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1.
In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair. 总被引:18,自引:0,他引:18
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C Andree W F Swain C P Page M D Macklin J Slama D Hatzis E Eriksson 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(25):12188-12192
This report details the transfer of a human epidermal growth factor (hEGF) expression plasmid to porcine partial-thickness wound keratinocytes by particle-mediated DNA transfer (Accell). After gene transfer an external sealed fluid-filled wound chamber was used to protect the wound, provide containment of the exogenous DNA and expressed peptide, and permit sampling of the wound fluid. Analysis of wound fluid for hEGF and total protein, an indicator of reformation of the epithelial barrier, showed that wounds bombarded with the hEGF plasmid exhibited a 190-fold increase in EGF concentration and healed 20% (2.1 days) earlier than the controls. EGF concentrations in wound fluid persisted over the entire 10-day monitored period, decreasing from 200 pg/ml to 25 pg/ml over the first 5 days. Polymerase chain reaction results showed that plasmid DNA was present in the wound for at least 30 days. These findings demonstrate the possible utility of in vivo gene transfer to enhance epidermal repair. 相似文献
2.
Journal für Ästhetische Chirurgie - Brustvergrößerungen mit Implantaten gehören zu den häufigsten ästhetisch chirurgischen Eingriffen. Trotz jahrzehntelanger... 相似文献
3.
Horch RE Andree C Kopp J Tánczos E Voigt M Bannasch H Walgenbach KJ Dai FP Bittner K Galla TJ Stark GB 《Zentralblatt für Chirurgie》2000,125(Z1):74-78
A variety of reasons can afflict wound healing. Current research is focussed on the acceleration of wound healing by stimulating molecular processes. Gene therapy may offer completely new ways to treat chronic wounds. Possible advantages of gene therapeutic modulation of wound healing might be a long term efficiency, systemic or local regulation of gene expression and low side-effects. Current goals comprise the improvement of transfection efficiency and specificity. In vivo applications are therefore focussed on optimized inducible or even cell-type specific promotors, as well as on improved local application techniques. Studies from our laboratory demonstrate the possibility to combine modern cell culture techniques with different types of gene transfer. This enables the simultaneous grafting of manipulated cells to the wound with the continuous delivery of specific proteins of interest. Experimentally, this lead to accelerated closure of partial and full thickness animal wounds. Clinically, gene therapy for the treatment of chronic wounds seems to be a realistic goal within the next years and might be applicable for a variety of novel indications. 相似文献
4.
Qiu Q Bell M Lu X Yan X Rodger M Walker M Wen SW Bainbridge S Wang H Gruslin A 《The Journal of clinical endocrinology and metabolism》2012,97(8):E1429-E1439
Background: Fetal growth restriction (FGR) is a leading cause of perinatal mortality and morbidity. Animal studies suggest dysregulation of IGF-binding protein (IGFBP)-4 is significant in the development of FGR, although human data are lacking. We postulated that IGFBP-4 is expressed at the maternal fetal interface and plays a role in regulating IGF bioavailability. Thus, maternal serum levels of IGFBP-4 may be associated with complications of abnormal placental growth and development including FGR. Methods: Circulating levels of IGFBP-4 and its protease, pregnancy-associated plasma protein-A (PAPP-A), were examined in healthy pregnancies. Their expression in villi and bed as possible sources of the circulating products were examined by immunohistochemistry. From the large Ottawa and Kingston (OaK) Birth Cohort, a nested case-control study was conducted to examine circulating levels of IGBP-4, PAPP-A, IGF-I, and IGF-II by Western blot in early gestation in 36 women who went on to develop FGR and 36 controls having normal-weight babies. Results: IGFBP-4 was elevated in early pregnancy compared with nonpregnant women and women in later pregnancy, consistent with the presence of abundant extravillous trophoblasts and decidual cells that highly expressed IGFBP-4. High expression of PAPP-A was observed in extravillous trophoblasts and decidual cells in early pregnancy but hardly detectable in the circulation at this time, suggesting maternal circulating PAPP-A originates more likely from syncytiotrophoblasts. Increased IGFBP-4 in the maternal circulation in early pregnancy was associated with the development of FGR [0.48 (0.28-0.74) in control vs. 1.22 (0.66-1.65) in FGR; odds ratio = 22 (95% confidence interval = 2.7-181)]. No difference was observed in circulating PAPP-A, IGF-I and IGF-II in the FGR vs. control group. Conclusion: Our findings support the role of IGFBP-4 in regulating IGF bioavailability and provide new clues for the prevention and treatment of FGR, raising the possibility of clinical use of IGFBP-4 as an early biomarker for this condition. 相似文献
5.
Objective
Caries adjacent to restorations is one of the main causes for restoration replacement. Antimicrobial substances incorporated into dental materials would potentially be able to reduce secondary caries initiation and progression. This study investigated biofilm growth of Streptococcus mutans UA159 on the surface of composite materials containing the biomolecule carolacton compared to materials containing chlorhexidine (CHX) and triclosan.Methods
Biofilm inhibition was investigated by counting colony forming units (CFU), viability staining (Life/Dead), and real-time quantitative PCR.Results
First, the antimicrobial substances were added to the cultivation medium at 2.5 μg/ml (0.0002%) and 0.25 μg/ml (0.00002%). CHX eliminated bacterial growth and biofilm formation completely. Triclosan was effective at 2.5 μg/ml, but at 0.25 μg/ml biofilm mass and viability were unchanged, yet the number of CFU increased due to disruption of cell chains and biofilm aggregates. Carolacton had a limited effect on biofilm growth and mass, but reduced viability significantly. When incorporated into composite materials carolacton (25 μg/ml resp. 0.002%, w/w) had no adverse effect on physical/mechanical properties and retained its biofilm inhibiting effect. Life/Dead staining revealed a reduction of biofilm viability of up to 64%. CFUs were reduced by 98% and qPCR demonstrated a mean inhibition of 87%. In contrast, materials containing CHX or triclosan showed an insignificant effect on biofilm formation, even at a 100fold increased concentration (0.2%). The anti-biofilm activity of composite material containing carolacton was stable over a period of 42 days.Significance
Carolacton incorporated into dental filling material has a strong biofilm-inhibiting effect on S. mutans and is therefore potentially able to prevent secondary caries formation. 相似文献6.
7.
8.
Leventhal L Smith V Hornby G Andree TH Brandt MR Rogers KE 《The Journal of pharmacology and experimental therapeutics》2007,320(3):1178-1185
There is increasing recognition that norepinephrine (NE) and serotonin (5-HT) reuptake inhibitors (NRIs and SRIs) are efficacious in treating some types of pain. To date, studies have not systematically evaluated the relative activity at the NE and/or 5-HT transporter required for maximal efficacy in rodent pain models. Known selective NE and 5-HT reuptake inhibitors reboxetine, desipramine, fluoxetine, and paroxetine were evaluated in both in vitro and in vivo assays. Using the spinal nerve ligation model of neuropathic pain, the compounds differentially reversed tactile allodynia. Evaluation of a broader spectrum of reuptake inhibitors in the para-phenylquinone (PPQ)-induced abdominal constriction model, a model of acute visceral pain, demonstrated that both the SRIs and the NRIs significantly blocked abdominal constrictions. However, the magnitude of this effect was greater following treatment with compounds having greater affinity for NRI compared with SRI affinity. In addition, isobolographic analyses indicated significant synergistic effects for all combinations of desipramine and fluoxetine in the PPQ model of visceral pain. Collectively, the present results support the hypothesis that compounds with greater NRI activity should be more effective for the treatment of pain than compounds having only SRI activity, and this hypothesis is also supported by clinical data. These studies also suggest that the potency and effectiveness of NRIs might be enhanced by the presence of 5-HT activity. 相似文献
9.
Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2 allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11
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Annelot Baert Eva Machackova Ilse Coene Carol Cremin Kristin Turner Cheryl Portigal‐Todd Marie Jill Asrat Jennifer Nuk Allison Mindlin Sean Young Andree MacMillan Tom Van Maerken Martin Trbusek Wendy McKinnon Marie E. Wood William D. Foulkes Marta Santamariña Miguel de la Hoya Lenka Foretova Bruce Poppe Anne Vral Toon Rosseel Kim De Leeneer Ana Vega Kathleen B. M. Claes 《Human mutation》2018,39(4):515-526
10.
Michael John Jackson Terrance H. Andree Matthew Hansard Diane C. Hoffman Mark R. Hurtt John H. Kehne Thomas A. Pitler Lance A. Smith Gary Stack Peter Jenner 《Journal of neural transmission (Vienna, Austria : 1996)》2010,117(1):55-67
Dopamine replacement therapy in Parkinson’s disease (PD) using l-dopa is invariably associated with a loss of drug efficacy (“wearing off”) and the onset of dyskinesia. The use of dopamine
receptor partial agonists might improve therapeutic benefit without increased dyskinesia expression but may antagonise the
effects of l-dopa. We now examine the effects of the novel high affinity, dopamine D2 receptor partial agonist, aplindore alone and in combination with l-dopa in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset. In non-dyskinetic MPTP treated animals,
aplindore (0.05–1.0 mg/kg p.o.) produced a dose-dependent reversal of motor disability and an increase in locomotor activity
that was maximal at doses of 0.2 mg/kg and above. In animals previously exposed to l-dopa to induce dyskinesia, escalating and repeated dosing of aplindore (0.05–0.5 mg/kg p.o.) produced a sustained, dose-related
improvement in motor disability and an increase in locomotor activity. The effects were maximal at a dose of 0.1 mg/kg and
above and not different from those produced by l-dopa (12.5 mg/kg plus carbidopa 12.5 mg/kg p.o.). Aplindore administration also led to dose-dependent expression of dyskinesia
but at 0.1 mg/kg, this was significantly less intense than that produced by l-dopa. Administration of aplindore (1.0 mg/kg p.o.) in combination with l-dopa (2.5 mg/kg plus carbidopa 12.5 mg/kg p.o.) did not inhibit the reversal of motor deficits but improved motor disability
and increased both locomotor activity and dyskinesia expression equivalent to that produced by l-dopa (12.5 mg/kg plus carbidopa 12.5 mg/kg p.o.). These data suggest that dopamine receptor partial agonists would be effective
in the treatment of Parkinson’s disease and would not inhibit the beneficial actions of l-dopa. 相似文献