Effects of daily intake of zidovudine-stavudine on rat pregnancy outcome: biological essay

Purpose: To evaluate the effects at term of a highly active antiretroviral drug association when administered for the whole period of rat pregnancy. Methods: Forty pregnant rats weighing about 200 g were randomly divided into four groups: a control group (Ctr = drug vehicle control, n = 10) and three experimental groups. which were treated with an oral solution of zidovudine-stavudine (Exp1x = 10/1 mg/kg b.w., n = 10; Exp3x = 30/3 mg/kg b.w., n = 10; Exp9x = 90/9 mg/kg b.w., n = 10) from "day 0" up to the 20th day of pregnancy. Maternal body weights were recorded at the start of the experiment and on the 7th, 14th and 20th day thereafter. At term (20th day) the rats were anesthetized and submitted to hysterotomy. Implantations, reabsorptions, living fetuses, placentae and intrauterine deaths were looked for and recorded. The collected fetuses and placentae were weighed and the concepts were examined by a stereoscopic microscope looking for external malformations. Results: No significant alterations due to the antiretroviral drug treatment could be detected regarding the number of implantations, fetuses, placentae, absorptions and malformations nor regarding maternal and fetal mortality. Conclusions: Administration of the association zidovudine/stavudine for the whole period of rat pregnancy did not interfere with the maternal, fetal and placental weight gain as well as abnormalities detectable by the employed methodology.

Desempenho, mortalidade e escore fecal de bezerros aleitados com diferentes dietas líquidas e terapias de reidratação quando acometidos por diarreias

O objetivo deste trabalho foi avaliar o efeito da utilização de sucedâneo lácteo com alto conteúdo proteico de origem vegetal no desempenho e saúde de bezerros, e avaliar métodos de reidratação para o tratamento de diarreias. No primeiro estudo foram utilizados 33 bezerros da raça Holandês distribuídos nos tratamentos: 1) Alto volume e baixa proteína (AV/BP): 8 litros, 21,4% PB; 2) Alto volume e alta proteína (AV/AP): 8 litros, 23,7% PB e 3) Baixo volume e alta proteína (BV/AP): 6 litros, 23,7% PB. Os bezerros foram alojados em abrigos individuais, com livre acesso a água e concentrado. Não houve efeito dos tratamentos para o desempenho animal (P>0,05). Os tratamentos AV/BP e AV/AP resultaram em maior consumo de sucedâneo (P<0,05), mas não afetaram o consumo de concentrado nem o consumo total (P>0,05). O escore fecal foi maior (P>0,05) para animais nos tratamentos AV/AP e BV/AP. Os animais nos tratamentos AV/BP permaneceram maior número de dias em diarreia (P<0,05), em comparação aqueles aleitados com BV/AP, os quais tiveram menos dias com vida (P<0,05). A concentração de lactato foi maior (P<0,05) para animais nos tratamentos AV/BP e AV/AP enquanto a concentração de proteína total foi maior (P<0,05) nos tratamentos AV/BP e BV/AP. Sucedâneos com elevado conteúdo de proteína de origem vegetal afetam negativamente o desempenho de bezerros podendo levar o animal a morte. No segundo estudo foram comparados três soluções de hidratação oral quanto a sua eficiência em repor eletrólitos e água, além de manter o desempenho de bezerros. Foram utilizados 42 bezerros mestiços Holandês-Jersey, distribuídos nos tratamentos: 1) Soro comum, 2) Glutellac® e 3) Soro comum + Aminogut®. Os animais foram aleitados com 4 L/d de sucedâneo lácteo até a oitava semana de vida quando foram desaleitados de forma abrupta. As terapias de reidratação foram oferecidas quando os animais apresentavam escore fecal >= 3 na escala de 1 a 5. Não houve efeito das terapias de reidratação no desempenho nem em metabólitos sanguíneos (P>0,05). O consumo voluntário de água foi maior para os animais reidratados com Glutellac®, mas o consumo total maior para os animais reidratados com Soro comum. As concentrações de HCO3 e Na+ foram maiores para os animais no tratamento Glutellac® (P=0,088 e P=0,073 respectivamente), sendo a concentração de glicose também afetada pelo protocolo de hidratação (P<0,05). A concentração de HCO3 aumentou do primeiro para o segundo dia, a de K+ e glicose diminuíram do primeiro para o segundo dia, enquanto que o Beecf teve um comportamento variável segundo a terapia de reidratação utilizada. Houve efeito da interação tratamento x dia de avaliação apenas para a concentração de BUN (P<0,05). O pH, a concentração de Na+ e Beecf foram maiores em animais mais velhos, enquanto K+, hematócrito e hemoglobina, foram menores (P<0,05). O consumo voluntário de água foi maior em animais reidratados com Glutellac®, o que junto com a simplicidade de uso, representam as principais vantagens deste método de reidratação.

Population pharmacokinetics of itraconazole and its active metabolite hydroxy-itraconazole in paediatric cystic fibrosis and bone marrow transplant patients

Objective: The objective of the study was to characterise the population pharmacokinetic properties of itraconazole and its active metabolite hydroxyitraconazole in a representative paediatric population of cystic fibrosis and bone marrow transplant (BMT) patients and to identify patient characteristics influencing the pharmacokinetics of itraconazole. The ultimate goals were to determine the relative bioavailability between the two oral formulations (capsules vs oral solution) and to optimise dosing regimens in these patients. Methods: All paediatric patients with cystic fibrosis or patients undergoing BMT at The Royal Children's Hospital, Brisbane, QLD, Australia, who were prescribed oral itraconazole for the treatment of allergic bronchopulmonary aspergillosis (cystic fibrosis patients) or for prophylaxis of any fungal infection (BMT patients) were eligible for the study. Blood samples were taken from the recruited patients as per an empirical sampling design either during hospitalisation or during outpatient clinic visits. ltraconazole and hydroxy-itraconazole plasma concentrations were determined by a validated high-performance liquid chromatography assay with fluorometric detection. A nonlinear mixed-effect modelling approach using the NONMEM software to simultaneously describe the pharmacokinetics of itraconazole and its metabolite. Results: A one-compartment model with first-order absorption described the itraconazole data, and the metabolism of the parent drug to hydroxy-itraconazole was described by a first-order rate constant. The metabolite data also showed one-compartment characteristics with linear elimination. For itraconazole the apparent clearance (CLitraconazole) was 35.5 L/hour, the apparent volume of distribution (V-d(itraconazole)) was 672L, the absorption rate constant for the capsule formulation was 0.0901 h(-1) and for the oral solution formulation was 0.96 h-1. The lag time was estimated to be 19.1 minutes and the relative bioavailability between capsules and oral solution (F-rel) was 0.55. For the metabolite, volume of distribution, V-m/(F (.) f(m)), and clearance, CL/(F (.) fm), were 10.6L and 5.28 L/h, respectively. The influence of total bodyweight was significant, added as a covariate on CLitraconazoie/F and V-d(itraconazole)/F (standardised to a 70kg person) using allometric three-quarter power scaling on CLitraconazole/F, which therefore reflected adult values. The unexplained between-subject variability (coefficient of variation %) was 68.7%, 75.8%, 73.4% and 61.1% for CLitraconazoie/F, Vd(itraconazole)/F, CLm/(F (.) fm) and F-rel, respectively. The correlation between random effects of CLitraconazole and Vd((itraconazole)) was 0.69. Conclusion: The developed population pharmacokinetic model adequately described the pharmacokinetics of itraconazole and its active metabolite, hydroxy-itraconazole, in paediatric patients with either cystic fibrosis or undergoing BMT. More appropriate dosing schedules have been developed for the oral solution and the capsules to secure a minimum therapeutic trough plasma concentration of 0.5 mg/L for these patients.

Paediatric population pharmacokinetics of itraconazole and its active metabolite hydroxy-itraconazole in cystic fibrosis and bone marrow transplant patients

Objectives: The aim of the study was to characterise the population pharmacokinetics (popPK) properties of itraconazole (ITRA) and its active metabolite hydroxy-ITRA in a representative paediatric population of cystic fibrosis (CF) and bone marrow transplant (BMT) patients. The goals were to determine the relative bioavailability between the two oral formulations, and to explore improved dosage regimens in these patients. Methods: All paediatric patients with CF taking oral ITRA for the treatment of allergic bronchopulmonary aspergillosis and patients undergoing BMT who were taking ITRA for prophylaxis of any fungal infection were eligible for the study. A minimum of two blood samples were drawn after the capsules and also after switching to oral solution, or vice versa. ITRA and hydroxy-ITRA plasma concentrations were measured by HPLC[1]. A nonlinear mixed-effect modelling approach (NONMEM 5.1.1) was used to describe the PK of ITRA and hydroxy-ITRA simultaneously. Simulations were used to assess dosing strategies in these patients. Results: Forty-nine patients (29CF, 20 BMT) were recruited to the study who provided 227 blood samples for the population analysis. A 1-compartment model with 1st order absorption and elimination best described ITRA kinetics, with 1st order conversion to hydroxy-ITRA. For ITRA, the apparent clearance (ClItra/F) and volume of distribution (Vitra/F) was 35.5L/h and 672L, respectively; the absorption rate constant for the capsule formulation was 0.0901 h-1 and for the oral solution formulation it was 0.959 h-1. The capsule comparative bioavailability (vs. solution) was 0.55. For hydroxy-ITRA, the apparent volume of distribution and clearance were 10.6 L and 5.28 L/h, respectively. Of several screened covariates only allometrically scaled total body weight significantly improved the fit to the data. No difference between the two populations was found. Conclusion: The developed popPK model adequately described the pharmacokinetics of ITRA and hydroxy-ITRA in paediatric patients with CF and patients undergoing BMT. High inter-patient variability confirmed previous data in CF[2], leukaemia and BMT[3] patients. From the population model, simulations showed the standard dose (5 mg/kg/day) needs to be doubled for the solution formulation and even 4 times more given of the capsules to achieve an adequate target therapeutic trough plasma concentration of 0.5 mg/L[4] in these patients.

Efecto del consumo concomitante de inhibidores de bomba protones y levotiroxina : revisión sistemática y metaanálisis

Estudios afirman que la acidez gástrica es importante en la absorción de levotiroxina (LT4) con resultados controversiales sobre la interacción entre inhibidores de bomba de protones (IBP) y LT4. El objetivo del estudio fue establecer el efecto del uso concomitante de LT4 e IBP en los niveles de TSH en pacientes adultos con hipotiroidismo primario. Se realizó una revisión sistemática mediante búsqueda en Medline, Embase, Lilacs, Bireme, Scielo, Cochrane y Universidad de York, Access Pharmacy, Google Scholar, Dialnet y Opengray. La búsqueda no se limito por lenguaje. Se evaluó el efecto en la diferencia de medias de TSH luego del consumo de LT4 y luego del consumo concomitante con IBP. Se hizo un metaanálisis, análisis de subgrupos y análisis de sensibilidad utilizando el programa Review Manager 5.3. Se eligieron 5 artículos para el análisis cualitativo y 3 para el metaanálisis. La calidad de los estudios fue buena y el riesgo de sesgos bajo. La diferencia de medias obtenida fue 0.21 mUI/L (IC95%: 0.02-0.40; p=0.03; I2:0%). En el análisis de subgrupos en pacientes mayores de 55 años la diferencia de medias fue 0.21 mUI/L (IC95%: 0.01-0.40; p=0.27; I2:19%). En el análisis de sensibilidad se excluyo el estudio con mayor muestra y la diferencia de medias fue 0.49 mUI/L (IC95%: -0.12 a 1.11; p=0.12; I2:0%). La diferencia de medias de TSH luego del consumo concomitante no se considera clínicamente significativa pues no representa riesgo para el paciente. Son necesarios estudios clínicos aleatorizados y evaluar el efecto en los niveles de T4 libre.

Oral administration of a 12% sucrose solution did not decrease behavioural indicators of distress in piglets undergoing tail docking, teeth clipping and ear notching

Sucrose has been shown to attenuate the behavioural response to painful procedures in human infants undergoing circumcision or blood collection via heelstick. Sucrose has also been found to have a behaviour-modifying effect in neonatal rats exposed to a hot plate. The effect was abolished in neonatal rats by injection of the opioid antagonist naltrexone, suggesting that it was mediated by endogenous opioids. In this experiment, the behaviour of 571 newborn Large White x Landrace hybrid piglets in a specific-pathogen-free piggery of the University of Queensland was recorded during and after the routine management practices of tail docking, ear notching and teeth clipping. Piglets were randomly assigned to receive 1.0 ml of a 12% sucrose solution (treatment group) or a placebo (1.0 ml of air) administered via syringe in the mouth, 60 s before commencement of one of the management procedures. Behaviours were recorded at the time of the procedure, and then 2 min after completion of the procedure. Piglets that received the sucrose solution did not behave significantly differently from piglets receiving the placebo. Regardless of whether sucrose or placebo was administered, piglets undergoing the routine management procedures showed significantly greater behavioural responses than piglets undergoing no procedure. It was concluded that under commercial conditions, a 12% sucrose solution administered I min prior to surgery was not effective in decreasing the behavioural indicators of distress in piglets undergoing routine management procedures, Further research into methods of minimising distress caused to piglets by these procedures is recommended.

Induction of labor with titrated oral misoprostol solution versus oxytocin in term pregnancy: randomized controlled trial

PURPOSE: To evaluate the effectiveness and the safety of orally administered misoprostol in comparison to intravenously infused oxytocin for labor induction in term pregnant women. METHODS: Between 2008 and 2010, a total of 285 term pregnant women whom were candidate for vaginal delivery were assessed for eligibility to enter the study. Twenty five patients were excluded for different reasons; and 260 included women were randomly assigned to one of the two groups according to the method of treatment, misoprostol or oxytocin. The misoprostol group received 25 µg every 2 hours for up to 24 hours for induction. The oxytocin group received an infusion of 10 IU which was gradually increased. The time from induction to delivery and induction to the beginning of the active phase and successful inductions within 12, 18, and 24 hours were recorded. The trial is registered at irct.ir, number IRCT2012061910068N1. RESULTS: Failure of induction, leading to caesarean section was around 38.3% in the oxytocin group and significantly higher than that of the misoprostol group (20.3%) (p<0.001). Despite the more prevalent failure in the oxytocin group, the mean time intervals from induction to active phase and labor of this group were both significantly less than the misoprostol group (10.1±6.1 and 13.2±7.7 versus 12.9±5.4 and 15.6±5.1 hours respectively, both p-values were <0.05). Maternal and fetal complications were comparable between groups except gastrointestinal symptoms which were encountered more frequently in the misoprostol (10.9 versus 3.9%, p=0.03). CONCLUSIONS: Misoprostol is a safe and effective drug with low complications for the induction of labor. Failure is seen less with misoprostol and caesarean sections are less frequently indicated as compared to oxytocin.

Anthelmintic efficacy of oral trichlorfon solution against ivermectin resistant nematode strains in cattle

Infected calves from two different rural estates in Brazil were studied to assess the anthelmintic efficacy of oral trichlorfon against naturally occurring ivermectin resistant parasitic nematode strains. In experiment 1, infected animals were from a region where ivermectin resistant populations of Haemoncus placei, Cooperia punctata,Cooperia spatulata and Trichuris discolor have recently been identified. Six calves with natural gastrointestinal nematode infections were treated with 48.5 mg/kg aqueous trichlorfon administered orally and six calves acted as a non-treated control group. In experiment 11 24 naturally infected calves were selected to enter one of four treatment groups, six animals each received: 48.5 mg/kg oral trichlorfon; 200 mu g/kg subcutaneous 1% ivermectin; 630 mu g/kg subcutaneous 3.15% ivermectin; or no treatment (control group). Gastrointestinal helminths were counted and identified post-mortem at 7 days (trichlorfon and 1% ivermectin treated and untreated animals) or 14 days (3.15% ivermectin treated and untreated animals) after administration of the test agents. Experiment I identified a high level efficacy for oral trichlorfon against four helminth species that have previously been shown to be ivermectin resistant in this geographical region: percentage efficacy was 99.82% against adult H. placei, 99.18% against C. punctata, 99.33% against C. spatulata, 81.06% against T. axei, 98.46% against Oesophagostomum radiatum and 100% against T. discolor. Trichlorfon also showed activity against the ivermectin (1% and 3.15%) resistant helminth species identified in experiment 11, attaining efficacy levels of 99.17% against H. placei, 98.46% against C punctata and 100.00% against T. discolor. These findings indicate that oral trichlorfon is an effective treatment option in the management of cattle infected with ivermectin resistant helminths. (C) 2009 Elsevier B.V. All rights reserved.

In vitro susceptibility of oral Candida albicans strains to different pH levels and calcium hydroxide saturated aqueous solution

Candida albicans is present in the oral cavity and in the whole digestive tract of humans and other animals, being frequently related to endodontic treatment failure. The present study determined the incidence of C. albicans in the oral cavity and the susceptibility of isolates to different pH values and saturated calcium hydroxide aqueous solution at pH 12.5. Sixty-five patients attending the Endodontic Clinic at the Sagrado Coração University participated in the study. The collected samples were cultivated in selective media for C. albicans and the isolates were tested in terms of resistance to both alkaline pH and saturated aqueous solution of calcium hydroxide. In relation to time variables, yeast viability was assessed by the Sabouraud's agar culture and fluorescein diacetate and ethidium bromide fluorescent staining method. Results from the different pHs and experimental times, including those from different techniques measuring fungal viability, were compared using the chi-square and Fisher's exact tests (α=0.05). The yeasts became completely inviable after 48 h of contact with the calcium hydroxide solution. On the other hand, when exposed to the alkaline culture broth, the yeasts were found to be viable at pHs 9.5 and 10.5 for up to 7 days. In conclusion, C. albicans can only be completely inhibited by direct contact with saturated calcium hydroxide aqueous solution after 48 h of exposure.

Intravenous Hypertonic Saline Solution (7.5%) and Oral Electrolytes to Treat of Calves with Noninfectious Diarrhea and Metabolic Acidosis

Objective The aim of this study was to compare the efficacy of treating osmotic diarrhea and dehydration in calves with hypertonic saline solution (HSS) IV, isotonic electrolyte solution (IES) PO, and a combination of these 2 solutions (HSS + IES). Experimental Design Eighteen male calves 830 days of age were used to evaluate the efficacy of 3 methods of fluid therapy after induction of osmotic diarrhea and dehydration. The diarrhea and dehydration were induced by administration of saccharose, spironolactone, and hydrochlorothiazide for 48 hours. The animals were randomly divided into 3 experimental groups: Group 1: 7.2% hypertonic saline solution-HSS (5 mL/kg IV); Group 2: oral isotonic electrolyte solution IES (60 mL/kg PO); or Group 3: HSS+IES. Clinical signs and laboratory finding observed 48 hours post-induction (Time 0) included diarrhea, dehydration, lethargy, and metabolic acidosis. Results Calves treated with HSS + IES experienced decreases in hematocrit, total protein concentration, albumin concentration, urea nitrogen concentration, and plasma volume as well as increases in blood pH, blood bicarbonate concentration, and central venous pressure between 1 and 3 hours post-treatment. These findings also were observed in animals treated with IES, however, at a slower rate than in the HSS + IES-treated animals. Animals treated with HSS continued to display signs of dehydration, lethargy, and metabolic acidosis 24 hours post-treatment. Conclusion Treatment with a combination of HSS and IES produced rapid and sustainable correction of hypovolemia and metabolic acidosis in calves with noninfections diarrhea and dehydration.

Oral Anticoagulation in the Elderly: New Oral Anticoagulants-Innovative Solution for an Old Problem?

Direct oral anticoagulants emerge as the most innovative and promising drug toward preventing and treating cardiovascular disease, raising great interest among the scientific community. Numerous studies and meta-analysis generated much data clarifying clinicians' doubts; however, uncertainties remain regarding their use in particular groups such as patients with prosthetic valves, in valvular atrial fibrillation (defined as atrial fibrillation related to mitral rheumatic heart disease or prosthetic heart valves), among the elderly, in paraneoplastic thromboembolism, in pulmonary embolism with hemodynamic compromise, and scarcity of specific antidotes. This review article intends to condense the vast scientific production addressing new oral anticoagulants by focusing on their advantages and disadvantages when used on the elderly.

Remediation Of 17-α-ethinylestradiol Aqueous Solution By Photocatalysis And Electrochemically-assisted Photocatalysis Using Tio2 And Tio2/wo3 Electrodes Irradiated By A Solar Simulator.

TiO2 and TiO2/WO3 electrodes, irradiated by a solar simulator in configurations for heterogeneous photocatalysis (HP) and electrochemically-assisted HP (EHP), were used to remediate aqueous solutions containing 10 mg L(-1) (34 μmol L(-1)) of 17-α-ethinylestradiol (EE2), active component of most oral contraceptives. The photocatalysts consisted of 4.5 μm thick porous films of TiO2 and TiO2/WO3 (molar ratio W/Ti of 12%) deposited on transparent electrodes from aqueous suspensions of TiO2 particles and WO3 precursors, followed by thermal treatment at 450 (°)C. First, an energy diagram was organized with photoelectrochemical and UV-Vis absorption spectroscopy data and revealed that EE2 could be directly oxidized by the photogenerated holes at the semiconductor surfaces, considering the relative HOMO level for EE2 and the semiconductor valence band edges. Also, for the irradiated hybrid photocatalyst, electrons in TiO2 should be transferred to WO3 conduction band, while holes move toward TiO2 valence band, improving charge separation. The remediated EE2 solutions were analyzed by fluorescence, HPLC and total organic carbon measurements. As expected from the energy diagram, both photocatalysts promoted the EE2 oxidation in HP configuration; after 4 h, the EE2 concentration decayed to 6.2 mg L(-1) (35% of EE2 removal) with irradiated TiO2 while TiO2/WO3 electrode resulted in 45% EE2 removal. A higher performance was achieved in EHP systems, when a Pt wire was introduced as a counter-electrode and the photoelectrodes were biased at +0.7 V; then, the EE2 removal corresponded to 48 and 54% for the TiO2 and TiO2/WO3, respectively. The hybrid TiO2/WO3, when compared to TiO2 electrode, exhibited enhanced sunlight harvesting and improved separation of photogenerated charge carriers, resulting in higher performance for removing this contaminant of emerging concern from aqueous solution.

Histologic grading and nucleolar organizer regions in oral squamous cell carcinomas

OBJECTIVE: The purposes of this study were to histologically assess different types of oral squamous cell carcinoma and the silver-binding nucleolar organizer region (AgNOR) morphology in neoplastic cells, as well as to quantify the number of AgNORs in each type of carcinoma in order to relate AgNOR count and histologic grading. MATERIAL AND METHODS: Twenty-eight cases of oral squamous cell carcinoma were divided into 4 groups, namely well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated. For NOR study, 3-µm-thick sections were stained with 50% aqueous silver nitrate solution. The predominant microscopic pattern of NORs was determined. Quantitative analyses of NORs were obtained of all cells present on each histological field using a 0.025 mm² eyepiece graticule. Different histological fields were analyzed until the total number of NORs was 120 cells for each tumor. Kruskall-Wallis test was applied to compare the groups of sample data at a significance level of p=0.05. RESULTS: The mean number of AgNORs per nucleus was 3.20 for the well-differentiated group, 5.33 for the moderately differentiated one, 8.27 for the poorly differentiated one, and 10.08 for the undifferentiated one. AgNOR count was significantly different (p<0.05) among all of the studied groups. CONCLUSION: AgNOR staining technique seems to be a useful diagnostic tool since differences in AgNOR numeric values can be identified in the different types of oral squamous cell carcinoma. This technique is easy to handle and inexpensive, thus justifying its large use in histopathology.

Effects of oral supplementation with glutamine and alanyl-glutamine on glutamine, glutamate, and glutathione status in trained rats and subjected to long-duration exercise

Objective: We investigated the effect of supplementation with the dipeptide L-alanyl-L-glutamine (DIP) and a solution containing L-glutamine and L-alanine, both in the free form, on the plasma and tissue concentrations of glutamine, glutamate, and glutathione (GSH) in rats subjected to long-duration exercise. Methods: Rats were subjected to sessions of swim training. Twenty-one days before sacrifice, the animals were supplemented with DIP (1.5 g/kg, n = 6), a solution of free L-glutamine (1 g/kg) and free L-alanine (0.61 g/kg; GLN + ALA, n = 6), or water (CON, n = 6). Animals were sacrificed before (TR, n = 6) or after (LD, n = 6) long-duration exercise. Plasma concentrations of glutamine, glutamate, glucose, and ammonia and liver and muscle concentrations of glutamine, glutamate, and reduced and oxidized (GSSG) GSH were measured. Results: Higher concentrations of plasma glutamine were found in the DIP-TR and GLN + ALA-TR groups. The CON-LD group showed hyperammonemia, whereas the DIP-LD and GLN + ALA-LD groups exhibited lower concentrations of ammonia. Higher concentrations of glutamine, glutamate, and GSH/GSSG in the soleus muscle and GSH and GSH/GSSG in the liver were observed in the DIP-TR and GLN + ALA-TR groups. The DIP-LD and GLN + ALA-LD groups exhibited higher concentrations of GSH and GSH/GSSG in the soleus muscle and liver compared with the CON-LD group. Conclusion: Chronic oral administration of DIP and free GLN + ALA before long-duration exercise represents an effective source of glutamine and glutamate, which may increase muscle and liver stores of GSH and improve the redox state of the cell. (C) 2009 Published by Elsevier Inc.