Determination of a new podophyllotoxin derivative, TOP-53, and its metabolite in rat plasma and urine by high-performance liquid chromatography with electrochemical detection

A high-performance liquid chromatographic method was developed for the determination of a new podophyllotoxin derivative, TOP-53 (I), and TOP-53 glucuronide (II) as its major metabolite in rat plasma and urine. For the analysis of I, the sample was chromatographed on a reversed-phase C18 column with electrochemical detection after consecutive two-step liquid-liquid extractions. Compound II was determined as I after enzymatic hydrolysis of II. This method was validated sufficiently with respect to specificity, accuracy, and precision. The limits of quantitation for both I and II were 2 ng/ml in plasma and 10 ng/ml in urine. The method is thus useful for the pharmacokinetic study of I.     

Hypercoagulability and chronic atrial fibrillation: the role of markers of thrombin generation

BACKGROUND: We have studied 64 patients with congestive heart failure, half of them also with chronic nonvalvular atrial fibrillation (AF). Patients were also stratified according to a history of prior stroke. METHODS: The generation of thrombin was investigated by means of the molecular markers prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III complex (TAT), because AF patients may have a hypercoagulable state. There was only a trend toward higher values of TAT and F1 + 2 for AF patients, while subjects with previous stroke (irrespective of AF) had increased levels of the markers of thrombin generation (TAT stroke+ 18.95 +/- 5.15 vs TAT stroke- 8.34 +/- 2.41; F1 + 2 stroke+ 2.22 +/- 0.29 vs F1 + 2 stroke- 1.32 +/- 0.12). The presence of spontaneous echo contrast (SEC) within left atrium was also investigated in 32 AF patients by transesophageal echocardiography. RESULTS: TAT were significantly higher in subjects (n = 11) with SEC (TAT sec+ 37.5 +/- 13.41 vs TAT sec- 8.7 +/- 2.51, p = 0.008). CONCLUSIONS: Finally, when we grouped into 1) those with both AF and stroke, 2) AF alone, 3) stroke alone and 4) sinus rhythm without stroke, levels of F1 + 2 were higher (and marginally higher TAT) in patients with AF and stroke than in those without stroke, revealing that there is a true clotting activation state in these subjects.     

Maternal nutrition and socio-economic status as determinants of birthweight in chronically malnourished African women

The birthweight is the most important determinant of mortality and morbidity in the neonatal period and may have an influence on health in adult life. The high rate of low birthweight in developing countries is therefore a major health problem. Maternal malnutrition is usually assumed to be a causal factor but other environmental factors are also involved. In this study we analysed maternal nutritional and socio-economic factors as determinants of birthweight in term infants from a rural African society characterised by a high rate of chronic malnutrition. Relations of maternal weight, gestational weight gain, parity, socio-economic status and infant sex with birthweight were analysed in 1,477 women and child pairs. The selected women were followed from early pregnancy and had an uncomplicated delivery at term of a living singleton child. The gestational weight gain was 5.6 (SD 6.0) kg and the mean birthweight 2.933 kg (SD 408). Maternal weight, representing the maternal long-term nutritional situation, was the most important independent determinant of birthweight, accounting for 13.0% of the variance in birthweight. The weight gain, representing the short-term nutritional situation, explained only 5.6% of the variance. Birthweight increased by 20 g (CI 18-23) for each kg maternal weight and by 15 g (CI 12-18) for each kg gestational weight gained. The socio-economic difference in birth-weight was 153 g (CI 109-196) 88 of which (CI 48-128) remained unexplained after adjustment for differences in maternal weight, parity and gender. Improved long-term nutritional situation and living conditions seems to be the most important prerequisites to counteract low birthweight in developing countries.     

Overly literal interpretations of speech in autism: understanding that messages arise from minds

Children with autism and children with Down's syndrome watched the following enactment. A protagonist put one item in location A and another in location B and then left the scene. Subsequently, the items were swapped the other way round. Finally, the protagonist (who remained ignorant of the swap) requested the item in A. The observing child participant was asked to judge (1) which item the protagonist wanted and (2) which item the protagonist put in A. Unlike children with Down's syndrome, those with autism made more errors in judging that the speaker wanted the item in B than in judging that the item the speaker put in A is now in B; children with autism wrongly tended to interpret utterances literally, and they did this significantly more frequently than children with Down's syndrome. We conclude that children with autism have a difficulty making nonliteral interpretations that cannot be explained as (1) a realist bias, (2) an inability to inhibit a prepotent response, and (3) a failure to keep track of the exchange of items.     

Replacement of the anterior cruciate ligament by cold preserved bone-cruciate ligament-bone allotransplants. An experimental study in the sheep

One ACL in each of 17 mature sheep was replaced with a deep-frozen bone-an ACL bone allograft. Allografts were obtained from skeletally mature sheep using a standard aseptic technique and stored deep frozen for at least 6 days (mean 21 days). Macroscopical, biomechanical, and histological changes were evaluated 12, 24, and 52 weeks following implantation. At autopsy all allograft ligaments were present and demonstrated no evidence of infection or immune reaction. We found slight arthrotic changes in 3 knees after 12 weeks, in 4 knees after 24 weeks, and in 3 knees after 52 weeks. Twelve weeks after the operation the maximum load of the allografts was 17.5% of the contralateral controls and increased to 20.9% after 24 weeks and to 32% of controls after 52 weeks. Ligament stiffness in the linear region also increased from 18.9% of control (12 weeks) to 32.5% after 52 weeks, whereas maximum load decreased from 112.2% of controls (12 weeks) to 98% of controls (52 weeks). Histologically, the allografts progressively matured with time, becoming nearly identical to normal ligaments at 52 weeks.     

Semiconductor laser dynamics for feedback from afinite-penetration-depth phase-conjugate mirror

Most of the previous treatments of semiconductor lasers subject to optical feedback from a phase-conjugate mirror (PCM) have assumed that the PCM responds instantaneously. Furthermore, the mechanism responsible for phase conjugation does not usually enter into the analysis. In this paper, we derive the time-dependent reflectivity of a PCM created through nondegenerate four-wave mixing in a Kerr-type nonlinear medium. The resulting laser dynamics are compared with the case of the ideal PCM, as a function of the external-cavity length, the PCM reflectivity, and the PCM interaction depth. The PCM with a significant interaction depth tends to suppress otherwise chaotic output and produces pulses whose repetition rate is tunable by varying PCM reflectivity. At high feedback levels, it stabilizes the laser output. We use the circle-map formalism to explain our numerical results     

Electron escape time from single quantum wells

A theoretical model for electrons escaping a quantum well under the influence of an applied electric field is developed. Both the thermionic emission and tunneling components of the currents are calculated, taking into account the proper partitioning between the two currents. The group velocity for a nonuniform electron distribution within the quantum well, which is a function of position and energy, and the continuous energy dependence of the quantum well density of states is considered. A comparison between this model and previously reported experimental results are made which demonstrates excellent agreement     

Finite-difference time-domain analysis and experimental examinationof the performance of a coupled-cavity MQW laser/active waveguide at1.54 μm

The performance characteristics of a coupled cavity InGaAsP-InP MQW laser/active waveguide made by one-step epitaxy and well-controlled reactive ion etching (RIE) have been theoretically analyzed and experimentally determined. A theoretical model based on a finite-difference time-domain (FDTD) technique was used to simulate the propagation of an optical wave launched in the coupled system and determine the reflectivity of the facets created by RIE. The calculated effective reflectivity of the coupling region consisting of two facets and an air gap is between 0.45 and 0.55, which is in good agreement with the experimentally measured value of 0.5. The reflectivity of a single etched mirror derived from this value is estimated to be 0.3. A 120-μm-long monolithically integrated active waveguide when biased as a modulator and excited by the laser shows a maximum extinction ratio of 8 dB and a modulation bandwidth ⩾14 GHz at a dc bias of -0.5 V with a bias swing of 2 V