This review presented recent data on initiation, regulation, and execution of neutrophil apoptosis with participation of «death receptors», mitochondria, Bcl-2 family proteins, PI3-K (phosphatidylinositol 3-kinase), p38 MAPK (mitogen-activated protein kinase), ERK (extracellular signal regulated kinase) and JNK (c-Jun N-terminal kinase) cascades, protein kinases A, B and C, сAMP, heat shock proteins, NF-κB (nuclear factor-κB), calpains, caspases and theirs inhibitors, reactive oxygen species, and other factors. A speculative model of the apoptotic processes involvement in the regulation of neutrophil differentiation and reactivity was proposed.

В обзоре представлены современные данные о механизмах инициации, регуляции и выполнении процесса апоптоза нейтрофилов с участием «рецепторов смерти», митохондрий, белков семейства Bcl-2, PI3-K (phosphatidylinositol 3-kinase), протеинкиназных каскадов p38 MAPK (mitogen-activated protein kinase), ERK (extracellular signal regulated kinase) и JNK (c-Jun N-terminal kinase), протеинкиназ А, В и С, сAMP, белков теплового шока, NF-kB (nuclear factor-kB), кальпаинов, каспаз и их ингибиторов, активных форм кислорода и других факторов. Предложена гипотетическая модель вовлечения апоптотических процессов в регуляцию дифференцировки и реактивности нейтрофилов. This review presented recent data on initiation, regulation, and execution of neutrophil apoptosis with participation of «death receptors», mitochondria, Bcl-2 family proteins, PI3-K (phosphatidylinositol 3-kinase), p38 MAPK (mitogen-activated protein kinase), ERK (extracellular signal regulated kinase) and JNK (c-Jun N-terminal kinase) cascades, protein kinases A, B and C, сAMP, heat shock proteins, NF-kB (nuclear factor-kB), calpains, caspases and theirs inhibitors, reactive oxygen species, and other factors. A speculative model of the apoptotic processes involvement in the regulation of neutrophil differentiation and reactivity was proposed.

We present here a review of the literature on the role of c-Jun N-terminal kinases (JNK) and their inhibitors in ischemic and reperfusion brain injuries. The functions of JNK in the signal mechanisms involved in brain damage in ischemia and reperfusion are discussed. Effects linked with inhibition of JNK with synthetic and natural compounds in experimental models of ischemia and reperfusion brain injury are described. Results from experimental studies show that JNK provide potential therapeutic targets for protecting the brain from ischemic stroke. However, the fact that JNK have numerous physiological functions prevents systematic use of nonspecific inhibitors of these kinases for therapeutic purposes. The authors conclude that this task requires a further search for selective JNK3 inhibitors.

o- and p-Hydroxybenzohydrazides reacted with various unsaturated aromatic aldehydes to give the corresponding N′-(hydroxybenzoyl)hydrazones. Inhibitory activity of the obtained hydrazones against cathepsin E was evaluated.

The article provides review of literature on the role of c Jun N terminal kinases (JNK) in ischemia/reperfusion injury of the myocardium. The classification of JNK is presented; JNK functions in signaling mechanisms are described in the context of ischemia/reperfusion injury. Authors discuss biological effects of pharmacological modulation of JNK by using synthetic and natural compounds in the models of myocardial ischemia/reperfusion. The role of JNK in the mechanisms of pre and postconditioning of the heart is highlighted. Results of experimental studies are demonstrated that JNK represent potential therapeutic targets for cardiac protection from ischemia/reperfusion injury. At the same time, the presence of multiple physiological JNK properties does not allow for systemic use of non specific JNK inhibitors for therapeutic purposes. Authors conclude that the actual problem is the further search for selective JNK3 inhibitors.

Amination reactions of guaianolide of estafiatine were investigated in this article. It is shown that secondary amines interact only with the conjugated exomethylene bond of the lactone cycle with the formation of Michael adducts. Discussed in this paper sesquiterpene lactone estafiatine (1) and its modified derivatives were studied in order to obtain new biologically active compounds and to determine of influence of structural features of the molecules of this series on their biological activity. It is found that the number of synthesized nitrogen- containing derivatives of estafiatine have anti-inflammatory and cytotoxic activity.

Authors submitted an analysis of papers given up an involvement of protein kinases in heart ischemic postconditioning. This analysis of literature source allowed to authors affirms that signaling system of postconditioning can involve kinases: PKC, PI3K, Akt, MEKl/2, ERK1/2, MTOR, p70s6K, GSK3b, PKG and also eNOS, NO, GC, motoKATP channel, ROS, MPT pore. At the same time it is unclear a real contributions of kinases mTOR, p70s6, AMPK and GSK3b in the mechanism of infarct limiting impact of postconditioning. It is required a further study of the chain of signaling events following JAK2 and p38 kinase activation. The knowledge of Ras and Raf-1 role in postconditioning has hypothetical character. The tyrosine kinase significance in postcondi-tioning is unclear, particular Src kinase, which plays an important role in the regulation of cardiac tolerance to an impact of ischemia and reperfusion.

Both metronidazole and aminotriazole increased while sanazole (drug AK-2123) decreased the NADPH/lucigenin-dependent chemiluminescence of liver microsomes of phenobarbital-treated rats. Sanazole strongly inhibited the lucigenin-dependent chemiluminescence in the enzyme system of xanthine-xanthine oxidase. Aminotriazole and metronidazole were less potent inhibitors of chemiluminescence less than sanazole. All these azole derivatives did not absorb light in the region of light emission of lucigenin. Both lucigenin and sanazole increased the rate of cytochrome c reduction by microsomes in case of using NADPH as a donor of electrons, whereas no effect of metronidazole and aminotriazole on this rate was found. The sanazole inhibition of lucigenin-dependent chemiluminescence could reflect competition between sanazole and lucigenin for electrons in the active centre of flavin reductases. Thus, microsomal NAD(P)H-reductases can be potentially involved in a bioactivation of sanazole. Lucigenin-dependent chemiluminescence cannot be used for measuring the modulating action of agents on reactive oxygen species production in the microsomes, but it may be used for luminometrical studies of enzyme complex NAD(P)H-reductases/cytochrome P450 in model systems.

The in vitro effect of sanazole (AK-2123; N-(2'-methoxyethyl)-2-[3"-nitro-1"-triazolyl]acetamide) and metronidazole (1-beta-hydroxyethyl-2-methyl-5-nitroimidazole) on phorbol-12-myristate-13-acetate (PMA)-stimulated and spontaneous (without stimulation by PMA) production of reactive oxygen species (ROS) by peritoneal and splenic murine macrophages was studied. ROS production was analyzed using fluorescent probe 2',7'-dichlorofluoresceine diacetate (DCFH-DA). An increase in the spontaneous production of ROS by macrophagal cells with therapeutic concentration of sanazole (0.6-1.25 mM) in the incubation medium was observed. At these concentrations metronidazole had no effect on spontaneous production of ROS by macrophagal cells. PMA-stimulated ROS production was inhibited by high concentrations (2.5-10 mM) of sanazole and metronidazole. The spontaneous generation of ROS by peritoneal macrophages was stimulated by sanazole at all tested concentrations (0.6-10 mM).

The mechanisms of formation, morphology and functions of macrophagal polykaryons are discussed. These giant multinuclear cells are formed by means of macrophagal cell fusion ("natural hybridization") and specialized on the extra- and intracellular processes of resorption of the foreign body and tissues of the proper organism. The formation of macrophagal polykaryons seems to be one of the possible manifestation of reactive histiocytosis in chronic inflammation and tumor growth. The role of macrophagal polykaryons in such disease as giant cell arteritis, giant cell granuloma and fibrohistiocytic tumors is considered in details. It is proposed that one and the same mechanism of regulations served as a basis of developing of both osteoclastic remodelling of the bone tissue (morphogenetic process) and resorption of the foreign body and tissues of the proper organism in inflammation in the process of evolution.

Activities of acid and alkaline phosphatases, collagenase, cathepsin D, trypsin-like proteinases, alpha(1)-proteinase inhibitor (alpha(1)-PI), alpha(2)-macroglobulin (alpha(2)-MG) were measured in blood plasma and tumor tissue of patients with giant-cell tumor of the bone (GCTB) and bone chondrosarcoma. These tumors differed by enzymatic activities. GCTB is characterized by increased activity of alkaline phosphatase, while in chondrosarcoma tissue the activities of collagenase and cathepsin D were the highest. Activities of acid phosphatase, collagenase, trypsin-like proteinases were increased in the plasma of patients with both tumors; alpha(1)-PI/alpha(2)-MG ratio was increased. Bone resorption parameters correlated with proteolysis inhibitors. Activities of collagenase and acid phosphatase were increased in tumor tissue and plasma in the presence of low activities of alpha(2)-MG and increased alpha(1)-PI/alpha(2)-MG index, which seems to require special attention during the postoperative period.

Spectrometry has been employed to assess the levels of collagenase, catepsin D, trypsin-like proteinases and their inhibitors as well as bone acid and alkaline phosphatase both in the center and along the periphery of giant cell tumor of bone (GCTB) and chondrosarcoma. The levels of collagenase, trypsin-like proteinases and their inhibitors in the center of chondrosarcoma were much higher while those of alkaline phosphatase--lower than along tumor periphery. The catepsin D and acid phosphatase concentrations of the center and periphery of chondrosarcoma were similar. It was suggested that an extremely low concentration of trypsin-like inhibitors may contribute to degradation of the matrix in tissues adjacent to chondrosarcoma and, consequently, to tumor invasion development.

The article discusses the possible mechanisms of the antineoplastic effect of hypoxic bioreducing agents (HBA) when they are used in low nonhypoxic doses. Experimental and clinical studies provide evidence of the occurrence of stages which in administration of HBA into the organisms of the tumor-carrier may develop in succession, leading to stimulation of antineoplastic immunity: GBA activation in the hypoxic neoplastic tissue, conjugation of HBA metabolites with the macromolecules of the tumor cells, and presentation of the epitopes of neoantigens in association with the main complex of class I histocompatibility (MCH) cytolysis of these cells by T-killers. This process may be similar to that in contact sensitivity to low-molecular compounds (a variant of the reaction of delayed hypersensitivity [DH]) in the neoplastic focus. It is suggested that direct control of the effect of HBA on the immunocompetent and/or tumor cells may occur additively to or synergically with this process as the result of interaction of these compounds with the surface or intracellular receptors. It cannot be excluded that the activated HBA may force the endogenic ligands out of the nucleophilic centers of these receptors and realize receptor-mediated control of gene expression.