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1.
Eur J Sport Sci ; 24(6): 758-765, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38874989

RESUMEN

Citrulline malate (CM) is purported to be an ergogenic aid during various types of exercise performance. However, the effects of CM on repeated sprint performance (RSP) are under-explored. In a placebo-controlled, double-blind, counterbalanced cross-over design, male university-level team sport athletes (n = 13) performed two familiarization trials, after which CM or placebo (PLA) (8 × 1 g tablets each day) were taken on the 2 days prior to, and with breakfast on the morning of, each main experimental trial. The main experimental trials employed a RSP protocol consisting of 10 repetitions of 40 m maximal shuttle run test (MST) with a 30 s interval between the start of each sprint. Sprint times and heart rate were recorded throughout the MST, and blood lactate concentrations were measured before, immediately after, and 5 min after completing the MST. CM resulted in better RSP compared to PLA, as indicated by a lower sprint performance decrement (Sdec: CM, 4.68% ± 1.82% vs. PLA, 6.10% ± 1.83%; p = 0.03; ES = 0.77), which was possibly influenced by the fastest sprint time being faster in CM (CM, 8.16 ± 0.34 s vs. PLA, 8.29 ± 0.39 s; p = 0.011; ES = 0.34). There were no differences between CM and PLA in average sprint time (p = 0.54), slowest sprint time (p = 0.48), blood lactate concentrations (p = 0.73) or heart rate (p = 0.18), nor was there a condition × time interaction effect across the 10 sprints (p = 0.166). Three days of CM supplementation (8 g daily) attenuated the sprint performance decrement during short-duration high-intensity exercise in the form of running RSP in male university-level team sport athletes.


Asunto(s)
Rendimiento Atlético , Citrulina , Estudios Cruzados , Suplementos Dietéticos , Frecuencia Cardíaca , Ácido Láctico , Malatos , Carrera , Humanos , Masculino , Carrera/fisiología , Rendimiento Atlético/fisiología , Método Doble Ciego , Adulto Joven , Citrulina/administración & dosificación , Citrulina/farmacología , Citrulina/análogos & derivados , Ácido Láctico/sangre , Malatos/administración & dosificación , Malatos/farmacología , Atletas , Deportes de Equipo , Sustancias para Mejorar el Rendimiento/administración & dosificación , Sustancias para Mejorar el Rendimiento/farmacología , Adulto
2.
Drug Deliv Transl Res ; 14(8): 2062-2078, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38517568

RESUMEN

To improve the therapeutic activity of inhaled glucocorticoids and reduce potential side effects, we designed a formulation combining the advantages of nanoparticles, which have an enhanced uptake by alveolar cells, allow targeted delivery and sustained drug release, as well as limited drug systemic passage, with those of microparticles, which display good alveolar deposition. Herein, a polymer-drug conjugate, poly(malic acid)-budesonide (PMAB), was first synthesized with either 11, 20, 33, or 43 mol% budesonide (drug:polymer from 1:8 to 3:4), the drug creating hydrophobic domains. The obtained conjugates self-assemble into nanoconjugates in water, yielding excellent drug loading of up to 73 wt%, with 80-100 nm diameters. In vitro assays showed that budesonide could be steadily released from the nanoconjugates, and the anti-inflammatory activity was preserved, as evidenced by reduced cytokine production in LPS-activated RAW 264.7 macrophages. Nanoconjugates were then embedded into microparticles through spray-drying with L-leucine, forming nano-embedded microparticles (NEMs). NEMs were produced with an aerodynamic diameter close to 1 µm and a density below 0.1 g.cm-3, indicative of a high alveolar deposition. NEMs spray-dried with the less hydrophobic nanoconjugates, PMAB 1:4, were readily dissolved in simulated lung fluid and were chosen for in vivo experiments to study pharmacokinetics in healthy rats. As it was released in vivo from NEMs, sustained distribution of budesonide was obtained for 48 h in lung tissue, cells, and lining fluid. With high loading rates, modulable release kinetics, and low cytotoxicity, these nanoconjugates delivered by NEMs are promising for the more efficient treatment of pulmonary inflammatory diseases.


Asunto(s)
Budesonida , Pulmón , Nanoconjugados , Animales , Ratones , Budesonida/administración & dosificación , Budesonida/farmacocinética , Budesonida/química , Células RAW 264.7 , Pulmón/metabolismo , Nanoconjugados/química , Nanoconjugados/administración & dosificación , Masculino , Polímeros/química , Polímeros/administración & dosificación , Malatos/química , Malatos/administración & dosificación , Malatos/farmacocinética , Administración por Inhalación , Tamaño de la Partícula , Ratas , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/farmacocinética , Liberación de Fármacos , Ratas Sprague-Dawley
3.
Int J Sport Nutr Exerc Metab ; 31(4): 350-358, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34010809

RESUMEN

Citrulline malate (CitMal) is a dietary supplement that is suggested to enhance strength training performance. However, there is conflicting evidence on this matter. Thus, the purpose of this meta-analysis was to determine whether supplementing with CitMal prior to strength training could increase the total number of repetitions performed before reaching voluntary muscular failure. A systematic search was conducted wherein the inclusion criteria were double-blind, placebo-controlled studies in healthy participants that examined the effect of CitMal on repetitions to failure during upper body and lower body resistance exercises. The Hedges's g standardized mean differences (SMD) between the placebo and CitMal trials were calculated and used in a random effect model. Two separate subanalyses were performed for upper body and lower body exercises. Eight studies, including 137 participants who consisted of strength-trained men (n = 101) and women (n = 26) in addition to untrained men (n = 9), fulfilled the inclusion criteria. Across the studies, 14 single-joint and multijoint exercises were performed with an average of 51 ± 23 total repetitions during 5 ± 3 sets per exercise at ∼70% of one-repetition maximum. Supplementing with 6-8 g of CitMal 40-60 min before exercise increased repetitions by 3 ± 5 (6.4 ± 7.9%) compared with placebo (p = .022) with a small SMD (0.196). The subanalysis for the lower body resulted in a tendency for an effect of the supplement (8.1 ± 8.4%, SMD: 0.27, p = .051) with no significant effect for the upper body (5.7 ± 8.4%, SMD: 0.16, p = .131). The current analysis observed a small ergogenic effect of CitMal compared with placebo. Acute CitMal supplementation may, therefore, delay fatigue and enhance muscle endurance during high-intensity strength training.


Asunto(s)
Citrulina/análogos & derivados , Malatos/farmacología , Sustancias para Mejorar el Rendimiento/farmacología , Resistencia Física/efectos de los fármacos , Rendimiento Físico Funcional , Entrenamiento de Fuerza/métodos , Adulto , Sesgo , Citrulina/administración & dosificación , Citrulina/farmacología , Método Doble Ciego , Femenino , Humanos , Malatos/administración & dosificación , Masculino , Resistencia Física/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Adulto Joven
4.
J Sport Health Sci ; 9(6): 553-561, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33308806

RESUMEN

BACKGROUND: Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic review and meta-analysis to determine the effect of citrulline supplements on the post-exercise rating of perceived exertion (RPE), muscle soreness, and blood lactate levels. METHODS: A random effects model was used to calculate the effect sizes due to the high variability in the study design and study populations of the articles included. A systematic search of PubMed, Web of Science, and ClinicalTrials.gov was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving healthy individuals and that investigated the acute effect of citrulline supplements on RPE, muscle soreness, and blood lactate levels. The supplementation time frame was limited to 2 h before exercise. The types and number of participants, types of exercise tests performed, supplementation protocols for L-citrulline or citrulline malate, and primary (RPE and muscle soreness) and secondary (blood lactate level) study outcomes were extracted from the identified studies. RESULTS: The analysis included 13 eligible articles including a total of 206 participants. The most frequent dosage used in the studies was 8 g of citrulline malate. Citrulline supplementation significantly reduced RPE (n = 7, p = 0.03) and muscle soreness 24-h and 48-h after post-exercise (n = 7, p = 0.04; n = 6, p = 0.25, respectively). However, citrulline supplementation did not significantly reduce muscle soreness 72-h post-exercise (n = 4, p = 0.62) or lower blood lactate levels (n = 8, p = 0.17). CONCLUSION: Citrulline supplements significantly reduced post-exercise RPE and muscle soreness without affecting blood lactate levels.


Asunto(s)
Citrulina/administración & dosificación , Suplementos Dietéticos , Ácido Láctico/sangre , Mialgia/prevención & control , Percepción/fisiología , Esfuerzo Físico/fisiología , Citrulina/efectos adversos , Citrulina/análogos & derivados , Jugos de Frutas y Vegetales , Humanos , Malatos/administración & dosificación , Malatos/efectos adversos , Entrenamiento de Fuerza
5.
Arch Anim Nutr ; 74(5): 380-396, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32403953

RESUMEN

The effects of treating sunflower seed (SS) and meal (SM), as well as of a mixture of both feeds (SSM; 45:55) with a solution of malic acid (1 M; 400 ml/kg feed) and heating for protection against ruminal degradation were studied. Four rumen-fistulated sheep were fed two mixed diets composed of oat hay and concentrate (40:60) and differing only in the concentrate, that contained either a mixture of untreated SS and SM (control diet) or treated SS and SM (MAH diet). A crossover design with two 24-d experimental periods was used, and each period included 10 d of diet adaptation, 9 d for in situ incubations of SS, SM and SSM, and 5 d for measuring ruminal fermentation characteristics and rumen emptying. From day 6 onwards a solution of (15NH4)2SO4 was continuously infused into the rumen of each sheep to label ruminal bacteria. Feeding the MAH diet did not affect either ruminal pH or concentrations of total volatile fatty acids and NH3-N, but decreased (p ≤ 0.01) the molar proportions of acetate and propionate and increased those of butyrate (p< 0.001). Organic matter and lipid contents of ruminal bacteria were lower whereas both N content and 15N enrichment were greater (p ≤ 0.05) in MAH-fed sheep. The in situ effective degradability (ED) of different fractions of SS, SM and SSM were calculated from the ruminal rates of particle comminution and passage, and values were corrected for microbial contamination. The MAH treatment decreased the ED of most fractions for all feeds and increased the supply of by-pass crude protein (CP) by 19.1% and 120% for SS and SM, respectively, and that of fat by 34% for SS. The MAH treatment also increased the in vitro intestinal digestibility of the by-pass CP for both SS (from 60.1% to 75.4%) and SM (from 83.2% to 91.0%). The simultaneous heating of both feeds (SSM) reinforced the protective effect of the MAH treatment and increased the by-pass CP without altering its intestinal digestibility, increasing the intestinally digested CP content by 16.8% compared with the value estimated from the results obtained for MAH-treated SS and SM incubated independently. These results indicate that the MAH treatment was effective to protect sunflower protein against rumen degradation and increased its intestinal digestibility.


Asunto(s)
Alimentación Animal/análisis , Digestión/efectos de los fármacos , Helianthus/química , Rumen/metabolismo , Oveja Doméstica/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Animales , Dieta/veterinaria , Femenino , Fermentación/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Malatos/administración & dosificación , Distribución Aleatoria , Semillas/química , Oveja Doméstica/microbiología
6.
Cell Host Microbe ; 27(6): 922-936.e6, 2020 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-32416061

RESUMEN

Initial enteropathogen growth in the microbiota-colonized gut is poorly understood. Salmonella Typhimurium is metabolically adaptable and can harvest energy by anaerobic respiration using microbiota-derived hydrogen (H2) as an electron donor and fumarate as an electron acceptor. As fumarate is scarce in the gut, the source of this electron acceptor is unclear. Here, transposon sequencing analysis along the colonization trajectory of S. Typhimurium implicates the C4-dicarboxylate antiporter DcuABC in early murine gut colonization. In competitive colonization assays, DcuABC and enzymes that convert the C4-dicarboxylates aspartate and malate into fumarate (AspA, FumABC), are required for fumarate/H2-dependent initial growth. Thus, S. Typhimurium obtains fumarate by DcuABC-mediated import and conversion of L-malate and L-aspartate. Fumarate reduction yields succinate, which is exported by DcuABC in exchange for L-aspartate and L-malate. This cycle allows S. Typhimurium to harvest energy by H2/fumarate respiration in the microbiota-colonized gut. This strategy may also be relevant for commensal E. coli diminishing the S. Typhimurium infection.


Asunto(s)
Ácido Aspártico/metabolismo , Fumaratos/metabolismo , Microbioma Gastrointestinal/fisiología , Malatos/metabolismo , Salmonella/metabolismo , Administración Oral , Animales , Ácido Aspártico/administración & dosificación , Proteínas Bacterianas/metabolismo , Ciclo del Ácido Cítrico , Modelos Animales de Enfermedad , Escherichia coli/metabolismo , Heces/microbiología , Femenino , Microbioma Gastrointestinal/genética , Intestinos/microbiología , Malatos/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Mutagénesis , ARN Ribosómico 16S/genética , Salmonella/genética , Salmonella/crecimiento & desarrollo , Salmonella typhimurium , Análisis de Secuencia de ADN , Ácido Succínico
7.
J Surg Res ; 245: 225-233, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31421367

RESUMEN

BACKGROUND: In the past, protective effects in terms of prolonged survival of malate-containing solutions were demonstrated in the treatment of experimental hemorrhagic shock (HS). The objective of the present study was to investigate malate's impact on the kidneys. Therefore, renal function and morphological and histological anomalies were examined. MATERIALS AND METHODS: Male Wistar rats were subjected to severe HS by dropping the mean arterial blood pressure to 25-30 mmHg. The depth was held for 60 min. Subsequently, reperfusion with Ringer's solution or a 10 mM malate-containing solution was performed both together with blood in a 2:1 relation, followed by an observation period of 150 min. RESULTS: Compared with the control group (Ringer's solution), malate increased diuresis and, thus, enhanced excretion of creatinine and urea. Shock-induced histopathological changes were reduced by malate administration. Renal hemorrhages in the straight proximal tubule and in the distal tubule were reduced and even significantly reduced in the proximal convoluted tubule. Malate significantly preserved the endothelial glycocalyx in the proximal tubule. Surprisingly, malate induced glucosuria in the absence of a significant renal dysfunction, morphological damage, or hyperglycemia. CONCLUSIONS: The protective effect of malate observed in the treatment of severe HS in the rat may be explained by a certain protective effect of this substance for the kidney.


Asunto(s)
Lesión Renal Aguda/prevención & control , Fluidoterapia/métodos , Malatos/administración & dosificación , Resucitación/métodos , Choque Hemorrágico/terapia , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Animales , Modelos Animales de Enfermedad , Humanos , Infusiones Intravenosas , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , Choque Hemorrágico/complicaciones , Choque Hemorrágico/diagnóstico , Resultado del Tratamiento
8.
J Diet Suppl ; 17(3): 249-260, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30458655

RESUMEN

Citrulline malate (CM) is purported to buffer lactic acid, enhance oxygen delivery, and attenuate muscle soreness. Anaerobic exercise trials with CM have produced conflicting results. The aim of the current investigation was to test the efficacy of CM on resistance training (RT) with the hypothesis that CM would improve performance. A double-blind, counter-balanced, randomized control trial was utilized to assess the effects of CM on RT. Nineteen participants (8 female) (25.7 ± 7.7 years), regularly engaged in RT, consumed either 8 g of CM (1.1:1 ratio) or a placebo (6 g citric acid). Participants attempted to perform a German Volume Training (GVT) protocol comprising 10 sets of 10 repetitions of barbell curls at 80% of their one repetition maximum. Repeated ANOVA suggested no effect of CM on RT performance (treatment × time × order p = .217). There was no difference (p = .320) in the total number of reps over the 10 sets (CM median = 57, IQR 45-73; placebo median = 61, IQR 51-69). Blood lactate and creatine kinase did not differ between CM and placebo (p > .05). Finally, total muscle soreness was reduced significantly in CM compared to placebo (treatment × time × order p = .004). These results require corroboration; an ergogenic benefit is yet to be established, and weight trainers should exercise caution when assessing the efficacy of CM. Future research should focus on the potential effects of loading doses of CM.


Asunto(s)
Citrulina/análogos & derivados , Suplementos Dietéticos , Malatos/administración & dosificación , Mialgia/prevención & control , Entrenamiento de Fuerza , Adolescente , Adulto , Citrulina/administración & dosificación , Creatina Quinasa/sangre , Estudios Cruzados , Método Doble Ciego , Femenino , Alemania , Voluntarios Sanos , Humanos , Ácido Láctico/sangre , Masculino , Fuerza Muscular , Músculo Esquelético/fisiología , Adulto Joven
9.
J Diet Suppl ; 17(6): 698-717, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31456449

RESUMEN

The ergogenic effects of citrulline malate (CitMal) and beetroot juice (BEET) have been widely studied, but their effects on physiological outcomes related to resistance exercise are not fully understood. The purpose of this randomized, double-blind, crossover study was to investigate the effects of CitMal (8 g) and BEET (400 mg nitrate) on blood pressure (BP), blood flow, and energy efficiency during submaximal leg extension. Recreationally active males (n = 27; age: 22 ± 4 yrs) completed familiarization, followed by three testing visits. Supine and standing BP were measured upon arrival, followed by supplement ingestion, a 2-h rest period, postsupplement BP measurement, and a bout of repeated submaximal isotonic leg extensions at 25% of maximal voluntary contraction torque. Diameter (aDIAM) and blood flow (aBF) of the superficial femoral artery, and cross-sectional area (CSA) and echo intensity (EI) of the vastus lateralis, were measured before and after exercise via ultrasonography. Muscle blood flow (mBF) and oxygen consumption (mVO2), along with whole-body energy expenditure (EE) and respiratory exchange ratio (RER), were measured before and during exercise via indirect calorimetry and near-infrared spectroscopy. Baseline RER values differed among treatments (p = 0.01); BEET was higher than CitMal (p = 0.01) but not PLA (p = 0.58); CitMal and PLA were not significantly different (p = 0.12). No other measurements were significantly affected by treatment (all p > 0.05). Results suggest that neither CitMal nor BEET significantly influence resting BP, blood flow, or metabolic efficiency during submaximal leg extension in recreationally active males.


Asunto(s)
Citrulina/análogos & derivados , Metabolismo Energético , Jugos de Frutas y Vegetales , Malatos/administración & dosificación , Músculo Esquelético/irrigación sanguínea , Entrenamiento de Fuerza , Adolescente , Adulto , Beta vulgaris , Citrulina/administración & dosificación , Estudios Cruzados , Suplementos Dietéticos , Método Doble Ciego , Humanos , Masculino , Consumo de Oxígeno , Flujo Sanguíneo Regional , Adulto Joven
10.
Int J Pharm ; 569: 118584, 2019 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-31376466

RESUMEN

This study aimed to develop biocompatible deep eutectic solvents (DESs) as carriers for improving the nasal delivery of insulin. The DES was prepared from malic acid and choline chloride broadly used in foods, drugs, or cosmetics as biocompatible additives. The DES of choline chloride and malic acid (CM-DES) demonstrated lower melting point (-59.1 °C) and higher viscosity (120,000 cP) compared with hydrogels based on sodium carboxyl methyl cellulose (CMC-Na). The conformational structure of insulin does not change in CM-DES as characterized by circular dichroism. The in vitro results showed that CM-DES dissociated gradually but did not disintegrate immediately upon contact with water. CM-DES was able to improve the hypoglycemic effect of insulin significantly at different doses compared with hydrogels or solutions of insulin, which could be ascribed to facilitated penetration of insulin across the nasal epithelia by CM-DES. The hypoglycemic effect of CM-DES loading insulin at a dose of 25 IU/kg was similar to that of subcutaneous insulin at 1 IU/kg. In addition, no evident toxicity to nasal epithelia was observed after nasal administration to rats for seven consecutive days. In conclusion, CM-DES showed promising potential in enhancing the hypoglycemic effect of insulin via the nasal route.


Asunto(s)
Colina/administración & dosificación , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Malatos/administración & dosificación , Solventes/administración & dosificación , Administración Intranasal , Animales , Glucemia/efectos de los fármacos , Colina/química , Liberación de Fármacos , Hidrogeles/administración & dosificación , Hidrogeles/química , Hipoglucemiantes/química , Insulina/química , Malatos/química , Mucosa Nasal/metabolismo , Ratas , Ratas Sprague-Dawley , Solventes/química , Agua/química
11.
Medwave ; 19(4): e7633, 2019 May 28.
Artículo en Español, Inglés | MEDLINE | ID: mdl-31150373

RESUMEN

INTRODUCTION: Fibromyalgia is characterized by myalgia and a combination of different symptoms including pain, fatigue, insomnia, morning rigidity, depression and a reduction in every-day functioning. Its aetiology is not clear, but it has been suggested that deficiency in certain minerals such as magnesium may play a role both in the physiopathology and in contributing to the symptoms. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified seven systematic reviews which included 11 primary studies of which one was a randomized trial. Our conclusion is that the use of magnesium and malic acid in patients with fibromyalgia makes little or no difference on pain and on depressive symptoms.


INTRODUCCIÓN: La fibromialgia es una condición reumática no articular caracterizada por distintos síntomas, donde destacan principalmente el dolor, sensibilidad muscular, fatiga, insomnio, rigidez matinal, depresión y disminución de la funcionalidad cotidiana. Aún no existe claridad respecto de su etiología, pero se ha planteado que la deficiencia de elementos tales como el magnesio podría tener un rol tanto en la fisiopatología de la fibromialgia como también contribuir a sus síntomas clínicos. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos siete revisiones sistemáticas que en conjunto incluyeron 11 estudios primarios, de los cuales solo uno corresponde a un ensayo aleatorizado. Concluimos que el uso de magnesio y ácido málico en pacientes con fibromialgia tiene poco o nulo impacto en dolor y en los síntomas depresivos.


Asunto(s)
Fibromialgia/tratamiento farmacológico , Magnesio/administración & dosificación , Malatos/administración & dosificación , Bases de Datos Factuales , Suplementos Dietéticos , Fibromialgia/fisiopatología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
12.
Insect Mol Biol ; 28(6): 798-806, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-30977928

RESUMEN

The dietary specialist fruit fly Drosophila sechellia has evolved resistance to the secondary defence compounds produced by the fruit of its host plant, Morinda citrifolia. The primary chemicals that contribute to lethality of M. citrifolia are the medium-chain fatty acids octanoic acid (OA) and hexanoic acid. At least five genomic regions contribute to this adaptation in D. sechellia and whereas the fine-mapped major effect locus for OA resistance on chromosome 3R has been thoroughly analysed, the remaining four genomic regions that contribute to toxin resistance remain uncharacterized. To begin to identify the genetic basis of toxin resistance in this species, we removed the function of well-known detoxification gene families to determine whether they contribute to toxin resistance. Previous work found that evolution of cytochrome P450 enzymatic activity or expression is not responsible for the OA resistance in D. sechellia. Here, we tested the role of the two other major detoxification gene families in resistance to Morinda fruit toxins - glutathione-S-transferases and esterases - through the use of the pesticide synergists diethyl maleate and tribufos that inhibit the function of these gene families. This work suggests that one or more esterase(s) contribute to evolved OA resistance in D. sechellia.


Asunto(s)
Antibiosis/genética , Caprilatos/metabolismo , Drosophila/genética , Esterasas/genética , Glutatión Transferasa/genética , Morinda/fisiología , Animales , Caproatos/metabolismo , Drosophila/enzimología , Esterasas/metabolismo , Evolución Molecular , Femenino , Glutatión Transferasa/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Insecticidas/administración & dosificación , Malatos/administración & dosificación , Masculino , Morinda/química , Familia de Multigenes , Organotiofosfatos/administración & dosificación , Especificidad de la Especie
13.
Int J Pharm ; 558: 380-387, 2019 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-30664995

RESUMEN

The aim of this work was to develop biocompatible ionic liquids (ILs) for enhancement of dermal delivery of hydrophilic macromolecules. The ILs were prepared from malic acid and choline, which are commonly used as food additives and generally regarded as safe. The choline malate IL (CM-IL) was formed via ionic interactions, which has been validated by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Analysis by differential scanning calorimetry confirmed a melting point of -65.2 °C for CM-IL. In skin penetration study, CM-IL was proved to be able to deliver a model hydrophilic macromolecule dextran into deep skin. The amount of dextran delivered to epidermis and dermis by CM-IL is approximately two folds that of by dextran solution. Enhanced in vivo skin penetration by CM-IL was proved as well. The fluorescence of FITC-dextran could be observed permeating pervasively throughout the skin from 4 h to 24 h, while in the control groups it was mainly concentrated in stratum cornea (SC) and hair follicles. In addition, CM-IL did not shown any irritation to mice skin within 7 days of successive treatment and any toxicity to human epidermal cells (HEK-A) within 24 h. In conclusion, CM-IL could be potentially used as enhancers or vehicles for dermal delivery of hydrophilic macromolecules.


Asunto(s)
Colina/administración & dosificación , Líquidos Iónicos/administración & dosificación , Malatos/administración & dosificación , Administración Cutánea , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colina/química , Dextranos/administración & dosificación , Dextranos/química , Fluoresceína-5-Isotiocianato/administración & dosificación , Fluoresceína-5-Isotiocianato/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Líquidos Iónicos/química , Sustancias Macromoleculares/administración & dosificación , Sustancias Macromoleculares/química , Malatos/química , Masculino , Ratas Sprague-Dawley , Piel/anatomía & histología , Piel/efectos de los fármacos , Piel/metabolismo , Absorción Cutánea/efectos de los fármacos , Porcinos
14.
ACS Nano ; 13(2): 1253-1271, 2019 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-30633492

RESUMEN

One of the major problems facing the treatment of neurological disorders is the poor delivery of therapeutic agents into the brain. Our goal is to develop a multifunctional and biodegradable nanodrug delivery system that crosses the blood-brain barrier (BBB) to access brain tissues affected by neurological disease. In this study, we synthesized a biodegradable nontoxic ß-poly(l-malic acid) (PMLA or P) as a scaffold to chemically bind the BBB crossing peptides Angiopep-2 (AP2), MiniAp-4 (M4), and the transferrin receptor ligands cTfRL and B6. In addition, a trileucine endosome escape unit (LLL) and a fluorescent marker (rhodamine or rh) were attached to the PMLA backbone. The pharmacokinetics, BBB penetration, and biodistribution of nanoconjugates were studied in different brain regions and at multiple time points via optical imaging. The optimal nanoconjugate, P/LLL/AP2/rh, produced significant fluorescence in the parenchyma of cortical layers II/III, the midbrain colliculi, and the hippocampal CA1-3 cellular layers 30 min after a single intravenous injection; clearance was observed after 4 h. The nanoconjugate variant P/LLL/rh lacking AP2, or the variant P/AP2/rh lacking LLL, showed significantly less BBB penetration. The LLL moiety appeared to stabilize the nanoconjugate, while AP2 enhanced BBB penetration. Finally, nanoconjugates containing the peptides M4, cTfRL, and B6 displayed comparably little and/or inconsistent infiltration of brain parenchyma, likely due to reduced trans-BBB movement. P/LLL/AP2/rh can now be functionalized with intra-brain targeting and drug treatment moieties that are aimed at molecular pathways implicated in neurological disorders.


Asunto(s)
Barrera Hematoencefálica/química , Leucina/farmacocinética , Malatos/farmacocinética , Nanoconjugados/química , Péptidos/farmacocinética , Polímeros/farmacocinética , Rodaminas/farmacocinética , Animales , Barrera Hematoencefálica/metabolismo , Sistemas de Liberación de Medicamentos , Inyecciones Intravenosas , Leucina/administración & dosificación , Leucina/química , Malatos/administración & dosificación , Malatos/química , Ratones , Nanoconjugados/administración & dosificación , Péptidos/administración & dosificación , Péptidos/química , Polielectrolitos , Polímeros/administración & dosificación , Polímeros/química , Rodaminas/administración & dosificación , Rodaminas/química , Distribución Tisular
15.
Medwave ; 19(4): e7632, 2019.
Artículo en Inglés, Español | LILACS | ID: biblio-997905

RESUMEN

INTRODUCCIÓN La fibromialgia es una condición reumática no articular caracterizada por distintos síntomas, donde destacan principalmente el dolor, sensibilidad muscular, fatiga, insomnio, rigidez matinal, depresión y disminución de la funcionalidad cotidiana. Aún no existe claridad respecto de su etiología, pero se ha planteado que la deficiencia de elementos tales como el magnesio podría tener un rol tanto en la fisiopatología de la fibromialgia como también contribuir a sus síntomas clínicos. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos siete revisiones sistemáticas que en conjunto incluyeron 11 estudios primarios, de los cuales solo uno corresponde a un ensayo aleatorizado. Concluimos que el uso de magnesio y ácido málico en pacientes con fibromialgia tiene poco o nulo impacto en dolor y en los síntomas depresivos.


INTRODUCTION Fibromyalgia is characterized by myalgia and a combination of different symptoms including pain, fatigue, insomnia, morning rigidity, depression and a reduction in every-day functioning. Its aetiology is not clear, but it has been suggested that deficiency in certain minerals such as magnesium may play a role both in the physiopathology and in contributing to the symptoms. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified seven systematic reviews which included 11 primary studies of which one was a randomized trial. Our conclusion is that the use of magnesium and malic acid in patients with fibromyalgia makes little or no difference on pain and on depressive symptoms.


Asunto(s)
Humanos , Fibromialgia/tratamiento farmacológico , Magnesio/administración & dosificación , Malatos/administración & dosificación , Fibromialgia/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Bases de Datos Factuales , Suplementos Dietéticos
16.
Anim Sci J ; 89(12): 1673-1679, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30270486

RESUMEN

This study was aimed to evaluate the effects of organic acid (OA) and medium-chain fatty acid (MCFA) blends on production performance of sows and their litters. A total of 36 sows (Landrace × Yorkshire, average parity is 3.3, SE = 0.2) were randomly allocated to three treatments with 12 replicates. Dietary treatments were as follows: CON, basal diet; MC1, CON + 0.1% OA, and MCFA blends; MC2, CON + 0.2% OA, and MCFA blends. During lactation, no differences were observed in body weight (BW) loss, average daily feed intake, backfat thickness, digestibility of dry matter, nitrogen, or energy of sows. There were linear increase (p < 0.05) in BW and average daily gain of sucking piglets. On parturition and weaning day, there was a linear increase (p < 0.05) in fecal Lactobacillus counts, as well as a linear decrease (p < 0.05) in fecal Escherichia coli counts of sows on weaning day. The sucking piglets also had a linear increase (p < 0.05) in fecal Lactobacillus counts and a linear decrease (p < 0.05) in fecal E. coli counts. In conclusion, dietary supplementation of OA and MCFA blends in sows exerts beneficial effects to sows shifted fecal microbiota by increasing Lactobacillus and decreased E. coli counts. It also improved the performance of piglets.


Asunto(s)
Alimentación Animal , Ácido Cítrico/administración & dosificación , Dieta/veterinaria , Suplementos Dietéticos , Digestión , Ácidos Grasos/administración & dosificación , Fumaratos/administración & dosificación , Malatos/administración & dosificación , Nutrientes/metabolismo , Porcinos/crecimiento & desarrollo , Porcinos/metabolismo , Animales , Carga Bacteriana , Escherichia coli , Heces/microbiología , Femenino , Lactancia , Lactobacillus , Masculino , Porcinos/microbiología
17.
Indian J Pharmacol ; 50(2): 75-83, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30100655

RESUMEN

OBJECTIVES: In our preliminary study, chromium malate could decrease the blood glucose level in mice with diabetes and exhibits good benefits in treating glycometabolism and adipose metabolization obstacle in rats with type 2 diabetes. This study was aimed at assessing the pharmacokinetics and bioavailability of chromium malate and influence on trace metals absorption in rats. METHODS: BAPP 2.3 pharmacokinetic calculating program (China Pharmaceutical University Medicine Center) was used to calculate the pharmacokinetic parameters. Models of type 2 diabetic mellitus rats were applied to analyzed Ca, Mg, Fe, Cu, and Zn contents. RESULTS: The results showed that mean retention time (MRT) in chromium malate group was significantly prolonged and the area under the curve (AUC) and relative bioavailability of chromium malate (male) group were significant increase compared to chromium picolinate group. The serum Ca, Mg, Fe, Cu, and Zn contents in chromium malate (at doses of 15 and 20 µg Cr/kg bw) groups were significantly increased compared to control group, chromium trichloride group, and chromium picolinate group in type 2 diabetes mellitus rats. CONCLUSIONS: Those results indicated that chromium malate can significantly prolong MRT and increase AUC (male). Moreover, chromium malate is more effective at treating increased serum Ca, Mg, Fe, Cu, and Zn contents compared to chromium trichloride and chromium picolinate.


Asunto(s)
Cloruros/farmacocinética , Compuestos de Cromo/farmacocinética , Malatos/farmacocinética , Metales/sangre , Ácidos Picolínicos/farmacocinética , Administración Intravenosa , Administración Oral , Animales , Disponibilidad Biológica , Cloruros/administración & dosificación , Compuestos de Cromo/administración & dosificación , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Tipo 2/sangre , Heces/química , Femenino , Malatos/administración & dosificación , Masculino , Ácidos Picolínicos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Distribución Tisular
18.
J Oral Sci ; 60(2): 278-284, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29925712

RESUMEN

Dry mouth sensation, also known as xerostomia, is a common clinical problem with an increasing prevalence. Although recent studies have reported promissory results of malic acid, none have evaluated the impact of malic acid on the oral health-related quality of life (OHRQoL) of patients with xerostomia. Thus, this study aimed to evaluate the impact of 1% malic acid, combined with fluoride and xylitol, on the OHRQoL of patients with xerostomia. We enrolled 70 patients and randomly allocated them into two groups: the intervention group (applied topical sialogogue with 1% malic acid) and the control group (applied a placebo). We assessed the OHRQoL and severity of xerostomia before and after treatment with the Spanish version of the Oral Health Impact Profile-14 questionnaire (OHIP-14sp) and a visual analogue scale (VAS), respectively. In addition, stimulated and non-stimulated salivary flow rates before and after treatments were also measured. In total, 60 patients completed the study. According to the VAS, both sprays significantly improved dry mouth sensation (P < 0.001). However, OHIP-14sp total scores decreased significantly in the intervention group from 20.8 ± 10.4 to 16.5 ± 9.5 (P < 0.001), indicating an improvement in the OHRQoL. No significant differences were observed in the control group (P > 0.05). Furthermore, non-stimulated salivary flow rates significantly increased in the intervention group from 0.25 ± 0.22 to 0.33 ± 0.33 mL/min (P < 0.001). Overall, this study demonstrated that malic acid improves the OHRQoL and dry mouth sensation in patients with xerostomia.


Asunto(s)
Malatos/administración & dosificación , Salud Bucal , Calidad de Vida , Xerostomía/tratamiento farmacológico , Xerostomía/fisiopatología , Administración Tópica , Adulto , Método Doble Ciego , Femenino , Fluoruros/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Vaporizadores Orales , Saliva/metabolismo , Salivación , Tasa de Secreción , Xilitol/administración & dosificación
19.
Nutrients ; 10(5)2018 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-29738462

RESUMEN

A previous in vivo study with rats suggested that a special milk protein drink manufactured using an acidification procedure to suppress the aggregation of milk proteins was absorbed quickly after feeding. We performed a randomized, double-blind, placebo-controlled, repeated-measure crossover study to investigate the short-term effects on cognitive performance in 29 healthy young adult men after they consumed this drink in the morning. After an overnight fast, subjects were tested for performance in the Uchida⁻Kraepelin serial arithmetic test and the Stroop test as well as for subjective feeling, body temperature, and heart rate variability before and after consumption of either the acidified milk protein drink or an isoenergetic placebo drink. Subjects showed a significant improvement in performance in the Uchida⁻Kraepelin test, the primary outcome measured, when they consumed the acidified milk protein drink compared with the placebo control condition. In addition, consumption of the acidified milk protein drink, compared with the placebo control, was associated with increases in vagally-mediated heart rate variability indices which, from recent theoretical perspectives, may reflect a higher ability to modulate cognitive and behavioral processes. There was no significant difference in subjective feelings and body temperature between the test drink conditions. These data suggest that consumption of the acidified milk protein drink may improve cognitive performance, with possible involvement of physiological systems that regulate cognition and behavior.


Asunto(s)
Cognición/efectos de los fármacos , Proteínas de la Leche/administración & dosificación , Adolescente , Adulto , Bebidas/análisis , Temperatura Corporal , Citratos/administración & dosificación , Ácido Cítrico/administración & dosificación , Estudios Cruzados , Método Doble Ciego , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Malatos/administración & dosificación , Masculino , Cooperación del Paciente , Citrato de Sodio , Test de Stroop , Encuestas y Cuestionarios , Resultado del Tratamiento , Vitamina B 6/administración & dosificación , Adulto Joven
20.
Biochem Genet ; 55(5-6): 387-394, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28664349

RESUMEN

The purpose of this study was to examine the effects of Citrulline/Malate supplementation with intensive training on blood lactate level in active handball players. The athletes were subjected to intense training for 4 weeks, 4 days a week, mainly pre-season strength and technique training. In this training period, stimol group (n = 11) athletes were given stimol 3 times a day as 1 g for breakfast, 1 g for lunch, and 1 g for dinner while the placebo group (n = 11) athletes were given only placebo in the same dosage and the same color at the same time. Blood lactate levels in athletes were measured 4 times, prior to and after a 1-month program as follows: rest (R), end effort (EE), recuperation 5 min (R5 m), and recuperation 20 min (R20 m). Blood lactate levels were compared both as intra-group and between the groups. In intra-group comparison, no change was observed in blood lactate levels in placebo group while a significant difference was found in the levels of stimol group as p < 0.05 with a 49.8% decrease in blood lactate level. In the measurements between groups, in the post-test measurements made after the training period, significant differences as p < 0.05 were found with a 60.7% decrease in blood lactate level EE. Considerable decline was seen especially immediately after exercise in blood lactate levels of the athletes being given stimol supplement. In this case, we can say that Citrulline/Malate supplementation may contribute positively to the performance of athletes and may help postpone fatigue at excessive or prolonged activity.


Asunto(s)
Citrulina/administración & dosificación , Ejercicio Físico/fisiología , Ácido Láctico/administración & dosificación , Malatos/administración & dosificación , Resistencia Física/efectos de los fármacos , Adolescente , Adulto , Humanos , Masculino , Resistencia Física/fisiología
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