Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study shows that a Photofrin-induced photodynamic therapy-resistant variant (RIF-8A) of a radiation-induced fibrosarcoma-1 cell line (RIF-1) is cross-resistant to cis-diamminedichloroplatinum(II) (cisplatin). This is the first study to show cross-resistance to cisplatin in photodynamic therapy-resistant variants in vitro. Resistance does not appear to be the result of elevated glutathione levels since neither the resistant variant (RIF-8A) nor the parental line (RIF-1) varied in total glutathione levels. However, cisplatin-DNA adduct levels differed significantly between the two cell types. Immediately following a 1-h exposure to cisplatin (50 microM), RIF-1 cells contained 44.6 +/- 2.0 (SEM) pg platinum/micrograms DNA while RIF-8A cells contained 24.8 +/- 6.3 pg platinum/micrograms DNA. In addition, the resistant variant had decreased plasma and mitochondrial membrane potentials. The plasma and mitochondrial membranes of the resistant variant accumulated 3- and 3.6-fold less rhodamine 123, respectively. The difference in rhodamine 123 accumulation could not be attributed to elevated P-glycoprotein expression because both the parental line and the variant contained similar amounts of P-glycoprotein. In conclusion, alterations in the plasma and/or mitochondrial membrane potentials may provide cells with a survival advantage when challenged with either photodynamic therapy or cisplatin in vitro. This appears to be a novel mechanism of resistance.
 ...
PMID:Cross-resistance to cisplatin in cells resistant to photofrin-mediated photodynamic therapy. 790 92

Photofrin is a light-activated compound used for photodynamic therapy (PDT) of malignant tumors. Although PDT with this drug has been approved for clinical use in the United States, Canada, Japan, and the Netherlands there are few published reports on the biodistribution of Photofrin in humans. In this study we report measurable amounts of Photofrin in human serum up to approximately 1 year following injection of two different Photofrin doses. Concentration-time data were collected from 3, 12, 19, and 10 patients after 0.75, 0.875, 1, and 2 mg Photofrin/kg body weight. Patients who received 2 mg Photofrin/kg were scheduled to undergo intraoperative PDT for the treatment of mesothelioma or carcinoma of the lung. Patients receiving 0.75, 0.875, or 1 mg Photofrin/kg were treated for basal cell carcinoma; 1 mg Photofrin/kg is now a standard dose for PDT of cutaneous malignancies at this institute. For the 1 mg Photofrin/kg dose, a triexponential 3-compartment pharmacokinetic model was fitted to 30 data points pooled from the 19 patients, as if we had one "superpatient." The alpha, beta, and gamma halflives were approximately 16 h, 7.53 days, and 155.56 days, respectively. The mean (+/- SEM) serum concentrations 48 after injection (when most tumors are exposed to drug-activating light) of 0.875, 1, or 2 mg Photofrin/kg were 2.70 +/- 0.47, 4.00 +/- 0.66, and 3.47 +/- 0.97 micrograms Photofrin/ml, respectively. No porphyrin fluorescence could be detected in serum collected from patients 560 to 1335 days after Photofrin injection.
 ...
PMID:A preliminary pharmacokinetic study of intravenous Photofrin in patients. 961 97

Plasma sodium (Na+) concentration, i.e. natraemia, results from body tonicity equilibrium. During exercise, a change in body tonicity can result from an imbalance between intake and loss of Na+, potassium (K+) and water (H2O) due to renal and/or extra-renal mechanisms. Whether exercise-induced changes in kidney function could be responsible for such an imbalance was studied by measuring glomerular filtration rate (creatinine clearance), proximal tubule activity (lithium clearance) and renal handling of Na+ and K+ at rest and during exercise. Since hyponatraemia during or after exercise has been reported, we also investigated whether a water load could be appropriately excreted during exercise. Ten young men pedalled on a cycle ergometer at 60% of maximal oxygen uptake for 45 min with (HE, hydrated exercise) or without (DHE, dehydrated exercise) a supply of water. In both conditions, creatinine, lithium, and electrolyte (Na+ + K+) clearances decreased and natraemia did not change. The DHE induced a loss of body mass (-1.29%), decreased diuresis and large extra-renal water loss [mean (SEM)] [880 (73) ml]. The HE led to no loss in body mass, increased diuresis and lower extrarenal water loss [680 (48) ml]. Electrolyte-free water excretion, negative for DHE, represented 60% of diuresis during HE. Thus the kidney, by increasing electrolyte reabsorption mainly in the proximal tubule, and appropriately excreting a water load, seems efficacious in regulating extracellular fluid volume and body tonicity and so not responsible for the imbalance between (Na+ + K+)/H2O intake and loss. Therefore, extra-renal changes could be the main causes of exercise-induced tonicity imbalances which could ultimately lead to dysnatraemia.
 ...
PMID:Renal handling of salt and water in humans during exercise with or without hydration. 1199 Jul 26

Effects of oxygen diffusion and reaction kinetics in photodynamic therapy are considered in the context of a multicell tumour spheroid model. Steady-state measurements of oxygen made with a Clark-style microelectrode (4 microm diameter tip) enable us to determine the rate of metabolic oxygen consumption and the oxygen diffusion coefficient in 500 microm diameter EMT6/Ro spheroids. These values are 5.77 micromol 1(-1) s(-1) and 1460 microm2 s(-1), respectively. Time-dependent electrode measurements of oxygen concentration during laser irradiation of individual Photofrin-sensitized spheroids are fitted to numerical solutions of a pair of diffusion-with-reaction equations. The analysis yields the rate of photodynamic oxygen consumption and a parameter that governs the oxygen sensitivity of photodynamic therapy. These experimentally derived quantities are used to calculate the temporal and spatial distributions of oxygen and the rate of oxygen consumption in a spheroid during irradiation at several fluence rates. The spatial distribution of photodynamic oxygen consumption is strongly fluence rate dependent. Using the experimental and theoretical results developed in this report, previously published survival data are analysed. The analysis indicates that the threshold dose of reacting singlet oxygen in the EMT6/Ro spheroid is 323 +/- 38 micromol 1(-1) (mean +/- SEM).
 ...
PMID:Oxygen diffusion and reaction kinetics in the photodynamic therapy of multicell tumour spheroids. 1555 46

Calcium sulfoaluminate (CSA) cement has recently gained increased attention due to its lower amount of CO2 emissions, as compared to that of the ordinary Portland cement (OPC). This paper evaluates the impact of different types of fibers on the engineering features of CSA-based concretes at different water-cement ratios of 0.35 and 0.28. In this study, metallic fibers including double hooked-end steel fibers and hooked-end steel fibers, and non-metallic fibers (i.e., polyvinyl alcohol (PVA) fibers) were utilized at fiber content of 1%. The mechanical properties of concretes were assessed at different curing ages. Dimensional stability of the concrete mixes was also examined. The morphology of the fractured specimens was studied by using the SEM method. The results indicate that the engineering properties of concrete were improved by introducing fibers to the concrete, irrespective of fiber type. The results show that DHE steel fiber has an important effect on the flexural performance of CSA cement-based concretes and results in deflection-hardening behavior. It was observed that fibers and particularly PVA fibers cause a decrease in shrinkage deformation. Microstructure tests demonstrate that prismatic ettringite is the main hydration product of CSA cement-based concrete. The SEM observation also confirms that the inclusion of CSA cement in concrete improves the cohesiveness between the fibers and cement matrix.
 ...
PMID:Evaluation of Engineering Properties of Calcium Sulfoaluminate Cement-based Concretes Reinforced with Different Types of Fibers. 3127 75