[Intracortical dedifferentiated chondrosarcoma]. / Intrakortikales dedifferenziertes Chondrosarkom.

Chondrosarcoma is the second most frequent mesenchymal malignant tumour of the bone. Classification of this kind of tumour is made by clinical, radiological und pathological means. A case of an intracortical chondrosarcoma was first reported by Babinet et al. 2003 [2]. During the staging examination of a 59-year-old patient referred to our clinic because of a squamous cell carcinoma of the oropharynx, we also found a highly malignant intracortical dedifferentiated chondrosarcoma of the distal femur shaft. Due to the primary assumption of bone metastasis of the oropharynx tumour, marginal extralesional tumour resection was performed followed by composite osteosynthesis. Considerations on differential diagnosis and their implications for further therapy are discussed.

Effects of silperisone on the excitation process in Ranvier nodes.

The effect of silperisone on single intact Ranvier nodes of the toad Xenopus was investigated by adding it to the bathing medium. At 100 micromol/l the following fully reversible effects were observed: 1. The spike amplitude decreased in a frequency-dependent manner. 2. Both the sodium activation and the inactivation curves as well as the potential dependence of taum were slightly shifted in the negative direction, while tauh did not change. 3. The sodium permeability constant PNa decreased by 50%. 4. The potassium currents acquired a phasic time course previously described for certain psoralens. They reached a relative maximum and then approached a lower steady state value, kappa(infinity) with a time constant of about 5 ms. Concentration-related responses of PNa, PK and of k(infinity), yielded: 5. The apparent dissociation constant of block of PNa was 110 micromol/l. 6. PK proved not to be changed by silperisone in the concentration range tested, while the variable kappa(infinity) yielded a relation similar to that of PNa except that the apparent dissociation constant was 24 micromol/l. The phasic course of the potassium currents in the presence of silperisone may be due to an open channel blockade. In view of the similarities between the actions of silperisone and 5-methoxypsoralen, it is entirely conceivable that silperisone has potential for an antispastic drug, e.g., in demyelinating diseases like multiple sclerosis.

Effects of three alkoxypsoralens on voltage gated ion channels in Ranvier nodes.

The effects of the phototoxic K+- channel blockers 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP) on Ranvier nodes were compared to those of 5,8-diethoxypsoralen (5,8-EOP) by means of the Hodgkin-Huxley formalism. When these test substances were added individually to the bathing solution (8-MOP: 100 micromol/l; 5-MOP: 50 micromol/l; 5,8-EOP: 10 micromol/l) the following completely reversible effects were observed: 1. 8-MOP, caused a nearly potential-independent decrease of the sodium permeability, P'Na, by ca. 17%. 5-MOP and 5,8-EOP merely decreased the maximal value of P'Na, by ca. 12 and 8% respectively, whereas with weak depolarisations P'Na was unchanged. 2. In the tested potential range the potassium permeability, P'K, was caused to decrease by ca. 9% by 8-MOP, ca. 21% by 5-MOP and ca. 19% by 5,8-EOP. 3. The potassium currents acquired a phasic time course previously described for 8-MOP and 5-MOP. They reached a relative maximum and approached a lower steady-state value, kinfinity, with a time constant tauk at V = 120 mV of about 16 ms (8-MOP), 20 ms (5-MOP) and 94 ms (5,8-EOP). To obtain dose-response relations the drug-induced effects on peak P'K and on the steady state value, kinfinity, were measured. The corresponding apparent dissociation constants (in micromol/l) were 66.6 and 80.1 (for 8-MOP), 87.6 and 25.8 (for 5-MOP), and 13.5 and 6.5 (for 5,8-EOP). In view of the similarity of the actions of 5-MOP and 5,8-EOP as well as the fact that 5,8-EOP is not phototoxic, in future 5,8-EOP may well prove to be a particularly suitable K+-channel blocker for the symptomatic therapy of multiple sclerosis and other demyelinating diseases.

Alkoxypsoralens, novel nonpeptide blockers of Shaker-type K+ channels: synthesis and photoreactivity.

A series of psoralens and structurally related 5,7-disubstituted coumarins was synthesized and investigated for their K+ channel blocking activity as well as for their phototoxicity to Artemia salina and their ability to generate singlet oxygen and to photomodify DNA. After screening the compounds on Ranvier nodes of the toad Xenopus laevis, the affinities of the most promising compounds, which proved to be psoralens bearing alkoxy substituents in the 5-position or alkoxymethyl substituents in the neighboring 4- or 4'-position, to a number of homomeric K+ channels were characterized. All compounds exhibited the highest affinity to Kv1.2. 5,8-Diethoxypsoralen (10d) was found to be an equally potent inhibitor of Kv1.2 and Kv1.3, while lacking the phototoxicity normally inherent in psoralens. The reported compounds represent a novel series of nonpeptide blockers of Shaker-type K+ channels that could be further developed into selective inhibitors of Kv1.2 or Kv1. 3.