Biomedical subjects

Ansgar Resch

Publications and source records attributed to Ansgar Resch.

6 recordsLinked to original sources

PubMed2006

The economic costs of overactive bladder in Germany.

OBJECTIVE: To estimate the annual direct costs of overactive bladder (OAB) in Germany from a societal perspective. METHODS: Direct costs were calculated based on prevalence figures and medical resource utilisation due to hospitalisation, office-based physician visits, visits to other health care professionals, medication, medical aids and devices, and nursing care. RESULTS: A total of 6.48 million adults>or=40 yr of age in Germany are affected by OAB, and 2.18 million of these individuals experience incontinence. The annual incidence of comorbidities attributable to OAB is 310,000 for skin infections, 40,000 for falls, 12,000 for fractures, and 26,000 for depression (based on 2004 census data). Direct OAB-related costs per year are euro3.98 billion, with euro1.76 billion covered by statutory health insurance, euro1.80 billion by nursing care insurance, and euro0.41 billion by the patients. Nursing care accounts for euro1.80 billion of total costs (45%), devices account for euro0.68 billion (17%), physician visits account for euro0.65 billion (16%), complications account for euro0.75 billion (19%), and medication accounts for euro0.08 billion (2%). CONCLUSION: OAB imposes a substantial economic burden on German health and nursing care, insurance, and on patients with OAB. Direct annual costs are comparable to those of other chronic diseases such as dementia or diabetes mellitus.

Comorbidity↗

PubMed2006

Oncostatin M induces growth arrest by inhibition of Skp2, Cks1, and cyclin A expression and induced p21 expression.

Oncostatin M has been characterized as a potent growth inhibitor for various tumor cells. Oncostatin M-treated glioblastoma cells cease proliferation and instigate astrocytal differentiation. The oncostatin M-induced cell cycle arrest in G(1) phase is characterized by increased level of the cyclin-dependent kinase (CDK) inhibitory proteins p21(Cip1/Waf1/Sdi1) and p27(Kip1). Induction of p21 protein corresponds to increased mRNA level, whereas p27 accumulates due to increased stability of the protein. Interestingly, stabilization of p27(Kip1) occurs even in S phase, showing that p27 stabilization is a direct consequence of oncostatin M signaling and not a result of the cell cycle arrest. Degradation of p27 in late G(1) and S phase is initiated by the ubiquitin ligase complex SCF-Skp2/Cks1. Oncostatin M inhibits expression of two components of this E3 ligase complex (Skp2 and Cks1). Although combined overexpression of Skp2 and Cks1 rescues p27 degradation in S phase, it can not override p27 accumulation in G(1) phase and cell cycle arrest by oncostatin M. In addition to increasing Cdk inhibitor level, oncostatin M also impairs cyclin A expression. Cyclin A mRNA and protein level decline shortly after oncostatin M addition. The accumulation of two CDK inhibitor proteins and the repression of cyclin A expression may explain the broad and potent antiproliferative effect of the cytokine.

Antineoplastic Agents↗

PubMed2005

Aptamers--basic research, drug development, and clinical applications.

Since its discovery in the early 1990s, aptamer technology has progressed tremendously. Automated selection procedures now allow rapid identification of DNA and RNA sequences that can target a broad range of extra- and intracellular proteins with nanomolar affinities and high specificities. The unique binding properties of nucleic acids, which are amenable to various modifications, make aptamers perfectly suitable for different areas of biotechnology. Moreover, the approval of an aptamer for vascular endothelial growth factor by the US Food and Drug Administration highlights the potential of aptamers for therapeutic applications. This review summarizes recent developments and demonstrates that aptamers are valuable tools for diagnostics, purification processes, target validation, drug discovery, and even therapeutic approaches.

Animals↗

PubMed2004

Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.

BACKGROUND: Hirudin (H)/iloprost (I)/paclitaxel (P)-coated stents represent a multifactorial approach to reducing the proliferative response caused by ballooning and stenting. The study presented compares the net effect of each individual compound of HIP-coated stents with the summed effect of the compounds in the stent coating. METHODS AND RESULTS: For proliferation prescreening studies, human coronary smooth muscle cells were incubated with H (0.005-500 microg/ml), I (0.00001-1 microg/ml), and P (0.0001-10 microg/ml). After 5 days, cell number was studied in a cell analyzer system. Secondly, 8-mm stents were coated with (1) HI, (2) HIP-10 microg/20 microg/40 microg (HIP5%/10%/20%), (3) P-40 microg (P), (4) IP-40 microg (IP), and (5) HP-40 microg (HP). After 5 days, the effect on cell proliferation and cytoskeletal structures was studied. No antiproliferative effect was found after incubation with H; significant inhibition was seen after incubation with I (p<0.05) or lipophilically dissolved P (p<0.001). After 5 days incubation with HIP5%-, HIP10%-, HIP20%-, P20%-, IP20%-, and HP20%-coated stents, cell proliferation was inhibited by 55.5% (p<0.05), 61% (p<0.05), 57.9% (p<0.05), 59.5% (p<0.001), 59.8% (p<0.001), and 63.3% (p<0.001), respectively. HI- and HIP-coated stents caused a severe destruction of the cytoskeletal structures smooth muscle alpha-actin and alpha-tubulin; despite the destruction, vital cells could be identified with positive FDA staining. CONCLUSIONS: Although both lipophilically dissolved P and hydrophilically dissolved I contributed to the antiproliferative effect, no additive effect of the two compounds was detected. In vivo P can be released more easily from the coating material due to the permanent lipophilic contact of the stent struts with the vessel wall. The current study is the first report on a clear and uncomplicated technique to obtain information on the antiproliferative potential of coated stents before large experimental studies are initiated.

Antineoplastic Agents, Phytogenic↗

PubMed2003

CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis.

We show that p27 localization is cell cycle regulated and we suggest that active CRM1/RanGTP-mediated nuclear export of p27 may be linked to cytoplasmic p27 proteolysis in early G1. p27 is nuclear in G0 and early G1 and appears transiently in the cytoplasm at the G1/S transition. Association of p27 with the exportin CRM1 was minimal in G0 and increased markedly during G1-to-S phase progression. Proteasome inhibition in mid-G1 did not impair nuclear import of p27, but led to accumulation of p27 in the cytoplasm, suggesting that export precedes degradation for at least part of the cellular p27 pool. p27-CRM1 binding and nuclear export were inhibited by S10A mutation but not by T187A mutation. A putative nuclear export sequence in p27 is identified whose mutation reduced p27-CRM1 interaction, nuclear export, and p27 degradation. Leptomycin B (LMB) did not inhibit p27-CRM1 binding, nor did it prevent p27 export in vitro or in heterokaryon assays. Prebinding of CRM1 to the HIV-1 Rev nuclear export sequence did not inhibit p27-CRM1 interaction, suggesting that p27 binds CRM1 at a non-LMB-sensitive motif. LMB increased total cellular p27 and may do so indirectly, through effects on other p27 regulatory proteins. These data suggest a model in which p27 undergoes active, CRM1-dependent nuclear export and cytoplasmic degradation in early G1. This would permit the incremental activation of cyclin E-Cdk2 leading to cyclin E-Cdk2-mediated T187 phosphorylation and p27 proteolysis in late G1 and S phase.

Active Transport, Cell Nucleus↗

PubMedDate not supplied

Economic evaluation of voriconazole versus conventional amphotericin B in the treatment of invasive aspergillosis in Germany.

OBJECTIVE: To assess the costs and cost-effectiveness of voriconazole in comparison to conventional amphotericin B (CAB) for the treatment of invasive aspergillosis in Germany. METHODS: The cost-effectiveness of voriconazole in comparison to CAB was evaluated with a lifetime Markov model, focusing on the long-term survival of patients treated for invasive aspergillosis. Long-term survival was extrapolated from survival after 12 weeks of treatment, obtained from a randomized aspergillosis study. Information on medical resource consumption and treatment pathways were obtained from this study and an expert committee. With probabilistic analysis the cost-effectiveness of voriconazole compared with amphotericin B was analyzed and expressed in incremental costs per life-weeks gained. The evaluation was performed from a limited societal perspective (both inpatient and outpatient costs) and hospital perspective (only inpatient costs). RESULTS: Average survival of patients treated with voriconazole was 174.4 life-weeks (95% confidence interval [CI] 159.4-191.3), compared with 119.4 life-weeks (95% CI 106.4-132.3) for amphotericin B. With voriconazole, the mean total costs per patient were 30,026 euros (95% CI 23 euros ,118-37,947) compared with 26,669 euros for amphotericin B (95% CI 21,259-34,263 euros ) from the limited societal perspective. The corresponding incremental cost-effectiveness ratio was 62 euros per life-week gained (i.e., 3224 euros per life-year gained). Hospital costs were approximately 90% of the mean total costs. CONCLUSIONS: In the treatment of invasive aspergillosis, voriconazole is cost-effective in comparison to amphotericin B. Hospital costs are comparable for both treatments and are expected to be reimbursed based on the German diagnosis-related groups (DRG) system 2005.

Amphotericin B↗