Tasa metabólica en reposo por calorimetría indirecta y ecuaciones de predicción en deportistas con amputación: Análisis de concordancia

La Tasa Metabólica en Reposo (TMR) suele calcularse utilizando ecuaciones de predicción por su fácil acceso y bajo costo. Sin embargo, estas ecuaciones no se encuentran validadas en población deportista con amputación. Objetivo: determinar la concordancia entre la medición de la TMR realizada por Calorimetría Indirecta (CI) y la calculada por ecuaciones de predicción en deportistas con amputación de miembros inferiores en Bogotá. Sujetos y métodos: Este estudio evaluó 16 deportistas adultos masculinos, con amputación de miembro inferior. La TMR se midió con CI y se calculó con las ecuaciones de predicción de Harris-Benedict, Cunningham, Mifflin -St. Jeor, Schofield y Oxford. Se utilizaron dos variables diferentes de masa corporal: masa corporal total (MCT) y masa magra (MM) determinada por Absorciometría de doble energía de rayos X (DEXA) y por el método antropométrico de fraccionamiento de masas en cinco componentes (5C). La concordancia se determinó a través del coeficiente de correlación intraclase (CCI) y se graficó mediante el método de Bland- Altman. Resultados y conclusión: La TMR determinada por la ecuación de Cunningham a partir de MM evaluada por DEXA, mostró la mejor concordancia con la CI (CCI= 0,709), seguida por Harris-Benedict con MCT (CCI= 0,697) y Cunningham con MM calculada por 5C (CCI= 0,693). La ecuación de Cunningham y Harris Benedict parecen ser las más adecuadas para calcular la TMR, sin embargo, se requieren más estudios con muestras mayores, lo cual permitirá obtener resultados más precisos.

Prediction equations for calculating resting metabolic rate (RMR) are widely used given their accessibility and low cost. However, they have not been yet validated in the amputee athlete population. Objective: to determine the concordance between the RMR measured by Indirect Calorimetry (IC) and that calculated by prediction equations in athletes with lower limb amputation in Bogota. Subjects and methods: sixteen adult male athletes with lower limb amputation were included. The RMR was measured with IC and calculated with the Harris-Benedict, Cunningham, Mifflin-St. Jeor, Schofield, and Oxford prediction equations. Three different body mass variables were used: total body mass (TBM) and lean body mass (LBM) determined by Dual Energy X-ray Absorptiometry (DEXA) and by the anthropometric method of mass fractionation into five components (5C). The agreement was determined by intraclass correlation coefficient (ICC) and plotted using the Bland-Altman method. Results and conclusions: RMR determined by the Cunningham equation from LBM assessed by DEXA showed the best agreement with CI (ICC= 0.709), followed by Harris-Benedict with MCT (ICC= 0.697) and Cunningham with LBM calculated by 5C (ICC= 0.693). The Cunningham and Harris-Benedict equation seems to be the most suitable for calculating RMR. However, more studies with larger samples are needed to obtain more accurate results.

A clinical cross-sectional study of resting energy expenditure in children with cerebral palsy / 中华实用儿科临床杂志

Objective:To investigate the characteristics of resting energy expenditure (REE) in children with cerebral palsy (CP) graded with different levels of Gross Motor Function Classification System (GMFCS), and to evaluate the accuracy and association of commonly used REE prediction formulas in children with CP.Methods:It was a retrospective study involving 36 children with CP aged 24-144 months who visited the Third Affiliated Hospital of Zhengzhou University between September 2021 and August 2022.REE was measured by the indirect calorimetry.Based on the GMFCS, children with CP were divided into grade Ⅰ-Ⅱ group (20 cases), grade Ⅲ group (6 cases) and grade Ⅳ-Ⅴ group(10 cases). During the same period, 11 age-matched healthy children were included in control group.The measured REE (MREE) between children with CP and healthy controls was compared.Predicted REE (PREE) calculated by the Harris-Benedict, WHO, Schofield-W, Schofield-WH and Oxford prediction formulas were compared with MREE in children for their consistency and correlation.Independent samples were analyzed using t-test or Mann- Whitney U test, and categorical data were analyzed using Chi- square test.Using paired t-test and Pearson linear correlation analysis to analyze the correlation between MREE and PREE.The accuracy of PREE values calculated by different formulas was assessed using the root mean square error. Results:The MREE in control group and children with CP were (952.18±270.56) kcal/d and (801.81±201.89) kcal/d, respectively.There was no significant difference in the MREE between grade Ⅰ-Ⅱ group versus control group[(868.30±194.81) kcal/d vs.(952.18±270.56) kcal/d, P>0.05], and grade Ⅲ group versus control group [(813.17±192.48) kcal/d vs.(952.18±270.56) kcal/d, P>0.05]. The MREE was significantly lower in grade Ⅳ-Ⅴ group than that of control group [666.00(513.50, 775.50) kcal/d vs.(952.18±270.56) kcal/d, P=0.011]. There were no significant difference between MREE and PREEs calculated by Harris-Benedict, WHO, Schofield-W, Schofield-WH, and Oxford (all P>0.05). The correct classification fraction calculated by the 5 formulas were 33.3%, 47.2%, 41.7%, 47.2%, and 41.7%, respectively.The r values of the consistency of PREE calculated by the 5 formulas were 0.585, 0.700, 0.703, 0.712, and 0.701, respectively.The Blande-Altman Limits of Agreement were (-297.77, 359.22), (-245.60, 326.94), (-250.62, 316.05), (-242.22, 177.36) and (-241.28, 325.81), respectively.The clinically acceptable range was -80.18 to 80.18 kcal/d.The root mean square error were 168.09 kcal/d, 149.64 kcal/d, 146.24 kcal/d, 144.23 kcal/d and 148.77 kcal/d, respectively. Conclusions:The MREE values decreased significantly in children with CP classified as CMFCS grade Ⅳ and Ⅴ.When REE cannot be regularly monitored by indirect calorimetry to develop nutritional support programs, children with CP may be prioritized to estimate REE using the prediction formula of Schofield-WH.

Determination of purity of a new anti-fatty liver drug IMH by differential scanning calorimetry method and uncertainty evaluation / 药学学报

The purity of 4,4′-dimethoxy-5,6,5′,6′-bis (methylenedioxy)-2′-morpholine methylenebiphenyl-2-methyl formate methanesulfonate (IMH), a new drug for fatty liver treatment, was determined through differential scanning calorimetry (DSC). Analysis of two-factor non repeatability method was performed in the investigation the effects of two factors (heating rate and sample weight) on purity determination. The DSC experimental parameters were optimized as follows: heating rate was 10 ℃·min-1, temperature range was 150-300 ℃, sample weight was 2.0-4.1 mg, and N2 flow rate was 80 mL·min-1. The linear correlation coefficient (r) of this DSC method was 0.999 8. The RSD value (n = 6) of precision was 0.03%. The standard value and uncertainty of the purity results of the multiple batches of IMH drugs were (99.74 ± 0.29)%, (99.91 ± 0.28)%, (99.90 ± 0.28)%, and (99.81 ± 0.28)% with inclusion factor (K) of 2 and confidence probability (P) of 0.95. The results were basically consistent with the results of the mass balance method. The DSC mehod is a simple, rapid and accurate method, and provides a new reference method for determining the purity of IMH drugs, improves the accuracy and reliability of purity determination.

Comparação entre Reciproc Blue e quatro instrumentos réplicas: aspectos metalúrgicos, geometria, comportamento em torção e flexão / Comparison between Reciproc Blue and four replicalike instruments: metallurgical aspects, geometry, and behavior in torsion and flexion

A introdução da liga NiTi na endodontia proporcionou a fabricação de instrumentos com excelentes propriedades mecânicas, e uma das principais características é a possibilidade de alteração das temperaturas de transformação da liga, o qual pode possibilitar a presença de martensita em temperatura ambiente e consequentemente um efeito memória de forma. Entretanto, alguns dos sistemas comercializados atualmente possuem pouca ou nenhuma informação científica relatando suas propriedades mecânicas, características de design e métodos de fabricação. O objetivo deste trabalho foi comparar características geométricas, metalúrgicas e propriedades mecânicas (resistência à torção e flexão) de instrumentos Reciproc Blue (VDW, Munique, Alemanha), e quatro sistemas reciprocantes réplicas. Um total de 39 instrumentos de cada um dos sistemas reciprocantes, Reciproc Blue (RB), Prodesign R (PDR), V File (VF), V+ File (V+) e Univy One (UO) foram utilizados na pesquisa. O programa de Image J foi utilizado para mensuração dos diâmetros a cada milímetro da parte ativa e da área da seção transversal a 3 mm da ponta dos instrumentos. Imagens de MEV da parte ativa foram realizados para avaliar o acabamento superficial dos instrumentos. A composição atômica, fases presentes e temperaturas de transformação foram verificadas através de EDS, DRX e DSC, respectivamente. A flexibilidade foi aferida através de ensaios de dobramento até 45º conforme a especificação ISO 3630-1, e os ensaios de resistência à torção foram realizados de acordo com a especificação Nº28 ANSI/ADA. Todos os instrumentos apresentaram uma quantidade aproximadamente equiatômica de níquel e titânio. A análise qualitativa das fases cristalinas realizada através de ensaios de DRX, demonstrou a predominância de Fase R em todos os grupos, com exceção do grupo UO que apresenta uma mistura de fase R e martensita B19'. Na avaliação da área da seção, o instrumento RB obteve valores intermediários, os instrumentos PDR e V+ possuem menores valores e os instrumentos VF e UO possuem maiores valores. Observou-se grande impacto da geometria sobre as propriedades mecânicas, sendo que aqueles sistemas que apresentavam menor área que RB (PDR, V+) mostraram-se mais flexíveis e menos resistentes à torção (p<0.05), e o instrumento VF que teve maior área apresentou, como esperado, menos flexibilidade (p<0.05) e resistência torcional semelhante (p>0.05). A única exceção se deu com o sistema UO, que embora apresentasse uma maior área de seção, mostrou-se mais flexível e menos resistente à torção, provavelmente por influência da maior quantidade de martensita presente à temperatura ambiente. Nenhum dos instrumentos réplicas avaliados apresentaram características e comportamento mecânico iguais ao sistema padrão RB. Sugere-se que mais estudos devem ser realizados para a comparação do comportamento clínico destes instrumentos.

The introduction of NiTi alloy in endodontics has allowed the manufacturing of instruments with excellent mechanical properties, and one of the main characteristics is the ability to change alloy's transformation temperature, which can enable the presence of martensite at room temperature and consequently favor a shape memory effect. However, some of the currently marketed systems have limited or no scientific information regarding their mechanical properties, design characteristics, and manufacturing methods. The aim of this study was to compare the geometric characteristics, metallurgical aspects, and mechanical properties (torsional and flexural strength) of Reciproc Blue instruments (VDW, Munich, Germany) with four replica-like reciprocating systems. A total amount of 39 instruments from each reciprocating system, namely Reciproc Blue (RB), Prodesign R (PDR), V File (VF), V+ File (V+), and Univy One (UO), were used in the study. The Image J program was used to measure the diameters at every millimeter along the instruments active portion and the cross-sectional area at 3 mm from the instrument tip. SEM images of the active portion were obtained to evaluate the surface finishing of the instruments. Atomic composition, phases present, and transformation temperatures were determined through EDS, XRD, and DSC analyses, respectively. Flexibility was assessed by bending tests up to 45° according to ISO 3630-1 specifications, and torsional strength tests were performed according with ANSI/ADA Specification No. 28. All instruments exhibited an approximately equiatomic composition of nickel and titanium. Qualitative analysis of the crystalline phases using XRD tests demonstrated the predominance of the R-phase in all groups, except for the UO group, which exhibited a mixture of Rphase and B19' martensite. In terms of diameter and cross-sectional area evaluation, the RB instrument obtained intermediate values, while the PDR and V+ instruments had smaller values, and the VF and UO instruments had larger values. A significant impact of geometry on mechanical properties was observed, with systems exhibiting a smaller area than RB (PDR, V+) being more flexible and less torsion-resistant (p<0.05), and the VF instrument with a larger area showed, as expected, less flexibility (p<0.05) and similar torsional resistance (p>0.05). The only exception was the UO system, which, despite having a larger geometric configuration, exhibited greater flexibility and less torsional resistance, likely due to the higher amount of martensite present at room temperature. None of the replica-like instruments evaluated showed identical characteristics and mechanical behavior to the standard RB system. Further studies are suggested to compare the clinical performance of these instruments.

Pre-exercise meal on oxidation of energy substrates during maximal exercise test in non-trained individuals

ABSTRACT Objective: This study aimed to compare the influence of a high carbohydrate meal versus high-fat meal on the oxidation of substrates during an exercise incremental test. Materials and methods: Ten untrained male subjects underwent two days of the protocol. Randomly, they received a high carbohydrate meal or a high-fat meal, receiving the other one in the next protocol. On both days, they performed an incremental treadmill test, with heart rate and maximal oxygen consumption to estimate the oxidation of substrates. Results: The high-fat meal showed an increase in the absolute amount of oxidized fat along with the incremental test (P < 0.05; effect size = 0.9528), and a reduction in the respiratory exchange ratio at low intensities (P < 0.05; effect size = 0.7765). Conclusions: The meals presented no difference when compared to maximum oxidation point of substrates, the oxidation rate of substrates over time, and heart rate. A pre-test high-fat meal in untrained individuals was shown to be a modulating factor of total oxidized fats throughout the exercise, although it did not exert a significant effect on the rate of this oxidation over time.

Evaluation of Physiochemical Properties, Thermal Behavior and Phytopharmaceutical Potential of Citrus aurantium’s Essential Oil

The study investigates the therapeutic potential of the Citrus aurantium var. amara essential oil extracted from the blossoms of the bitter orange plant by examining its chemical composition, thermal stability, and potency against infectious disease-causing pathogens. Initially, the volatile components of the essential oil were evaluated by obtaining a chromatographic fingerprint using HPTLC and FTIR spectrum identification. Furthermore, a thermal profile of the essential oil was obtained using the thermogravimetric-differential thermal analysis and differential scanning calorimetric analysis. A predetermined set of antibiotic-resistant microorganisms were used to examine the antibacterial activity of the essential oil. Lastly, its anti-inflammatory activity was assessed using the albumin denaturation assay. The research concluded that the Citrus aurantium var. Amara essential oil exhibits potential therapeutic characteristics which can be further explored through in vivo studies.

A hemagglutinin from Pongamia pinnata (L.) Pierre seed

Lectins are diverse proteins that bind to carbohydrates and are involved in many important physiological processes. They are highly specific to the sugar molecules they bind and therefore, have many therapeutic and diagnostic applications. There are several lectins that display antiviral, antibacterial antifungal and antitumour activities. Characterization of new lectins paves way for comprehension of their diverse biological roles and mechanism of action, thus aiding in further exploration of lectins in various domains of biology. Here, we endeavoured to purify and characterize lectin from the seed of the legume,Pongamia. Pongamia pinnata (L.) Pierre (syn. Millettia pinnata), seed lectin (PPSL) was purified conventionally by ammonium-sulfate precipitation followed by size exclusion chromatography. The further lectin was physicochemically characterized by CD, fluorescence spectroscopy, mass spectroscopy and isothermal calorimetry. Hemagglutination studies with various mono and disaccharides showed specificity towards galactose. This specificity was reaffirmed by isothermal studies with appreciable thermodynamic parameters. Lectins have tremendous diagnostic applications. They are used as second-generation drug delivery systems.

Efectos agudos del ejercicio aeróbico en estado de ayuno sobre el metabolismo y utilización de carbohidratos y grasas en adultos sedentarios con sobrepeso y obesidad: Un estudio piloto

RESUMEN Objetivo: Comparar los efectos agudos del ejercicio aeróbico en ayuno y postprandial sobre la utilización de carbohidratos y grasas de hombres sedentarios con sobrepeso y obesidad. Métodos: Diseño cuantitativo, experimental, randomizado, cruzado. Siete hombres adultos (37,9 ± 2,4 años), sedentarios, con sobrepeso u obesidad (índice de masa corporal= 29,3 ± 1,9 kg/m2). Todos realizaron 60 min de ejercicio aeróbico al 50% de potencia aeróbica máxima tanto en ayuno (FASTED) como postprandial (FED), iniciando aleatoriamente. En cada oportunidad se midieron la tasa de intercambio respiratorio (RER) mediante calorimetría indirecta basal, durante, y después del ejercicio; glicemia, cuerpos cetónicos, lactato capilares basales, pre-inicio, post inmediato, y 40 minutos post ejercicio. La utilización de carbohidratos y grasas fue estimada desde el RER según ecuaciones estequiométricas. Resultados: Durante el ejercicio no hubo diferencias significativas en utilización de sustratos entre FASTED y FED. Posterior al ejercicio sólo FASTED tuvo aumento (p<0,05) en oxidación de grasas relativo al peso corporal (Pre 0,010 ± 0,006 kJ/min/kg vs Post 0,020 ± 0,014 kJ/min/kg), oxidación de carbohidratos (Pre 0,060 ± 0,010 kJ/min/kg vs Post 0,070 ± 0,012 kJ/min/kg), y gasto energético total (Pre 0,070 ± 0,017 kJ/min/kg vs Post 0,090 ± 0,028 kJ/min/kg). No hubo diferencias en FED, ni entre FASTED y FED. Conclusión: El ejercicio aeróbico moderado en ayuno aumenta la oxidación de grasas y carbohidratos posterior a la sesión en hombres con sobrepeso y obesidad. Esto podría ser útil para su prescripción en pacientes sedentarios con exceso de peso.

ABSTRACT Purpose: To compare the acute effects of fasting and postprandial aerobic exercise on carbohydrate and fat utilization in sedentary overweight and obese men. Methods: Quantitative, experimental, randomized, crossover design. Seven sedentary, overweight or obese (body mass index [BMI]= 29.3 ± 1.9 kg/m2) adult men (37.9 ± 2.4 years) performed 60 min of aerobic exercise at 50% of maximal aerobic power both fasting (FASTED) and postprandial (FED). The first exercise type was randomly assigned. We measured the respiratory exchange ratio (RER) by basal indirect calorimetry during and after exercise; glycemia, ketone bodies and capillary lactate at baseline, pre-start, immediately and 40 minutes post exercise were measured in each exercise protocol. Oxidation of carbohydrates and fats was estimated from the RER according to stoichiometric equations. Results: During exercise there were no significant differences in the use of substrates between FASTED and FED. After exercise, only FASTED had an increase (p<0.05) in fat oxidation relative to body (Pre 0.010 ± 0.006 kJ/min/kg vs Post 0.020 ± 0.014 kJ/min/kg), carbohydrate oxidation (Pre 0.060 ± 0.010 kJ/min/kg vs Post 0.070 ± 0.012 kJ/min/kg), and total energy expenditure (Pre 0.070 ± 0.017 kJ/min/kg vs Post 0.090 ± 0.028 kJ/min/kg). There were no differences in FED, nor significant differences between FASTED and FED. Conclusion: Moderate aerobic fasting exercise increases post-session fat and carbohydrate oxidation in overweight and obese men. This could be useful for application in sedentary patients with excess weight.

Effect of diet and physical exercise on weight, body composition, and resting metabolic rate in obese chilean adults

ABSTRACT Background: Diet and exercise are the mainstay of weight reduction programs. Aim: To evaluate the effect of diet and exercise on body weight and composition and resting metabolic rate (RMR) in obese adults. Material and Methods: Twenty-eight obese adults aged 22 to 61 years (18 women) completed four months of diet and exercise. They attended monthly nutritional consultations, and two-three weekly exercise sessions. At baseline and the end of the intervention, anthropometry, body composition by bioimpedance and RMR by indirect calorimetry (IC) were measured. Metabolic adaptation, defined as a decrease in thermogenesis to an extent greater than predicted based on the change in body weight and composition, was calculated. Results: Significant reductions in body weight and fat mass were observed in both genders. Fat-free mass decreased in women and remained unchanged in men. RMR remained stable. Metabolic adaptation was observed in 11/27 participants. Fat mass change in participants with and without metabolic adaptation was 8 Kg and 4,4 kg, respectively (p = 0,018). In the linear regression analysis, male sex accounted for a higher RMR (247.80 Kcal, p = 0,006) than females. For each kg of fat and fat free mass, the RMR varies 7.25 Kcal, (p = 0.02) and 9.79 Kcal (p = 0,006), respectively. Conclusions: The intervention reduced body weight and fat mass and maintained RMR. Fat free mass decreased in women. Participants with metabolic adaptation showed greater changes in fat mass.

Antecedentes: Para el tratamiento de la obesidad, la dieta y ejercicio físico (EF) contribuyen a reducir el peso corporal (PC), masa grasa (MG) y a mantener la masa libre de grasa (MLG) y tasa metabólica en reposo (TMR). Objetivo: Evaluar el efecto de la dieta y EF sobre el PC, composición corporal (CC), TMR y la presencia de adaptación metabólica. Material y Métodos: Veintiocho adultos obesos completaron cuatro meses de dieta y EF. Los adultos asistieron a consulta nutricional mensual y a 2-3 sesiones de EF semanal. En el período basal y después de la intervención se midió antropometría, CC por bioimpedanciometria y TMR por calorimetría indirecta. Se calculo la presencia de adaptación metabólica, definida como una disminución de la termogénesis mayor que la predicha por el cambio en peso y composición corporal. Resultados: Se observó una disminución significativa de PC y MG en hombres y mujeres. La MLG disminuyó en las mujeres y se mantuvo en los hombres. La TMR se mantuvo estable. Se observó adaptación metabólica en 11/27 participantes y una relación significativa con el cambio en MG (p = 0,018). En la regresión lineal, el sexo masculino da cuenta de una mayor TMR (247,80 Kcal, p = 0,006) que el sexo femenino. Por cada kg de MG y MLG la TMR varía 7,25 Kcal, (p = 0,02) y 9,79 Kcal, (p = 0,006) respectivamente. Conclusiones: La intervención redujo el PC y la MG, y mantuvo TMR. La MLG disminuyó en las mujeres. Los sujetos con adaptación metabólica mostraron mayores cambios de MG.

Time to achieve steady state for an accurate assessment of resting energy expenditure in adolescents with healthy weight and obesity: A cross-sectional study

ABSTRACT Objective: The present study investigated the time needed to achieve a steady state for an accurate assessment of resting energy expenditure (REE) in adolescents with healthy weight and obesity. Materials and methods: Thirty adolescents aged 12-17 years were assigned to a group with healthy weight (GHW; n = 12, body mass index [BMI] 22.5 ± 3.6 kg/m2) and another group with obesity (GO; n = 18, BMI 34.1 ± 5.2 kg/m2). Participants underwent test-retest reliability of REE assessment as follows: a) 24 h of abstention from physical exercise, soft drinks, or caffeine; b) fasting for ~12 h; c) acclimation period of 10 min; d) 30-min assessment in a supine position. Results and discussion: A significant change occurred during the 30 min in REE. Significant differences existed between consecutive means until the 20th and 25th min for the GHW and GO, respectively. Although significant differences between trials 1 and 2 were detected during the first 5-10 min of assessment, the REE for each 5-min time point exhibited high test-retest reliability across trials in both groups (intraclass correlation coefficients range 0.79-0.99). Conclusion: The following recommendations are provided to promote accurate assessment of REE among adolescents: a) initiate the REE assessment with 10 min of acclimation to decrease restlessness; b) determine REE for a minimum of 20 min if healthy weight and 25 min if obesity; c) determine REE for a further 5 min, with the average of this last 5 min of REE data being regarded as the REE.

Analysis of Olibanum and Myrrha by Differential Scanning Calorimetry and Fourier Transform InfraRed / 国际中医中药杂志

Objective:To distinguish the differences between Olibanum and Myrrha by using modern analytical methods such as Differential Scanning Calorimeter (DSC) and Fourier Transform InfraRed (FT-IR). Methods:By collecting Olibanum and Myrrha in different growing areas and different processed prosecures, this paper to analizes the influence of temperature increase and its speed , as well as the particle size on the DSC experiment. The DSC method was used to perform a differential thermal map of Olibanum and Myrrha scanning and analysis; FT-IR was used to scan and analyze 20 batches of Olibanum and Myrrha. Results:TThe results of DSC analysis showed that the DSC experimental condition ranged between 30-600 ℃; the speed of temperature increase was 30 ℃/min; the particle size was 100 mesh. The DSC spectra of of Olibanum and Myrrha were significantly different. Only the processed products of frankincense had endothermic peak near 297 ℃, and there was no characteristic peak in this temperature range. Their exothermic peaks are close at 326 ℃, but their enthalpy values are quite different. The position of endothermic peak near 100 ℃ is close to the size of peak shape. FT-IR test showed that the absorption peaks of Olibanum and Myrrha at wave numbers 2 925, 1 710, 1 454, 1 371, 1 242, 1 029 cm -1 appeared, and the positions of strong peaks were also similar. The intensity of the characteristic peak of Myrrha wave number 1 029 cm -1 is greater than that of Olibanum. Conclusion:The DSC spectra of Olibanum and Myrrha are significantly different, and the difference between the two FT-IR spectra is small. Differential scanning Calorimetry is an effective, fast, and simple way to identify resinous Chinese medicinal materials, and is worthy of further popularization.

Study on the consistency and correlation of different methods for measuring energy consumption in patients with severe acute pancreatitis / 中华消化杂志

Objective:To analyze the consistency and correlation of indirect calorimetry (IC) and Harris-Benedict estimation method (H-B) in measuring energy consumption in patients with severe acute pancreatitis (SAP), as well as the characteristics of energy metabolism at resting state of SAP patients with different etiologies, and so as to guide the formulation of clinical energy nutrition support program.Methods:From February 1 to December 31, 2019, 61 SAP patients admitted into the intensive care unit of the First Affiliated Hospital of Nanchang University were enrolled. Collected relevant data of patients, such as the etiology of SAP, whether mechanical ventilation was needed, as well as the metabolic status. All SAP patients accepted IC test on the first day after admission to intensive care unit. According to the energy consumption measured by IC (hereinafter referred to as IC value) and the energy consumption measured by H-B (hereinafter referred to as H-B value), SAP patients were determined to be in high, normal or low metabolic state. Bland-Altman method and Pearson linear regression were used to analyze the consistency and correlation of the two methods in measuring energy consumption, and the linear equation was fitted. Paired t test was used for statistical analysis. Results:Among the 61 SAP patients, 13 cases were biliary SAP, 30 cases were hyperlipidemic SAP, 6 cases were alcoholic SAP, and 12 cases were SAP of other causes or unknown causes. Nineteen cases needed mechanical ventilation and 42 cases did not need mechanical ventilation. There were 70.5% (43/61) of SAP patients in high metabolic state, 13.1%(8/61) of SAP patients in normal metabolic state, and 16.4% (10/61) of SAP patients in low metabolic state. The IC value in 61 SAP patients was higher than H-B value((8 604.7±367.8) kJ/d vs. (6 491.2±133.7) kJ/d), and the difference was statistically significant ( t=5.95, P<0.001). The IC value in patients with hyperlipidemic, alcoholic and biliary SAP was (8 815.2±537.9), (7 631.2±890.5), and (8 108.0±933.1) kJ/d, respectively, and the H-B value was (6 869.6±204.5), (5 916.8±153.7), and (5 974.2±200.9) kJ/d, respectively. The IC value in patients with biliary or hyperlipidemic SAP were higher than H-B value, and the differences were statistically significant( t=2.29 and 3.38, both P<0.05). The IC value and H-B value in SAP patients with mechanical ventilation and without mechanical ventilation were (10 485.0±741.1) and (6 462.6±222.8) kJ/d, (6 595.1±364.7) and (6 503.2±166.7) kJ/d, respectively. The IC value in SAP patients with mechanical ventilation was higher than H-B value and the IC value in SAP patients without mechanical ventilation, and the differences were statistically significant ( t=4.71 and 5.20, both P<0.001). The consistency analyzed by Bland-Altman method showed that the two methods had obvious biases, and the average bias value was 92.2 kJ/d. The result of Pearson linear regression analysis indicated that there was a linear relationship between two methods ( r=0.44, P<0.001). The linear equation fitted by the univariate regression was Y=1.240 6 X+ 154.42, in which X was the H-B value and Y was the IC value. Conclusions:SAP patients are mostly in a hypermetabolic state in the early stages of the disease. The IC value is higher than H-B value, and it is recommended to use IC to measure energy consumption in SAP patients.

Preparação e caracterização de nanocarreadores de beta-lactose à base de pectina e lisozima / Preparation and characterization of beta-lactose nanocarriers based on pectin and lysozyme

O objetivo deste trabalho foi preparar e caracterizar nanocarreadores via auto-organização a partir da pectina de citros e lisozima para o encapsulamento da ß-lactose. Foram estudadas três condições de interação entre os biopolímeros variando a razão molar pectina/lisozima (3:1, 2:1, 1:1, 1:2 e 1:3), o pH e o tempo de aquecimento. A confirmação da interação foi determinada por espectroscopia no infravermelho por transformada de Fourier (FTIR) e por calorimetria de varredura diferencial (DSC). Os espectros de infravermelho evidenciaram que ligações de hidrogênio foram as principais forças envolvidas na formação dos nanocarreadores e sugeriram a ausência de ß-lactose livre na superfície das nanopartículas. Os termogramas evidenciaram que as nanopartículas formadas na presença de ß-lactose têm maior estabilidade térmica do que as nanopartículas sem ß-lactose. Para ambas as formulações estudadas, na presença e na ausência de ß-lactose, a formação das nanopartículas ocorreu entre os valores de pKa e ponto isoelétrico (pI) da pectina e lisozima, respectivamente, sendo a melhor razão de interação pectina/lisozima 1:2, em pH 10, a 80 ºC por 30 min. As nanopartículas foram formadas via auto-organização e todos as partículas apresentaram distribuição de tamanho homogênea, formato esférico, diâmetro inferior a 100 nm e carga superficial negativa. A morfologia e o tamanho das partículas pouco alteraram com a incorporação da -lactose. A eficiência de encapsulação (EE) da ß-lactose foi superior a 96% para as concentrações estudadas. Ensaios preliminares in vitro, em células epiteliais de câncer de cólon (HCT-116), evidenciaram que as nanopartículas formadas são capazes de adentrar no meio intracelular, possivelmente, por via endocitose

This work aimed to prepare and characterize nanocarriers via self-assembly using citrus pectin and lysozyme for ß-lactose encapsulation. Three interaction conditions between the biopolymers were studied, varying the pectin/lysozyme molar ratio (3:1, 2:1, 1:1, 1:2 and 1:3), pH and heating time. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) determined the interaction's confirmation. The infrared spectra showed that hydrogen bonds were the main forces involved in the formation of nanocarriers and suggested the absence of free ß-lactose on the surface of the nanoparticles. The thermograms showed that nanoparticles formed in the presence of ß-lactose have greater thermal stability than nanoparticles without ß-lactose. For both formulations studied, in the presence and absence of lactose, the formation of nanoparticles occurred between the pKa and isoelectric point (pI) values of pectin and lysozyme, respectively, with the best pectin/lysozyme interaction molar ratio 1:2, at pH 10, at 80 °C for 30 min. Nanoparticles were formed via self-assembly, and all particles presented homogeneous size distribution, spherical shape, diameter less than 100 nm, and negative surface charge. The morphology and size of the particles changed little with the incorporation of ß-lactose. The encapsulation efficiency (EE) of ß-lactose was higher than 96% for the concentrations studied. Preliminary in vitro assays in colon cancer epithelial cells (HCT-116) showed that the nanoparticles formed are capable of entering the intracellular medium, possibly via endocytosis

Caracterização mecânica, termodinâmica e química de fios CuNiTi ­ um estudo comparativo clínico e laboratorial / Mechanical, thermodynamic and chemical characterization of CuNiTi wires ­ a clinical and laboratory comparative study

Introdução: Os fios Copper Ni-Ti (CuNiTi) possuem indicações de uso clínico específicas, permanecendo no ambiente bucal por um longo período. Por esse motivo suas características mecânicas, termodinâmicas e estruturais devem ser preservadas durante todo o período de uso. Objetivos: Investigar se ocorrem alterações no comportamento mecânico, termodinâmico, estrutura e composição química superficial em fios CuNiTi 35°C submetidos ao envelhecimento in vivo (uso clínico) e in vitro (termociclagem), evidenciando as possíveis diferenças entre os métodos de envelhecimento. Material e Métodos: A amostra total foi constituída de 30 arcos pré-contornados 0.016", termodinâmicos com adição de cobre, e temperatura austenítica final (Af) de 35°C, da marca Ormco®. As análises destes fios resultaram em dois capítulos. Para o experimento clínico, 10 unidades de fios foram instaladas em 05 pacientes e permaneceram em meio bucal durante 30, 60 e 90 dias, e 05 fios foram analisados como recebidos (CR). A cada período, um hemiarco completo mais 1/3 (um terço) do hemiarco inferior direito foi retirado para análises. Para o experimento in vitro os 15 fios restantes foram submetidos à termociclagem para simulação do envelhecimento em ambiente oral durante 30 (600 ciclos), 60 (1200 ciclos) e 90 dias (1800 ciclos) com variação de temperatura entre 5°C e 55°C, com banhos de 90 segundos em cada temperatura, e transição de 15 segundos entre os banhos. Após cada período de envelhecimento in vivo e in vitro, os fios foram submetidos a um teste de padronização das suas dimensões através da medição dos diâmetros com paquímetro, Microscopia Eletrônica de Varredura (MEV), Espectrometria por Raios X Fluorescentes (FRX), ensaios de tração uniaxial e ensaio de Varredura Diferencial de Calorimetria (DSC). Resultados: No capítulo 1 a comparação entre os fios CR e os envelhecidos revelou que não houve diferença significativa entre os diâmetros das amostras, das forças obtidas ou mesmo das temperaturas Af, independentemente do tempo de permanência em boca. Foram encontrados predominantemente Ni, Ti, Cu e Al nas amostras, além de outros elementos químicos em concentrações variadas. No capítulo 2 não houve diferença significativa entre os diâmetros das amostras, das forças obtidas ou mesmo das temperaturas Af entre as amostras, independentemente do tempo ou do método de envelhecimento. Conclusão: As análises laboratoriais dos fios envelhecidos in vivo e in vitro foram comparadas, evidenciando que as características mecânicas, termodinâmicas e químicas dos fios permanecem estáveis mesmo até 90 dias de uso clínico ou 1800 ciclos de termociclagem. O método de envelhecimento in vitro se mostra uma alternativa viável para a análise destes parâmetros, em substituição aos métodos in vivo (AU).

Introduction: Copper Ni-Ti wires (CuNiTi) have specific indications for clinical use, remaining in the oral environment for a long period. For this reason, their mechanical, thermodynamic and structural characteristics must be preserved throughout the period of use of these materials. Objectives: To investigate whether there are changes in the mechanical, thermodynamic, structure and surface chemical composition of CuNiTi 35°C wires subjected to in vivo aging (clinical use) and in vitro (thermocycling), highlighting the possible differences between the aging methods. Material and Methods: The total sample was obtained from 30 pre-contoured Ormco® 0.016 thermodynamic archwires with copper addition and austenitic final temperature (Af) of 35°C. The analysis of these archwires resulted in two articles. For the clinical experiment, 10 units of wires were installed in 05 patients and remained in the oral environment for 30, 60 and 90 days, and 05 wires were analyzed as received. At each period, a complete hemiarch plus 1/3 of the right lower hemiarch was removed for analysis. For the in vitro experiment, the 15 remaining wires underwent thermocycling to simulate the aging of the oral environment for 30 (600 cycles), 60 (1200 cycles) and 90 days (1800 cycles) with a temperature range between 5°C and 55°C, with 90 second baths at each temperature, and 15 second transition between baths. After each in vivo and in vitro aging period, the wires underwent to a standardization test of their dimensions, by defining the diameters with a caliper, Scanning Electron Microscopy (SEM), Fluorescent X-Ray Spectrometry (FRX), tests of Uniaxial traction and Differential Scanning Calorimetry (DSC) test. Results: In chapter 1, the comparison between CR and aged wires revealed that there was no significant difference between the sample diameters, the forces obtained or even the temperatures Af, regardless the time spent in the mouth. Predominantly Ni, Ti, Cu and Al were found in the samples, in addition to other chemical elements in different concentrations. In chapter 2 there was no significant difference between the diameters of the samples, the forces obtained or even the temperatures Af between the samples, regardless of time or aging method. Conclusion: The comparison of the laboratoral analyzes of the archwires aged in vivo and in vitro showed that the mechanical, thermodynamic and the surface chemical characteristics were stable, even up to 90 days of clinical use or 1800 thermocycling cycles. The in vitro aging method is a viable alternative for the analysis of these parameters, replacing the in vivo methods (AU).

Avaliação do gasto energético de repouso em pacientes com doença hepática gordurosa não alcoólica / Evaluation of rest energy expenditure in patients with non alcoholic fatty liver disease

ABSTRACT BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently considered a global public health problem, with changes in lifestyle being the effective way to treat the disease. To date, there is no recommended standard of assessment to determine the resting energy expenditure (REE) of patients with NAFLD, so that dietary therapy can be properly guided. OBJECTIVE: To evaluate the REE of patients with NAFLD through indirect calorimetry and compare with different predictive formulas of REE and with REE by electrical bioimpedance analysis (BIA). Assess body composition through BIA, with NAFLD staging and the presence of comorbidities. METHODS: They were evaluated in patients with NAFLD over 18 years of age treated at the Gastroenterology outpatient clinic of a tertiary level hospital in southern Brazil. NAFLD staging was performed using liver biopsy or a non-invasive method. Weight, height and body mass index (BMI) were determined in all patients. The short version of the International Physical Activity Questionnaire was used to assess physical activity. Comorbidities as arterial hypertension, diabetes mellitus and dyslipidemia were evaluated. To estimate energy expenditure at rest, Harris-Benedict, Jeor Mifflin-St, World Health Organization and Schofield formulas were used. BIA was used to assess resting metabolic rate (RMR) and body mass, and to measure RMR, indirect calorimetry was also used. Associations between categorical variables were tested with Pearson's χ2 test and between groups with McNemar's test. The level of significance assumed was 5%. The degree of agreement between the REE measurement methods was assessed using the Blan-Altman test. RESULTS: A total of 67 patients were evaluated, 70.5% male, with a mean age of 59 years and a mean BMI of 33.08 kg/m2 ±5.13. The average RMR per CI was 1,753 kcal ±614.58. When comparing the RMR estimate by different formulas with indirect calorimetry, only the Jeor Mifflin-St formula showed a statistically significant difference (P=0.0001), with a difference of +318.49 kcal. BIA and Harris Benedict's formula presented values closer to CI, 1,658 and 1,845 kcal respectively. CONCLUSION: We suggest that the Jeor Mifflin-St formula should not be used to estimate the RMR in patients with NAFLD. In the absence of indirect calorimetry, some alternatives can be used safely in this population, such as BIA and the predictive formulas of Harris Benedict, Schofield and the World Health Organization.

RESUMO CONTEXTO: A doença hepática gordurosa não alcoólica (DHGNA) é considerada, atualmente, um problema de saúde pública global, sendo a mudança no estilo de vida a forma efetiva de tratar a doença. Até o momento não há um padrão de avaliação recomendado para determinar o gasto energético de repouso (GER) de pacientes com DHGNA, para que se possa nortear adequadamente a conduta dietoterápica. OBJETIVO: Avaliar o GER de pacientes com DHGNA através da calorimetria indireta (CI) e comparar com diferentes fórmulas preditivas do GER e com GER através da bioimpedância elétrica (BIA). Avaliar a composição corporal através da BIA, com o estadiamento da DHGNA e com a presença de comorbidades. MÉTODOS: Foram avaliados em pacientes com DHGNA maiores de 18 anos de idade atendidos no ambulatório de Gastroenterologia de um Hospital de nível terciário do Sul do Brasil. O estadiamento da DHGNA foi realizado através de biópsia hepática ou método não invasivo. Peso, altura e índice de massa corporal (IMC) foram determinados em todos os pacientes. Para avaliação da atividade física foi utilizada a versão curta do International Physical Activity Questionnaire. Foram avaliadas as comorbidades hipertensão arterial, diabetes mellitus e dislipidemia. Para a estimativa do gasto energético de repouso utilizou-se as fórmulas de Harris-Benedict, de Jeor Mifflin-St, da Organização Mundial de Saúde e de Schofield. A BIA foi utilizada para avaliação do GER e da massa corporal, e para aferição do GER também se utilizou a CI. Associações entre variáveis categóricas foram testadas com teste χ2 de Pearson e entre grupos com teste de McNemar. O nível de significância assumido foi de 5%. O grau de concordância entre os métodos de mensuração do GER foi aferido pelo teste de Blan-Altman. RESULTADOS: Foram avaliados 67 pacientes, sendo 70,5% do sexo masculino, com média de idade de 59 anos e média de IMC 33,08 kg/m2 ±5,13. O GER médio por CI foi de 1.753 kcal ±614,58. Ao comparar a estimativa do GER por diferentes fórmulas com a calorimetria indireta, apenas a fórmula de Jeor Mifflin-St apresentou diferença estatisticamente significativa (P=0,0001), com uma diferença de +318,49 kcal. A BIA e a fórmula de Harris Benedict apresentaram valores mais próximos à CI, 1.658 e 1.845 kcal respectivamente. CONCLUSÃO: Sugerimos que a fórmula de Jeor Mifflin-St não deva ser utilizada para estimativa do GER em pacientes com DHGNA. Na ausência da CI algumas alternativas podem ser utilizadas com segurança nesta população, como a BIA e as fórmulas preditivas de Harris Benedict, de Schofield e da Organização Mundial de Saúde.

Estado nutricional y gasto energético basal de pacientes chilenos con síndrome de down / Nutritional status and basal energy expenditure of chilean patients with down syndrome

Introducción: se ha reportado una alta prevalencia de malnutrición por exceso en pacientes con Síndrome de Down (SD), tanto en niños, como en adolescentes y adultos. Evaluar correctamente el gasto energético basal (GEB) en estos pacientes, es un aspecto crítico del control de peso, que ha sido escasamente explorado. Objetivo: evaluar el estado nutricional y el GEB mediante calorimetría indirecta y dos ecuaciones predictivas, en pacientes con SD de Concepción, Chile. Materiales y método: estudio descriptivo y transversal en 6 pacientes con SD: 2 niños y 4 mujeres adultas. Se midieron el peso y la talla y se calcularon el índice peso/edad (niños) y el índice de masa corporal (adultos). La determinación del GEB, se realizó mediante calorimetría indirecta y utilizando dos ecuaciones predictivas: Harris & Benedict y FAO/OMS (1985). Los resultados se expresaron como medianas y rangos, y la comparación de los valores del GEB, se realizó a través de la prueba de Wilcoxon (α= 0,05). Resultados: se encontró que el 50% de los pacientes presentó sobrepeso. No se encontraron diferencias estadísticamente significativas entre el GEB calculado por las ecuaciones predictivas, y el obtenido por calorimetría indirecta. Conclusión: en el grupo de pacientes con SD evaluados, se podría estimar la GEB a través de las ecuaciones predictivas (Harris & Benedict y FAO/OMS, 1985), dada su concordancia con los valores obtenidos por calorimetría indirecta, lo que puede ser muy útil en la práctica clínica, permitiendo la elaboración de planes de alimentación adecuados para estos pacientes(AU)

Introduction: a high prevalence of malnutrition due to overweight and obesity has been reported in patients with Down Syndrome (DS), in children, adolescents and adults. A correct evaluation of the basal energy expenditure (BEE) in these patients is a critical aspect of weight control; however, this aspect has not been thoroughly studied. Objective: to evaluate the nutritional status and BEE using indirect calorimetry and two predictive equations in patients with DS from Concepción, Chile. Materials and methods: a descriptive and cross-sectional study was carried out in 6 patients with DS: 2 boys and 4 adult women. Weight and height were measured, and the weight/age index (children) and the body mass index (adults) were calculated. The determination of the BEE was carried out by indirect calorimetry and using two predictive equations: Harris & Benedict and FAO/WHO (1985). The results were expressed as means, standard deviations, medians and ranges, and the comparison of the BEE values was performed using the Wilcoxon test (α = 0.05). Results: 50% of the patients were overweight. No statistically significant differences were found between the BEE calculated by the predictive equations, and that obtained by indirect calorimetry. Conclusion: In the group of patients with DS evaluated, BEE could be estimated through the predictive equations (Harris & Benedict and FAO/ WHO, 1985), given its agreement with the values obtained by indirect calorimetry, which can be very useful in clinical practice, allowing the elaboration of adequate feeding plans for these patients(AU)

Design of ultrahigh-affinity and dual-specificity peptide antagonists of MDM2 and MDMX for P53 activation and tumor suppression

Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53

Comparison of indirect calorimetry and formula estimation of total daily energy expenditure in patients with acute pancreatitis / 中华肝胆外科杂志

Objective:To investigate the consistency of indirect calorimetry, Harris-Benedict (H-B) formula method and rule of thumb in calculating the daily total energy expenditure (TDEE) of patients with acute pancreatitis (AP), and provide the basis for the formulation of reasonable nutritional support program.Methods:A total of 66 AP patients admitted to Henan Provincial People's Hospital from June 2020 to December 2020 were included and retrospectively analyzed, including 35 males and 31 females with an average age of 41.8 years. They were divided into mild acute pancreatitis (MAP) group ( n=20) and moderate to severe AP group ( n=46) according to severity. TDEE was calculated by indirect calorimetry, H-B formula and rule of thumb, and Pearson correlation analysis and Bland-Altman diagram were used to analyze the correlation and consistency of the three methods, respectively. Results:There were no statistical significances in the TDEE of MAP group calculated by indirect calorimetry, H-B formula method and rule of thumb (both P>0.05). TDEE calculated by indirect calorimetry were higher than that of calculated by H-B formula and thumb method both in moderate and severe AP groups, and the difference was statistically significant (both P<0.05). Pearson correlation analysis showed that H-B formula method was positively correlated with the TDEE calculated by indirect calorimetry, and the correlation was 0.61 ( P<0.05). Bland-Altman plot analysis showed the consistence of the two methods. TDEE calculated by rule of thumb was positively correlated with that calculated by indirect calorimetry, and the correlation was 0.75 ( P<0.05). The bland-Altman plot analysis showed a good consistency between the two methods. Conclusion:For MAP patients, TDEE can be calculated by the H-B formula method and rule of thumb. In moderate and severe AP patients, TDEE should be calculated by indirect calorimetry as the basis for the formulation of nutritional support plan.

Agreement between equations-estimated resting metabolic rate and indirect calorimetry-estimated resting metabolic rate in low-income obese women

ABSTRACT Objectives Indirect calorimetry is established as a gold standard to determine the resting metabolic rate (RMR), however, its clinical use is limited, especially in low-income settings. Thus, the use of predictive equations appear as an alternative to estimate the RMR, but its precision is debatable, especially in obese individuals and in populations without specifically developed equations. To evaluate the agreement between the RMR estimated by equations and by indirect calorimetry in low-income obese women. Subjects and methods A cross-sectional study with adult and obese women, which estimated the RMR by indirect calorimetry and compared with 13 predictive equations using the concordance correlation coefficient, root mean square error (RMSE) and Bland-Altman methods. The maximum allowed differences were predefined as 10%. Results No equation presented its confidence intervals for the Bland-Altman limits of agreement inside the predefined acceptable range. The Harris-Benedict equation achieved better agreement (bias of 2.9% and RMSE of 274.3kcal) whereas the Henry-Rees equation achieved better precision (42.3% of the sample within the 10% maximum allowed difference). Conclusion None of the studied equations satisfactorily estimated the RMR estimated by indirect calorimetry. In the absence of specific equations for this population, the use of the Harris-Benedict and Henry-Rees equations could be considered.

Pharmaceutical polymorphism of a 5´-O-oxalatoyl prodrug of zidovudine (azidothymidine)

The importance of polymorphism in pharmaceuticals makes its study relevant. The aim of this study was to investigatethe solid-state forms in which 3´-azido-2´, 3´-dideoxi-5´-O-oxalatoyl-thymidinic acid (AZT-Ac), a zidovudine (AZT)prodrug with improved pharmacokinetic properties, may exist. Samples were prepared using different crystallizationconditions and characterized using powder X-ray diffraction, solid-state nuclear magnetic resonance, differentialscanning calorimetry, thermogravimetry, and hot-stage microscopy. Pharmaceutical relevant properties such assolid-state stability and intrinsic dissolution rate (IDR) at 37°C in simulated gastric fluid (SGF) were also evaluated.AZT-Ac was found to able to exist as a crystalline polymorph (AZT-Ac-C) and an amorphous phase (AZT-Ac-A),which were thoroughly characterized. At 40°C/75% relative humidity (RH), AZT-Ac-A, in part, devitrified toAZT-Ac-C and partially hydrolyzed to AZT after 7 and 14 days of storage, respectively. AZT-Ac-C was physicallystable at 40°C/75% RH but partly hydrolyzed to AZT after 14 days of storage. In SGF, AZT-Ac-C exhibited a linearID profile and provided an ID rate of 0.494 mg/min/cm2, whereas AZT-Ac-A exhibited a nonlinear profile. Therefore,the crystalline form demonstrated the advantages over the amorphous one in terms of solid-state stability and IDR, butthe approaches to enhance its stability should be considered for further formulation of this prodrug.