Highly Water-Soluble Orotic Acid Nanocrystals Produced by High-Energy Milling

Compri, Jéssica de Cássia Zaghi; Felli, Veni Maria Andres; Lourenço, Felipe Rebello; Takatsuka, Takayuki; Fotaki, Nikoletta; Löbenberg, Raimar; Bou‐Chacra, Nádia Araci; Araujo, Gabriel Lima Barros de

doi:10.1016/j.xphs.2018.12.015

Cited by 16 publications

(7 citation statements)

References 53 publications

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“…Positive immunoreactivity for BRAF V600E can support the diagnosis of ATC, although these mutations are also present in a variety of other tumor types (79). IHC for BRAF V600E can also serve as a surrogate for molecular testing preoperatively and in the immediate postdiagnostic period and thus can be used theranostically for targeted BRAF inhibition (33,80). However, the correlation between immunoreactivity and mutation is not complete and confirmatory molecular diagnostics should be performed.…”

Section: Immunohistochemistrymentioning

confidence: 99%

2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer

Bible

Kebebew

Brierley

et al. 2021

Thyroid

413

423

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Background: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Since the guidelines for the management of ATC by the American Thyroid Association were first published in 2012, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, and researchers on published evidence relating to the diagnosis and management of ATC. Methods: The specific clinical questions and topics addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of the Task Force members (authors of the guideline). Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. Results: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, targeted/systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues, including end of life. The guidelines include 31 recommendations and 16 good practice statements. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of ATC. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with ATC.

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Section: Immunohistochemistrymentioning

confidence: 99%

2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer

Bible

Kebebew

Brierley

et al. 2021

Thyroid

413

423

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“…Mechanoactivated magnesium orotate is more active in vitro [14] and changes the ratio of CD68+ macrophages in the thymus [15]. It is important that the state of the compounds achieved by processing in high-energy devices under the regimes does not lead to destruction or change in the crystal or isomeric structure of the substance [6,16]. In the magnesium orotate molecule, not only magnesium plays a significant biological role, but also the orotic acid anion, which is an intermediate in the biosynthesis of pyrimidine and provides a wide range of usefull effects [17][18][19].…”

Section: Resultsmentioning

confidence: 99%

Morphofunctional characterization of rat thymus mast cells after administration of magnesium orotate mechanically activated forms

Чучкова

Сметанина

Shklyaev

et al. 2021

Vestn. Ross. univ. družby nar., Ser. Med.

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Relevance. The topicality of the work is determined by the wide spread of hypomagnesemia among the people, which makes it necessary to correct it. The aim of the work is to elucidate the cell-mediated response of the thymus mastocytic link to magnesium deficiency and its correction by the mechanoactivated form of magnesium orotate. Materials and Methods . Animals with drug-induced magnesium deficiency (administration of furosemide 30 mg/kg for 14 days) were administered either the initial preparation Magnerot (Magnerot, Vervag Pharma, Germany), or its mechanoactivated form. The level of magnesium in the blood was determined by test systems ARKREY (Japan). The concentration of magnesium in the thymus tissue was determined by the method of emission spectroscopy with inductively coupled (argon) plasma on an atomic emission spectrometer. Density of mastocytes and the indices of degranulation and granulolosis were calculated on paraffin sections of the thymus after coloration with toluidine blue. Results and Discussion . It was shown that furosemide administration the amount of magnesium decreased in the blood (from 1,750,08 to 0,9020,18 mmol/l, p0,05), but increased in the thymus (from 1,60,6 in the control to 3,71,2 mg/l); in the gland tissue, the number of mastocytes of morphotype A decreased and the number of mastocytes of morphotype D, after active degranulation, increased (by 7,1 times, p0,05). The type of mastocyte secretion in hypomagnesemia is represented by the merocrine variant. The administration of the initial magnesium orotate led to an increase in the concentration of magnesium in the blood to 1,150,25 mmol/l, which is 65,7% of the initial level, the amount of magnesium in the thymus remained elevated (3,41,1 mg/l), the number of actively degranulating cells (morphotype D) was increased. Mechanoactivated magnesium orotate restored the concentration of Mg2+ in the blood to 89,1% (1,560,18 mmol/l, p0,05) and decreased in the thymus (to 2,30,7 mg/l), restored the subpopulation of mastocytes saturated with heparin (type A), reduced the number of mastocytes of morphotype D. Conclusion . The mechanoactivated form of magnesium orotate has a normalizing effect on the population of thymic mastocytes, shows pronounced immunomodulatory activity, which allows us to consider it as a potential therapeutic agent for clinical testing in the complex therapy of hypomagnesemia and associated immunodeficiency.

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“…23 Recently, a few studies reported that OA nanocrystals also had significant effects that can be achieved by the use of proper stabilizers. 24,25 In the study presented here, 41 different coformers based on supramolecular synthons have been selected to assess the ability of OA to form multicomponent crystal forms (Table S1 and Scheme 1). 11,26 Affinity prediction was performed on the COSMOthermX19 program.…”

Section: Introductionmentioning

confidence: 99%

“…Kumar and co-workers attempted to improve the solubility by developing salts of OA with bipyridines and amino pyridines, but the coformers were not pharmaceutically acceptable . Recently, a few studies reported that OA nanocrystals also had significant effects that can be achieved by the use of proper stabilizers. , …”

Section: Introductionmentioning

confidence: 99%

Intermolecular Interactions and Solubility Behavior of Multicomponent Crystal Forms of Orotic Acid: Prediction and Experiments

Lin

Liu

Wang

et al. 2021

Crystal Growth & Design

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Multicomponent crystal forms for drugs with poor solubility, such as orotic acid (OA), can potentially promote dissolution behavior and bioavailability. Herein an affinity prediction was carried out to predict the formation of multicomponent crystal forms between OA and 41 coformers. Amino acids were selected as coformers to solve the solid-state solubility problem of OA. Six new multicomponent crystal forms, including five salts and one salt hydrate, were characterized and confirmed by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Spectroscopic techniques, such as Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, were used to validate the cocrystal/salt dichotomy. In the crystal packing, all salts exhibit N+–H···O– intermolecular interactions, which is well explained by molecular electrostatic potential surfaces. Finally, a powder dissolution study was conducted. The powder dissolution of all salts presented a higher apparent solubility (1.15–1.32 times) and a faster dissolution rate in comparison to those of OA, which is ascribed to the strength of the crystal lattice and the solvation of components.

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Highly Water-Soluble Orotic Acid Nanocrystals Produced by High-Energy Milling

Cited by 16 publications

References 53 publications

2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer

2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer

Morphofunctional characterization of rat thymus mast cells after administration of magnesium orotate mechanically activated forms

Intermolecular Interactions and Solubility Behavior of Multicomponent Crystal Forms of Orotic Acid: Prediction and Experiments

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