ABSTRACT
BACKGROUND/AIM: Sarcopenia is recognized as a condition related to quality of life and prognosis in patients with chronic liver disease, although no useful strategy for improving muscle volume and strength has been established. Here, we evaluated the efficacy of supplementation with branched-chain amino acid (BCAA) administration and walking exercise. PATIENTS AND METHODS: From December 2015 to July 2016, 33 Japanese outpatients with liver cirrhosis were enrolled (median: 67 years, HCV : HBV : alcohol : others=26 : 2 : 2 : 3, male : female=13 : 20, Child-Pugh A : B=30 : 3). None had a history of BCAA supplementation. After calculating the average number of daily steps using a pedometer for a 2-3-week period, BCAA supplementation (protein 13.5 g, 210 kcal/day) as a late evening snack and walking exercise (additional 2000 steps/day prescribed) were started. Body composition including muscle volume was analyzed using a bioelectrical impedance analysis method, and serological data and muscle strength (leg, handgrip) were evaluated at enrollment, and then 1, 2, and 3 months after starting the protocol. RESULTS: The median average number of daily steps was 3791 (interquartile range: 2238-5484). The average period of BCAA supplementation was 2.7±0.7 months. During the period from enrollment to 3 months after starting the protocol, HbA1c and NH3 were not significantly changed, whereas the BCAA/tyrosine ratio improved (4.3±1.35 to 5.24±2.04, P=0.001). In addition, the ratios for average daily steps (1.595, P=0.02) as well as muscle volume, leg strength, and handgrip strength (1.013, 1.110, and 1.056, respectively; all P<0.01) were increased at 3 months. CONCLUSION: BCAA supplementation and walking exercise were found to be effective and easily implemented for improving muscle volume and strength in liver cirrhosis patients.
Subject(s)
Amino Acids, Branched-Chain/therapeutic use , Dietary Supplements , Liver Cirrhosis/complications , Muscle, Skeletal/pathology , Sarcopenia/prevention & control , Walking/physiology , Aged , Amino Acids, Branched-Chain/blood , Ammonia/blood , Body Composition , Exercise Test , Exercise Therapy , Female , Glycated Hemoglobin/metabolism , Hand Strength , Humans , Liver Cirrhosis/blood , Lower Extremity/physiopathology , Male , Middle Aged , Organ Size , Sarcopenia/blood , Sarcopenia/etiology , Tyrosine/bloodABSTRACT
OBJECTIVES: The effect of intracellular cyclic guanosine monophosphate (GMP) increase on neuronal damage was tested using a newly developed nitric oxide-related injury model of cultured spinal cord neurons. METHODS: Neuronal damage after 24-hour-exposure to sodium nitroprusside (SNP), a nitric oxide (NO) donor, was evaluated by measuring the activity of released lactate dehydrogenase from injured neurons. RESULTS: Oxygen radical scavengers had a protective effect, indicating that the neuronal damage, elicited by 10 µM SNP, was largely due to peroxynitrite formation. Alternatively, a strong inhibition of the NO-induced damage could also be achieved by an intracellular cyclic GMP increase resulting from the addition of 100 µM 8-bromo-cyclic GMP. Propentofylline (PPF, 1-100 µM), a xanthine derivative and rather selective phosphodiesterase (PDE) inhibitor, enhanced intracellular cyclic GMP elevation induced by SNP exposure. The neuronal damage induced by 10 µM SNP exposure for 24 hours was almost completely blocked in the presence of 1 µM PPF. DISCUSSION: These results suggest that NO has an ambiguous action, i.e. toxic by favoring the formation of, but protective by intracellular cyclic GMP elevation which can be reinforced by PDE inhibition. Therefore, PDE inhibitors, such as PPF, may be useful therapeutic drugs to limit oxidative neuronal damage in the central nervous system.
