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In the range of clinical decision points for response-guided therapy of HCV, there is still insufficient data concerning the conformity of quantification results obtained by different assays and their correlation with the HPS/CTM v2 assay which was used for initial clinical studies. In a head-to-head comparison, assay accuracy and detection rates of six quantitative assays [ artus HCV QS-RGQ, COBAS Ampliprep/COBAS TaqMan HCV v1/v2, High Pure System/COBAS TaqMan (HPS), RealTi me HCV, and Versant HCV1.0] were assessed by measuring WHO and PEI standards at dilution steps near clinical decision points. Detection rates and mean differences between assays were evaluated by analyzing twenty clinical samples at 10, 100, and 1,000 IU/mL. Ten replicates from specimens with different HCV genotypes were used to analyze pan-genotypic intra-assay variation. At ≤25 IU/mL, RealTi me demonstrated the highest detection rates. With 0.1 log difference when testing clinical samples, results obtained from the Versant and RealTi me assays matched best with results from HPS. Mean difference analysis across all assay results revealed wide differences between 0.01 and 0.75 log IU/mL. RealTi me showed the lowest intra-assay variation across genotypes 1-4 (25, 100, 1,000 IU/mL). There are substantial analytical differences between viral load assays clinicians should be aware of. These variations may have impact on clinical decisions for patients on HCV triple therapy and may argue for assay-specific decision points equivalent to reference values established in studies using HPS. A comparison of quantification is recommended prior to a switch of assays during ongoing therapy. [ABSTRACT FROM AUTHOR]

Background: Aim of this study was to assess the direct costs of Parkinson's disease (PD) within a 3-month period (i.e. the accounting period for the German statutory health insurance) in 12 neurological outpatient practices in Berlin during 2006. Material and Methods: A total of 425 patients (age 69.1±9.3 years, 185 females) were recruited, and sociodemographic and clinical data were obtained by a specific questionnaire. The distribution of costs was analyzed based on several clinical and patient parameters. The costs were calculated with different approaches: (1) prospectively, with the practices' accounting according to German uniform scales (GoÄ, EbM) and (2) retrospectively, with questionnaires for the Parkinson's patients. Costs were calculated according to current German guidelines of the statutory health insurance. Clinical parameters were assessed with a questionnaire for physicians. Results: The direct medical costs totaled 1,667 EUR (range 1,436-1,995 EUR, CI 95%) per patient per 3 months. Charges by physicians were 42 EUR (39-45 EUR, CI 95%) for patients with statutory health insurance and 135 EUR (106-177 EUR, CI 95%) for those with private insurance. Disease severity and disease duration correlated with higher direct medical costs. Motor fluctuations and depression also were major factors influencing cost. Conclusion: Our study emphasizes the large economic burden caused mainly by PD medication and hospitalization. For the first time a direct comparison between costs and actual physicians' reimbursement was possible. In combination with further economic studies, this comparison will help to define shortcomings and excesses in PD health care services. [ABSTRACT FROM AUTHOR]

The identification of drug targets for pharmaceutical screening can be greatly accelerated by gene databases and expression studies. The identification of lead-ing compounds from growing libraries is realized by high throughput screening platforms. Subsequently, for optimization and validation of identified leading compounds studies of their functionality have to be carried out, and just these functionality tests are a limiting factor. A rigorous preselection of identified compounds by in vitro cellular screening is necessary prior to using the drug candidates for the further time consuming and expensive stage, e.g. in animal models. Our efforts are focused to the parallel development, adaptation and integration of different microelectronic sensors into miniaturized biochips for a multiparametric, functional on-line analysis of living cells in physiologically environments. Parallel and on-line acquisition of data related to different cellular targets is required for advanced stages of drug screening and for economizing animal tests. [ABSTRACT FROM AUTHOR]

Due to their amphiphilic properties, detergents readily disrupt cellular membranes and cause rapid cytolysis. In this study we demonstrate that treatment of cells with sublytic concentrations of detergents such as Triton X-100, Nonidet P-40, n-octylglucoside and the bile salt sodium deoxycholate induce typical signs of apoptosis including DNA fragmentation and cleavage of poly(ADP-ribose) polymerase molecules. The detergent concentration required for apoptosis was below the critical micellar concentration. Induction of apoptosis was not restricted to human cells but similarly occurred in a variety of other vertebrate cell lines. Unstimulated peripheral blood mononuclear cells were susceptible to apoptosis induction by detergent suggesting that apoptosis in this circumstance is not mediated by CD95. Cell death was not due to influx of calcium from the medium. Apoptosis was blocked and cytolysis prevented by treatment with peptide inhibitors of caspases. These findings suggest a process of apoptosis that is initiated upon nonspecific alterations at the cell membrane level. Physiologic correlates of this process still have to be defined. [ABSTRACT FROM AUTHOR]

Critical parameters to be assessed in cell culture are the number of viable cells and cell viability. Growth, product formation, toxicity effects and the overall success of cell culture can depend largely on these. With interdigitated electrode structures (IDES) adherent cells are cultured directly on a pair of interdigitated electrodes, and the impedance of the system gives insight into the adhesive behaviour of the cells. The signal is influenced by the changes in number, growth and morphological behaviour of adherently growing cells, mainly owing to the insulating effects of the cell membranes. Five different cell lines are used, and their divergent behaviour is monitored over a period of four days, from inoculation of the cells to killing of the cells at the end of the experiments. Even when the cells from close monolayers, great fluctuations in the impedance signal can be observed. Nevertheless, for a more complete description of cellular systems, other parameters, such as acidification and respiration, have to be included in the measuring system. [ABSTRACT FROM AUTHOR]

Within the Constrained Minimal Supersymmetric Standard Model (CMSSM) it is possible to predict the low energy gauge couplings and masses of the 3. generation particles from a few parameters at the GUT scale. In addition the MSSM predicts electroweak symmetry breaking due to large radiative corrections from Yukawa couplings, thus relating the Z boson mass to the top quark mass. From a x analysis, in which these constraints can be considered simultaneously, one can calculate the probability for each point in the MSGUT parameter space. The recently measured top quark mass prefers two solutions for the mixing angle in the Higgs sector: tan β in the range between 1 and 3 or alternatively tan β≈25−50. For both cases we find a unique x minimum in the parameter space. From the corresponding most probable parameters at the GUT scale, the masses of all predicted particles can be calculated at low energies using the RGE, albeit with rather large errors due to the logarithmic nature of the running of the masses and coupling constants. Our fits include full second order corrections for the gauge and Yukawa couplings, low energy threshold effects, contributions of all (s)particles to the Higgs potential and corrections to m from gluinos and higgsinos, which exclude (in our notation) positive values of the mixing parameter μ in the Higgs potential for the large tan β region. Further constraints can be derived from the branching ratio for the radiative (penguin) decay of the b-quark into sγ and the lower limit on the lifetime of the universe, which requires the dark matter density due to the Lightest Super-symmetric Particle (LSP) not to overclose the universe. For the low tan β solution these additional constraints can be fulfilled simultaneously for quite a large region of the parameter space. In contrast, for the high tan β solution the correct value for the b→ sγ rate is obtained only for small values of the gaugino scale and electroweak symmetry breaking is difficult, unless one assumes the minimal SU(5) to be a subgroup of a larger symmetry group, which is broken between the Planck scale and the unification scale. In this case small splittings in the Yukawa couplings are expected at the unification scale and electroweak symmetry breaking is easily obtained, provided the Yukawa coupling for the top quark is slightly above the one for the bottom quark, as expected e.g. if the larger symmetry group would be SO(10). For particles, which are most likely to have masses in the LEP II energy range, the cross sections are given for the various energy scenarios at LEP II. For low tan β the production of the lightest Higgs boson, which is expected to have a mass below 103 GeV, is the most promising channel, while for large tan β the production of charginos and/or neutralinos covers the preferred parameter space. [ABSTRACT FROM AUTHOR]

The Minimal Supersymmetric Standard Model (MSSM) distinguishes itself from other GUT's by a successful prediction of many unrelated phenomena with a minimum number of parameters. Among them: a) Unification of the gauge couplings constants; b) Unification of the b-quark and τ-lepton masses; c) Proton stability; d) Electroweak symmetry breaking at a scale far below the unification scale and the corresponding relation between the gauge boson masses and the top quark mass. A combined fit of the free parameters in the MSSM to these low energy constraints shows that the MSSM model can satisfy these constraints simultaneously. From the fitted parameters the masses of the as yet unobserved superpartners of the SM particles are predicted, the top mass is constrained to a range between 140 and 200 GeV, and the second order QCD coupling constant is required to be between 0.108 and 0.132. The complete second order renormalization group equations for the gauge and Yukawa couplings are used and analytical solutions for the neutral gauge boson, the Higgs masses and the sparticle masses are derived, taking into account the one-loop corrections to the Higgs potential. [ABSTRACT FROM AUTHOR]