The pharmacokinetics and pharmacodynamics of the oral iron chelator deferiprone (L1) in relation to hemoglobin levels

Recently, we demonstrated that administration of the orally active iron chelating agent deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one (L1)) at 6-hour intervals results in significantly greater urinary iron excretion than that induced during administration of the drug at 12-hour intervals. That study was conducted in thalassemia patients, all of whom had received a packed red cell transfusion of 15 cc/kg. 72 hours prior to evaluation of urinary iron excretion, at a time when endogenous erythropoiesis would be expected to be at its lowest. In clinical practice however, thalassemia patients, suppression of endogenous erythropoiesis is not sustained between transfusions. We set out to determine the influence that administration of deferiprone has on urinary iron excretion at lower hemoglobin concentrations, immediately prior to transfusion. We hypothesized that hemoglobin levels will affect the ability of deferiprone to chelate iron. Ten regularly transfused patients with homozygous beta-thalassemia (HBT) aged mean +/- SD, 20.9 +/- 4.7, range 13 - 27 years, receiving long-term therapy with deferiprone, were treated with deferiprone 75 mg/kg/day, administered every 6 hours (or every 12 hours) for 72 hours immediately prior to a blood transfusion in the first month. One month later each patient received the other of the 2 dosing regimens for 72 hours immediately prior to transfusion. The deferiprone-induced 24-hour urinary iron excretion was similar during both dosing regimens; 0.56 +/- 0.45 mg/kg when L1 was given every 6 hours and 0.48 +/- 0.52 mg/kg when L1 was administered every 12 hours (p = 0.79). However, the calculated 24-hour area under the plasma concentration-time curve (AUC0-24) of deferiprone was significantly lower when deferiprone was administered at 6-hour intervals (6,762.8 +/- 1,601.6 mg*min/l), than that observed when deferiprone was administered every 12 hours (8,250.1 +/- 1,235.7 mg*min/l) (p = 0.04). The pharmacokinetics of deferiprone when administered immediately prior to transfusions are different from those following transfusions. More studies assessing total body iron excretion are needed to determine the contribution of the fecal route in iron excretion.     

Structure and dynamics of suspensions of silica particles in liquidcrystals under a low frequency AC applied voltage

Silica particles dispersed in liquid crystals exhibit a novel behavior such as a unique migrating behavior and alignment. These characteristics are found to depend on the size of the nanoparticles, the surface state of nanoparticles, the liquid crystal (LC) phases, the amplitude and the frequency of applied voltage. These are discussed in terms of anisotropic particle-particle and particle-LC molecules interactions in the anisotropic environment of liquid crystal matrix     

Forming mental models in learning operating procedures for terminalequipment

People faced with an unfamiliar product or service tend to fall back on mental models based on analogical relationships with familiar products or services. Two experiments on the analogical relationships or metaphors that people might use when operating a communications terminal are described. In the first experiment, the role previously acquired operating knowledge has in determining the mental models people use when directory dialing with novel equipment is examined. In a second experiment, it is shown that an explicit appeal to an analogy between conventional mail and electronic mail can help users learn to use an electronic mail system, and make it easier for them to remember how to use the system as long as 90 days after initial exposure. It is concluded that the mental model is constructed only from the user's operating knowledge acquired as a result of past experiences, and the metaphor method is effective when the instructions are metaphorically taught     

Using precise data sets on farming and pesticide properties to verify a diffuse pollution hydrological model for predicting pesticide concentration.

Verification of a diffuse pollution model involves comparing results actually observed with those predicted by precise model inputs. Acquisition of precise model inputs is, however, problematic. In particular, when the target catchment is large and substantial estimation uncertainty exists, not only model verification but also prediction is difficult. Therefore, in this study, rice-farming data were collected for all paddy fields from all farmers in a catchment and pesticide adsorption and degradation rates in paddy field soil samples were measured to obtain precise model inputs. The model inputs successfully verified the model's capability to predict pesticide concentrations in river water. Sensitivity analyses of the model inputs elucidated the processes significantly affecting pesticide runoff from rice farms. Pesticide adsorption and degradation rates of the soil did not significantly affect pesticide concentrations, although pesticide discharge to river water accounted for less than 50% of the total quantity of pesticide applied to fields, possibly owing to pesticide adsorption and degradation. The timing of increases in pesticide concentrations in river water was affected mostly by the farming schedule, including the time of pesticide application and irrigation, and secondarily by rainfall events.     

A new voltage control equipment using fuzzy inference

Power system control equipment needs higher sensitivity and operational reliability. Advanced voltage control equipment is needed for reducing the frequency of tap changes and improving the characteristics (the relationship between the actual voltage and reference voltage) of the voltage to meet today's power system requirements. However, these objectives are in a trade-off relationship. Studies of voltage control derived from a knowledge base suitable for electric power systems can satisfy these objectives using fuzzy inference. Compared with corresponding conventional equipment, the new equipment improved the deviation of 30 min average voltage of 30 percent. This paper describes the design concept of new voltage control equipment using fuzzy inference. In addition, field test results are described along with rules of fuzzy inference, membership functions, and the deviation of 30 min average voltage through detailed simulation.     

Zinc enhancement of 17beta-estradiol''s anabolic effect in osteoblastic MC3T3-E1 cells

Annexin V belongs to a family of phospholipid binding proteins, the Annexins. It binds in the presence of Ca(2+)-ions with high affinity to negatively charged phospholipids like phosphatidylserine (PS). On the basis of its protein structure and biological activity Annexin V is considered as a protein exhibiting its hitherto unknown function within the intracellular environment. One argument comes from the understanding that PS is predominantly located in membrane leaflets, which face the cytosol. However, recent findings show that each cell type has the molecular machinery to expose PS at its cell surface. This machinery is activated during the execution of apoptosis. Once PS is exposed at the cell surface it exhibits procoagulant and proinflammatory activities. Annexin V will bind to the PS-exposing apoptotic cell and can inhibit thereby the procoagulant and pro-inflammatory activities of the dying cell. These findings together with the presence of Annexin V in the extracellular space depict a novel (patho)Physiological significance for Annexin V in vivo.     

Detection of hypervascular hepatocellular carcinoma by using spiral volumetric CT: comparison of US and MR imaging

BACKGROUND: Most hepatocellular carcinomas (HCCs) are hypervascular and arise in the liver with chronicity. Spiral volumetric CT (SVCT) is a new rapid-scan technique that offers whole-liver scanning during the arterial-dominant phase. The main aim of the present study is to evaluate the detectability of hypervascular HCC with SVCT as compared with ultrasonography (US) and magnetic resonance (MR) imaging. METHODS: Forty-three hypervascular HCCs in 512 patients with chronic liver disease were examined with US, precontrast SVCT, postcontrast SVCT during the arterial-dominant phase (CT-ADP) and during the equivalent-phase (CT-EP) noncontrast MR imaging and angiography including SVCT during arteriography and arterial portography. Angiographic and follow-up findings were used as the gold standard if the lesion was not confirmed histologically. RESULTS: The sensitivity was 61% with precontrast CT, 84% with CT-ADP, 58% with CT-EP, 70% with US, 72% with MR, and 95% with the combination of these five modalities. Five HCCs (12%) were detected with only CT-ADP. The vascularity of HCC was correctly evaluated as hypervascular in 38 nodules (88%) with the combination of precontrast CT and CT-ADP. CONCLUSIONS: We suggest that the combination of precontrast SVCT and CT-ADP is an essential modality to screen for HCC in patients with chronic liver disease. CT-EP did not contribute to the detection of hypervascular HCC.     

Gaussian-beam open resonator with highly reflective circularcoupling regions

A high-Q open resonator with quasi-optical coupling regions is described. The resonator consists of a pair of spherical mirrors, on each of which a highly reflective, partially transparent circular region is fabricated with a diameter larger than several wavelengths. The signal is coupled in and out as a Gaussian beam by means of these regions. Both very weak coupling and very efficient mode conversion are simultaneously achieved. This results in a Q-factor over 2×10⁵ and a high signal-to-noise ratio at 105.9 GHz. The Q-factor of the open resonator can be varied by rotating the output mirror to change the angle between the directions of the conducting stripes on the two mirrors     

The Gmicro/500 superscalar microprocessor with branch buffers

The Gmicro/500, which features a RISC-like dual-pipeline structure for high-speed execution of basic instructions and represents a significant advance for the TRON architecture, is presented. Upwardly-object-compatible with earlier members of the Gmicro series, this microprocessor uses resident dedicated branch buffers to greatly enhance branch instruction execution speed. Its microprograms simultaneously use dual execution blocks to execute high-level language instructions effectively. Fabricated with a 0.6-μm CMOS technology on a 10.9-mm×16-mm die, the chip operates at 50/66 MHz and achieves a processing rate of 100/132 MIPS