ß-lactams may cause potentially life-threatening allergic reactions. The trace detection of ß-lactam antibiotics in cleaning rinse solutions of common reactors and manufacturing aids in pharmaceutical facilities is very crucial. Therefore, the common facilities adopt sophisticated cleaning procedures and develop analytical methods to assess traces of these compounds in rinsed solutions. For this, a highly sensitive and reproducible ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the analysis of Cephapirin and Ceftiofur. As per the FDA guidelines described in FDA-2011-D-0104, the contamination of these ß-lactam antibiotics must be regulated. The analysis was performed on an XBridge C18 column with 100 mm length, 4.6 mm diameter, and 3.5 µm particle size at an oven temperature of about 40 °C. The mobile phase was composed of 0.15% formic acid in water and acetonitrile as mobile phases A and B, and a flow rate was set to 0.6 mL/min. The method was validated for Cephapirin and Ceftiofur. The quantification precision and accuracy were determined to be the lowest limit of detection 0.15 parts per billion (ppb) and the lowest limit of quantification 0.4 ppb. This method was linear in the range of 0.4 to 1.5 ppb with the determination of coefficient (R2 > 0.99). This sensitive and fast method was fit-for-purpose for detecting and quantifying trace amounts of ß-lactam contamination, monitoring cross contamination in facility surface cleaning, and determining the acceptable level of limits for regulatory purposes.


Assuntos
Cefapirina , Humanos , Espectrometria de Massas em Tandem/métodos , Antibacterianos/análise , Reprodutibilidade dos Testes , Cromatografia Líquida/métodos , beta-Lactamas , Monobactamas , Penicilinas
5.
Biomed Pharmacother ; 156: 113937, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36411624

RESUMO

Over production of reactive oxygen species (ROS) caused by altered redox regulation of signaling pathways is common in many types of cancers. While PET imaging is recognized as the standard tool for cancer imaging, there are no clinically-approved PET radiotracers for ROS-imaging in cancer diagnosis and treatment. An ascorbate-based radio ligand promises to meet this urgent need. Our laboratory recently synthesized [18F] KS1, a fluoroethoxy furanose ring-containing ascorbate derivative, to track ROS in prostate tumor-bearing mice. Here we report cell uptake assays of [18F]KS1 with different ROS-regulating agents, PET imaging in head and neck squamous cell carcinoma (HNSCC) mice, and doxorubicin-induced rats; PET imaging in healthy and irradiated hepatic tumor-bearing rhesus to demonstrate its translational potential. Our preliminary evaluations demonstrated that KS1 do not generate ROS in tumor cells at tracer-level concentrations and tumor-killing properties at pharmacologic doses. [18F]KS1 uptake was low in HNSCC pretreated with ROS blockers, and high with ROS inducers. Tumors in high ROS-expressing SCC-61 took up significantly more [18F]KS1 than rSCC-61 (low-ROS expressing HNSCC); high uptake in doxorubicin-treated rats compared to saline-treated controls. Rodent biodistribution and PET imaging of [18F]KS1 in healthy rhesus monkeys demonstrated its favorable safety, pharmacokinetic properties with excellent washout profile, within 3.0 h of radiotracer administration. High uptake of [18F]KS1 in liver tumor tissues of the irradiated hepatic tumor-bearing monkey showed target selectivity. Our strong data in vitro, in vivo, and ex vivo here supports the high translational utility of [18F]KS1 to image ROS.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Hepáticas , Masculino , Animais , Ratos , Camundongos , Ligantes , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual , Carcinoma de Células Escamosas de Cabeça e Pescoço , Roedores/metabolismo , Ácido Ascórbico , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Doxorrubicina , Primatas/metabolismo
6.
Saudi J Biol Sci ; 29(2): 689-701, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35197734

RESUMO

AXL kinase is an attractive cancer target for drug design and it is involved in different cancers. A set of molecule databases with 1072 secondary metabolites from seaweeds were screened against the AXL kinase active site and eight molecules were shortlisted for further studies. From the docking analysis of the complexes, four molecules GA011, BE005, BC010, and BC005 are showing prominent binging. From the 100 ns of molecular dynamics simulations and ligand-bound complex MM-PBSA free energy analysis, two molecules BC010 (ΔG = -135.38 kJ/mol) and BE005 (ΔG = -141.72 kJ/mol) are showing molecule stability in the active site also showing very strong binding free energies. It suggests these molecules could be the potent molecules for AXL kinase.

7.
Bioelectrochemistry ; 143: 107935, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34637962

RESUMO

Serum 25-hydroxyvitamin D (25(OH)D) has been clinically considered as a novel biomarker for vitamin D deficiency. The current standard technologies for the detection of 25(OH)D are performed in sophisticated laboratories exhibiting the practical limitations for onsite and affordable testing. Therefore, the development of a cost-effective device for Vitamin D is extremely necessary to provide an earlier diagnosis. Herein, for the first time, we propose a novel label-free impedimetric immunosensor for the detection and quantification of 25-hydroxyvitamin D3 (25(OH)D3) biomarker in serum samples based on the Au nanoparticles functionalized GCN-ß-CD nanocomposite. To fabricate the sensing probe, Ab-25(OH)D3 antibodies were covalently immobilized on GCN-ß-CD@Au/GCE using carbodiimide chemistry. The surface morphology and structural properties of constructed immunosensor were confirmed by different analytical techniques. Electrochemical impedance spectroscopy technique (EIS) has been selected as the main detection method to measure the Antibody (Ab) and Antigen (Ag) interaction at the immunosensor surface because it is label-free, less destructive to the activities of the biomolecule, and highly sensitive. The as-prepared immunosensor exhibited an excellent concentration range from 0.1 ng/ml to 500 ng/ml with the lowest limit of detection of 0.01 ng/ml. Furthermore, the sensing probe was validated in serum samples and obtained results were compared with the standard CLIA technique. The results have revealed that the sensing probe could be used for clinical diagnosis of Vitamin D deficiency in the clinical laboratories.


Assuntos
Técnicas Biossensoriais , Ouro
8.
Molecules ; 26(23)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34885659

RESUMO

Aqueous fluorescent dispersions containing dyed acrylic-based copolymer nanoparticles possess significant credentials concerning green technology as compared to those prepared with the conventional vinyl-based monomers in textile and garment sectors; however, their essential textile fastness properties are yet to achieve. In the present work, a series of acrylic nanodispersions were synthesized by varying the moles ratio of benzyl methacrylate (BZMA), methyl methacrylate (MMA), and 2-hydroxypropyl methacrylate (HPMA) monomers. This was done to study their effect on dye aggregation and dyed polymer particles agglomeration. FT-IR spectral analysis showed the formation of polymer structures, while Malvern Analyzer, Transmission Electron Microscopy, and Scanning Electron Microscopy analysis suggested that the particles are spherical in shape and their size is less than 200 nm. The obtained nanodispersions were later applied on cotton fabrics for the evaluation of wash fastness and colour migration. Premier color scan spectrophotometer and zeta potential measurement studies suggested that colour migration of printed cotton fabrics increased with an increasing agglomeration of particles and it was also observed to increase with the moles ratio of MMA and zeta potentials.

9.
Saudi J Biol Sci ; 28(4): 2168-2174, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33935564

RESUMO

Due to their less expensive, environment friendly nature, and their natural abundance of cobalt have attained more significant attention for the synthesis of cobalt nanoparticles. In the present study, we report the facile synthesis of cobalt nanoparticles using a straight forward chemical reduction approach of cobalt chloride with sodium borohydride and capping of sulfadimidine. sulfadimidine has strong capping eligibility on the surface of nanoparticles due to its chemical stability and is an applicable as stabilizer due to the existence of an amine bond. The as-synthesized sulfadimidine stabilized cobalt nanoparticles (Co-SD NPs) were characterized by using various spectroscopic and microscopic analysis like UV-Visible spectroscopy (UV-Vis), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), High-Resolution Transmission electron microscopy (HR-TEM), and Fourier-transform infrared spectroscopy (FT-IR). The XRD analysis exhibited the triclinic crystal structure of the as-synthesized cobalt nanoparticles and FT-IR analysis confirmed the capping of sulfadimidine via monodentate interaction. The HR-TEM analysis displayed the size of the cobalt nanoparticles approximately 3-5 nm. The antibacterial properties of the sulfadimidine stabilized cobalt nanoparticles (Co-SD NPs) were tested against various bacterial strains such as Klebsiella pneumonia (KP), Escherichia coli (EC) and Pseudomonas syringae (PS) by using agar disc diffusion approach. The results of sulfadimidine capped cobalt nanoparticles displayed the enhanced biological properties against the tested gram-negative bacteria.

10.
Eur J Mass Spectrom (Chichester) ; 27(2-4): 126-140, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33823624

RESUMO

Stress study of a drug substance or pharmaceutical drug product provides a vision into degradation pathways and degradation products of the active pharmaceutical ingredient and helps in interpretation of the chemical structure of the degradation impurities. In the current study, Ganirelix active ingredient presented in the Orgalutran® was stressed with acidic and alkali hydrolysis, photolysis, thermal and oxidation conditions as per the guidelines of International Conference on Harmonization (ICH) Q1A (R2). Ganirelix was found to be labile under thermal and alkali hydrolytic stress conditions, while it was stable to acid hydrolytic, oxidative and photolytic stress. All degradation products were separated with a resolution > 1.5 on a C18 column (2.6 µm, 25 cm×4.6 mm) using a hydrophilic ion pair such as sodium perchlorate, at a concentration <0.04 M. In total, four major degradant impurities were found during stress study. These impurities were fractionated and desalted by flash chromatography for identification of chemical structures. LC-MS-QTOF analysis revealed that two degradation products are diastereomers of Ganirelix, one degradation product is a deamination compound and other degradation product result from the insertion of a new amino acid residue in the Ganirelix peptide sequence. The developed method is sensitive enough to quantify the related substances of Ganirelix at the 0.04% level with that of Ganirelix test concentration.


Assuntos
Hormônio Liberador de Gonadotropina , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Estabilidade de Medicamentos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hidrólise , Oxirredução
11.
J Biomol Struct Dyn ; 39(6): 2056-2070, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32178589

RESUMO

AXL kinase has been over expressed in many tumors and its involvement in cell proliferation, migration, survival, and resistance makes the kinase as attractive therapeutic target for many cancers. In this study, we performed a virtual screening of the food and drug administration (FDA) approved drug molecule database against AXL kinase for repurposing studies of breast cancer. We have identified three non-cancer drugs with good binding energies were subjected to in vitro breast cancer MCF-7 cell lines. Three drug molecules showing the activity with good IC50 values toward the cancer cell line. We also carried out a 2 dimensional (2 D) quantitative structure activity relation (QSAR) studies on N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides derivatives to design potent inhibitors for AXL kinase. The final QSAR equation was robust with good predictivity and the statistical validation having R2 and Q2 values are 0.91 and 0.86, respectively. QSAR equation descriptors informs about the chemical properties of AXL inhibitors and helpful for designing novel inhibitors. Communicated by Ramaswamy H. Sarma.


Assuntos
Neoplasias da Mama , Preparações Farmacêuticas , Neoplasias da Mama/tratamento farmacológico , Simulação por Computador , Detecção Precoce de Câncer , Feminino , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade
12.
J Mass Spectrom ; 55(10): e4610, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32786175

RESUMO

Ganirelix is a linear polypeptide consisting of covalently bonded 10 amino acid residues. The amino acid sequence in a peptide determines the properties of the molecule. The slightest change in the primary structure (amino acid sequence) of therapeutic peptides can significantly impact its safety, efficacy, and immunogenicity. Hence, the primary structure analysis of therapeutic peptides is regarded as a critical quality attribute (CQA). A vast array of analytical techniques can be used to capture the primary structure of the peptide. In this study, we applied matrix-assisted laser desorption ionization (MALDI)/tandem time of flight mass spectroscopic (TOF/TOF MS) method to demonstrate the primary structure of Ganirelix in an injectable formulation. The apparent monoisotopic molecular mass of Ganirelix is 1,568.9 Da. The attained primary amino acid sequence of Ganirelix in temperature-stressed generic product matched with the theoretical sequence and showed homology with those of the reference listed drug (RLD).

13.
J Chromatogr Sci ; 58(8): 687-694, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32676669

RESUMO

Ganirelix is a synthetic decapeptide linked with nine different amino acids. To understand the peptide amino acid sequence or primary structure, the first step is to determine the amino acid composition of the peptide which can be a determining factor for the peptide immunogenicity. Edman degradation is not a suitable analytical technique to identify amino acid sequence present in Ganirelix due to the absence of uncharged N-terminal amino group. To address this challenge, a pre-column derivatization method was developed with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate reagent. In the present work, the Ganirelix active pharmaceutical ingredient present in the injectable formulation was isolated by fraction collection and further purified by flash chromatography. The amino acid composition of Ganirelix is assayed by carrying out acid hydrolysis with 6 mol L-1 hydrochloric acid solution containing 1% phenol at 100°C for 24 h and derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate reagent solution, followed by determination of individual amino acids by reverse-phase chromatography using a C18 column. High resolution was achieved for the nine amino acid mixture. The amino acid composition results of temperature-stressed Ganirelix generic product and reference listed drug are in good agreement with the theoretical molar ratio of label information.


Assuntos
Aminoácidos/análise , Aminoquinolinas/química , Carbamatos/química , Hormônio Liberador de Gonadotropina/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Medicamentos Genéricos/análise , Medicamentos Genéricos/química , Hormônio Liberador de Gonadotropina/análise , Hormônio Liberador de Gonadotropina/química , Reprodutibilidade dos Testes
15.
Bioorg Med Chem Lett ; 29(23): 126707, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31630858

RESUMO

We have synthesized a new series of 1,2,3-triazolo piperazine and piperidine carboxylate derivatives using a simple and one-pot click chemistry with significantly reduced reaction times (~5 min) and enhanced reaction yields (~95-98%). The fourteen novel compounds thus synthesized were tested for ability to target GPR119, a G-protein coupled target receptor that plays critical role in regulation of type-2 diabetes mellitus. Four analogs (3e, 3g, 5e and 5g) demonstrated similar or better EC50 values over previously reported AR231453 activity towards GPR119.


Assuntos
Química Click/métodos , Piperazina/uso terapêutico , Piperidinas/uso terapêutico , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Humanos , Estrutura Molecular , Piperazina/farmacologia , Piperidinas/farmacologia , Relação Estrutura-Atividade
16.
EJNMMI Res ; 9(1): 43, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101996

RESUMO

BACKGROUND: Reactive oxygen species (ROS)-induced oxidative stress damages many cellular components such as fatty acids, DNA, and proteins. This damage is implicated in many disease pathologies including cancer and neurodegenerative and cardiovascular diseases. Antioxidants like ascorbate (vitamin C, ascorbic acid) have been shown to protect against the deleterious effects of oxidative stress in patients with cancer. In contrast, other data indicate potential tumor-promoting activity of antioxidants, demonstrating a potential temporal benefit of ROS. However, quantifying real-time tumor ROS is currently not feasible, since there is no way to directly probe global tumor ROS. In order to study this ROS-induced damage and design novel therapeutics to prevent its sequelae, the quantitative nature of positron emission tomography (PET) can be harnessed to measure in vivo concentrations of ROS. Therefore, our goal is to develop a novel translational ascorbate-based probe to image ROS in cancer in vivo using noninvasive PET imaging of tumor tissue. The real-time evaluations of ROS state can prove critical in developing new therapies and stratifying patients to therapies that are affected by tumor ROS. METHODS: We designed, synthesized, and characterized a novel ascorbate derivative (E)-5-(2-chloroethylidene)-3-((4-(2-fluoroethoxy)benzyl)oxy)-4-hydroxyfuran-2(5H)-one (KS1). We used KS1 in an in vitro ROS MitoSOX-based assay in two different head and neck squamous cancer cells (HNSCC) that express different ROS levels, with ascorbate as reference standard. We radiolabeled 18F-KS1 following 18F-based nucleophilic substitution reactions and determined in vitro reactivity and specificity of 18F-KS1 in HNSCC and prostate cancer (PCa) cells. MicroPET imaging and standard biodistribution studies of 18F-KS1 were performed in mice bearing PCa cells. To further demonstrate specificity, we performed microPET blocking experiments using nonradioactive KS1 as a blocker. RESULTS: KS1 was synthesized and characterized using 1H NMR spectra. MitoSOX assay demonstrated good correlations between increasing concentrations of KS1 and ascorbate and increased reactivity in SCC-61 cells (with high ROS levels) versus rSCC-61cells (with low ROS levels). 18F-KS1 was radiolabeled with high radiochemical purity (> 94%) and specific activity (~ 100 GBq/µmol) at end of synthesis (EOS). Cell uptake of 18F-KS1 was high in both types of cancer cells, and the uptake was significantly blocked by nonradioactive KS1, and the ROS blocker, superoxide dismutase (SOD) demonstrating specificity. Furthermore, 18F-KS1 uptake was increased in PCa cells under hypoxic conditions, which have been shown to generate high ROS. Initial in vivo tumor uptake studies in PCa tumor-bearing mice demonstrated that 18F-KS1 specifically bound to tumor, which was significantly blocked (threefold) by pre-injecting unlabeled KS1. Furthermore, biodistribution studies in the same tumor-bearing mice showed high tumor to muscle (target to nontarget) ratios. CONCLUSION: This work demonstrates the strong preliminary support of 18F-KS1, both in vitro and in vivo for imaging ROS in cancer. If successful, this work will provide a new paradigm to directly probe real-time oxidative stress levels in vivo. Our work could enhance precision medicine approaches to treat cancer, as well as neurodegenerative and cardiovascular diseases affected by ROS.

17.
Radiat Prot Dosimetry ; 147(3): 423-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21147790

RESUMO

Exposure of children to ionising radiation is considered to carry higher risk than that of adults; therefore a need to suggest diagnostic reference levels (DRLs) for the common paediatric diagnostic X-ray procedures was recognised for the X-ray machines meeting the requirements of the recently implemented Safety Code for Medical Diagnostic X-ray Equipment and Installations in India. Measurements were carried out for entrance surface air kerma (free in air) in conventional paediatric X-ray diagnostic examinations among four age groups: <1, 1-4, 5-9 and 10-15 y. A total of 2240 air kerma measurements at different fixed focus to skin distances were studied for 7 paediatric diagnostic examinations with 11 different projections on 62 X-ray machines installed in 22 selected hospitals in the country. The third quartile values of air kerma per paediatric examination for the age group of 5-9 y were considered as values of paediatric DRLs. The suggested values of DRLs are 0.2 mGy for chest AP/PA, 0.3 mGy for chest LAT, 0.7 mGy for lumber spine AP, 1.3 mGy for lumber spine LAT, 0.3 mGy for thoracic spine AP, 0.6 mGy for thoracic spine LAT, 0.5 mGy for abdomen AP, 0.7 mGy for pelvis AP, 0.6 mGy for skull PA, 0.5 mGy for skull LAT and 0.8 mGy for hip joints AP.


Assuntos
Exame Físico/normas , Guias de Prática Clínica como Assunto , Doses de Radiação , Proteção Radiológica/estatística & dados numéricos , Padrões de Referência , Abdome/efeitos da radiação , Adolescente , Ar , Criança , Pré-Escolar , Articulação do Quadril/efeitos da radiação , Humanos , Índia , Lactente , Pelve/efeitos da radiação , Radiometria , Valores de Referência , Eficiência Biológica Relativa , Crânio/efeitos da radiação , Coluna Vertebral/efeitos da radiação , Tórax/efeitos da radiação , Raios X
18.
J Med Phys ; 35(4): 229-34, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21170188

RESUMO

We conducted a radiological safety and quality assurance (QA) audit of 118 medical X-ray diagnostic machines installed in 45 major hospitals in India. The main objective of the audit was to verify compliance with the regulatory requirements stipulated by the national regulatory body. The audit mainly covered accuracy check of accelerating potential (kVp), linearity of tube current (mA station) and timer, congruence of radiation and optical field, and total filtration; in addition, we also reviewed medical X-ray diagnostic installations with reference to room layout of X-ray machines and conduct of radiological protection survey. A QA kit consisting of a kVp Test-O-Meter (ToM) (Model RAD/FLU-9001), dose Test-O-Meter (ToM) (Model 6001), ionization chamber-based radiation survey meter model Gun Monitor and other standard accessories were used for the required measurements. The important areas where there was noncompliance with the national safety code were: inaccuracy of kVp calibration (23%), lack of congruence of radiation and optical field (23%), nonlinearity of mA station (16%) and timer (9%), improper collimator/diaphragm (19.6%), faulty adjustor knob for alignment of field size (4%), nonavailability of warning light (red light) at the entrance of the X-ray room (29%), and use of mobile protective barriers without lead glass viewing window (14%). The present study on the radiological safety status of diagnostic X-ray installations may be a reasonably good representation of the situation in the country as a whole. The study contributes significantly to the improvement of radiological safety by the way of the steps already taken and by providing a vital feed back to the national regulatory body.

20.
Food Addit Contam ; 21(8): 786-93, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15370830

RESUMO

Aflatoxins occur naturally in many agricultural crops causing health hazards and economic losses. Despite improved handling, processing and storage, they remain a problem in the peanut industry. Therefore, new ways to detoxify contaminated products are needed to limit economic/health impacts and add value to the peanut industry. The study was conducted (1) to evaluate the effectiveness of ozonation and mild heat in breaking down aflatoxins in peanut kernels and flour, and (2) to quantify aflatoxin destruction compared with untreated samples. Peanut samples were inoculated with known concentrations of aflatoxins B1, B2, G1 and G2. Samples were subjected to gaseous ozonation and under various temperatures (25, 50, 75 degrees C) and exposure times (5, 10, 15 min). Ozonated and non-ozonated samples were extracted in acetonitrile/water, derivatized in a Kobra cell and quantified by high-performance liquid chromatography. Ozonation efficiency increased with higher temperatures and longer treatment times. Regardless of treatment combinations, aflatoxins B1 and G1 exhibited the highest degradation levels. Higher levels of toxin degradation were achieved in peanut kernels than in flour. The temperature effect lessened as the exposure time increased, suggesting that ozonation at room temperature for 10-15 min could yield degradation levels similar to those achieved at higher temperatures while being more economical.


Assuntos
Aflatoxinas/química , Arachis/química , Contaminação de Alimentos/prevenção & controle , Ozônio/farmacologia , Aflatoxina B1/química , Temperatura Alta , Fatores de Tempo
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