Mucociliary clearance in patients with continuous ambulatory peritoneal dialysis.

INTRODUCTION: Mucociliary clearance (MC) is a critical defense mechanism for the protection of the entire respiratory system. Nasal colonization of some pathogens and chronical nasal infections are important risk factors for peritonitis. Any disturbance in the MC causes stasis of secretions and secondary infections. OBJECTIVE: The aim of the study was to evaluate the patients with chronic kidney disease (CKD) receiving continuous ambulatory peritoneal dialysis (CAPD) in terms of nasal MC. More specifically, the goal is to investigate the possible correlation between the nasal MC and peritonitis. METHODS: Forty CAPD patients and 39 healthy volunteers were involved in the study. The nasal MC was evaluated with the saccharin test, in which a 1mm diameter saccharin particle was carefully placed on the antero-medial surface of inferior nasal concha. The time taken by the subjects from the placement of particle to the perception of the sweet taste was taken as mucociliary clearance time (MCT). The groups were compared in terms of MCT. The patient group was evaluated in terms of a peritonitis history, and the correlations with MC were analyzed. RESULTS: Patient group with CKD consisted of 16 females and 24 males with a mean age of 32.4 years; healthy individuals in the control group consisted of 17 women and 22 men with a mean age of 33.3 years. There was not a significant difference in terms of mean MC time in patients with CKD when compared with the individuals in the control group. The comparison between the mean MCT in the patients who had a history of peritonitis and patients without peritonitis was statistically significant (p<0.05). CONCLUSIONS: Unique for being conducted with patients in continuous ambulatory peritoneal dialysis, the current study shows that although the MC of CKD patients and healthy individuals is similar, patients with low rates of MC appear to present an increased incidence of peritoneal infection. Considering the small sample investigated, an invitation to future confirmatory studies would be appropriate.

PET imaging during hypoglycaemia to study adipose tissue metabolism.

BACKGROUND: Disturbances in adipose tissue glucose uptake may play a role in the pathogenesis of type 2 diabetes, yet its examination by 2-deoxy-2-[18 F]fluorodeoxyglucose ([18 F]FDG) PET/CT is challenged by relatively low uptake kinetics. We tested the hypothesis that performing [18 F]FDG PET/CT during a hypoglycaemic clamp would improve adipose tissue tracer uptake to allow specific comparison of adipose tissue glucose handling between people with or without type 2 diabetes. DESIGN: We enrolled participants with or without diabetes who were at least overweight, to undergo a hyperinsulinaemic hypoglycaemic clamp or a hyperinsulinaemic euglycaemic clamp (n = 5 per group). Tracer uptake was quantified using [18 F]FDG PET/CT. RESULTS: Hypoglycaemic clamping increased [18 F]FDG uptake in visceral adipose tissue of healthy participants (P = 0.002). During hypoglycaemia, glucose uptake in visceral adipose tissue of type 2 diabetic participants was lower as compared to healthy participants (P < 0.0005). No significant differences were observed in skeletal muscle, liver or pancreas. CONCLUSIONS: The present findings indicate that [18 F]FDG PET/CT during a hypoglycaemic clamp provides a promising new research tool to evaluate adipose tissue glucose metabolism. Using this method, we observed a specific impairment in visceral adipose tissue [18 F]FDG uptake in type 2 diabetes, suggesting a previously underestimated role for adipose tissue glucose handling in type 2 diabetes.

Redox mediators and irradiation improve fenton degradation of acesulfame.

Widely recognized as a promising approach to degrading recalcitrant pollutants, Advanced Oxidation Processes (AOPs) have drawn much attention for their effectiveness and efficiency. Among all the AOPs, the Fenton system has been widely applied for oxidation and mineralization of micropollutants due to its ease of implementation and high catalytic efficiency. However, the necessity of preceding acidification, together with rapid consumption and slow regeneration of Fe(II) resulting in deterioration of reactivity, has reduced its competitiveness as a practical option for water treatment. Acknowledging the above drawbacks, this study investigates the potential viable option to enhance the Fenton system. Acesulfame was chosen as the model compound due to its ubiquitous occurrence and persistence in the environment. UV-assisted photo-Fenton treatment was found to remove the parent compound effectively; the transformation profile of acesulfame was identified and elucidated with the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Prolonged UV photo-Fenton treatment was effective for mineralization of the majority of the transformation products, without increasing the overall toxicity as indicated by Vibrio fischeri bioluminescence assay. The positive effects of the addition of redox mediators to Fenton systems at neutral pH were confirmed in this study. The results could be the basis for further development of homogeneous catalytic degradation techniques for the oxidation of environmental contaminants at circumneutral pHs to neutral pHs.

Quantitative determination of mogroside V in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

Mogroside V is the most abundant (approximately 0.50%) cucurbitane-type triterpene glycoside in Siraitia grosvenorii and exhibits significant antitussive, expectorant, anti-carcinogenic, and anti-inflammatory effects. A sensitive, robust and selective liquid chromatography tandem with mass spectrometry (LC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of mogroside V in rat plasma. Samples were prepared through an one-step deproteinization procedure with 250 µL of methanol to a 75-µL plasma sample. Plasma samples were effectively separated on a Shiseido Capcell Pak UG120 C18 column (2.0 × 50mm, 3.0µm) using a mobile phase consisting of methanol: water (60:40, v/v) with an isocratic elution program. The running time for each sample was 7.0 min and the elution times of mogroside V and IS were 2.0 and 4.8 min, respectively. The detection relied on a triple-quadrupole tandem with mass spectrometer equipped with negative-ion electrospray ionization interface by selected-reaction monitoring (SRM) of the transitions at m/z 1285.6 → 1123.7 for mogroside V and m/z 1089.6 → 649.6 for IS. The calibration curve was linear over the range of 96.0-96000ng/mL with a limit of quantitation (LOQ) of 96.0ng/mL. Intra-day and inter-day precisions were both <10.1%. Mean recovery and matrix effect of mogroside V in plasma were in the range of 91.3-95.7% and 98.2-105.0%, respectively. This method was successfully applied in the pharmacokinetic study of mogroside V after intravenous or intraperitoneal administration of 1.12mg/kg mogroside V in rats.

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats / Cambios bioquímicos e histológicos producidos por edulcorantes y citarabina en el cerebro de ratas jóvenes

Objective: The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. Methods: Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda. Cytarabine was given intravenously (IV) while stevia and splenda were administered orally for five days, using orogastric tube. At the end of treatment, the animals were sacrificed and glucose levels in blood were measured. The brains were dissected for histological analysis and homogenated to measure levels of dopamine, lipid peroxidation (TBARS), serotonin metabolite (5-HIAA), Na+, K+ ATPase activity, and glutathione (GSH), using validated methods. Results: Sweeteners increased the glucose in animals that received cytarabine. Dopamine increased in cortex and decreased in striatum of animals that received stevia alone and combined with cytarabine. 5-HIAA decreased in striatum and cerebellum/medulla oblongata of animals that received sweeteners and cytarabine alone or combined. GSH increased in animals that received sweeteners and decreased with cytarabine. Lipoperoxidation decreased in groups that received sweeteners and cytarabine. Histopathological changes revealed marked degeneration of neuronal cells in animals treated with cytarabine. Conclusion: These results show that sweeteners as stevia or splenda may lead to the onset of unfavorable changes in dopamine and 5-HIAA. Antioxidant effects may be involved. Besides, histological changes revealed marked lesions of neuronal cells in experimental animals treated with cytarabine (AU)

Objetivo: el objetivo fue evaluar el efecto de edulcorantes (splenda y stevia) sobre los niveles de dopamina, acido 5-hidroxiindolacetico (HIAA) y algunos biomarcadores de estrés oxidativo en presencia de citarabina. Métodos: cuarenta y ocho ratas Wistar machos con un peso aproximado de 80 g (cuatro semanas de edad), distribuidas en seis grupos de ocho animales cada uno, fueron tratados como sigue: grupo 1, control (NaCl 0,9% vehículo); grupo 2, citarabina (0,6 g/kg); grupo 3, stevia (0,6 g/kg); grupo 4, citarabina + stevia; grupo 5, splenda; y el grupo 6, citarabina + splenda. La citarabina fue administrada por vía intravenosa y la stevia y la splenda, por vía oral durante cinco días, utilizando una sonda orogastrica. Al final del tratamiento, los animales fueron sacrificados y se midieron los niveles de glucosa en sangre. Los cerebros fueron disecados para su análisis histológico y homogenizados para medir los niveles de dopamina, peroxidacion lipidica (TBARS), metabolito de la serotonina (5-HIAA), actividad de la Na+, K+ ATPasa y glutatión (GSH), usando métodos validados. Resultados: los edulcorantes aumentaron la glucosa en los animales que recibieron citarabina. La dopamina aumento en la corteza y disminuyo en el estriado de los animales que recibieron stevia sola y combinada con citarabina. La 5-HIAA disminuyo en el estriado y el cerebelo/ medula oblongata de animales que recibieron edulcorantes y citarabina sola o combinada. El GSH se incrementó en los animales que recibieron edulcorantes. La lipoperoxidacion disminuyo en los grupos que recibieron edulcorantes y citarabina. Estudios histopatológicos revelaron una degeneración neuronal importante en animales tratados con citarabina. Conclusión: los resultados muestran que los edulcorantes como stevia o splenda pueden conducir a la aparición de cambios desfavorables en los niveles de dopamina y 5-HIAA. Los cambios histológicos revelaron, además, lesiones marcadas de células neuronales en animales tratados con citarabina (AU)

Oxidative Stress as a Mechanism Involved in Kidney Damage After Subchronic Exposure to Vanadium Inhalation and Oral Sweetened Beverages in a Mouse Model.

Kidney diseases have notably increased in the last few years. This is partially explained by the increase in metabolic syndrome, diabetes, and systemic blood hypertension. However, there is a segment of the population that has neither of the previous risk factors, yet suffers kidney damage. Exposure to atmospheric pollutants has been suggested as a possible risk factor. Air-suspended particles carry on their surface a variety of fuel combustion-related residues such as metals, and vanadium is one of these. Vanadium might produce oxidative stress resulting in the damage of some organs such as the kidney. Additionally, in countries like Mexico, the ingestion of sweetened beverages is a major issue; whether these beverages alone are responsible for direct kidney damage or whether their ingestion promotes the progression of an existing renal damage generates controversy. In this study, we report the combined effect of vanadium inhalation and sweetened beverages ingestion in a mouse model. Forty CD-1 male mice were distributed in 4 groups: control, vanadium inhalation, 30% sucrose in drinking water, and vanadium inhalation plus sucrose 30% in drinking water. Our results support that vanadium inhalation and the ingestion of 30% sucrose induce functional and histological kidney damage and an increase in oxidative stress biomarkers, which were higher in the combined effect of vanadium plus 30% sucrose. The results also support that the ingestion of 30% sucrose alone without hyperglycemia also produces kidney damage.

Evaluation of nasal mucociliary clearance using saccharin test in smokers: A prospective study.

BACKGROUND AND AIM: Nasal mucociliary clearance time (NMCT) can be measured with the saccharine clearance test which is an inexpensive and easy method. The aim of the present study was to compare and evaluate NMCT using the saccharine clearance test in smokers and non-smokers. MATERIALS AND METHODS: Eighty-five patients whose ages ranged from 18 to 65 years were included in the study. Fifty of the patients were smokers (Group 1) while 35 were healthy, non-smoking volunteers (Group 2). Saccharin clearance test was used to evaluate NMCT in both groups. The results obtained were compared and the statistical analyses were performed using the Statistical Package for Social Sciences (SPSS). RESULTS: NMCT was statistically significantly higher in Group 1 as compared to Group 2 (P < .001, Mann-Whitney U test). However, in cumulative smoking duration (pack-year), Fagerström test values and gender categories, there was no statistically significant difference in the average NMCT values of the two groups (P = .943 vs P = .812 respectively), P = .45). CONCLUSION: Mucociliary activity, the primary defence mechanism of the respiratory epithelium, is significantly depressed in smokers. Our findings showed that the said depression is not associated with the number of cigarettes smoked, duration of smoking or nicotine dependence.

Torsemide Fast Dissolving Tablets: Development, Optimization Using Box-Bhenken Design and Response Surface Methodology, In Vitro Characterization, and Pharmacokinetic Assessment.

The present study planed to develop new fast dissolving tablets (FDTs) of torsemide. Solid dispersions (SDs) of torsemide and sorbitol (3:1) or polyvinylpyrrolidone (PVP) k25 were prepared. The prepared SDs were evaluated for in-vitro dissolution. Fourier transform infrared spectroscopy and differential scanning calorimetry for SDs revealed no drug/excipient interactions and transformation of torsemide to the amorphous form. Torsemide/sorbitol SD was selected for formulation of torsemide FDTs by direct compression method. Box-Bhenken factorial design was employed to design 15 formulations using croscarmellose sodium and crospovidone at different concentrations. The response surface methodology was used to analyze the effect of changing these concentrations (independent variables) on disintegration time (Y1), percentage friability (Y2), and amount torsemide released at 10 min. The physical mixtures of torsemide and the used excipients were evaluated for angle of repose, Hausner's ratio, and Carr's index. The prepared FDTs tablets were evaluated for wetting and disintegration time, weight variation, drug content, percentage friability, thickness, hardness, and in vitro release. Based on the in-vitro results and factorial design characterization, F10 and F7 were selected for bioavailability studies following administration to Albino New Zealand rabbits. They showed significantly higher C max and (AUC0-12) and shorter T max than those obtained after administration of the corresponding ordinary commercial Torseretic ® tablets. Stability study was conducted for F10 that showed good stability upon storage at 30°C/75% RH and 40°C/75% RH for 3 months.

A randomized control trial for reduction of caloric and non-caloric sweetened beverages in young adults: effects in weight, body composition and blood pressure / Ensayo clínico controlado para evaluar el efecto de la reducción de bebidas dulces calóricas y no calóricas sobre peso, composición corporal y presión arterial

Introduction: Recently has been documented that the consumption of sweetened non-caloric beverages has increased as an option to weight control, however randomized control trials have demonstrated a modest weight loss. Objective: To evaluate the effect of reducing consumption of beverage with caloric and non-caloric sweeteners on weight, body composition and blood pressure in young Mexican adults. Methods: In an experimental study 148 nursing students were randomly assigned to one of 3 groups: 1) no sweetened beverages were permitted, only plain water, tea or coffee without sugar; 2) consumption of beverages with non-caloric sweeteners was allowed; and 3) no restriction of sweetened beverages was imposed. All groups were given individualized isocaloric diets monitored by a 24-hour record of consumption and food frequency questionnaire and blood pressure, weight, waist circumference and body composition by tetrapolar bioelectric impedance were taken at the beginning of the study and three and six months later. Results: Differences between groups were found in body mass index at 3 months that decrease in group 1 and 2 and increase in group 3 (-1.75 vs. -0.61 vs. 0.54% of change, p < 0.001). At six months there were also statistical differences in waist circumference (-4.07 vs. -1.23 vs. 0.62% of change, p < 0.001) and sugar consumption (-62.0 vs. -54.61 vs. 11.08% of change, p < 0.001) in groups 1, 2 and 3 respectively. Conclusions: The reduction in consumption of both caloric and non-caloric sweetened beverages contributes to significant body mass index loss and waist circumference (AU)

Introducción: recientemente se ha documentado que el consumo de bebidas dulces calóricas y no calóricas ha incrementado como una opción para el control de peso. Sin embargo, algunos ensayos clínicos han demostrado solo pérdidas de peso modestas. Objetivo: evaluar el efecto de la reducción del consumo de bebidas con endulzantes calóricos y no calóricos en el peso, composición corporal y presión arterial en adultos jóvenes mexicanos. Métodos: en un ensayo clínico controlado fueron asignados al azar 148 estudiantes de enfermería a 3 grupos: 1) no se permitió consumo de bebidas endulzadas, solo agua simple, café o infusiones sin azúcar; 2) consumo de bebidas con endulzantes no calóricos; y 3) ninguna restricción en el consumo de bebidas. A todos los grupos se les proporcionó una dieta individualizada isocalórica que fue monitoreada mediante un recordatorio de 24 horas y un cuestionario de frecuencia consumo de alimentos. Al inicio del estudio, tres y seis meses después se tomó la presión arterial, peso, circunferencia de cintura y composición corporal mediante impedancia bioeléctrica tetrapolar. Resultados: se encontraron diferencias estadísticamente significativas en el cambio del índice de masa corporal a los tres meses, el cual disminuyó en los grupos 1 y 2 y aumentó en el grupo 3 (-1,75 vs. -0,61 vs. 0,54% de cambio, p < 0,001). A los 6 meses se encontraron diferencias en el cambio de la circunferencia de cintura (-4,07 vs. -1,23 vs. 0,62% de cambio, p < 0,001) y en el consumo de azúcar (-62,0 vs. -54,61 vs. 11,08% de cambio, p < 0,001) en los grupo 1, 2 y 3 respectivamente. Conclusiones: la reducción del consumo de bebidas endulzadas calóricas y no calóricas contribuye a una reducción significativa del índice de masa corporal y la circunferencia de cintura (AU)

Biological fate of low-calorie sweeteners.

With continued efforts to find solutions to rising rates of obesity and diabetes, there is increased interest in the potential health benefits of the use of low- and no-calorie sweeteners (LNCSs). Concerns about safety often deter the use of LNCSs as a tool in helping control caloric intake, even though the safety of LNCS use has been affirmed by regulatory agencies worldwide. In many cases, an understanding of the biological fate of the different LNSCs can help health professionals to address safety concerns. The objectives of this review are to compare the similarities and differences in the chemistry, regulatory status, and biological fate (including absorption, distribution, metabolism, and excretion) of the commonly used LNCSs: acesulfame potassium, aspartame, saccharin, stevia leaf extract (steviol glycoside), and sucralose. Understanding the biological fate of the different LNCSs is helpful in evaluating whether reports of biological effects in animal studies or in humans are indicative of possible safety concerns. Illustrations of the usefulness of this information to address questions about LNCSs include discussion of systemic exposure to LNCSs, the use of sweetener combinations, and the potential for effects of LNCSs on the gut microflora.

Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale.

Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels.

Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro.

Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions.

Occurrence of artificial sweeteners in human liver and paired blood and urine samples from adults in Tianjin, China and their implications for human exposure.

In this study, acesulfame (ACE), saccharin (SAC) and cyclamate (CYC) were found in all paired urine and blood samples collected from healthy adults, with mean values of 4070, 918 and 628 ng mL(-1), respectively, in urine and 9.03, 20.4 and 0.72 ng mL(-1), respectively, in blood. SAC (mean: 84.4 ng g(-1)) and CYC (4.29 ng g(-1)) were detectable in all liver samples collected from liver cancer patients, while ACE was less frequently detected. Aspartame (ASP) was not found in any analyzed human sample, which can be explained by the fact that this chemical metabolized rapidly in the human body. Among all adults, significantly positive correlations between SAC and CYC levels were observed (p < 0.001), regardless of human matrices. Nevertheless, no significant correlations between concentrations of SAC (or CYC) and ACE were found in any of the human matrices. Our results suggest that human exposure to SAC and CYC is related, whereas ACE originates from a discrete source. Females (or young adults) were exposed to higher levels of SAC and CYC than males (or elderly). The mean renal clearance of SAC was 730 mL per day per kg in adults, which was significantly (p < 0.001) lower than those for CYC (10 800 mL per day per kg) and ACE (10 300 mL per day per kg). The average total daily intake of SAC and ACE was 9.27 and 33.8 µg per kg bw per day, respectively.

Chemical-specific adjustment factors (inter-species toxicokinetics) to establish the ADI for steviol glycosides.

The acceptable daily intake (ADI) of commercially available steviol glycosides is currently 0-4 mg/kg body weight (bw)/day, based on application of a 100-fold uncertainty factor to a no-observed-adverse-effect-level value from a chronic rat study. Within the 100-fold uncertainty factor is a 10-fold uncertainty factor to account for inter-species differences in toxicokinetics (4-fold) and toxicodynamics (2.5-fold). Single dose pharmacokinetics of stevioside were studied in rats (40 and 1000 mg/kg bw) and in male human subjects (40 mg/kg bw) to generate a chemical-specific, inter-species toxicokinetic adjustment factor. Tmax values for steviol were at ∼8 and ∼20 h after administration in rats and humans, respectively. Peak concentrations of steviol were similar in rats and humans, while steviol glucuronide concentrations were significantly higher in humans. Glucuronidation in rats was not saturated over the dose range 40-1000 mg/kg bw. The AUC0-last for steviol was approximately 2.8-fold greater in humans compared to rats. Chemical-specific adjustment factors for extrapolating toxicokinetics from rat to human of 1 and 2.8 were established based on Cmax and AUC0-last data respectively. Because these factors are lower than the default value of 4.0, a higher ADI for steviol glycosides of between 6 and 16 mg/kg bw/d is justified.

[FREE CONSUMPTION OF GLUCOSE SOLUTION BY RATS AS A CRITERION FOR EVALUATION ITS ABSORPTION IN THE SMALL INTESTINE (Experimental study and mathematical modeling)].

The aim of the work is to analyze the relationship between consumption of glucose solution by rats and its absorption, and to use this fact for assessment of the absorptive capacity of the small intestine in non anesthetized animals in vivo. Consumption of glucose solution (200 g/l) by fasted rats was recorded in the control, and after administration of phloridzin--inhibitor of glucose active transport- or 3 hours after the restriction stress. On the mathematical model we studied the relative role of factors that can influence the temporal dynamics of glucose consumption by rats. The rate of glucose consumption was observed being decreased in the presence of phloridzin (1 mM), and be increased after the stress. The results of modeling are consistent with the experimental data and show that the rate of consumption of glucose solutions considerably more depends on the transport activity of the small intestine than on glucose concentration in the solution, or on the substrate regulation of the stomach emptying. Analysis of dynamics of consumption of glucose solution by intact rats may be considered as one of promising approaches to assessing the absorptive capacity of the small intestine under natural conditions.

Exploring in vitro, in vivo metabolism of mogroside V and distribution of its metabolites in rats by HPLC-ESI-IT-TOF-MS(n).

Mogroside V, a cucurbitane-type saponin, is not only the major bioactive constituent of traditional Chinese medicine Siraitiae Fructus, but also a widely used sweetener. To clarify its biotransformation process and identify its effective forms in vivo, we studied its metabolism in a human intestinal bacteria incubation system, a rat hepatic 9000g supernatant (S9) incubation system, and rats. Meanwhile, the distribution of mogroside V and its metabolites was also reported firstly. Seventy-seven new metabolites, including 52 oxidation products formed by mono- to tetra- hydroxylation/dehydrogenation, were identified with the aid of HPLC in tandem with ESI ion trap (IT) TOF multistage mass spectrometry (HPLC-ESI-IT-TOF-MS(n)). Specifically, 14 metabolites were identified in human intestinal bacteria incubation system, 4 in hepatic S9 incubation system, 58 in faeces, 29 in urine, 14 in plasma, 34 in heart, 33 in liver, 39 in spleen, 39 in lungs, 42 in kidneys, 45 in stomach, and 51 in small intestine. The metabolic pathways of mogroside V were proposed and the identified metabolic reactions were deglycosylation, hydroxylation, dehydrogenation, isomerization, glucosylation, and methylation. Mogroside V and its metabolites were distributed unevenly in the organs of treated rats. Seven bioactive metabolites of mogroside V were identified, among which mogroside IIE was abundant in heart, liver, spleen and lung, suggesting that it may contribute to the bioactivities of mogroside V. Mogroside V was mainly excreted in urine, whereas its metabolites were mainly excreted in faeces. To our knowledge, this is the first report that a plant constituent can be biotransformed into more than 65 metabolites in vivo. These findings will improve understanding of the in vivo metabolism, distribution, and effective forms of mogroside V and congeneric molecules.

Aspartame sensitivity? A double blind randomised crossover study.

BACKGROUND: Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. METHODS: This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. RESULTS: Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. CONCLUSION: Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans. TRIAL REGISTRATION: ISRCTN Registry ISRCTN39650237.

Low and no calorie sweeteners (LNCS); myths and realities / Edulcorantes hipocalóricos; mitos y realidades

Since their introduction in the market, there has been much debate regarding the health effects of low and no calorie sweetners (LNCS). Therefore, through this review, we aim to establish scientific information about the most commonly used LNCS by the food industry. Key questions about uses, safety, and weight control are reviewed. Scientific evidence revised concludes that LNCS available on the market are safe and no epidemiological relationship has been established with the development of non-communicable diseases, including different kind of cancer in humans. Also, LCNS combined with physical activity and a healthy lifestyle can play a significant role in weight loss and the maintenance of a healthy weight. But non nutritive sweeteners will be helpful only as long as people don’t eat additional calories later as compensation. Even more, LNCS represent an additional instrument in the dietary treatment of people with diabetes for metabolic control, without avoiding sweet taste (AU)

Desde su introducción, ha habido mucho debate acerca de los efectos sobre la salud de los edulcorantes hipocalóricos y sin calorías (LNCS). Por lo tanto, en esta revisión, nuestro objetivo es revisar la información científica disponible acerca de los edulcorantes hipocalóricos y sin calorías más utilizados en la industria alimentaria. Se revisan aspectos clave acerca de los usos, la seguridad y el control del peso. A partir de la evidencia científica revisada se concluye que los LNCS disponibles en el mercado son seguros, no existe ninguna relación epidemiológica con el desarrollo de enfermedades no transmisibles, incluyendo diferentes tipos de cáncer en humanos. Además, los LCNS, junto con la actividad física y un estilo de vida saludable pueden jugar un papel significativo en la pérdida de peso y en el mantenimiento del peso saludable. Pero los edulcorantes no nutritivos únicamente serán útiles si los usuarios no realizan una compensación, comiendo posteriormente un exceso de calorías. Es más, los LNCS representan un instrumento adicional en el tratamiento dietético de las personas con diabetes para el control metabólico, sin renunciar al sabor dulce (AU)

Evaluación de la inocuidad de Stevia rebaudiana Bertoni cultivada en el sureste de México como edulcorante de alimentos / Safety assessment of Stevia rebaudiana Bertoni grown in Southeastern Mexico as food sweetener

Las hojas de Stevia rebaudiana y sus glucósidos recientemente se han comenzado a utilizar de manera importante como edulcorantes. Sin embargo, existen reportes acerca del efecto antihiperglucemiante de extractos y un componente glucósido. El objetivo de este trabajo fue cuantificar los glucósidos de S. rebaudiana, evaluar la citotoxicidad y el efecto de la administración aguda y crónica del extracto sobre la glucemia en modelos animales como en humanos. Los glucósidos de los extracto de las variedades Morita II y Criolla se cuantificaron por HPLC, empleando una columna C18 (250 mm x 4.6 mm y tamaño de partícula de 5µm), con detector UV a 210 nm, fase móvil de acetonitrilo/amortiguador fosfato de sodio 10 mmol/L, pH 2.6 (32:68 v/v). Se realizó un estudio de citotoxicidad en células Vero, una prueba de tolerancia a la glucosa intraperitoneal y ensayo de consumo crónico (4 semanas) en un modelo animal de diabetes y finalmente, se determinó el índice glicémico (I.G) en individuos sanos. El contenido de glucósidos fue mayor en la variedad Morita II aunque la CC50 en ambas es >300 µg/mL. Las áreas bajo la curva de la IPGTT así como la glucosa en ayuno de los animales no fueron significativamente diferentes (p>0.05) y el I.G. del extracto fue 11.11%, lo cual lo clasifica como I.G. bajo. El extracto de S. rebaudiana Morita II es de bajo índice glicémico y, en las dosis evaluadas, no es citotóxico ni posee efecto agudo o crónico sobre la glucemia, lo cual lo hace un edulcorante inocuo (AU)

Stevia rebaudiana leaves and their glycosides have been recently and significantly used so important as sweeteners. However, it has been reported an antihyperglycemic effect of the extract and a glycoside. The aim of this study was to quantify S. rebaudiana glycosides, assess cytotoxicity of the extract and its acute and chronic effect on blood glucose in animal models and in human. The glycosides of the Morita II and Criolla extract were quantified by HPLC, using a C18 column (250 mm x 4.6 mm and particle size of 5 uM) with UV detection at 210 nm, mobile phase of acetonitrile/sodium phosphate buffer 10 mmol/L, pH 2.6 (32:68 v/v). Cytotoxicity study was performed in Vero cells, whereas an intraperitoneal glucose tolerance test (IPGTT) and a chronic consumption assay (4 weeks) were executed in an animal model of diabetes; finally the glycemic index (G.I.) was determined in healthy individuals. The glycoside content is higher in the Morita variety II although both had a CC50 >300 µg/mL. The areas under the curve of the IPGTT and fasting glucose of the animals were not significantly different (p> 0.05) and the I.G. extract was 11.11 %, which classifies the extract as low I.G. The extract of S. rebaudiana Morita II has a low glycemic index and, in the doses tested, is not cytotoxic nor has acute or chronic effect on blood sugar, which makes it a safe sweetener (AU)

Propriedades terapêuticas de Stevia rebaudiana Bertoni / Propriedades terapéuticas de Stevia rebaudiana Bertoni / Therapeutic properties of Stevia rebaudiana Bertoni

Stevia rebaudiana é uma planta de porte herbáceo originária da Amé-rica do Sul com elevada capacidade adoçante devido à presença de glicósidos do esteviol: esteviósido e rebaudiósido A. Atualmente, re-presenta um dos adoçantes mais seguros e versáteis cujo consumo está a aumentar, podendo constituir uma possível alternativa tera-pêutica nos casos de diabetes tipo 2, hipertensão e diarreia. Existem também artigos publicados que referem uma ação antimicrobiana e antioxidante. Tais propriedades são conferidas pelos seus constituin-tes, tais como os glicósidos do esteviol, taninos, fruto-oligossacáridos e ácidos gordos obtidos a partir de diversos extratos e de diferentes partes da planta. São necessários mais estudos para melhor conhecer as potencialidades desta planta

Stevia rebaudiana es una planta herbácea de América del Sur con capacidad edulcorante debido a glucósidos de esteviol: esteviósido y rebaudiósido A. En la actualidad, es uno de los edulcorantes más seguros y versátiles cuyo consumo va en aumento y puede constituir una posible alternativa terapéutica en casos de diabetes tipo 2, hipertensión y diarrea. También hay artículos publicados que citan su actividad antimicrobiana y antioxidante. Estas propiedades son debidas a sus constituyentes, como los glucósidos de esteviol, taninos, frutooligosacáridos y ácidos grasos obtenidos a partir de extractos de diferentes partes de la planta. Se necesitan más estudios para comprender mejor el potencial de esta planta (AU)

Stevia rebaudiana is a shrub from South America with sweetener capacity due to the presence of steviol glycosides: stevioside and rebaudioside A. Currently, is one of the safest and versatile sweetener whose consumption is increasing, being a possible therapeutic alternative in type 2 diabetes, hypertension and diarrhoea. Studies referring to its antimicrobial and antioxidant activity have also been published. Such properties are from its constituents: steviol glycosides, tannins, fructooligosaccharides and fatty acids obtained from extracts and from different plant parts. More studies ere needed to better understand the plant activities (AU)