Enteral Protein Supplementation in Critically Ill Children: A Randomized Controlled Pilot and Feasibility Study.

BACKGROUND: Loss of muscle mass in critically ill children can negatively impact outcomes. The aims of this study were to conduct a pilot randomized control trial (RCT) to examine the difference in protein delivery and nitrogen balance in critically ill children with enteral protein supplementation vs controls. We also aimed to assess the feasibility, safety, and tolerance of the pilot trial. METHODS: This is a 3-arm RCT in critically ill children eligible for enteral nutrition (EN) therapy. Patients were randomized to 1 of the 3 groups: (1) control (routine EN), (2) polymeric protein module added to EN to reach protein goal by day 4, or (3) oligomeric protein supplementation. Demographics, clinical characteristics, nutrition status, and daily nutrition intake variables were recorded. Protein delivery, nitrogen balance, feasibility variables, and rate of adverse events were the outcomes. RESULTS: After screening 286 consecutive patients admitted to the pediatric intensive care unit over 11 months, we enrolled and randomized 25 patients. Twenty-two patients (88% of the enrolled) completed the study procedures. Significantly higher protein prescription and actual protein intake within the first 5 days was achieved in the intervention groups, compared with the control group. Nitrogen balance was obtained in 15 patients. There was no significant difference between the groups for the rate of adverse effects and clinical outcomes. CONCLUSION: In our pilot trial, protein supplementation was safe and well tolerated. Our preliminary results suggest that a larger RCT is potentially feasible, with some modifications of the entry criteria. Trial enrollment was low, likely due to restrictive entry criteria.

DNA damage and inhibition of akt pathway in mcf-7 cells and ehrlich tumor in mice treated with 1,4-naphthoquinones in combination with ascorbate.

The aim of this study was to enhance the understanding of the antitumor mechanism of 1,4-naphthoquinones and ascorbate. Juglone, phenylaminonaphthoquinone-7, and 9 (Q7/Q9) were evaluated for effects on CT-DNA and DNA of cancer cells. Evaluations in MCF-7 cells are DNA damage, ROS levels, viability, and proliferation. Proteins from MCF-7 lysates were immunoblotted for verifying PARP integrity, γH2AX, and pAkt. Antitumor activity was measured in Ehrlich ascites carcinoma-bearing mice. The same markers of molecular toxicity were assessed in vivo. The naphthoquinones intercalate into CT-DNA and caused oxidative cleavage, which is increased in the presence of ascorbate. Treatments caused DNA damage and reduced viability and proliferation of MCF-7 cells. Effects were potentiated by ascorbate. No PARP cleavage was observed. Naphthoquinones, combined with ascorbate, caused phosphorylation of H2AX and inhibited pAkt. ROS were enhanced in MCF-7 cells, particularly by the juglone and Q7 plus ascorbate. Ehrlich carcinoma was inhibited by juglone, Q7, or Q9, but the potentiating effect of ascorbate was reproduced in vivo only in the cases of juglone and Q7, which caused up to 60% inhibition of tumor and the largest extension of survival. Juglone and Q7 plus ascorbate caused enhanced ROS and DNA damage and inhibited pAkt also in Ehrlich carcinoma cells.

La complementación con antioxidantes atenúa el estrés oxidativo en pacientes con hepatitis C crónica / Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients

Resumen La generación excesiva de especies reactivas de oxígeno está implicada en la patogénesis de la hepatitis C. El objetivo de este estudio fue evaluar el estado antioxidante de la sangre en pacientes infectados por VHC tratados o sin tratamiento con la terapia estándar, antes y después de la complementación con vitaminas E, C y Zinc. Se evaluaron los biomarcadores de estrés oxidativo en sangre de tres grupos de pacientes: grupo 1 - controles, grupo 2 - pacientes con VHC sin tratamiento examinados antes y después de una complementación diaria de antioxidantes (800mg de vitamina E, 500mg de vit. C, y 40mg de zinc) durante 6 meses y grupo 3 - pacientes con VHC tratados con interferón pegilado combinado con ribavirina, también examinados antes y después de la misma complementación diaria con antioxidantes. Antes del tratamiento antiviral los pacientes con VHC mostraban una mayor actividad del superóxido dismutasa, la catalasa y el glutatión peroxidasa y una actividad reducida de la glutatión reductasa, (..) (AU)

Abstract Reactive oxygen species (ROS) overgeneration is involved in the pathogenesis of hepatitis C. The aim of this study was to evaluate the antioxidant status in the blood of HCV infected patients treated or not with standard therapy before and after supplementation of vitamins E, C and zinc. Biomarkers of oxidative stress were evaluated in the blood of three groups of patients: group 1 - controls; group 2 - HCV patients without treatment examined before and after a daily antioxidant supplementation (vitamin E 800mg, C 500mg and zinc 40mg) for 6 months; and group 3 - HCV patients treated with pegylated interferon combined with ribavirin, also examined before and after the same antioxidant supplementation. Before antiviral treatment HCV patients showed enhanced superoxide dismutase, catalase and glutathione peroxidase activities and decreased glutathione reductase activity, while lipoperoxidation was increased and reduced glutathione showed decreased levels compared to controls. Treatment with standard therapy enhanced the activities of catalase and glutathione S-transferase, increased contents of protein carbonyl and promoted further reduced glutathione depletion. After antioxidant supplementation, decreased catalase and glutathione S-transferase activities, decreased lipoperoxidation in group 2, and increased reduced glutathione contents in both supplemented groups were detected. Before antioxidant supplementation, alanine aminotransferase and gamma glutamyl transferase contents showed significant increases in group 2. Conclusion: Untreated HCV patients and also those treated with the standard therapy are coping with a systemic oxidative stress. The antioxidant supplementation conferred an antioxidant protection to both supplemented groups attenuating oxidation processes related to the disease (AU)

Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients.

UNLABELLED: Reactive oxygen species (ROS) overgeneration is involved in the pathogenesis of hepatitis C. The aim of this study was to evaluate the antioxidant status in the blood of HCV infected patients treated or not with standard therapy before and after supplementation of vitamins E, C and zinc. Biomarkers of oxidative stress were evaluated in the blood of three groups of patients: group 1 - controls; group 2 - HCV patients without treatment examined before and after a daily antioxidant supplementation (vitamin E 800 mg, C 500 mg and zinc 40 mg) for 6 months; and group 3 - HCV patients treated with pegylated interferon combined with ribavirin, also examined before and after the same antioxidant supplementation. Before antiviral treatment HCV patients showed enhanced superoxide dismutase, catalase and glutathione peroxidase activities and decreased glutathione reductase activity, while lipoperoxidation was increased and reduced glutathione showed decreased levels compared to controls. Treatment with standard therapy enhanced the activities of catalase and glutathione S-transferase, increased contents of protein carbonyl and promoted further reduced glutathione depletion. After antioxidant supplementation, decreased catalase and glutathione S-transferase activities, decreased lipoperoxidation in group 2, and increased reduced glutathione contents in both supplemented groups were detected. Before antioxidant supplementation, alanine aminotransferase and gamma glutamyl transferase contents showed significant increases in group 2. CONCLUSION: Untreated HCV patients and also those treated with the standard therapy are coping with a systemic oxidative stress. The antioxidant supplementation conferred an antioxidant protection to both supplemented groups attenuating oxidation processes related to the disease.