Monocyte/macrophage response to β2-microglobulin modified with advanced glycation end products

Monocyte/macrophage response to β2-microglobulin modified with advanced glycation end products. We recently found that acidic β2-microglobulin (β2m), a major isoform of β2m in amyloid fibrils of patients with dialysis-related amyloidosis (DRA), contained early Amadori products and advanced glycation end products (AGEs) formed nonenzymatically between sugar and protein. Further analysis revealed that acidic β2m induces monocyte chemotaxis and macrophage secretion of bone-resorbing cytokines, suggesting the involvement of acidic β2m in the pathogenesis of DRA. Acidic β2m, however, is a mixture of heterogeneous molecular adducts due to various types of modification. In the present study, we investigated the modification responsible for the biological activity of acidic β2m toward monocytes/macrophages. The presence of a fair amount of β2m species with deamidation was detected in acidic β2m isolated from urine of non-diabetic long-term hemodialysis patients, but deamidated β2m had no biological activity. In contrast, normal β2m acquired the activity upon incubation with glucose in vitro. Among the glycated β2m, the pigmented and fluorescent β2m that formed after a long incubation period, that is, AGE-modified β2m, exhibited biological activity, whereas β2m modified with Amadori products, major Maillard products in acidic β2m, had no such activity. These findings suggest that AGEs, although only a minor constituent of acidic β2m, are responsible for monocyte chemotaxis and macrophage secretion of cytokines, implicating the contribution of AGEs to bone and joint destruction in DRA

Intensity-modulated radiation therapy dose verification using fluence and portal imaging device

Patient-specific quality assurance for intensity-modulated radiation therapy (IMRT) dose verification is essential. The aim of this study is to provide a new method based on the relative error distribution by comparing the fluence map from the treatment planning system (TPS) and the incident fluence deconvolved from the electronic portal imaging device (EPID) images. This method is validated for 10 head and neck IMRT cases. The fluence map of each beam was exported from the TPS and EPID images of the treatment beams were acquired. Measured EPID images were deconvolved to the incident fluence with proper corrections. The relative error distribution between the TPS fluence map and the incident fluence from the EPID was created. This was also created for a 2D diode array detector. The absolute point dose was measured with an ionization chamber, and the dose distribution was measured by a radiochromic film. In three cases, MLC leaf positions were intentionally changed to create the dose error as much as 5% against the planned dose and our fluence-based method was tested using gamma index. Absolute errors between the predicted dose of 2D diode detector and of our method and measure­ments were 1.26% ± 0.65% and 0.78% ± 0.81% respectively. The gamma passing rate (3% global / 3 mm) of the TPS was higher than that of the 2D diode detector (p< 0.02), and lower than that of the EPID (p < 0.04). The gamma passing rate (2% global / 2 mm) of the TPS was higher than that of the 2D diode detector, while the gamma passing rate of the TPS was lower than that of EPID (p < 0.02). For three modified plans, the predicted dose errors against the measured dose were 1.10%, 2.14%, and -0.87%. The predicted dose distributions from the EPID were well matched to the measurements. Our fluence-based method provides very accurate dosimetry for IMRT patients. The method is simple and can be adapted to any clinic for complex cases

Piezoresistive Strain Sensors Made from Carbon Nanotubes Based Polymer Nanocomposites

In recent years, nanocomposites based on various nano-scale carbon fillers, such as carbon nanotubes (CNTs), are increasingly being thought of as a realistic alternative to conventional smart materials, largely due to their superior electrical properties. Great interest has been generated in building highly sensitive strain sensors with these new nanocomposites. This article reviews the recent significant developments in the field of highly sensitive strain sensors made from CNT/polymer nanocomposites. We focus on the following two topics: electrical conductivity and piezoresistivity of CNT/polymer nanocomposites, and the relationship between them by considering the internal conductive network formed by CNTs, tunneling effect, aspect ratio and piezoresistivity of CNTs themselves, etc. Many recent experimental, theoretical and numerical studies in this field are described in detail to uncover the working mechanisms of this new type of strain sensors and to demonstrate some possible key factors for improving the sensor sensitivity

Growth Hormone Responses to Thyroid Hormone in the Neonatal Rat: RESISTANCE AND ANAMNESTIC RESPONSE

Differences in the growth hormone (GH) responses to primary and to secondary stimulation with triiodothyronine (T3) were studied in rats deprived of thyroid hormone from birth. Neonatal hypothyroidism was induced in pups by feeding pregnant rats an iodine-deficient, propylthiouracil-containing diet. T3 stimulation was carried out in pups by subcutaneous injection of a single dose of 50 μg T3/100 g body wt. Pituitary GH content, rate of GH synthesis in vitro, and GH messenger (m)RNA activity in a cellfree translation system were measured. No significant differences in body weight and in pituitary GH content were observed between hypothyroid and normal pups at ages 1, 3, and 6 d. 10- and 28-d-old hypothyroid pups showed a significant arrest of growth, decreased pituitary GH content, and development of GH responsiveness to T3. In contrast, serum thyroxine concentration in hypothyroid pups was <0.15 μg/dl, significantly lower than normal at all ages. GH synthesis and GH mRNA activity studied in pituitaries of 28-d-old rats were expressed as percent total protein synthesis and percent mRNA activity, respectively. GH synthesis and mRNA activity were 3.0 and 2.6% in hypothyroid rats, 3.3 and 2.9% in hypothyroid rats given a single T3 injection 14 d earlier (T3-withdrawn rats), and 26.8 and 27.1% in normal rats. Administration of T3 to hypothyroid rats induced an increase in GH synthesis and GH mRNA activity, reaching 5.8 and 5.6% 12 h after primary stimulation and 12.2 and 16.1% 12 h after secondary stimulation. The response rates were linear but 2.5-fold more rapid after secondary stimulation. The latter response was similar to that observed after T3 stimulation of rats rendered hypothyroid during adulthood. The responses of GH synthesis and mRNA activity were concordant after both primary and secondary T3 stimulation. A twofold increase in both parameters was observed as early as 2 h after T3 injection. Four conclusions can be drawn from these experiments. First, during neonatal life, GH accumulation in rat pituitaries is independent of thyroid hormone and is insensitive to T3. Second, GH dependence on and sensitivity to thyroid hormone is acquired between the 6th and 10th d of neonatal life. Third, secondary T3 stimulation produces an anamnestic response manifested by an increased rate of GH synthesis and mRNA activity. Fourth, primary T3 stimulation is not associated with a lag in the endogenous translation of the newly accumulated GH mRNA

Thyroid Function in a Uremic Rat Model: EVIDENCE SUGGESTING TISSUE HYPOTHYROIDISM

The main objective of this study was to determine whether the principal abnormality of thyroid function observed in patients with chronic renal failure, low serum triiodothyronine (T(3)) concentration, causes hypothyroidism at the tissue level. A partially nephrectomized (Nx) uremic rat model was developed and the following parameters of thyroid function were assessed: serum total thyroxine (TT(4)), total T(3) (TT(3)), and thyrotropin and liver T(3) content, and activity of two thyroid hormone-dependent enzymes, mitochondrial α-glycerophosphate dehydrogenase (α-GPD) and cytosol malate dehydrogenase (MDH). The results were compared to those of intact control (C), thyroidectomized (Tx), and nephrectomized-thyroidectomized (NxTx) littermates. Results expressed as mean±SEM showed that Nx rats had a fivefold increase in blood urea nitrogen, (112±20 mg/dl in Nx, and 22±1 mg/dl in C) and manifested all the changes of of thyroid function observed in uremic men, including a low serum TT(3) level (30±7 ng/dl in Nx and 50±6 ng/dl in C). In the liver, T(3) was significantly reduced (18±2 ng/total liver in Nx and 35±3 ng/total liver in C) as well as the activities of αGPD (8.8±1.0 and 16.1±1.5 ΔOD/min per total liver in Nx and C, respectively) and MDH (6.3±1.6 and 12.6±2.2 U/total liver in Nx and C, respectively). The reduction in liver enzyme activities correlated significantly with the decrease in T(3) content. The changes in Tx rats were as expected, showing a profound reduction in serum hormone levels, liver T(3) content, and liver enzyme activities. Serum thyrotropin was markedly elevated to 2,390±212 ng/ml as compared to 703±61 in C and 441±87 ng/ml in Nx rats. The NxTx rats showed the combined effects of nephrectomy and thyroidectomy; blood urea nitrogen was elevated to 203, and serum levels of TT(4), TT(3), and thyrotropin were 0.4, <10, and 2,525, respectively. Total liver T(3) and αGPD and MDH were strikingly low; the corresponding values were 3.5, 2.4, and 2.5. l-triiodothyronine replacement (0.4 μg/100 g body wt/d) for 4 wk in the Nx rats resulted in significant increases in liver enzyme activities, αGPD and MDH rose by 70 and 60% over their respective basal values without alteration in the severity of azotemia. From these data, we conclude that the reduction of liver T(3) content in the uremic rats, accompanied by a decrease in αGPD and MDH activity, indicates the presence of hypothyroidism at the tissue level. Restoration of enzyme activities toward normal levels after T(3) administration provided further supporting evidence that the diminution in liver enzyme activity was causally related to tissue T(3) deficiency