1,3-Dichloroadamantyl-Containing Ureas as Potential Triple Inhibitors of Soluble Epoxide Hydrolase, p38 MAPK and c-Raf.

Soluble epoxide hydrolase (sEH) is an enzyme involved in the metabolism of bioactive lipid signaling molecules. sEH converts epoxyeicosatrienoic acids (EET) to virtually inactive dihydroxyeicosatrienoic acids (DHET). The first acids are "medicinal" molecules, the second increase the inflammatory infiltration of cells.

Fluorine and chlorine substituted adamantyl-urea as molecular tools for inhibition of human soluble epoxide hydrolase with picomolar efficacy.

Series of 1,3-disubstituted ureas and diadamantyl disubstituted diureas with fluorinated and chlorinated adamantane residues were shown to inhibit human soluble epoxide hydrolase (sEH) with inhibition potency ranging from 40 pM to 9.2 nM. The measured IC values for some molecules were below the accuracy limit of the existing assays.

Adamantyl-ureas with pyrazoles substituted by fluoroalkanes as soluble epoxide hydrolase inhibitors.

A series of soluble epoxide hydrolase (sEH) inhibitors containing halogenated pyrazoles was developed. Inhibition potency of the obtained compounds ranges from 0.8 to 27.

[Improvement of results of surgical treatment of patients syndrome of diabetic foot].

Results of complex treatment of 121 patients with syndrome of diabetic foot, complicated by purulent-necrotic affection of tissues, were analyzed. Individually differentiated approach in the choice of surgical tactics had permitted to improve the result of treatment.

[Surgical treatment of elderly patients with acute cholecystitis].

The experience with surgical treatment of 136 elderly and senile patients with acute cholecystitis has been summarized. In presence of pronounced concomitant pathology and reduced adaptation-compensatory resources of an organism, the authors consider microcholecystostomy to be a method of choice. The use of this method permits to improve the results of surgical treatment and decrease the postoperative lethality.