Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells

Etoposide (VP-16) is a topoisomerase II (topo II) inhibitor chemotherapeutic agent. Studies indicate that VP-16 enhances proinflammatory cytokines secretion from tumour cells, including IL-8, a chemokine associated with proangiogenic effects. Fluoroquinolones inhibit topo II activity in eukaryotic cells by a mechanism different from that of VP-16. The fluoroquinolone moxifloxacin (MXF) has pronounced anti-inflammatory effects in vitro and in vivo. We studied the effects of MXF and VP-16 on purified human topo II activity and further analysed their combined activity on proliferation, apoptosis and caspase-3 activity in THP-1 and Jurkat cells. Moxifloxacin alone slightly inhibited the activity of human topo II; however, in combination with VP-16 it led to a 73% reduction in enzyme activity. VP-16 inhibited cell proliferation in a time and dose-dependent manner. The addition of moxifloxacin for 72 h to low-dose VP-16 doubled its cytotoxic effect in THP-1 and Jurkat cells (1.8- and 2.6-fold decrease in cell proliferation, respectively) (P<0.004). Moxifloxacin given alone did not induce apoptosis but enhanced VP-16-induced apoptosis in THP-1 and Jurkat cells (1.8- and two-fold increase in annexin V positive cells and caspase-3 activity, respectively) (P<0.04). VP-16 induced the release of IL-8 in a time and dose-dependent manner from THP-1 cells. Moxifloxacin completely blocked the enhanced release of IL-8 induced by 0.5 and 1 μg ml−1 VP-16, and decreased IL-8 release from cells incubated for 72 h with 3 μg ml−1 VP-16 (P<0.001). VP-16 enhanced the release of IL-1β and TNF-α from THP-1 cells, whereas the addition of MXF prevented the enhanced cytokine secretion (P<0.001). We conclude that MXF significantly enhances VP-16 cytotoxicity in tumour-derived cells while preventing VP-16-induced proinflammatory cytokine release. This unique combination may have clinical benefits and cytotoxic drug ‘sparing effect' and should be further studied in vivo

[Cinematography, a new diagnostic procedure in evaluation of the injured painful wrist joint]

By the X-ray Cineradiografie we are able to examine and to judge the dynamic of the wrist bones by 50 pictures/sec. in comparison to one another and also depending on their ligaments. We did an investigation of 170 patients with painful wrist. With the method we were able to make up a clear diagnosis and to propose the therapy. I.e.: If consecutive shortening of the radius after distal radius fracture resulting ingruency of the wrist joint is relevant, or a scaphoid pseudarthrosis is fixed elastically, or a scaphoic dissociation is effective. The variations were shown in comparison to normal circumstances

Biomechanical effect of isolated capitate shortening in Kienbock's disease: an anatomical study.

Multiple operations have been proposed to slow the progression of osteonecrosis and secondary carpal damage in Kienböck's disease. To assess the biomechanical changes after capitate shorting, we inserted pressure-testing devices into the carpal and radiocarpal joints in an anatomical study. Pressure sensors were placed into eight thawed non-fixated human cadaver arms to measure the forces transmitted in physiological loading. Longitudinal 9.8 N and 19.6 N forces were applied before and after capitate shortening. After capitate shortening, significant load reduction on the lunate was evident in all specimens. An average decrease of 49% was seen under a 9.8 N load and 56% under a 19.6 N load. The load was transferred to the radial and ulnar intercarpal joints. More relief of pressure on the lunate after isolated capitate shortening is achieved with a shallow angle between the scaphoid and capitate in the posteroanterior radiograph

External fixation of distal radial fractures: four compared with five pins: a randomized prospective study.

BACKGROUND: The purpose of this study of distal radial fractures was to compare the radiographic and clinical results after use of a standard four-pin external fixator with those after use of a five-pin fixator with the fifth pin stabilizing the distal radial articular fragment. METHODS: In an open prospective trial, fifty patients with an unstable distal radial fracture were randomized for treatment with closed reduction and either a standard small Association for the Study of Internal Fixation (ASIF) four-pin fixator (twenty-five patients) or a five-pin external fixator (twenty-five patients). The fixators were removed at nine weeks, and all patients were assessed radiographically and clinically at six months. RESULTS: Follow-up radiographs demonstrated significantly less loss of alignment and length with the five-pin external fixator. Pin site infections were more prevalent with the four-pin fixator. The range of motion of the wrist and forearm, the grip strength, and the Lidstrom functional ratings at six months were all significantly better after use of the five-pin fixator. CONCLUSIONS: The use of a five-pin external fixator, with the fifth pin stabilizing the distal radial articular fragment, yields better radiographic and functional results than does a four-pin fixator