Home About us Contact
|
Home About us Contact | ||
|
|
||
Systemic Application (systemic + application)
Selected AbstractsEffects on litter-dwelling earthworms and microbial decomposition of soil-applied imidacloprid for control of wood-boring insectsPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 2 2008David P Kreutzweiser Abstract BACKGROUND: Imidacloprid is an effective, systemic insecticide for the control of wood-boring insect pests in trees. Systemic applications to trees are often made by soil injections or drenches, and the resulting imidacloprid concentrations in soil or litter may pose a risk of harm to natural decomposer organisms. The authors tested effects of imidacloprid on survival and weight gain or loss of the earthworms Eisenia fetida (Savigny) and Dendrobaena octaedra (Savigny), on leaf consumption rates and cocoon production by D. octaedra and on microbial decomposition activity in laboratory microcosms containing natural forest litter. RESULTS:Dendrobaena octaedra was the most sensitive of the two earthworm species, with an LC50 of 5.7 mg kg,1, an LC10 of about 2 mg kg,1 and significant weight losses among survivors at 3 mg kg,1. Weight losses resulted from a physiological effect rather than from feeding inhibition. There were no effects on cocoon production among survivors at 3 mg kg,1. The LC50 for E. fetida was 25 mg kg,1, with significant weight losses at 14 mg kg,1. There were no significant effects on microbial decomposition of leaf material at the maximum test concentration of 1400 mg kg,1. CONCLUSION: The results indicate that, when imidacloprid is applied as a systemic insecticide to the soil around trees, it is likely to cause adverse effects on litter-dwelling earthworms if concentrations in the litter reach or exceed about 3 mg kg,1. Copyright © 2007 Her Majesty the Queen in the Right of Canada, Canadian Forest Service. Published by John Wiley & Sons, Ltd. [source] 22-ene-25-oxa-vitamin D: a new vitamin D analogue with profound immunosuppressive capacitiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2005C. Daniel Abstract Background, The biologic role of 1,25-dihydroxyvitamin D3, such as anti-inflammatory functions, reduction of cytokine production by T cells and immunoglobulin production by B cells, is well established. However, its clinical use as an immunosuppressive agent is limited because of the hypercalcemic toxicity occurring after systemic application. The purpose of this study was to investigate the immunmodulatory effects of 22-ene-25-oxa-vitamin D (ZK156979), a novel low calcemic vitamin D analogue. Materials and methods, Human peripheral blood mononuclear cells (PBMCs) from healthy donors were isolated using the Ficoll Hypaque technique, cultured for 24 h and treated with different concentrations of ZK156979 ranging from 10,5 to 10,10 mol L,1 compared with 1,25-dihydroxyvitamin D3[10,5,10,10 mol L,1] following phytohaemagglutinin (PHA) stimulation. Interferon gamma (IFN,), tumour necrosis factor alpha (TNF,), interleukin 1 beta (IL-1,), interleukin 10 (IL-10) and interleukin 4 (IL-4) secretion in supernatants were measured by ELISA. Results, ZK156979 inhibited the PHA-induced Th1-response (IFN, and TNF, levels) and the macrophage-product IL-1, in a concentration-dependent manner (10,10,10,5 mol L,1) with the efficiency on cytokine expression compared with 1,25-dihydroxyvitamin D3 being slightly reduced. In contrast, ZK156979 and 1,25-dihydroxyvitamin D3 both affected the Th2 response, leading to significantly increased IL-10- and IL-4 secretion. Conclusions, ZK156979 is a member of novel vitamin D analogues revealing prominent immunomodulatory and suppressive characteristics with distinctive inhibition of Th1-cytokines whereas the Th2 compartment is augmented, thus providing a considerable therapeutic potential in T-cell -mediated diseases. [source] Increase of MCP-1 (CCL2) in myelin mutant Schwann cells is mediated by MEK-ERK signaling pathwayGLIA, Issue 8 2008Stefan Fischer Abstract Macrophages are critically involved in the pathogenesis of genetically caused demyelination, as it occurs in inherited demyelinating neuropathies. On the basis of the observation that upregulation of the Schwann cell-derived chemokine MCP-1 (CCL2) is a pathologically relevant mechanism for macrophage activation in mice heterozygously deficient for the myelin component P0 (P0+/,), we posed the question of the intracellular signaling cascade involved. By using western blot analysis of peripheral nerve lysates the MAP-kinases extracellular signal-regulated kinase 1/2 (ERK1/2) and MAP kinase/ERK kinase 1/2 (MEK1/2) showed an early and constantly increasing activation in P0 mutants. Furthermore, in nerve fibers from the P0+/, mutants, Schwann cell nuclei were much more often positive for phosphorylated ERK1/2 than in nerve fibers from wild type mice. In vitro experiments using the MEK1/2-inhibitor CI-1040 decreased ERK1/2-phosphorylation and MCP-1 expression in a Schwann cell-derived cell line. Finally, systemic application of CI-1040 lead to a decreased ERK1/2-phosphorylation and substantially reduced MCP-1-production in peripheral nerves of P0+/, mutant mice. Our study identifies MEK1/2-ERK1/2 signaling as an important intracellular pathway that connects the Schwann cell mutation with the activation of pathogenetically relevant macrophages in the peripheral nerves. These findings may have important implications for the treatment of inherited peripheral neuropathies in humans. © 2008 Wiley-Liss, Inc. [source] Periodontal dressing (Vocopac®) influences outcomes in a two-step treatment procedureJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2005B. W. Sigusch Abstract Objectives: It is not clear if periodontal dressing influences the long-term results in a non-surgical treatment procedure. Material and Methods: The periodontal parameters (pre-baseline) of 36 patients with aggressive periodontitis were obtained before the patients were treated initially (1st step) by a dental hygienist, who completely removed the supra- and subgingival concrements. Baseline parameters were raised 3 weeks after the 1st step, before the 2nd therapy step was conducted. It consisted of a non-surgical procedure, which comprised a closed full-mouth manual root curettage (root planing), immediate systemic application of metronidazole, and the placement of a periodontal dressing (Vocopac®, Voco). The patients were randomized to two test groups having their periodontal packs removed after 3,4 days (group 1, n=12) and 7,8 days (group 2, n=12), respectively and a control group (n=12) without periodontal dressing. Clinical parameters were raised again after 6 and 24 months. Results: Six and 24 months later, changes in probing pocket depth (PPD) and probing attachment level (PAL) were observed in all three groups compared with baseline, but the difference was significant in group 2 only. In addition, group 2 showed a greater reduction in mean PPD and also a significantly greater gain of attachment in comparison with the controls. Conclusion: Wound dressing has a positive effect on clinical long-term results using a two-step non-surgical procedure. Moreover, removing the dressing after 7,8 days leads to clearly better results than removing it earlier. [source] Etanercept reduces hyperalgesia in experimental painful neuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2001Claudia Sommer Abstract Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been successfully used in patients with rheumatoid arthritis, where it reduces pain and inflammation. Because locally produced proinflammatory cytokines play a role in pain after nerve injury, we investigated whether etanercept can reduce pain and hyperalgesia in an animal model of painful neuropathy, the chronic constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or sham treatment by local near-nerve injection to the injured nerve or by systemic application. Treatment with etanercept reduced thermal hyperalgesia and mechanical allodynia significantly in both modes of application. The effect of etanercept was present in animals that were treated from the time of surgery and in those that were treated from day 6, when hyperalgesia was already present. These results suggest the potential of etanercept as a treatment option for patients with neuropathic pain. [source] Chemical stress induces the unfolded protein response in olfactory sensory neuronsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 10 2010Neeraja Sammeta Abstract More than any other neuron, olfactory sensory neurons are exposed to environmental insults. Surprisingly, their only documented response to damaging stress is apoptosis and subsequent replacement by new neurons. However, they expressed unfolded protein response genes, a transcriptionally regulated defense mechanism activated by many types of insults. The unfolded protein response transcripts Xbp1, spliced Xbp1, Chop (Ddit3), and BiP (Hspa5) were decreased when external access of stressors was reduced by blocking a nostril (naris occlusion). These transcripts and Nrf2 (Nfe2l2) were increased by systemic application of tunicamycin or the selective olfactotoxic chemical methimazole. Methimazole's effects overcame naris occlusion, and the unfolded protein response was independent of odor-evoked neuronal activity. Chemical stress is therefore a major and chronic activator of the unfolded protein response in olfactory sensory neurons. Stress-dependent repression of the antiapoptotic gene Bcl2 was absent, however, suggesting a mechanism for disconnecting the UPR from apoptosis and tolerating a chronic unfolded protein response. Environmental stressors also affect both the sustentacular cells that support the neurons and the respiratory epithelia, because naris occlusion decreased expression of the xenobiotic chemical transformation enzyme Cyp2a5 in sustentacular cells, and both naris occlusion and methimazole altered the abundance of the antibacterial lectin Reg3g in respiratory epithelia. J. Comp. Neurol. 518:1825,1836, 2010. © 2009 Wiley-Liss, Inc. [source] Modification of pLL/DNA complexes with a multivalent hydrophilic polymer permits folate-mediated targeting in vitro and prolonged plasma circulation in vivoTHE JOURNAL OF GENE MEDICINE, Issue 5 2002Christopher M. Ward Abstract Background Gene delivery vectors based on poly(L -lysine) and DNA (pLL/DNA complexes) have limited use for targeted systemic application in vivo since they bind cells and proteins non-specifically. In this study we have attempted to form folate-targeted vectors with extended systemic circulation by surface modification of pLL/DNA complexes with hydrophilic polymers. Methods pLL/DNA complexes were stabilised by surface modification with a multivalent reactive polymer based on alternating segments of poly(ethylene glycol) and tripeptides bearing reactive ester groups. Folate moieties were incorporated into the vectors either by direct attachment of folate to the polymer or via intermediate poly(ethylene glycol) spacers of 800 and 3400,Da. Results Polymer-coated complexes show similar morphology to uncoated complexes, their zeta potential is decreased towards zero, serum protein binding is inhibited and aqueous solubility is substantially increased. Intravenous (i.v.) administration to mice of coated complexes produced extended systemic circulation, with up to 2000-fold more DNA measured in the bloodstream after 30,min compared with simple pLL/DNA complexes. In further contrast to simple pLL/DNA complexes, coated complexes do not bind blood cells in vivo. Folate receptor targeting is shown to mediate targeted association with HeLa cells in vitro, leading to increased transgene expression. We demonstrate for the first time that DNA uptake via the folate receptor is dependent on pEG spacer length, with the transgene expression relatively independent of the level of internalised DNA. Conclusions We show increased systemic circulation, decreased blood cell and protein binding, and folate-targeted transgene expression using pLL/DNA complexes surface-modified with a novel multireactive hydrophilic polymer. This work provides the basis for the development of plasma-circulating targeted vectors for in vivo applications. Copyright © 2002 John Wiley & Sons, Ltd. [source] Utilizing endocrine secretory pathways in salivary glands for systemic gene therapeutics,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2004Antonis Voutetakis Mammalian salivary glands are commonly used models of exocrine secretion. However, there is substantial experimental evidence showing the physiological existence of endocrine secretory pathways in these tissues. The use of gene transfer technology in vivo has allowed the unambiguous demonstration of these endocrine pathways. We and others have exploited such findings and evaluated salivary glands as possible target tissues for systemic applications of gene therapeutics. Salivary glands present numerous advantages for this purpose, including being well encapsulated, which limits extra-glandular vector dissemination, and having the luminal membranes of almost all parenchymal cells accessible via intraoral delivery of vectors through the main excretory ducts. Existing studies suggest that clinical benefits will result from salivary gland targeted systemic gene therapeutics. J. Cell. Physiol. 199: 1,7, 2004. Published 2003 Wiley-Liss, Inc. [source] | |||||||||||||