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Summary Previous studies have demonstrated that verapamil may overcome resistance to anthracyclines. In vitro and in vivo experiments were performed on wild-type and resistant Ehrlich ascites tumor cells.Verapamil in concentrations of 25–50 M enhances the accumulation of daunorubicin (DNR) in resistant cells to the same level as in wild-type cells. No significant effect of verapamil on influx or nuclear binding could be demonstrated, indicating that verapamil enhances DNR uptake by blocking active drug extrusion. Exposure of cells to a high concentration of Ca2+ did not influence the effect of verapamil on DNR accumulation, suggesting a different mode of verapamil action apart from the Ca2+-blocking effect. Attempts to circumvent acquired resistance to DNR in vivo with verapamil showed that the combination of the two drugs was more toxic than DNR given alone. The LD10 of DNR was determined as 3 mg/kg and the LD10 of the combination, as 2.5 mg/kg. The therapeutic effect of verapamil at a dose of 50 mg/kg and DNR of 2.5 mg/kg increased the life span of the mice by 50%. No difference was seen in the wild-type tumor in vivo.These data lead us to conclude that verapamil can reverse DNR resistance completely, but that verapamil at non-toxic dosage only reduces DNR resistance by 50% in vivo.The Danish Cancer Society, Copenhagen, Denmark, the Kathrine and Vigo Skovgaard Foundation, Holbæk, Denmark and the Anders Hasselbalch Foundation, Copenhagen, Denmark, kindly supported this work. 相似文献
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Preclinical evaluation of potential infection‐imaging probe [68Ga]Ga‐DOTA‐K‐A9 in sterile and infectious inflammation 下载免费PDF全文
Karin M. Nielsen Nis P. Jørgensen Majbritt H. Kyneb Per Borghammer Rikke L. Meyer Trine R. Thomsen Dirk Bender Svend B. Jensen Ole L. Nielsen Aage K.O. Alstrup 《Journal of labelled compounds & radiopharmaceuticals》2018,61(10):780-795
The development of bacteria‐specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N?‐tetraacetic acid (DOTA) conjugated peptide [68Ga]Ga‐DOTA‐K‐A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [68Ga]Ga‐DOTA‐K‐A9 synthesis omitting the use of acetone was developed, yielding 93 ± 0.9% radiochemical purity. The in vivo infection binding specificity of [68Ga]Ga‐DOTA‐K‐A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine‐induced inflammation and compared with 2‐deoxy‐2‐[18F]fluoro‐D‐glucose ([18F]FDG). The scans showed that [68Ga]Ga‐DOTA‐K‐A9 accumulated in all the infected mice at injected doses ≥3.6 MBq. However, the tracer was not found to be selective towards infection, since the [68Ga]Ga‐DOTA‐K‐A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5‐carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA‐K‐A9, the microscopy results suggested that TAMRA‐K‐A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [68Ga]Ga‐DOTA‐K‐A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria. 相似文献
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Larsen PB Gätke MR Fredensborg BB Berg H Engbaek J Viby-Mogensen J 《Acta anaesthesiologica Scandinavica》2002,46(9):1131-1136
BACKGROUND: The orbicularis oculi (OO) muscle has been recommended for neuromuscular monitoring when the adductor pollicis (AP) muscle is not available. We investigated whether neuromuscular block could be measured reliably from the orbital part of the OO muscle by the use of acceleromyography. METHODS: During propofol, fentanyl, and alfentanil anaesthesia two TOF-Guards (Organon Teknika NV, Boxtel, the Netherlands) with acceleration transducers placed on the distal phalanx of the thumb and over the middle of the eyebrow, respectively, were used to measure neuromuscular block simultaneously in 23 patients during vecuronium-induced and neostigmine-antagonized neuromuscular block. For both muscles, the simultaneously recorded first response (T1) in the train-of-four (TOF) and TOF-ratio were measured both during onset and recovery of the block. Furthermore, both the AP muscle T1 and TOF-ratio responses were plotted against 10% intervals of the OO muscle responses during onset and recovery, respectively. RESULTS: The orbicularis oculi muscle had a shorter latency and a faster recovery to TOF-ratio 0.80 compared with the AP muscle. During onset and recovery, pronounced variations of the AP muscle T1 and TOF-ratio responses were observed when compared with the OO muscle. CONCLUSION: A significant clinical disagreement exists between the degree of paralysis measured at the OO and the AP muscles. It is impossible to obtain a reasonable estimate of the degree of block at the AP muscle when the block is measured from the OO muscle with acceleromyography. If used, there is substantial risk of overlooking a residual block, and adequate recovery of the block should be confirmed by a final AP muscle measurement. 相似文献
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PURPOSE: To investigate the current status of screening for diabetic retinopathy in Denmark, focussing on organization, methods of screening and regional differences. METHODS: A questionnaire was sent out in 2002 to 14 departments of ophthalmology and one ophthalmology practice, covering all 15 counties in Denmark. RESULTS: Six counties reported having systematic screening, defined as organized screening, including a database; three reported having plans for systematic screening; two reported having undetermined plans for systematic screening and four reported having no plans for systematic screening. In counties with systematic screening, both the organization and the method of screening varied. CONCLUSION: Approximately 43% of Danish patients with diabetes currently live in a county without systematic screening for diabetic retinopathy. Should all counties contemplating systematic screening implement their plans, this proportion will be reduced to approximately 17%. 相似文献
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