Design, synthesis and cardiovascular evaluation of some aminoisopropanoloxy derivatives of xanthone.

A series of aminoisopropanoloxy derivatives of xanthone has been synthesized and their pharmacological properties regarding the cardiovascular system has been evaluated. Radioligand binding and functional studies in isolated organs revealed that title compounds present high affinity and antagonistic potency for α1-(compound 2 and 8), ß-(compounds 1, 3, 4, 7), α1/ß-(compounds 5 and 6) adrenoceptors. Furthermore, compound 7, the structural analogue of verapamil, possesses calcium entry blocking activity. The title compounds showed hypotensive and antiarrhythmic properties due to their adrenoceptor blocking effect. Moreover, they did not affect QRS and QT intervals, and they did not have proarrhythmic potential at tested doses. In addition they exerted anti-aggregation effect. The results of this study suggest that new compounds with multidirectional activity in cardiovascular system might be found in the group of xanthone derivatives.

Synthesis, alpha-adrenoceptors affinity and alpha 1-adrenoceptor antagonistic properties of some 1,4-substituted piperazine derivatives.

A series of different 1,4-substituted piperazine derivatives (1-11) was synthesized. It comprised 1-(substituted-phenoxyalkyl)-4-(2-methoxyphenyl)piperazine derivatives (1-5); 1,4-bis(substituted-phenoxyethyl)piperazine derivatives (6-8) and 1-(substituted-phenoxy)-3-(substituted-phenoxyalkylpiperazin-1-yl)propan-2-ol derivatives (9-11). All compounds were evaluated for affinity toward alpha 1- and alpha 2-receptors by radioligand binding assays on rat cerebral cortex using [3H]prazosin and [3H]clonidine as specific radioligand, respectively. Furthermore alpha 1-antagonistic properties were checked for most promising compounds (1-5 and 10) by means of inhibition of phenylephrine induced contraction in isolated rat aorta. Antagonistic potency stayed in agreement with radioligand binding results. The most active compounds (1-5) displaced [3H]prazosin from cortical binding sites in low nanomolar range (Ki = 2.1-13.1 nM). Compound 10 showed slightly lower affinity for alpha 1-adrenoceptor (Ki = 781 nM). Compounds 2-5 displayed the strongest antagonistic activity with pA2 values ranging from 8.441 to 8.807. Compound 1 gave a pA2 value of 7.868, while compound 10 showed the weakest antagonistic potency, giving a pA2 value of 6.374. 1-[3-(2-Chloro-6-methylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride (5) showed the best alpha 1- affinity properties with a Ki(alpha 1) value of 2.1 nM and it was 61.05 fold more selective toward alpha 1 than alpha 2-receptors. The best properties showed 1-[3-(2,6-dimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride (4) with a Ki(alpha 1) value of 2.4 nM, a 142.13 fold better selectivity to alpha 1 - over alpha 2-adrenoceptors and the best antagonistic potency (pA2 = 8.807). It is worth to emphasized that all most promising compounds possessed an 1-(o-methoxyphenyl)piperazine moiety which probably plays an important role in the affinity to alpha-adrenoceptors.

Soluble L-selectin and interleukin-8 in otitis media with effusion.

OBJECTIVE: adhesion of leukocytes to vascular endothelium and their invasion into local tissues are important steps in inflammation. L-selectin plays a crucial role in leukocyte rolling and adhesion on endothelial cell surface. Interleukin-8 (IL-8) is a potent chemotactic substance toward neutrophils and lymphocytes-T and mediate their migration to local inflammation. The levels of soluble L-selectin (sL-selectin) and IL-8 were measured in middle ear effusions (MEE) from children with otitis media (OM) to estimate their role in pathogenesis of inflammation in middle ear. METHODS: MEE were collected from 113 ears of 62 children during routine myringotomy. The entire specimen was diluted with phosphate-buffered saline (PBS) to 2 ml and centrifugated at 1500 rpm for 15 min to separate cellular components. Supernatants of MEE were stored frozen at -20 degrees C for sL-selectin and at -80 degrees C for IL-8 assessment. The concentration of sL-selectin and IL-8 were estimated with ELISA and compared with total protein concentration measured by Bradford assay. RESULTS: MEEs from children with chronic mucous otitis media contained significantly higher mean concentrations of IL-8 559.4 pg/mg total protein (TP) (+/-535.6) in comparison with normal serum 17.79 pg/mg TP (+/-10.9), serous OM 40.3 pg/mg TP (+/-28.1) and purulent OM 104.4 pg/mg TP (+/-128.6). High concentration of IL-8 was found in MEE from the children with early recurrence of OMS. The levels of sL-selectin were higher in purulent effusions 77.2 ng/mg TP (+/-67.4) than those of chronic mucoid 27.6 ng/mg TP (+/-36.7) and serous OM 26.3 ng/mg TP (+/-27.1). CONCLUSION: the results support a hypothesis that IL-8 can be responsible for prolongation of inflammatory process in middle ear, therefore long-term treatment and observation of children with the high levels of IL-8 in MEE may be necessary. Elevated level of sL-selectin in acute OM suggests the involvement of L-selectin in the acute phase of OM.

[A case of cylindroma of the parapharyngeal space]. / Przypadek oblaka przestrzeni przygardlowej.

The authors show a case of parapharyngeal space cylindroma paying attention to large diagnostic difficulties. This tumor has been characterized by a slow local growth but after five years disease involved many organs with metastases.

[Chondrocalcinosis: rarely diagnosed frequent disease. A case report]. / Chondrokalcynoza--rzadko diagnozowana czesta choroba--opis przypadku.

In this paper we described a case of 56 old patient with history of joint disease. We diagnosed chondrocalcinosis with hypomagnesemia. The patient was treated for gout during last 13 years. The frequency of chondrocalcinosis is estimated about 10% in patients after 50 years of age, but it is very rare diagnosed. A correct diagnosis is possible on the basis of simple tests and it allows to avoid the drugs which are not effective in this disease.