Aminophylline increases respiratory muscle activity during hypercapnia in humans.

BACKGROUND: Theophylline is an old drug traditionally used as a bronchodilator, although it was recently shown to possess anti-inflammatory properties, enhance the actions of corticosteroid actions, and stimulate the respiratory neuronal network. Theophylline has been recognized as an important drug for not only asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses in humans, we analyzed the effects of aminophylline administered at the usual clinical therapeutic doses on ventilation and augmentation of respiratory muscle contractility in room air and under 3 conditions of hypercapnia. STUDY DESIGN: We performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and transversus abdominis muscle (TA) in 7 healthy subjects and recorded both ventilatory parameters and EMG data in room air and under 3 conditions of hypercapnia before (control) and during aminophylline administration. RESULTS: Before aminophylline administration (control), hypercapnic stimulation elicited ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory parameters (tidal volume, frequency of respiration, and minute ventilation) showed significant increases from lower PaCO2 levels during aminophylline administration when compared with the corresponding values before aminophylline administration. EMG activity of both PARA and TA increased significantly at each level of hypercapnia, and those augmentations were shown from lower PaCO2 levels during aminophylline administration. CONCLUSION: Aminophylline administered at the usual clinical therapeutic dose increases ventilation and EMG activity of both inspiratory and expiratory muscles during hypercapnia in healthy humans.

Is there a relation between triglyceride concentrations in very low density lipoprotein and the index of insulin resistance in nondiabetic subjects?

BACKGROUND: Serum very low density lipoprotein (VLDL) levels increase during the early stages of insulin resistance; therefore, determination of VLDL levels would be useful for evaluating the progression of metabolic syndrome and diabetes mellitus. The aim of this study was to clarify the clinical utility of triglyceride in VLDL (VLDL-TG) level, determined using a homogeneous assay kit (Shino-test Corporation, Tokyo, Japan), as an index of insulin resistance. METHODS: We enrolled 74 subjects in this study (diabetic subjects, n = 42; nondiabetic subjects, n = 32). The levels of VLDL-TG, remnant-like lipoprotein particle cholesterol, preheparin lipoprotein lipase mass, and other biochemical markers were determined. RESULTS: VLDL-TG levels were significantly higher in the diabetic group (1.04 ± 0.84 mmol/l vs. 0.64 ± 0.42 mmol/l, P < 0.01) than in the nondiabetic group. In the nondiabetic group, VLDL-TG was significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), the index for insulin resistance (r = 0.513, P = 0.003). VLDL-TG levels, but not TG levels, were higher in the highest quartile (HOMA-IR) of the nondiabetic group. CONCLUSION: VLDL-TG level was a useful early marker for insulin resistance, especially in nondiabetic subjects. The homogeneous VLDL-TG assay is a simple, low-cost method for determining insulin resistance.

Semiquantitative analysis of apolipoprotein A-I modified by advanced glycation end products in diabetes mellitus.

BACKGROUND: Apolipoprotein A-I (Apo A-I), the major component of high-density lipoprotein (HDL), is modified by reactive α-oxoaldehydes, such as methylglyoxal (MG) and glycolaldehyde (GA), and these modifications affect the function of Apo A-I. GA- and MG-modified Apo A-I serum levels were semiquantitatively evaluated in diabetic patients to elucidate the association of each protein with diabetes and to determine its appropriateness as a serum marker of diabetes. METHODS: We enrolled 44 subjects in this study (diabetic subjects, n = 24; nondiabetic subjects, n = 20). GA- and MG-modified Apo A-I levels in serum were determined by sandwich enzyme-linked immunosorbent assay (ELISA) by using anti-GA or anti-MG antibody and anti-Apo A-I antibody. RESULTS: The GA-modified Apo A-I levels did not significantly differ between the diabetic and nondiabetic subjects (1.00 ± 0.38 vs. 0.96 ± 0.22). However, the MG-modified Apo A-I levels in the diabetic subjects were significantly higher than those in the nondiabetic subjects (1.33 ± 0.52 vs. 0.90 ± 0.20). In addition, MG-modified Apo A-I levels correlated with the glycated hemoglobin (HbA1c) levels, HDL-cholesterol levels, and the homeostasis model assessments of insulin resistance, which are indicators of insulin resistance. CONCLUSION: The MG-modified Apo A-I level may be an indicator of diabetic dyslipidemia and insulin resistance.

Air contamination of therapeutic drug monitoring assay reagents results in falsely high plasma ammonia levels.

BACKGROUND: Accumulating evidence shows that contamination of blood samples by atmospheric ammonia affects blood ammonia test levels; however, reports on the effect of ammonia contamination of assay reagents are limited. Here, we aimed to clarify the effect of ammonia contamination of assay reagents, particularly the therapeutic drug monitoring (TDM) reagents, on the detection levels of blood ammonia using enzymatic assays. METHODS: Ammonia gas was measured in the refrigerator compartment of the automatic analyser and the reaction tank water, probe wash water and drain outlets connected to the automatic analyser. At different time points following the closure of the cold storage, ammonia levels in quality control plasma samples were measured using three commercial assay reagents to evaluate the effect of air contamination. The distribution of evaporated ammonia in the reagent was measured using the CicaLiquid NH3 assay kit containing the assay reagent most affected by air contamination. RESULTS: It was confirmed that ammonia gas was generated in the cold storage of the automatic analyser. More than half of the reagents detected >0.25 ppm ammonia, and the highest concentration was detected in the TDM reagent. The ammonia levels obtained using all three reagents increased significantly after 3 h of air contamination. The effect was resolved by measuring a 'dummy' sample or mixing the reagents by inversion. CONCLUSIONS: We demonstrated that air contamination by TDM reagents placed in cold storage could result in significantly falsely high ammonia measurements. Preventing this effect would improve the accuracy of ammonia measurements.