Informal carers' experiences in everyday life and the use of digital assistive technology for time management in persons with dementia or mild cognitive impairment.

BACKGROUND: Digital assistive technology (DAT) may support time management in people with dementia or mild cognitive impairment (MCI), but research on DAT for time management is limited. We aimed to explore how everyday could be supported by DAT for time management in persons with dementia or MCI from informal carers' perspectives. This study focused on a DAT device for time management called MEMOplanner (MMP). METHOD: Using a mixed-methods design, we utilized the Time-Proxy© questionnaire and a study-specific interview guide to investigate the perspectives of informal carers (n = 8) regarding the use of MMP by individuals with dementia or MCI. RESULT: The MMP was helpful in keeping track of time and activity. It helped to maintain an active lifestyle and facilitated communication. However, the MMP did not reduce the need for assistance from the informal carers, and it took time to learn the different functions of the device. Further research into employing a more extensive array of DAT for time management or other areas to assist individuals with dementia will yield valuable insights into enhancing and sustaining a higher quality of life despite cognitive decline.

Caspases uncouple p27(Kip1) from cell cycle regulated degradation and abolish its ability to stimulate cell migration and invasion.

In addition to their role in programmed cell death, caspases exert non-lethal functions in diverse developmental processes including cell differentiation or tissue remodeling. Terminal cell cycle exit and differentiation can be promoted by increased level of the CDK inhibitor p27(Kip1). Activated caspases cause proteolytic processing of p27, and we identified a novel caspase cleavage site in human p27 that removes a C-terminal fragment of 22 amino acids from the CDK inhibitor, including a phosphodegron. Thereby, caspases protect the inhibitor from SCF-Skp2-mediated degradation in S, G2 and M phases of the cell cycle. As a consequence, p27 becomes stabilized and remains an efficient nuclear inhibitor of cell cycle progression. Besides controlling cyclin/CDK kinase activity, p27 also regulates cytoskeletal dynamics, cell motility and cell invasion. Following processing by caspases, p27 fails to bind to RhoA and to inhibit its activation, and thereby abolishes the ability of p27 to stimulate cell migration and invasion. We propose that the stabilization of the CDK inhibitor and elimination of RhoA-induced cytoskeletal remodeling upon caspase processing could contribute to cell cycle exit and cytoskeletal remodeling during non-lethal caspase controlled differentiation processes.

[Development of a claim form for the initiation of post-treatment rehabilitation for nationwide use by all reimbursement agencies: a report and plea for reducing administrative barriers]. / Entwicklung eines bundeseinheitlichen und kostenträger- übergreifenden Antragsformulars für die Einleitung der Anschlussrehabilitation: Projektbericht und Plädoyer zum Abbau administrativer Hürden.

We describe the results of a survey of claim forms that are used when starting rehabilitation following inpatient treatment and of an evaluation of a claim form developed on the basis of the results. The survey of different existing forms shows a high overlapping in content, suggesting the possibility of unification to one claim form that can be accepted by all insurers. In analogy to the Delphi method criteria for evaluation were consented and applied by the author group to assess the relevance of the claim forms content items for the process of initiating rehabilitation. A group of further experts added their evaluations. We prioritised the results and extracted the essential contents to conceive a unified claim form eligible for all types of rehabilitation. The claim form was discussed in 3 focus groups, revised accordingly and tested in the Hannover Medical School. Test results show that all relevant information is asked for and that the form is well manageable. The users' request for an IT-based solution and further ideas for improvement were integrated into the revised and validated version of the claim form. It is now available for all stake holders, in particular for insurers, as a means to improve quality of care and efficiency by standardisation of rehabilitation claim forms.

LRP1b shows restricted expression in human tissues and binds to several extracellular ligands, including fibrinogen and apoE-carrying lipoproteins.

OBJECTIVE: To investigate low-density lipoprotein receptor-related protein 1b (LRP1b) expression in human tissues and to identify circulating ligands of LRP1b. METHODS AND RESULTS: Using two independent RT-PCR assays, LRP1b mRNA was detected in human brain, thyroid gland, skeletal muscle, and to a lesser amount in testis but absent in other tissues, including heart, kidney, liver, lung, and placenta. Circulating ligands were purified from human plasma by affinity chromatography using FLAG-tagged recombinant LRP1b ectodomains and identified by mass spectrometry. Using this technique, several potential ligands (fibrinogen, clusterin, vitronectin, histidine rich glycoprotein, serum amyloid P-component, and immunoglobulins) were identified. Direct binding of LRP1b ectodomains to fibrinogen was verified by co-immunoprecipitation. ApoE-carrying lipoproteins were shown to bind to LRP1b ectodomains in a lipoprotein binding assay. Furthermore, binding as well as internalization of very low density lipoproteins by cells expressing an LRP1b minireceptor was demonstrated. DISCUSSION: LRP1b expression in humans appears to be confined to few tissues, which could point out to specialized functions of LRP1b in certain organs. Most of the newly identified LRP1b ligands are well-known factors in blood coagulation and lipoprotein metabolism, suggesting a possible role of LRP1b in atherosclerosis.

Influence of moderate cycling on scrotal temperature.

Testicular temperature highly correlates with scrotal temperature. It has been postulated that cycling is associated with increased scrotal temperatures with time and consecutively with impaired semen quality. The aim of this study was to evaluate the influence of moderate cycling on scrotal temperature during highly standardized conditions in an experimental lab. A total of 25 volunteers without a history of infertility and normal andrological examination were included for scrotal temperature evaluation. Scrotal temperatures were measured every minute with a portable data recorder connected with two thermistor temperature sensors, which were attached on either side of the scrotum. A further thermistor sensor was attached on the central surface of the bicycle saddle. Ambient temperature in the study room was adjusted to 22 degrees C throughout the whole experiment. All volunteers started the experiment at the same daytime. Clothing of the volunteers consisted of standardized cotton wool trousers and shirts fitting to body size. After acclimatization to the study room in a sitting posture, each volunteer cycled on an exercise cycle for 60 min with a power of 25 Watt representing a speed of 25.45 km/h respectively. The saddle surface temperature reached in the median 35.59 degrees C after 60 min cycling. Median values of scrotal temperatures increased from 35.75 degrees C at the beginning to 35.82 degrees C after 60 min for the left side and from 35.50 to 35.59 degrees C for the right side. No correlation between cycling duration and scrotal temperatures could be found using multivariate anova for repeated measurements. However, scrotal temperatures during cycling were significantly lower (p < 0.001) compared with the last 10 min in sitting posture before starting cycling with a difference of 1.31 degrees C for the left and 1.46 degrees C for the right side. The present study suggests that moderate cycling under standardized conditions with a power of 25 Watt is not a major genital heat stress factor.

Irreversible pan-ErbB tyrosine kinase inhibitor CI-1033 induces caspase-independent apoptosis in colorectal cancer DiFi cell line.

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of colorectal carcinomas and represents a target for therapeutic interventions with signal transduction inhibitors. We investigated the ability of CI-1033 to induce apoptosis and inhibition of proliferation in the colorectal cancer cell lines DiFi and Caco-2, which both express high levels of EGFR. While in Caco-2 cells CI-1033 treatment at a concentration 0.1 microM for 72 hours demonstrated only antiproliferative (53.7 +/- 4.3%) but no pro-apoptotic effects, treatment of DiFi cells resulted in a reduced proliferation rate (31.4 +/- 3.1%) and in apoptosis (44.2 +/- 8.9%). In order to define proteins involved in the regulation of apoptosis, we aimed to determine differences in the proteome profile of both cell lines before and after treatment with CI-1033. Cellular proteins were analyzed by 2-D gel electrophoresis followed by computational image analysis and mass spectrometry. Our data show that DiFi cells differ from Caco-2 cells in nine significantly upregulated proteins, and their potential role in apoptosis is described. We demonstrate that induction of apoptosis was triggered via caspase-independent pathways. Overexpression of leukocyte elastase inhibitor (LEI) and translocation of cathepsin D to the cytosol accompanied by upregulation of other defined proteins resulted in Bax-independent AIF translocation from mitochondria into the nucleus and apoptosis. Definition of these proteins can pave the way for functional studies and contribute to a better understanding of the effects of CI-1033 and the pathways of caspase-independent cell death.

[Investigation of color vision using a web-based color vision test]. / Untersuchungen des Farbsinns mittels eines web-basierten Farbsehtests.

BACKGROUND: Screening tests of visual functions using the Internet are theoretically possible. To use these tests as a screening test, they must deliver comparable results with conventional test procedures. A web-based color vision test was developed based on pseudoisochromatic color plates. METHOD: The web-based color vision test was developed according to the pseudoisochromatic color plates by Velhagen and Broschmann using the programming-languages HTML, Java, and Perl. Sixty-five voluntary subjects, including nine color-deficient subjects, were examined by luminescence color plates (via web-based color vision test) and pigment color plates (via book). The statistical analysis was performed by determining the correspondence and the 95%-confidence interval. RESULTS: The correspondence of the test results for all subjects was 0.98 and the 95%-confidence interval was within 0.91 and 0.99. The correspondence of the test results in the group of color-deficient subjects was 1.0 and because of the limited number the 95%-confidence interval was within 0.71 and 1.0. CONCLUSIONS: The web-based color vision test with luminescence color plates for color-efficient and color-deficient subjects delivers test results comparable to pigment color plates under standardized examination conditions. Further studies are needed to examine if the web-based color vision test can also be used as an Internet screening test.

Visual function tests on the Internet--sense or nonsense?

BACKGROUND: The quantitative capability of the visual system can be tested using graphic presentations with defined size, form and color. For presentations, a chart projector or monitor can be used. Today, the number of visual function tests on the Internet is increasing constantly. Options and limitations of visual function tests using the METHODS: Internet and the authors' own test results are described. RESULTS: Several visual function tests, such as visual acuity tests, the Amsler-Grid, stereo and color vision tests, can already be given via Internet. The variability of the tests ranges from the simple presentation of graphic elements to the laboriously programmed interactive input by the user to specify the test result. Under standardized examination conditions, there was a very high correspondence between the results of the authors' own web-based color vision test and those of luminescence color test plates and conventional pigment color plates. CONCLUSIONS: However, the interpretation of the test results is difficult due to the absence of controls during the test as well as the heterogeneity of the hardware. In order to obtain comparable test results, differences in size and resolution as well as in brightness, contrast and color of computer monitors must be taken into consideration. Due to the deficits described in the tests, the value of visual function tests on the Internet is rather limited. Currently, the data of test distributers with respect to the test conditions are all still insufficient. Standards need to be defined for Internet-based visual function tests. However, visual function tests on the Internet can achieve test results comparable to those of conventional visual function tests under standardized examination conditions in clinical practice. Further studies are needed to check the accuracy of web-based screening examinations in ophthalmology.

[Influence of long term occupational exposure to solvents on colour vision]. / Einfluss langjähriger beruflicher Lösemittelexposition auf das Farbensehen.

BACKGROUND: The study was designed to determine the influence of chronic occupational exposition of organic solvent mixtures on colour vision of car painters. SUBJECTS AND METHODS: The 123 subjects (2 groups differing in organic solvents exposure and 1 control group) were examined using Ishihara-Panel, Lanthony Desaturated Panel D-15, Velhagen-Panel, and Tritan-Album. RESULTS: In the Velhagen-Panel 3% of the probands currently exposed to organic solvents, and 11% of formerly exposed probands developed a blue/yellow vision defect for the right eye. All control subjects perfectly finished this panel. In the Tritan-Album 3% of currently exposed subjects and 26% of formerly exposed painters expressed a blue/yellow vision defect for the right eye, but also 7% of controls showed anomalies. Similar results were found for both panels with the left eye. The CCI difference in the D-15 test was significant between all three groups. CONCLUSION: The impaired colour vision may also be an important indicator of neuro-ophthalmological effects after long-term occupational exposure to organic solvents.

[Options and limits of visual function tests available on the internet]. / Möglichkeiten und Grenzen der Testung visueller Funktionen mittels Internet Eine Analyse von Sehtests im Internet.

BACKGROUND: The quantitative capability of the visual system can be tested using graphic presentations with defined size, form and colour. For presentations a chart projector or personal computer (PC) can be used. In the meantime the number of visual function tests on the internet is continually increasing. These tests are potentially available for over 400 million internet users with different hard- and software requirements. METHODS: From 38 on-line visual acuity tests and 19 on-line colour vision tests found by means of search engines on german language web pages, the offerer of the test, the type of chart used and the data for the test conditions, as well as hard- and software adjustment were registered. RESULTS. Various visual function tests, such as visual acuity tests, the Amsler grid, stereo and colour vision tests, can already be planned via internet. The variability of the tests ranges from a simple presentation of graphic elements to a laboriously programmed interactive input by the user to specify the test result. Most of the tests are presented by opticians and the optical industry. DISCUSSION: The analysed tests allow for a considerable variability of the test conditions, for example by missing data concerning the room lighting and lacking monitor calibration. Furthermore, problems of the web-based colour presentation were not considered or not considered sufficiently in most of the on-line colour tests. CONCLUSIONS: Because of the test deficits determined, the results of visual function tests on the internet are to be classified as doubtful. At present, most data of test offerers are not sufficient with respect to the test conditions. Standards should be defined for internet-based visual function tests and further studies should be followed to check the effectiveness of these tests for screening examinations.

Polymer erosion in PLGA microparticles produced by phase separation method.

This article deals with polymer erosion in biodegradable microparticles produced using the phase separation method. Poly(lactic-co-glycolic acid) copolymers with different compositions and molecular weights were employed. The microparticles were stored in phosphate buffer for 6 months. The molecular weight of the polymers was determined by size exclusion chromatography, and the weight loss was monitored gravimetrically. No weight loss was measured in the first weeks, although the molecular weight decreased significantly already from the start. After a certain storage period which was found to be specific for the type of polymer, the weight of the microparticles decreased rapidly. The start of this weight loss occurred when the molecular weight of the polymer in the degrading microparticles reached a threshold of approximately 15,000. This critical molecular weight was found to be identical for all investigated polymers, i.e. it was independent of the initial molecular weight of the polymer and of the lactic-glycolic ratio.

Hyperphosphorylation of histone H2A.X and dephosphorylation of histone H1 subtypes in the course of apoptosis.

Chromatin condensation paralleled by DNA fragmentation is one of the most important nuclear events occurring during apoptosis. Histone modifications, and in particular phosphorylation, have been suggested to affect chromatin function and structure during both cell cycle and cell death. We report here that phosphate incorporation into all H1 subtypes decreased rapidly after induction of apoptosis, evidently causing a strong reduction in phosphorylated forms of main H1 histone subtypes. H1 dephosphorylation is accompanied by chromatin condensation preceding the onset of typical chromatin oligonucleosomal fragmentation, whereas H2A.X hyperphosphorylation is strongly correlated to apoptotic chromatin fragmentation. Using various kinase inhibitors we were able to exclude some of the possible kinases which can be involved directly or indirectly in phosphorylation of histone H2A.X. Neither DNA-dependent protein kinase, protein kinase A, protein kinase G, nor the kinases driven by the mitogen-activated protein kinase (MAP) pathway appear to be responsible for H2A.X phosphorylation. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA), however, markedly reduced the induction of apoptosis in TNFalpha-treated cells with a simultaneous change in the phosphorylation pattern of histone H2A.X. Hyperphosphorylation of H2A.X in apoptotic cells depends indirectly on activation of caspases and nuclear scaffold proteases as shown in zVAD-(OMe)-fmk- or zAPF-cmk-treated cells, whereas the dephosphorylation of H1 subtypes seems to be influenced solely by caspase inhibitors. Together, these results illustrate that H1 dephosphorylation and H2A.X hyperphosphorylation are necessary steps on the apoptotic pathway.

Age-dependent deamidation of asparagine residues in proteins.

Nonenzymatic deamidation of peptides and proteins represents an important degradation reaction occurring in vitro in the course of isolation or storage and in vivo during development and/or aging of cells. This review first presents a synopsis of the influence of structure on deamidation reaction proceeding via a five-membered succinimide intermediate, followed by an outline of procedures for separation and detection of deamidated forms. Selected examples for in vitro and in vivo deamidation are reviewed including the possible biological consequences of this protein degradation. Finally, the reaction of protein methyltransferase with L-isoaspartyl- and D-aspartyl residues and its possible role in protein repair is elucidated.

Bladder cancer cells acquire competent mechanisms to escape Fas-mediated apoptosis and immune surveillance in the course of malignant transformation.

Mechanisms of resistance against Fas-mediated cell killing have been reported in different malignancies. However, the biological response of immune escape mechanisms might depend on malignant transformation of cancer cells. In this study we investigated different mechanisms of immune escape in 2 well-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high-grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas-ligand, is expressed and shedded by human transitional bladder carcinoma cell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays demonstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agonistic apoptosis-inducing monoclonal antibody against Fas. In poorly differentiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT112 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malignant transformation. In co-culture experiments we show that poorly differentiated cells can induce apoptosis and cell death in Jurkat cells and activated peripheral blood mononuclear cells. This in vitro study suggests that bladder cancer cells can take advantage of different mechanisms of immune evasion and become more competent in avoiding immune surveillance during transformation to higher-grade malignant disease.

Room temperature activates human blood platelets.

Temperatures ranging from room temperature (20 degrees C) to 42 degrees C are generally not considered to have an activating effect on platelets. However, this assumption is not supported by clinical phenomena that result in hemostatic failure related to hypothermia. In this study, we investigated the effect of temperatures between room temperature (20 degrees C) and 42 degrees C on human blood platelets and found that room temperature causes marked activation of platelets. Major changes in platelet morphology were seen at 20 degrees C compared to resting platelets at 37 degrees C. Platelet morphology was investigated with noninvasive live cell techniques (light microscopy and dynamic and static light scattering), as well as with transmission and scanning electron microscopy. The changes in platelet morphology correlated with the expression of the activation marker, activated glycoprotein (GP) IIb-IIIa, measured by flow cytometry. Twenty-five percent to 30% of platelets expressed activated GPIIb-IIIa after exposure to 20 degrees C for 10 minutes. In the presence of serotonin re-uptake inhibitors, the serotonin content of platelets at 20 degrees C was twice that of resting platelets. In comparison, moderate heat shock conditions (42 degrees C for 10 minutes) caused no signs of platelet activation as indicated by the absence of morphological alterations, no expression of activated GPIIb-IIIa, and no changes in serotonin content. These results show that room temperature by itself significantly activates platelets and has an effect on the platelet serotonin content. This may contribute to both the functional lesion associated with 22 degrees C storage of platelets for transfusion and the in vivo hemostatic failure after hypothermia.

[Illumination conditions of visually impaired people under private domestic circumstances - clinical study on 91 patients]. / Die Beleuchtung des Leseplatzes im privaten Wohnbereich Sehbehinderter - Eine klinische Studie an 91 Sehbehinderten.

BACKGROUND: The illuminance and quality of illumination are important factors for visually impaired people to improve contrast sensitivity and reduce glare sensitivity at domestic reading places. The ability of visually impaired people to read can often be improved by simple strategies. At the onset of multiple ophthalmic diseases an optimum of lighting is often the tool of choice to restore reading capability. PATIENTS AND METHODS: 91 visually impaired people were included in this study. 76 were equipped with optical reading tools and 15 used a television reading aid. The illumination conditions of reading places were investigated. This included measurements of illuminance and information about the light source and localization, direction of light and modelling. The understanding of the importance of optimal illumination was judged by a graded scale from 1 - 5. RESULTS: Twenty-two of the 76 visually impaired people equipped with optimal reading tools were using an extra reading place. All others used livingroom or kitchen tables as their preferred reading place. 10 % of the reading places had a illuminance of above 5000 lx, whereas 63 % had less than 500 lx. Incandescent lamps dominated as artificial light sources. In 60 % of all reading places ceiling light sources were predominant. Only 40 % of the patients used an additional reading place illumination. For television reading aids the ceiling light caused a decrease of contrast sensitivity in 1 % - 7 %. If questioned, 90 % of the patients were highly sensitive to problems of good illumination of their reading places. This is, as our study revealed, in contrast to the conditions under which most of the visually impaired people read. CONCLUSIONS: Domestic reading places revealed considerable deficits concerning the illumination. Most visually impaired people do not realize this problem. Ophthalmologists, opticians, low-vision-, orientation- and mobility-trainers are recommended for rehabilitation.

Structure and lipophilicity profile of 2,3-anhydro-alpha-cyclomannin and its ethanol inclusion complex.

Readily available from alpha-cyclodextrin in three steps, 2,3-anhydro-alpha-cyclomannin composed of six alpha-(1-->4)-linked 2,3-anhydro-D-mannopyranose residues, crystallizes well when precipitated from aqueous ethanol. An X-ray structure reveals the macrocycle to contain ethanol in its cavity, thus representing the first inclusion complex of a non-glucose cyclooligosaccharide. The wider rim of the torus-shaped macrocycle holds the six epoxide rings whose oxygens point away from the cavity, thereby sculpturing the unique over-all shape of a six-pointed star.

Reverse signaling through transmembrane TNF confers resistance to lipopolysaccharide in human monocytes and macrophages.

We have previously reported that the CD14+ monocytic subpopulation of human PBMC induces programmed cell death (apoptosis) in cocultured endothelial cells (EC) when stimulated by bacterial endotoxin (LPS). Apoptosis is mediated by two routes, first via transmembrane TNF-alpha (mTNF) expressed on PBMC and, in addition, by TNF-independent soluble factors that trigger apoptosis in EC. Neutralizing anti-TNF mAb completely blocked coculture-mediated apoptosis, despite the fact that there should have been additional soluble cell death factors. This led to the hypothesis that a reverse signal is transmitted from the TNF receptor on EC to monocytes (MO) via mTNF that prevents the production of soluble apoptotic factors. Here we have tested this hypothesis. The results support the idea of a bidirectional cross-talk between MO and EC. Peripheral blood MO, MO-derived macrophages (MPhi), or the monocytic cell line Mono Mac 6 were preincubated with human microvascular EC that constitutively express TNF receptor type I (TNF-R1) and subsequently stimulated with LPS. Cell-free supernatants of these preparations no longer induced EC apoptosis. The preincubation of MO/MPhi with TNF-reactive agents, such as mAb and soluble receptors, also blocked the production of death factors, providing further evidence for reverse signaling via mTNF. Finally, we show that reverse signaling through mTNF mediated LPS resistance in MO/MPhi as indicated by the down-regulation of LPS-induced soluble TNF and IL-6 as well as IL-1 and IL-10.

Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells.

alpha-Tocopheryl succinate (alpha-TS) is a potent inhibitor of tumor cell proliferation. The goal of the present study was to investigate whether and to what extent alpha-TS associates with plasma lipoproteins and if alpha-TS-enriched lipoproteins inhibit breast cancer cell growth in a manner comparable to the free drug. In vitro enrichment of human plasma revealed that alpha-TS readily associated with the main lipoprotein classes, findings confirmed in vivo in mice. At the highest alpha-TS concentrations, lipoproteins carrying 50000 (VLDL), 5000 (LDL) and 700 (HDL) alpha-TS molecules per lipoprotein particle were generated. alpha-TS enrichment generated lipoprotein particles with slightly decreased density and increased particle radius. To study whether the level of LDL-receptor (LDL-R) expression affects alpha-TS uptake from apoB/E containing lipoprotein particles human breast cancer cells with low (MCF-7) and normal (HBL-100) LDL-R expression were used. The uptake of free, VLDL- and (apoE-free) HDL(3)-associated alpha-TS was nearly identical for both cell lines. In contrast, uptake of LDL-associated alpha-TS by HBL-100 cells (normal LDL-R expression) was about twice as high as compared to MCF-7 cells (low LDL-R expression). VLDL and LDL-associated alpha-TS inhibited proliferation most effectively at the highest concentration of alpha-TS used (100% inhibition of MCF-7 growth with 20 microg/ml of lipoprotein-associated alpha-TS). However, also alpha-TS-free VLDL and LDL inhibited HBL-100 cell proliferation up to 55%. In both cell lines, alpha-TS-enriched HDL(3) inhibited cell growth by 40-60%. Incubation of both cell lines in the presence of free or lipoprotein-associated alpha-TS resulted in DNA fragmentation indicative of apoptosis. Collectively, the present findings demonstrate that: (1) alpha-TS readily associates with lipoproteins in vitro and in vivo; (2) the lipoprotein-enrichment efficacy was dependent on the particle size and/or the triglyceride content of the lipoprotein; (3) uptake of LDL-associated alpha-TS was apparently dependent on the level of LDL-R expression; and (4) lipoproteins were efficient alpha-TS carriers inducing reduced cell proliferation rates and apoptosis in human breast cancer cells as observed for the free drug.

Topography of the 1:1 alpha-cyclodextrin-nitromethane inclusion complex.

Dissolution of alpha-cyclodextrin (alpha-CD) in 9:1 water-nitromethane smoothly generates the title compound, which crystallizes as the pentahydrate in the orthorhombic space group P2(1)2(1)2(1) with a = 9.452(4), b = 14.299(3), c = 37.380(10) A, and Z = 4. Its crystal structure analysis revealed the alpha-CD macrocycle in an unstrained conformation stabilized through a ring of O-2...O-3' hydrogen bonds between five of the six adjacent glucose residues. The nitromethane is located in the alpha-CD cavity in an orientation parallel to the plane of the macrocycle, and assumes two sites of equal population with the nitro group in excessive thermal motion; the guest is held by van der Waals contacts and C-H...O-type hydrogen bonds to the pyranose H-3 and H-5 protons. The packing of the macrocycles in the crystal lattice is of cage herringbone-type with an extensive intra- and intermolecular hydrogen bonding network. The ready formation of a nitromethane inclusion complex in aqueous nitromethane, and the subtleties of its molecular structure amply demonstrate the ease with which water is expelled from the alpha-CD cavity by a more hydrophobic co-solvent.