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  • 2000-2004  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    International journal of cosmetic science 26 (2004), S. 0 
    ISSN: 1468-2494
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The ambivalent consequences of mitochondrial stimulation on cellular activity have been well established. Mitochondria supply the cell with energy through a process of oxidative phosphorylation but thereby generate free radicals, resulting in the accumulation of hydrogen peroxide in the cytoplasm. We have investigated the impact of cellular senescence as well as UV irradiation, on the balance between these two activities.The adenosine triphosphate (ATP) level, DNA and protein synthesis in fibroblasts obtained from donors between 30 and 90 years of age appeared to be significantly influenced by the aging process. Both DNA and protein synthesis could be stimulated by increasing intracellular ATP levels. In-vitro senescent fibroblasts showed a reduction in the level of ATP as well as a shift in mitochondrial membrane potential. At the same time, there was an increase in intracellular hydrogen peroxide with increasing population doubling, indicating a clear dysfunction of the metabolic machinery in the mitochondria of senescent cells. To counteract this degradation of the energy pool, we treated cells with creatine, which is known to restore the pool of phosphocreatine in the mitochondria. Creatine treatment significantly increased cell survival after UV exposure, stimulated the repair of UVB-induced DNA damage in keratinocytes and caused a significant reduction in the number of sunburn cells in a UVB-exposed reconstituted skin model. These results clearly indicate that restoration of the energy pool in mitochondria increased cellular self-defense mechanism. These data show the important role played by the mitochondrial energy metabolism on the aging process, and indicate a possible therapy that can be used to counteract this negative effect. Treatment with creatine seems to provide the necessary boost to the cellular metabolism, which leads to an induction of a significant amount of protection and repair to human skin cells.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid-related disease.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:1960 patients with endoscopy-confirmed reflux oesophagitis (RO) were randomized to once daily esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double-blind trial. The primary efficacy variable was the proportion of patients healed at week 8. Secondary variables included healing and heartburn resolution at week 4, time to first resolution and sustained resolution of heartburn, and per cent of heartburn-free days and nights. Safety and tolerability were also evaluated.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Significantly more patients were healed at week 8 with esomeprazole 40 mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life table estimates, ITT analysis (each P 〈 0.05). Esomeprazole 40 mg was also significantly more effective than omeprazole for healing at week 4 and for all secondary variables evaluating heartburn resolution. The most common adverse events in all treatment groups were headache, abdominal pain and diarrhoea.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusion:Esomeprazole was more effective than omeprazole in healing and symptom resolution in GERD patients with reflux oesophagitis, and had a tolerability profile comparable to that of omeprazole.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-6822
    Keywords: apoptosis ; differentiation ; keratinocytes ; UVB radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract UVB irradiation can induce apoptotic, necrotic, and differentiation pathways in normal human keratinocytes. The present study was undertaken to determine at what dose of UVB each of these pathways is induced and whether these pathways are distinct or overlapping. We have observed that UVB induces fragmentation of DNA in human HaCaT keratinocytes, in a bimodal manner. Low doses of UVB, 5–20 mJ/cm2, increase the levels of apoptosis as shown by increased levels of fragmented DNA, Fas, PARP, and FasL protein, and the number of apoptotic cells as assessed by FACS analysis. At higher doses of UVB (20 and 30 mJ/cm2) the number of apoptotic cells becomes reduced, as does the amount of Fas, PARP, and FasL protein. At these higher doses, cell viability is decreased as measured by DNA synthesis (BrdU labeling) neutral red uptake, which represents an increasing necrotic phenotype. Expression of markers of keratinocyte differentiation, involucrin, keratin K1, and keratin K10, are also observed to decrease with increasing UVB dose. These changes are accompanied by a further increase in DNA fragmentation. We conclude that low doses of UVB (5–20 mJ/cm2) induced an apoptotic pathway, whereas increasing doses (greater than 20 mJ/cm2) of UVB produce a direct necrotic effect and inhibit terminal differentiation.
    Type of Medium: Electronic Resource
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