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At least 361 records · Page 20Linked to original sources
PubMed1994

Curcumin-derived transients: a pulsed laser and pulse radiolysis study.

In this paper we report a time-resolved investigation of transients derived from curcumin, which may be intimately involved in the processes leading to its biological activity. Fluorescence and triplet quantum yields are respectively 0.06 and 0.11. The high percentage of internal conversion is proposed to proceed via H-transfer within the thermodynamically favored enol structure of what is formally a 1,3-diketone. The triplet energy (191 +/- 2 kJ mol-1), natural lifetime (1.5 microseconds) and self-quenching rate constant (5.0 x 10(8) L mol-1 s-1) have been determined. Oxygen quenching of the triplet leads to the production of singlet oxygen with unit efficiency. Curcumin quenches the latter species very inefficiently (2.5 x 10(5) L mol-1 s-1). The curcumin radical has been produced via three mechanistically distinct methods. This species is unreactive toward oxygen but is repaired by vitamins C and E and anthralin.

Curcumin↗
PubMed1997

On-line synthesis of the human ascending aortic pressure pulse from the finger pulse.

Although systolic pressure in the ascending aorta (AA) can be determined accurately from the radial arterial waveform using a single generalized transfer function (TF) of the upper limb, a better on-line methods is needed for accurate noninvasive synthesis of the AA pressure contour to characterize left ventricular contractile function and ventricular-vascular coupling. AA, tonometric carotid (CA), and photoplethysmographic finger (FA) arterial pressure waveforms were recorded in 12 subjects (10 male, aged 59.1+/-10.3 years, mean+/-SD) during cardiac catheterization. The AA-FA TF was estimated using (1) a single generalized TF (GAA), (2) individualized TFs directly determined from CA-FA recordings in each patient (DAA), and (3) individualized TFs computed from CA-FA recordings in each patient with a mathematical model of the human upper limb (MAA). AA pressure waveforms were synthesized from FA recordings in real time using convolution windows derived from these TFs. Under steady state conditions, the root mean square error (RMSE) between measured and synthesized AA was lower by DAA (3.3+/-1.3 mm Hg) and MAA (3.9+/-1.2 mmHg) than by GAA (4.8+/-2.0 mm Hg, P<.05). During dynamic load alteration induced by the Valsalva maneuver, however, the MAA method performed better (5.4+/-2.8 mm Hg) than both the GAA (5.8+/-3.3 mm Hg, P<.05) and DAA (6.5+/-2.7 mm Hg, P<.01) methods. The beat-to-beat AA contour can be accurately and noninvasively synthesized on-line using individualized TFs. During dynamic load alteration, individualized TFs derived with an upper limb arterial model provide greater accuracy.

Adult↗
PubMed2001

A Phase I trial of pulse calcitriol in patients with refractory malignancies: pulse dosing permits substantial dose escalation.

BACKGROUND: Calcitriol is the principal biologically active metabolite of vitamin D. Calcitriol's activity against many neoplasms is well documented, but calcitriol's therapeutic application has been hampered by predictable hypercalcemia when it is given daily. Because laboratory data has suggested that intermittent exposure to high levels of calcitriol may be sufficient to produce antiproliferative effects, the authors developed a Phase I trial to determine the maximal tolerated dose, dose-limiting toxicity, and the pharmacokinetic profile of calcitriol given weekly by mouth. METHODS: Patients with refractory malignancies were enrolled for 4 weeks of treatment followed by 4 weeks of observation. Reenrollment at a higher dose level was permitted for patients who had evidence of response or stable disease and no Grade 3 or greater toxicity. The starting dose was 0.06 microg/kg. RESULTS: Fifteen patients received 20 cycles of therapy. Doses up to 2.8 microg/kg of calcitriol weekly produced no dose-limiting toxicity. While peak levels and the area under the serum concentration-time curve of calcitriol increased in a linear fashion at lower doses, saturable absorption was observed at doses above 0.48 microg/kg. Doses of 0.48 microg/kg and above produced mean peak calcitriol levels of 1625 pg/mL, approximately 25-fold greater than top normal levels and well within the therapeutic range suggested by in vitro experiments. Eight patients experienced self-limiting Grade 1 hypercalcemia. CONCLUSIONS: Weekly dosing of oral calcitriol permitted substantial dose escalation with minimal toxicity. Peak serum calcitriol levels were in the predicted therapeutic range. A dose of 0.5 microg/kg was selected for evaluation in Phase II studies.

Adult↗