Changes in doxorubicin distribution and toxicity in mice pretreated with the cyclosporin analogue SDZ PSC 833

SDZ PSC 833 (PSC 833) is a cyclosporin A analogue that is under clinical investigation in combination with doxorubicin (Dx) or other anticancer agents as a type-1 multidrug resistance (MDR-1)-reversing agent. The present study was focused on the effects of PSC 833 on the distribution and toxicity of Dx in non-tumor-bearing CDF1 male mice. Mice were given PSC 833 i.p. at 30 min before i.v. Dx treatment. Dx levels were determined by a high-performance liquid chromatography (HPLC) assay at different times during a 72-h period following Dx treatment in the serum, heart, intestine, liver, kidney, and adrenals of mice. In all tissues, Dx area under the concentration-time curve (AUC) values were much greater in mice receiving 10 mg/kg Dx in combination with 12.5 or 25 mg/kg PSC 833 than in mice receiving Dx alone. The highest increase in Dx concentrations was found in the intestine, liver, kidney, and adrenals. Lower, albeit significant, differences were found in the heart. PSC 833 did not appear to influence either urinary or fecal Dx elimination or Dx metabolism to a great extent. Doses of PSC 833 devoid of any toxicity potentiated the acute and delayed toxicity of Dx dramatically. The mechanism responsible for this enhanced toxicity has not yet been elucidated but is likely to be related to an increased tissue retention of Dx due to inhibition of the P-glycoprotein (Pgp) pump by PSC 833, as has recently been proposed for cyclosporin A.     

Twenty-five years of subway construction in Mexico City

Construction of Mexico City's subway system began in 1968. At that time, the nature of the Mexico City subsoil, as well as aggressive regional settlements and seismicity conditions, posed serious challenges to the project. Despite the obstacles, to date more than 150 km of subway line have been constructed. The first lines were constructed using the underground, open caisson method; later lines were built overhead, in tunnel (successfully using the NATM), and on the surface. In some cases, excavations down to more than 15 m depth were executed close to buildings of significant historical and architectural value. To accomplish this, accurate construction procedures were used to cross the existing lines without discontinuing their operation at any time. This paper summarizes these experiences and offers some reflections on the future of underground excavations in Mexico's capital city for uses such as parking lots and commercial passageways.     

Fatal rhino-orbital-cerebral zygomycosis

Rhinocerebral zygomycosis is usually an aggressive, fulminant and, at times, fatal disease most often affecting poorly controlled diabetics of all ages. We report the case of a 13-month-old white boy, a previously undiagnosed diabetic. He came to our hospital with recurrent epistaxis, decreasing consciousness, and a small visible infection at the inner canthus of the left eye. Initial evaluation revealed that the patient was in diabetic ketoacidosis. Despite aggressive medical and surgical treatment, his condition deteriorated rapidly, including the development of diabetes insipidus, and he died 4 days after admission. At autopsy, he was found to have fungal cerebritis (Rhizopus) with multiple areas of infarction and massive cerebral edema.     

Polymere und Copolymere mit reaktionsfähigen Gruppen. Copolymerisation von Glycidyl-β-methylitaconat und Styrol

In part I of this series the results of sedimentation velocity experiments with the polyelectrolyte Polyvinylpyrrolidone-Blancophor are described. The combination of the Svedberg formula and an equation of Tiselius describing the charge- and salt-effects gives the possibility to describe the change of the frictional coefficient as a function of charge and screening quantitatively. The resulting frictional coefficients resp. the dimensions of the coil of this polyelectrolyte change in a wide range with the charge density and the counterion concentration.     

The adsorption of trifluoromethanesulfonate anions at the mercury/electrolyte interface

Recently, there has been much interest in the use of trifluoromethanesulfonic acid as an electrolyte in advanced fuel cell systems because of the enhanced rate of oxygen reduction in this medium. In order to elucidate this characteristic from a double layter point of view, the present work was undertaken to study the adsorption of trifluoromethanesulfonate ions on mercury electrodes. Differential capacities and potentials of zero charge were measured in constant ionic strength solutions of composition X M CF₃SO₃ K + (1-X) M KF at 25°C. Analysis of the results shows that the extent of specific adsorption of CF₃SO₃^? anions is small, and the anions even desorb from the surface at sufficiently positive electrode charges. The structure of the inner layer is elucidated, and an isotherm for the adsorption of CF₃SO₃^? based on electrostatic models of the double layer is derived. The results indicate that at the potentials for the electroreduction of oxygen CF₃SO₃^? anions will not interfere with the adsorption of the reactant and of intermediates, allowing faster rates to be achieved.     

Reliability of electrochemical methods applied to the study of Alumina coated stainless steel prosthesis

The corrosion resistance of alumina-covered stainless steel prosthesis is discussed in this report. The test material was an AISI 316L steel with a plasma sprayed on alumina coating, applied directly or through an intermediate nickel base layer, whose mission is to guarantee a perfect adherence between the ceramic material and the steel. Use was made in the laboratory of Hank's solution as test medium since this solution is similar to organic fluids. In order to increase the reliability of the results the simultaneous use of various of the following electrochemical methods are recommended: Determination of corrosion potential with the time, polarization resistance method, coulostatic method and a.c. methods. The use of electrochemical methods to study ceramic-covered stainless steel in the passive state poses some specific difficulties accruing from the disturbance of the working electrode by the applied electrical signals which limit the accuracy of the corrosion rate measurements. These difficulties do not appear in the case of a material having a intermediate layer which is more active.     

A Technique for Determining Solar Irradiance Deficits

A novel analytic technique, involving the use of computer-assisted data-reduction techniques, has been developed to determine the variation of solar irradiance from long-term averages. The objective of the study was to develop a tool that would enable solar system designers to assess and improve overall system reliability by determining the amount of backup and/or storage capability required to supplement a baseline system sized according to long-term averages. The technique allows the determination of variations for intervals of time up to 60 days. This paper presents results of the analysis of 13 sites in the continental USA. Cost-effective accommodation of solar irradiance deficits includes both increasing the collector area by about 15% to cover long-term year-to-year variations from the average, and adding energy storage or backup to cover short-term deficits such as those caused by local storms. Site-to-site dependency exists, causing a range of required short-term storage capacities of 1 to 7 no-sun days to accommodate the weather-caused deficits for this broad variety of sites.     

Effects of salinity on synthesis of DNA, acidic polysaccharide, and growth in the blue-green alga, Gomphosphaeria aponina

A blue-green alga, Gomphosphaeria aponina, was grown in artificial sea water at salinities 20–36%. Fair to good growth was obtained at all salinities, and growth constants (K_e) were obtained. A parabolic relationship was obtained for the growth salinity relationship, e.g. (S−S_max)² = −2p(K_e−K′_e), where S and S_max is the given salinity and the maximum salinity, respectively, for which growth constants K_e and K_e^′ were obtained; p is a constant. The rate of DNA synthesis increased linearly with growth constant above K_e = 0.95 day⁻¹. Linear correlation coefficients were obtained for rate of polysaccharide synthesis and the rate of DNA synthesis, as well as for the rate of DNA synthesis and the rate of synthesis of aponin. The latter is material isolated from G. aponina and has cytolytic activity toward the Florida red tide organism, Gymnodinium breve, an unarmoured dinoflagellate.     

Endogenous acetylcholine in the dorsal hippocampus reduces anxiety through actions on nicotinic and muscarinic? receptors.

Dorsal hippocampal cholinergic modulation of behavior in different tests of anxiety was investigated by direct injection of the muscarinic M? and M? receptor antagonists, pirenzepine and gallamine, and the nicotinic receptor antagonist mecamylamine. In the social interaction test, the anxiogenic effect of pirenzepine (30–100 ng) provided evidence for a tonic cholinergic anxiolytic action mediated by postsynaptic M? receptors. The anxiogenic action of mecamylamine (30 and 100 ng) was most likely mediated by its action of presynaptic nicotinic receptors to reduce acetylcholine release. Gallamine (10–1,000 ng) was without effect, suggesting that M? receptors in this brain region do not play a significant role in this behavioral test. On Trial 1 in the elevated plus-maze, the receptor antagonists were without any effect, but in those with a previous 5-min experience of the plus-maze pirenzepine and mecamylamine had anxiogenic effects in the dose range of 30–300 ng; gallamine (100 and 300 ng) was without significant effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mutations in new cell cycle genes that fail to complement a multiply mutant third chromosome of Drosophila

We have simultaneously screened for new alleles and second site mutations that fail to complement five cell cycle mutations of Drosphila carried on a single third chromosome (gnu, polo, mgr, asp, stg). Females that are either transheterozygous for scott of the antartic (scant) and polo, or homozygous for scant produce embryos that show mitotic defects. A maternal effect upon embryonic mitoses is also seen in embryos derived from females transheterozygous with helter skelter (hsk) and either mgr or asp. cleopatra (cleo), fails to complement asp but is not uncovered by a deficiency for asp. The mitotic phenotype of larvae heterozygous for cleo and the multiple mutant chromosome is similar to weak alleles of asp, but there are no defects in male meiosis. Mutations that failed to complement stg fell into two complementation groups corresponding to stg and a new gene noose. Three of the new stg alleles are early zygotic lethals, whereas the fourth is a pharate adult lethal allele that affects both mitosis and meiosis. Mutations in noose fully complement a small deficiency that removes stg, but when placed in trans to certain stg alleles, result in late lethality and mitotic abnormalities in larval brains.