A doxycycline loaded, controlled-release, biodegradable fiber for the treatment of aortic aneurysms.

The pathogenesis of aortic aneurysm (AA) is characterized by degradation of extracellular matrix with increased matrix metalloproteinases (MMPs) and inflammatory reaction. Doxycycline (DOXY) has been reported to control the extension of AA by regulation of MMP. However, systemic administration may cause adverse side effects. In this study, we demonstrated the possibility of local administration of DOXY controlled-release biodegradable fiber (DCRBF) for AA in mice. DCRBF was fabricated by biodegradable polymer (polylactic acid; PLA) mixed with DOXY using an electrospinning technique. DCRBF was cocultured with SMCs, macrophages and aortic tissue, and placed on an abdominal aortic aneurysm which induced apolipoprotein E-deficient mice. We evaluated gene and protein expression of proteases, elastin and inflammatory markers. In the presence of DCRBF, MMP-12 was significantly decreased, TGF-ß1 and Lox were significantly increased in SMC gene expression, MMP-9 and -12 significantly decreased gene expression of macrophages. The DCRBF preserved elastin content and decreased MMP-2 and -9 in aortic tissue. In addition, IGF-1 and TIMP-1 were significantly increased and IL-6 and TNF-α were significantly decreased with DCRBF in vivo. In conclusion, our results suggested that local administration of DCRBF may become a promising alternative therapeutic strategy for AA.

Troglitazone improves whole-body insulin resistance and skeletal muscle glucose use in type II diabetic patients.

UNLABELLED: Recently, troglitazone has emerged as an insulin sensitizer for the treatment of type II diabetes. However, its effect on skeletal muscle glucose use (SMGU) has not been studied. METHODS: To investigate the effect of troglitazone on SMGU in patients with type II diabetes, we undertook skeletal muscle (18)F-FDG PET dynamic imaging under insulin clamping before and after administration of SMGU to 20 patients with type II diabetes. Data were compared with those for 12 age-matched healthy volunteers. RESULTS: The whole-body glucose disposal rate (GDR) was significantly lower in patients (29.9 +/- 9.83 micromol/min/kg) than in control subjects (55.6 +/- 16.5 micromol/min/kg, P < 0.01), as was the SMGU (patients, 3.27 +/- 2.17 micromol/min/kg; control subjects, 10.9 +/- 6.4 micromol/min/kg; P < 0.01). After the therapy, GDR significantly improved in patients (29.3 +/- 14.6 micromol/min/kg, P < 0.05), as did SMGU (5.06 +/- 2.11 micromol/min/kg, P < 0.05). When results for patients with and without hypertension were separately analyzed, a significant improvement in SMGU after troglitazone was seen in both normotensive and hypertensive patients (normotensive [n = 10]: baseline, 3.67 +/- 2.89 micromol/min/kg; after therapy, 5.28 +/- 2.61 micromol/min/kg; P < 0.05; hypertensive [n = 10]: baseline, 2.89 +/- 1.22 micromol/min/kg; after therapy, 4.72 +/- 1.39 micromol/min/kg; P < 0.05). GDR in patients with and without hypertension was significantly improved by troglitazone (normotensive: baseline, 17.9 +/- 10.2 micromol/min/kg; after therapy, 31.9 +/- 15.9 micromol/min/kg; P < 0.01; hypertensive: baseline, 39.6 +/- 15.1 micromol/min/kg; after therapy, 47.7 +/- 23.8 micromol/min/kg; P < 0.05). The plasma free fatty acid concentration during insulin clamping was not changed by troglitazone (baseline, 1.1 +/- 0.86 mEq/L; after therapy, 0.93 +/- 0.65 mEq/L; P = not significant). CONCLUSION: Troglitazone can improve whole-body insulin resistance through the improvement of SMGU but not through a decline in plasma free fatty acid concentration in patients with type II diabetes with or without hypertension.

Hybrid logistic characterization of isometric twitch force curve of isolated ferret right ventricular papillary muscle.

We previously found that the isovolumic pressure curve of the left ventricle and the isometric twitch force curve of the right ventricular in situ papillary muscle, both of the blood-perfused canine heart, were precisely fitted by our newly proposed hybrid logistic function. This function describes the difference between the two S-shaped logistic functions for the rising and falling components: A/[1+exp{-(4B/A)(t-C)}]-D/[1+exp{-(4E/D)(t-F)}]+G. This function characterizes comprehensively both ventricular and in situ papillary muscle contraction and relaxation. In the present study, we hypothesized that this function could also characterize the force curve of the most popular, standard-type, isolated and Tyrode-superfused papillary muscle preparation. To test this hypothesis, we investigated how precisely the hybrid logistic function could fit 112 isometric twitch force curves observed in eight isolated and Tyrode-superfused ferret right ventricular papillary muscles at different muscle lengths and extracellular Ca2+ concentrations. We always obtained a precise curve fitting with a correlation coefficient above 0.9987. This fitting was much more precise than sinusoidal and polynomial exponential function curve fittings. These results supported the present hypothesis. We conclude that our hybrid logistic function reasonably characterizes the force curve of the isolated myocardial preparation. This result broadens the generality of the hybrid logistic characterization of ventricular isovolumic pressure and myocardial isometric twitch force generation. The hybrid logistic characterization seems to be an integrative expression of contractile processes in myocardial twitch contraction.

Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs.

We have developed a method for the noninvasive estimation of regional tissue glucose utilization in humans that employs positron emission tomography (PET) and 2-(18F)fluoro-2-deoxy-d-glucose (FDG). Unlike other methods, the input function used in this method is obtained from the corrected time-activity curve of the descending aorta, not the left ventricle, because the descending aorta is relatively free of spillover from other organs and extends from the upper thorax to the lower abdomen. With this method the time-activity curve of the descending aorta must be corrected for the partial volume effect and the difference in counts between plasma and whole blood. Using the noninvasively obtained input function, regional tissue glucose utilization was calculated by Patlak graphic analysis. k1k3/(k2 + k3) was in good agreement with k1k3/(k2 + k3) calculated from the plasma input function by arterial sampling (r = 0.9995). These results suggest that the input function and regional tissue glucose utilization (not only of myocardium but also of other thoracic and abdominal organs) can be determined noninvasively.