Proliferative and anti-proliferative effects of titanium- and iron-based metallocene anti-cancer drugs

In previous work we have found that Cp2TiCl2 and its corresponding deriv. of tamoxifen, Titanocene tamoxifen, show an unexpected proliferative effect on hormone dependent breast cancer cells MCF-7. In order to check if this behavior is a general trend for titanocene derivs. we have tested two other titanocene derivs., Titanocene Y and Titanocene K, on this cell line. Interestingly, these two titanocene complexes behave in a totally different manner. Titanocene K is highly proliferative on MCF-7 cells even at low concns. (0.5 .mu.M), thus behave almost similarly to Cp2TiCl2. This proliferative effect is also obsd. in the presence of bovine serum albumin (BSA). In contrast, Titanocene Y alone has almost no effect on MCF-7 at a concn. of 10 .mu.M, but exhibits a significant dose dependent cytotoxic effect of up to 50% when incubated with BSA (20-50 .mu.g/mL). This confirms the crucial role played by the binding to serum proteins in the expression of the in vivo, cytotoxicity of the titanocene complexes. From the hydridolithiation reaction of 6-p-anisylfulvene with LiBEt3H followed by transmetallation with iron dichloride [bis-[(p-methoxy-benzyl)cyclopentadienyl]iron(II)] (Ferrocene Y) was synthesized. This complex, which was characterized by single crystal X-ray diffraction, contains the robust ferrocenyl unit instead of Ti assocd. with easily leaving groups such as chlorine and shows only a modest cytotoxicity against MCF-7 or MDA-MB-231 cells.

In situ calibration of atmospheric air conductivity instruments

A new method of measuring the total conductivity of atmospheric air is described. It depends on determination of the electrical relaxation time of a horizontal wire, mounted between two insulators, which is initially grounded and then allowed to charge freely. The total air conductivity derived is compared with that from an ion mobility spectrometer. Results from the two techniques agreed to within 1.2 fS m(-1). (c) 2006 American Institute of Physics.

Intercomparison of aircraft instruments on board the C-130 and Falcon-20 over southern Germany during EXPORT2000

In the summer 2000 EXPORT aircraft campaign (European eXport of Precursors and Ozone by long-Range Transport), two comprehensively instrumented research aircraft measuring a variety of chemical species flew wing tip to wing tip for a period of one and a quarter hours. During this interval a comparison was undertaken of the measurements of nitrogen oxide (NO), odd nitrogen species (NOy), carbon monoxide (CO) and ozone (O3). The comparison was performed at two different flight levels, which provided a 10-fold variation in the concentrations of both NO (10 to 1000 parts per trillion by volume (pptv)) and NOy (200 to over 2500 pptv). Large peaks of NO and NOy observed from the Falcon 20, which were at first thought to be from the exhaust of the C-130, were also detected on the 4 channel NOxy instrument aboard the C-130. These peaks were a good indication that both aircraft were in the same air mass and that the Falcon 20 was not in the exhaust plume of the C-130. Correlations and statistical analysis are presented between the instruments used on the two separate aircraft platforms. These were found to be in good agreement giving a high degree of correlation for the ambient air studied. Any deviations from the correlations are accounted for in the estimated inaccuracies of the instruments. These results help to establish that the instruments aboard the separate aircraft are reliably able to measure the corresponding chemical species in the range of conditions sampled and that data collected by both aircraft can be co-ordinated for purposes of interpretation.

Global estimates of snow water equivalent from passive microwave instruments: history, challenges and future developments

Snow properties have been retrieved from satellite data for many decades. While snow extent is generally felt to be obtained reliably from visible-band data, there is less confidence in the measurements of snow mass or water equivalent derived from passive microwave instruments. This paper briefly reviews historical passive microwave instruments and products, and compares the large-scale patterns from these sources to those of general circulation models and leading reanalysis products. Differences are seen to be large between the datasets, particularly over Siberia. A better understanding of the errors in both the model-based and measurement-based datasets is required to exploit both fully. Techniques to apply to the satellite measurements for improved large-scale snow data are suggested.

High resolution photoacoustic overtone spectroscopy of monofluoroacetylene, HCCF, with a titanium:sapphire ring laser

Intracavity photoacoustic overtone spectrum of monofluoroacetylene, HCCF, has been recorded in the wave number region 10 750–14 500 cm−1 with a titanium:sapphire ring laser. The spectrum contains many dense vibration–rotation band systems which can be resolved with Doppler limited resolution. Altogether 58 individual overtone bands have been analyzed rotationally. Many of the observed bands show perturbations of which some have been attributed to anharmonic resonance interactions. A Fermi resonance model based on conventional rectilinear normal coordinate theory has been used to assign vibrationally bands from this work and from earlier studies. Many of the observed vibrational term values and rotational constants can be reproduced well with this model. The results show the importance of the Fermi resonance interactions at the high overtone excitations.

Topotactic oxidation of TiGaPO-1, a pyridine-templated titanium gallophosphate with a new octahedral-tetrahedral 3-D framework structure containing Ti-III/Ti-IV

The first 3-D open-framework TiGaPO complex, constructed from (TiO6)-O-III, (TiO6)-O-IV, GaO4, and PO4 polyhedra, contains pyridinium cations in a 1-D pore network and can be oxidized in air at 543 K with retention of the original framework structure.

Tin and tin-titanium as catalyst components for reversible hydrogen storage of sodium aluminium hydride

This paper is concerned with the effects of adding tin and/or titanium dopant to sodium aluminium hydride for both dehydrogenation and re-hydrogenation reactions during their reversible storage of molecular hydrogen. Temperature programmed decomposition (TPD) measurements show that the dehydrogenation kinetics of NaAlH4 are significantly enhanced upon doping the material with 2 mol% of tributyltin hydride, Sn(Bu)(3)H but the tin catalyst dopant is shown to be inferior than titanium. On the other hand, in this preliminary work, a significant synergetic catalytic effect is clearly revealed in material co-doped with both titanium and tin catalysts which shows the highest reversible rates of dehydrogenation and re-hydrogenation (after their hydrogen depletion). The re-hydrogenation rates of depleted Sn/Ti/NaAlH4 evaluated at both 9.5 and 140 bars hydrogen are also found to be favourable compared to the Ti/NaAlH4, which clearly suggest the importance of the catalyst choice. Basing on these results some mechanistic insights for the catalytic reversible dehydrogenation and re-hydrogenation processes of Sn/Ti/NaAlH4 are therefore made. (C) 2006 Elsevier Ltd. All rights reserved.

Antitumour activity of [1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride in xenografted Ehrlich's ascites tumour

The effects of a new titanocene compound with an ansa ligand in the cyclopentadienyl rings, the 1,2-di(cyclopentadienyl)-1,2-di(p-NNdimethylaminophenyl)-ethanediyl] titanium dichloride (TITANOCENE X), on the growth and differentiation of granulocyte-macrophage progenitor cells [colony-forming unit-granulocyte-macrophage (CFU-GM)] and Natural killer (NK) cell activity in Ehrlich's ascites tumour (EAT)-bearing mice were studied. Myelosuppression concomitant with increased numbers of spleen CFU-GM was observed in tumour-bearing mice. Treatment of these animals with TITANOCENE X (2.5-50mg/kg/day) produced an increase in myelopoicsis, in a dose-dependent manner, and reduced spleen colony formation. In addition, the treatment of EAT-bearing mice with 3 doses of 20 or 50 mg/kg TITANOCENE X restored to normal values the reduced Natural killer cell function observed during tumour growth. In parallel, TITANOCENE X prolonged, in a dose-dependent manner, the survival of mice inoculated with Ehrlich's ascites tumour. The highest dose of 50 mg/kg prolonged in 50% the survival time of EAT-bearing mice, compared to non-treated tumour-bearing controls. In comparison with previous results from our laboratory addressing the effects of titanocenes on haematopoiesis, we observed with TITANOCENE X a similar effective profile as for bis(cyclopentadienyl) dithiocyanate titanium(IV), being both less effective than di(cyclopentadienyl) dichloro titanium(IV), since the latter not only prolonged, but also increased the rate of survival. These differences in efficacy may be due to the nature of the ansa-cyclopentadienyl ligand used in TITANOCENE X, since the C, bridge between the two cyclopentadienyl groups will increase the hydrolytic stability by an organometallic chelate effect. Also, the introduction of two dimethylamino substituents increases the water solubility of TITANOCENE X when compared to titanocene dichloride itself (c) 2006 Elsevier B.V. All rights reserved.

Health-related quality of life in Huntington's disease: a comparison of two generic instruments, SF-36 and SIP

Whereas several clinical endpoints in monitoring the response to treatment in patients with Huntington's disease (HD) have been explored, there has been a paucity of research in the quality of life in such patients. The aim of this study was to validate the use of two generic health-related quality of life instruments (the Short Form 36 health survey questionnaire [SF-36] and the Sickness Impact Profile [SIP]) and to evaluate their psychometric properties. We found that both instruments demonstrated acceptable convergent validity and reliability for patients and carers. However, there was an advantage in using the SF-36 because of its more robust construct validity and test-retest reliability; furthermore, motor symptoms appeared to influence some strictly nonmotor dimensions of the SIP. On a pragmatic level, the SF-36 is shorter and quicker to administer and, therefore, easier for patients at various stages of the disease to complete. Thus, the SF-36 would appear to be the recommended instrument of choice for patients with HD and their carers, although further work needs to be done to investigate the sensitivity of this instrument longitudinally. (C) 2004 Movement Disorder Society.

A review of instruments developed to measure outcomes for carers of people with mental health problems

Objective: Community-based care for mental disorders places considerable burden on families and carers. Measuring their experiences has become a priority, but there is no consensus on appropriate instruments. We aimed to review instruments carers consider relevant to their needs and assess evidence for their use. Method: A literature search was conducted for outcome measures used with mental health carers. Identified instruments were assessed for their relevance to the outcomes identified by carers and their psychometric properties. Results: Three hundred and ninety two published articles referring to 241 outcome measures were identified, 64 of which were eligible for review (used in three or more studies). Twenty-six instruments had good psychometric properties; they measured (i) carers' well-being, (ii) the experience of caregiving and (iii) carers' needs for professional support. Conclusion: Measures exist which have been used to assess the most salient aspects of carer outcome in mental health. All require further work to establish their psychometric properties fully.

Efficacy of three screening instruments in the identification of autistic-spectrum disorders

Background Screening instruments for autistic-spectrum disorders have not been compared in the same sample. Aims To compare the Social Communication Questionnaire (SCQ), the Social Responsiveness Scale (SRS) and the Children's Communication Checklist (CCC). Method Screen and diagnostic assessments on 119 children between 9 and 13 years of age with special educational needs with and without autistic-spectrum disorders were weighted to estimate screen characteristics for a realistic target population. Results The SCQ performed best (area under receiver operating characteristic curve (AUC)=0.90; sensitivity. 6; specificity 0.78). The SRS had a lower AUC (0.77) with high sensitivity (0.78) and moderate specificity (0.67). The CCC had a high sensitivity but lower specificity (AUC=0.79; sensitivity 0.93; specificity 0.46). The AUC of the SRS and CCC was lower for children with IQ < 70. Behaviour problems reduced specificity for all three instruments. Conclusions The SCQ, SRS and CCC showed strong to moderate ability to identify autistic-spectrum disorder in this at-risk sample of school-age children with special educational needs.