Solid-State NMR Characterization of Mefloquine Resinate Complexes Designed for Taste-Masking Pediatric Formulations.

Mefloquine (MQ) is an antimalarial medication prescribed to treat or malaria prevention.. When taken by children, vomiting usually occurs, and new doses of medication frequently need to be taken. So, developing pediatric medicines using taste-masked antimalarial drug complexes is mandatory for the success of mefloquine administration. The hypothesis that binding mefloquine to an ion-exchange resin (R) could circumvent the drug's bitter taste problem was proposed, and solid-state 13C cross-polarization magic angle spinning (CPMAS) NMR was able to follow MQ-R mixtures through chemical shift and relaxation measurements. The nature of MQ-R complex formation could then be determined. Impedimetric electronic tongue equipment also verified the resinate taste-masking efficiency in vitro. Variations in chemical shifts and structure dynamics measured by proton relaxation properties (e.g., T1ρH) were used as probes to follow the extension of mixing and specific interactions that would be present in MQ-R. A significant decrease in T1ρH values was observed for MQ carbons in MQ-R complexes, compared to the ones in MQ (from 100-200 ms in MQ to 20-50 ms in an MQ-R complex). The results evidenced that the cationic resin interacts strongly with mefloquine molecules in the formulation of a 1:1 ratio complex. Thus, 13C CPMAS NMR allowed the confirmation of the presence of a binding between mefloquine and polacrilin in the MQ-R formulation studied.

The effect of the molecular structure of hydroxypropyl methylcellulose on the states of water, wettability, and swelling properties of cryogels prepared with and without CaO2.

Hydroxypropyl methylcellulose (HPMC) belongs to the cellulose ether family that has hydroxyl groups substituted by hydrophobic methyl groups (DS) and hydrophilic hydroxypropyl groups (MS). Herein, the interactions between water molecules and cryogels prepared with HPMC in the presence and absence of a linear nonionic surfactant, as well as CaO2 microparticles, which react with water producing O2, were systematically investigated by sorption experiments and Time-Domain Nuclear Magnetic Resonance. Regardless of the DS and MS, most water molecules presented transverse relaxation time t2 typical of intermediate water and a small population of more tightly bound water. HPMC cryogels with the highest DS of 1.9 presented the slowest swelling rate of 0.519 ± 0.053 gwater/(g.s) and the highest contact angle values 85.250o ± 0.004o, providing the best conditions for a slow reaction between CaO2 and water. The presence of surfactant favored hydrophobic interactions that allowed the polar head of the surfactant to be exposed to the medium, resulting in a higher swelling rate and lower contact angle values. The HPMC with the highest MS presented the fastest swelling rate and the lowest contact angle. These findings are relevant for the formulations and reactions, where tuning the swelling kinetics is crucial for the final application.

Fetal cardiac dysfunction in pregnancies affected by intrahepatic cholestasis of pregnancy: A cohort study.

AIM: To analyze the presence of fetal myocardial dysfunction in intrahepatic cholestasis of pregnancy (ICP) at diagnosis. METHODS: This prospective cohort study included 49 pregnant participants with ICP at diagnosis and 49 nonaffected controls from a single public hospital. ICP was diagnosed based on clinical symptoms after excluding other causes of pruritus and presence of autoimmune diseases. Total bile acids were not obtained in this cohort. ICP pregnancies were assessed with a functional echocardiography at diagnosis including PR-interval, isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) for electrical, systolic, and diastolic function, respectively. Controls were assessed at recruitment. Perinatal outcomes were obtained from delivery books. The main outcome was the presence of PR-interval prolongation or first-degree fetal heart block, and echographic signs of diastolic and systolic dysfunction. RESULTS: Compared to controls, ICP were above upper limit in conjugated bilirubin (2.0% vs. 20.4%; p = 0.008), aspartate aminotransferase (2.0% vs. 24.5%; p = 0.002), and alanine aminotransferase (4.1% vs. 28.6%; p = 0.002). ICP was associated with a higher PR-interval (130 ± 12 ms vs. 121 ± 6 ms; p < 0.0001) with five first-degree fetal heart blocks. IRT was significantly higher in ICP (42 ± 6 ms vs. 37 ± 5 ms; p = 0.0001), with no differences in ICT and ET. PR-interval trend was only positively correlated with IRT in ICP pregnancies (p = 0.04 and p = 0.34, in ICP and controls, respectively). CONCLUSIONS: Our study demonstrates that fetuses affected by maternal ICP are associated with electrical and diastolic myocardial dysfunction. More studies focused on antenatal and postnatal functional echocardiography are necessary to validate our results and consider these markers in the clinical management of ICP pregnancies.

Value of Contrast-enhanced Magnetic Resonance Imaging (MRI) in the Diagnosis of Breast Cancer.

This review article aims to address the main features of breast cancer. Thus, the general aspects of this disease have been shown since the first evidence of breast cancer in the world until the numbers today. In this way, there are some ways to prevent breast cancer, such as the woman's lifestyle (healthy eating habits and physical activities) that helps to reduce the incidence of this anomaly. The first noticeable symptom of this anomaly is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer are discovered when the woman feels a lump being present and about 90% of the cases, the cancer is noticed by the woman herself. Currently, the most used method for the detection of cancer and other injuries is the Magnetic Resonance Imaging (MRI) technique. This technique has been shown to be very effective, however, for a better visualization of the images, Contrast Agents (CAs) are used, which are paramagnetic compounds capable of increasing the relaxation of the hydrogen atoms of the water molecules present in the body tissues. The most used CAs are Gd3+ complexes, although they are very efficient, they are toxic to the organism. Thus, new contrast agents have been studied to replace Gd3+ complexes; we can mention iron oxides as a promising substitute.

Adjusting the Néel relaxation time of Fe3O4/ZnxCo1-xFe2O4 core/shell nanoparticles for optimal heat generation in magnetic hyperthermia.

In this work it is shown a precise way to optimize the heat generation in high viscosity magnetic colloids, by adjusting the Néel relaxation time in core/shell bimagnetic nanoparticles, for Magnetic Fluid Hyperthermia applications. To pursue this goal, Fe3O4/ZnxCo1-xFe2O4 core/shell nanoparticles were synthesized with 8.5 nm mean core diameter, encapsulated in a shell of ~1.1 nm of thickness, where the Zn atomic ratio (Zn/(Zn+Co) at%) changes from 33 at% to 68 at%. The magnetic measurements are consistent with a rigid interface coupling between the core and shell phases, where the effective magnetic anisotropy systematically decreases when the Zn concentration increases, without a significant change of the saturation magnetization. Experiments of magnetic fluid hyperthermia of 0.1 wt% of these particles dispersed in water, DMEM (Dulbecco modified Eagles minimal essential medium) and a high viscosity butter oil, result in a large specific loss power (SLP), up to 150 W/g, when the experiments are performed at 571 kHz and 200 Oe. The SLP was optimized adjusting the shell composition, showing a maximum for intermediate Zn concentration. This study shows a way to maximize the heat generation in viscous media like cytosol, for those biomedical applications that requiere smaller particle sizes .

Tailoring the Diameters of Electro-Mechanically Spun Fibers by Controlling Their Deborah Numbers.

Polymer solutions with different concentrations of SU-8 2002/poly(ethylene) glycol/tetrabutyl ammonium tetrafluoroborate (SU-8/PEO/TBATFB) were electrospun in a low-voltage near-field electrospinning platform (LVNFES) at different velocities. Their diameters were related to the concentration contents as well as to their Deborah (De) numbers, which describes the elasticity of the polymer solution under determined operating conditions. We found a direct correlation between the concentration of PEO/TBATFB, the De and the diameter of the fibers. Fibers with diameters as thin as 465 nm can be achieved for De ≈ 1.

Corneal relaxation time estimation as a function of tear oxygen tension in human cornea during contact lens wear.

The purpose is to estimate the oxygen diffusion coefficient and the relaxation time of the cornea with respect to the oxygen tension at the cornea-tears interface. Both findings are discussed. From the experimental data provided by Bonanno et al., the oxygen tension measurements in vivo for human cornea-tears-contact lens (CL), the relaxation time of the cornea, and their oxygen diffusion coefficient were obtained by numerical calculation using the Monod-kinetic model. Our results, considering the relaxation time of the cornea, observe a different behavior. At the time less than 8 s, the oxygen diffusivity process is upper-diffusive, and for the relaxation time greater than 8 s, the oxygen diffusivity process is lower-diffusive. Both cases depend on the partial pressure of oxygen at the entrance of the cornea. The oxygen tension distribution in the cornea-tears interface is separated into two different zones: one for conventional hydrogels, which is located between 6 and 75 mmHg, with a relaxation time included between 8 and 19 s, and the other zone for silicone hydrogel CLs, which is located at high oxygen tension, between 95 and 140 mmHg, with a relaxation time in the interval of 1.5-8 s. It is found that in each zone, the diffusion coefficient varies linearly with the oxygen concentration, presenting a discontinuity in the transition of 8 s. This could be interpreted as an aerobic-to-anaerobic transition. We attribute this behavior to the coupling formalism between oxygen diffusion and biochemical reactions to produce adenosine triphosphate. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:14-21, 2020.

Non-enzymatic browning kinetics in sucrose-glycine aqueous and dehydrated model systems in presence of MgCl2.

The development of non-enzymatic browning in the presence of MgCl2 was evaluated in liquid and dehydrated sucrose-glycine model systems, in relation to interactions of the salt with water and/or with sucrose. In both systems, browning was accelerated by the presence of MgCl2 because of the increased sugar hydrolysis (ten times faster) and the reduction of water mobility (1H NMR T2 relaxation times) caused by this salt (between 6 and 14% lower), counteracting the inhibitory effect of water on the Maillard reaction. MgCl2 also provoked a 40% reduction on the fluorophores quantum yield, responsible also of the fluctuations observed in the fluorescence development as a function of time after 50 h at 70 °C. Molecular and supramolecular effects of the presence of MgCl2 have been observed on the Maillard reaction kinetics. These results are of high technological interest when strategies to control the Maillard reaction rate are required for a particular application.

Xylanase activity and T2 (MRI) relationship during lulo la selva P32 ripening process / Relación entre la actividad de la xilanasa con medidas del T2 (IRM) durante el proceso de maduración del lulo La Selva P32 / Relação entre e atividade com as medidas xilanase T2 (IRM) durante a maturação lulo A Selva P32

The lulo La Selva P32 is a cross over different kinds of lulo. Though its sensory characteristics improvement, its life span is very short. Due to it is a new kind of lulo, there are not so many studies over the ripening process. In order to understand some softening processes, in this work it is evaluated the xylanase kinetics at the lulo peel during ripening, and the results are correlated with the MRI (Magnetic Resonance Imaging) relaxation time T2 . During ripening time, it is observed that the xylanase is one of the enzymes involved in the hydrolysis of the cell wall polymers. In addition, two T2 values regimes were distinguished by the xylanase kinetics. Although the correlation coefficient of 0.82 and p = 0.024 values, the results suggest that T2 weighted MRI can be useful as a non-invasive tool for ripening process monitoring.

El Lulo La Selva P32 es un fruto producto del entrecruzamiento de varias especies de lulo. Aunque tiene mejores características organolépticas, su vida útil es corta. Dado que se trata de una variedad relativamente nueva de lulo, no hay muchos estudios sobre su proceso de maduración. En este trabajo, con el fin de entender algunos de los procesos de ablandamiento de esta variedad de lulo, por una parte, se evalúa la cinética de la xilanasa en la corteza durante la maduración y, por otra parte, estos resultados se correlacionan con el tiempo de relajación T2 , de la Imágenes de Resonancia Magnética Nuclear (IRM). Durante la maduración se observó que la xilanasa es una de las enzimas involucradas en la hidrólisis de los polímeros de la pared celular. Además, a partir de los resultados de la cinética de la xilanasa, se pudieron distinguir dos regímenes de valores T2 . Aunque el coeficiente de correlación fue de 0.82 y p = 0.024, los resultados sugieren que la determinación de T2 por medio de IRM se puede utilizar como una herramienta no invasiva en el proceso de monitoreo de maduración.

O Lulo La Selva P32 é um produto fruto do cruzamento de várias espécies de lulo com um tempo de vida útil curto. Existem poucos estudos para entender os mecanismos que influenciam o amolecimento no lulillo. Este artigo se relaciona com a atividade da xilanase na casca do lulillo com a mobilidade das águas livres (tempo de relaxamento T2 ). O T2 se quantificou por imagens de ressonáncia magnética e a atividade da xilanase por métodos bioquímicos. Se observou uma tendencia no comportamiento dos valores do T2 na mobilidade das águas livres semelhantes á atividade da xilanase, associando-se a migração da água desde o exterior do fruto pela ação da enzima, involucrada na hidrólise de polímeros da parede celular. Apesar do coeficiente de correlação (0.82) e do p (0.024), os resultados sugerem que as imagens de ressonáncia poderiam ser uma alternativa nao destrutiva na indústria de exportação, visto que permite determinar o início da senescencia do fruto, baseado em condições fisiológicas e bioquímicas.

Detección del receptor de factor de crecimiento epidérmico en lesiones orales premalignas por relaxometría / Detection of the epidermal growth factor receptor by relaxometry of oral premalignant lesions

OBJETIVO: detectar la sobreexpresión del receptor de factor de crecimiento epidérmico en células epiteliales de lesiones premalignas de la mucosa bucal, marcadas magnéticamente por relaxometría. MÉTODOS: las células exfoliadas de mucosa oral de individuos sanos y enfermos se marcaron con el sistema: IgG anti-EGF-R biotinilada/IgG anti-biotina conjugada con partículas superparamagnéticas y se midieron los tiempos de relajación T1 y T2. RESULTADOS: disminuyeron los tiempos de relajación (T1 y T2) de las células marcadas respecto a las no marcadas, en todas las muestras analizadas. Al comparar los valores de T1 y T2 de las células marcadas de la lesión con los valores de las células sanas, se encontró una disminución estadísticamente significativas del tiempo de relajación. Al comparar los tiempos de relajación de células marcadas sanas con los de las células de las diferentes lesiones encontramos diferencias estadísticamente significativas para los casos de células de leucoplasias y liquen plano tanto en T1 como T2; no así con células de queratosis. CONCLUSIONES: los resultados muestran que es posible detectar por relaxometría células que expresen el receptor de factor de crecimiento epidérmico, utilizando el sistema conjugado empleado y que el EGF-R se sobreexpresa en células de lesiones como leucoplasia y liquen plano.

OBJECTIVE: Detect the overexpression of the epidermal growth factor receptor in epithelial cells of premalignant lesions of the oral mucosa magnetically marked by relaxometry. METHODS: Exfoliated oral mucosa cells from healthy and sick individuals were marked with the system biotinylated anti-EGF-R IgG / anti-biotin IgG conjugated with supermagnetic particles and measurements were taken of relaxation times T1 and T2. RESULTS: In all the samples analyzed there was a decrease in the relaxation times (T1 and T2) of marked cells with respect to unmarked cells. Comparison of the T1 and T2 values of marked cells from the lesion with the values of healthy cells revealed a statistically significant decrease in relaxation time. Comparison of the relaxation times of healthy marked cells with those of cells from the various lesions revealed statistically significant differences in both T1 and T2 in cells from lichen planus and leukoplakias, but not in cells from keratoses. CONCLUSIONS: Results show that relaxometry may be used to detect cells expressing the epidermal growth factor receptor, using the conjugated system described herein, and that EGF-R is overexpressed in cells from lesions such as leukoplakia and lichen planus.

Multiple echo multi-shot diffusion sequence.

PURPOSE: To measure both transversal relaxation time (T2 ) and diffusion coefficients within a single scan using a multi-shot approach. Both measurements have drawn interest in many applications, especially in skeletal muscle studies, which have short T2 values. Multiple echo single-shot schemes have been proposed to obtain those variables simultaneously within a single scan, resulting in a reduction of the scanning time. However, one problem with those approaches is the associated long echo read-out. Consequently, the minimum achievable echo time tends to be long, limiting the application of these sequences to tissues with relatively long T2 . MATERIALS AND METHODS: To address this problem, we propose to extend the multi-echo sequences using a multi-shot approach, so that to allow shorter echo times. A multi-shot dual-echo EPI sequence with diffusion gradients and echo navigators was modified to include independent diffusion gradients in any of the two echoes. RESULTS: The multi-shot approach allows us to drastically reduce echo times. Results showed a good agreement for the T2 and mean diffusivity measurements with gold standard sequences in phantoms and in vivo data of calf muscles from healthy volunteers. CONCLUSION: A fast and accurate method is proposed to measure T2 and diffusion coefficients simultaneously, tested in vitro and in healthy volunteers.

Cardiac function and arterial biophysical properties in small for gestational age infants: postnatal manifestations of fetal programming.

OBJECTIVE: To investigate the differences in cardiac function and arterial biophysical properties between term-born appropriate for gestational age (AGA) infants and small for gestational age (SGA) infants. Our hypothesis was that adaptation to intrauterine growth restriction induces changes in cardiac and arterial indices. STUDY DESIGN: This was a prospective observational echocardiographic evaluation of cardiac and arterial indices in SGA infants and AGA infants. Demographic and echocardiographic data were compared between 20 inborn term SGA infants with birth weight <3rd percentile for gestational age and 20 AGA infants. RESULTS: The Ponderal index was significantly lower and blood pressure was significantly higher in the SGA infants compared with the AGA infants. Left ventricular output was lower in the SGA infants (170 ± 31 mL/kg/min vs 197 ± 39 mL/kg/min). Diastolic dysfunction was greater in the SGA infants (ie, reduced E and A wave velocities, higher E/A ratio [1.08 ± 0.16 vs 0.85 ± 0.07], and prolonged isovolumic relaxation time [73 ± 6.2 ms vs 62.6 ± 3.6 ms]). Aortic intima-media thickness was significantly greater in the SGA infants (822 ± 105 µm vs 694 ± 52 µm), as were arterial wall stiffness index and input impedance. CONCLUSION: Cardiac function and arterial biophysical properties were altered in the SGA infants. The findings complement the information on the association between in utero growth and cardiovascular morbidity in later life.