Neuromuscular electrical stimulation in the intensive care unit prevents muscle atrophy in critically ill older patients: A retrospective cohort study.

Critically ill patients in the intensive care unit (ICU) develop muscle atrophy and decreased physical function. Though neuromuscular electrical stimulation (NMES) therapy has been shown to be effective in preventing this, but its effect on older patients is unknown. To examine the course of critically ill older patients treated with NMES in the ICU and to define the impact of its use. A retrospective cohort study was conducted using older ICU patients (≥65 years) categorized into a control group (n = 20) and an NMES group (n = 22). For subgroup analysis, each group was further classified into pre-old age (65-74 years) and old age (≥75 years). The control group showed significant decrease in muscle thickness during ICU and hospital stay. The NMES group showed lower reduction in muscle thickness and showed decrease in muscle echo intensity during hospital stay, compared to the control group. NMES inhibited decrease in muscle thickness in the pre-old age group versus the old age group. The decreasing effect of NMES on echo intensity during hospital stay manifested only in the pre-old age group. We did not find much difference in physical functioning between the NMES and control groups. Lower limb muscle atrophy reduces in critically ill older patients (≥65 years) with NMES and is pronounced in patients aged < 75 years. The impact of NMES on the physical functioning of older patients in ICU needs to be further investigated.

Effects of salmeterol xinafoate and fluticasone propionate on immunological activation of human cultured mast cells.

BACKGROUND: The clinical efficacy of combination therapy comprising a long acting beta(2)-agonist (LABA) and corticosteroid is widely recognized for the treatment of adult asthma. Here we examine the effect of salmeterol xinafoate (SX) and fluticasone propionate (FP) alone and in combination on the immunological activation of human cultured mast cells (HCMC)in vitro. METHODS: HCMC were passively sensitized with IgE antibody and then activated by challenging with anti-IgE antibody. The effect of drugs on the activation of mast cells was examined by measuring the amount of released chemical mediators (histamine, leukotrienes (LT) and prostaglandin D(2) (PGD(2))) and granulocyte macrophage colony stimulating factor (GM-CSF). RESULTS: The release of each chemical mediator was inhibited by 10-9-10-8M SX but not by 10-10-10-7M FP. The production of GM-CSF was inhibited by a concentration of 10-8M in both drugs and the inhibition was augmented by combined treatment with 10-11M of each drug. CONCLUSIONS: The immunological release of chemical mediators (histamine, LT, PGD(2)) from HCMC was inhibited by SX but not by FP. SX and FP inhibited the production of GM-CSF by HCMC and both drug showed synergistic inhibition in the production of GM-CSF.

Buformin suppresses the expression of glyceraldehyde 3-phosphate dehydrogenase.

The biguanides metformin and buformin, which are clinically used for diabetes mellitus, are known to improve resistance to insulin in patients. Biguanides were reported to cause lactic acidosis as a side effect. Since the mechanism of the side effect still remains obscure, we have examined genes whose expression changes by treating HepG2 cells with buformin in order to elucidate the mechanisms of the side effect. A subtraction cDNA library was constructed by the method of suppressive subtractive hybridization and the screening of the library was performed with cDNA probes prepared from HepG2 cells treated with or without buformin for 12 h. The expression of the gene and the protein obtained by the screening was monitored by real-time RT-PCR with specific primers and Western blotting with specific antibody. The amounts of ATP and NAD+ were determined with luciferase and alcohol dehydrogenase, respectively. We found that expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPD) gene was suppressed by treating HepG2 cells with 0.25 mM buformin for 12 h as a result of the library screening. The decrease in the expression depended on the treatment period. The amount of GAPD protein also decreased simultaneously with the suppression of the gene expression by the treatment with buformin. The amount of ATP and NAD+ in the HepG2 cells treated with buformin decreased to 10 and 20% of the control, respectively. These observations imply that the biguanide causes deactivation of the glycolytic pathway and subsequently the accumulation of pyruvate and NADH and a decrease in NAD+. Therefore, the reaction equilibrium catalyzed by lactate dehydrogenase leans towards lactate production and this may result in lactic acidosis.