Political violence in North Caucasus from 1994 to 2009.

Политичко насиље као један од појавних облика социјалног насиља је од 1994. до 2009. године представљало основно средство у борби за власт, контролу над природним ресурсима и остварење националних, верских и других циљева великих друштвених група, па и читавих етничких заједница на Северном Кавказу. Да би се дошло до свеобухватних научних сазнања о овој теми, потребно је извршити анализу досадашњих достигнућа на плану дефинисања политичког насиља, као и друштвено-економских релација и противречности из којих проистичу његови стварни и потенцијални узроци, попут унутрашње политичке, социјално-економске и безбедносне кризе, сложених регионалних и међународних односа, интереса и сл. Политичко насиље уопште, па и на Северном Кавказу, има материјално-економске, идејно-идеолошке, алијенационо-интерперсоналне и политичко-организационе основе, а може се класификовати према различитим критеријумима, као што су садржај, начин вршења, носиоци, односно квантитативан обим субјекта, распрострањеност, време трајања, одговарајућа функција, итд. У севернокавкаском региону политичко насиље има дубоке корене, чије сагледавање подразумева мултидисциплинарни приступ, превасходно заснован на политичким наукама, историји, социологији, културологији и етнопсихологији, како би се утврдили узроци и приказала генеза, континуитет и специфичности ове појаве. Правилно поимање историје Северног Кавказа је битан предуслов за објективно истраживање и оцену конкретних савремених примера основних (претња силом, принуда и притисак, психофизичко злостављање – мучење, политичко убиство и атентат и диверзија) и сложених облика (насилни протести, побуне, нереди и немири, тероризам, субверзија, репресија, терор, герила, устанак, војна интервенција и рат) политичког насиља који су се догодили у овом региону или су настали као последица збивања на тим просторима. Свака држава која се суочи с политичким насиљем настоји да му се супротстави на ефикасан начин. Стога истраживање овог политичког феномена на Северном Кавказу подразумева подробно теоријско проучавање позиције, улоге и значаја свих актера укључених у процес супротстављања, а нарочито специјалних (контраобавештајних и обавештајних) служби и јединица. Имајући у виду да супротстављање политичком насиљу у савременим условима подразумева знатно шири приступ од искључивог ослањања на репресивне методе, неопходно је сагледати све могућности које стоје на располагању субјектима супротстављања. Основни критеријуми за оцену квалитета примењених метода представљају садржај, ефекти, домети и границе достигнуте током супротстављања политичком насиљу на Северном Кавказу, на основу чега се на теоријском нивоу могу формулисати предлози за модификацију постојећих и примену нових, делотворнијих методаIn the period from 1994 to 2009, political violence as a form of social violence, has been an indispensable instrument in the struggle for power, control over natural resources and for achieving various national, religious and other goals of large social groups, or even entire ethnic communities in the North Caucasus region. To reach any comprehensive scientific conclusions on this subject matter, it is crucial to examine current scientific accomplishments towards defining political violence. It is also necessary to analyze socio-economic relations and contradictions that are the underlying actual or potential causes of political violence, which include internal political, socio-economic and security crisis, complex regional and international relations, interests, etc. Fundamental, principles political violence in North Caucasus, as in general, is based upon can be perceived as economic, ideology, interpersonal alienation, political organization. It can be classified according to different criteria like substance, method of delivery, perpetrators, quantitative scope of the participants, prevalence, duration, apparent function, etc. In the region of North Caucasus political violence is deeply rooted and to comprehend it properly demands a multidisciplinary approach, predominantly based on political sciences, history, sociology, culturology and ethno-psychology to determine all the causes, genesis, continuity and specificities of this phenomenon. Proper understanding of history of North Caucasus region is an essential prerequisite for objective analysis and interpretation of concrete contemporary examples of elementary (threat of violence, coercion, pressure, psychophysical abuse – torture, political murder, assassination and diversion) and complex forms (violent protests, rebellions, riots, acts of terrorism, subversive activity, repression, terror, guerilla warfare, uprisings and insurgencies, military interventions, and war) of political violence that have arisen as a direct consequence of the situation in this region. Every state faced with political violence aims to counter it in a most efficient way. Therefore, research of this phenomenon in North Caucasus implies thorough theoretical study of the position, role and significance of all the factors involved in opposing political violence, particularly special operations (intelligence and counter-intelligence) services and units. Having in mind that opposing political violence in contemporary terms necessitates a much more comprehensive approach than exclusively relying on repressive methods, it is crucial to analyze all the options agents acting in opposition to political violence have at their disposal. Effectiveness of applied methods can be assessed on the basis of substance, effects, reach and limitations of what has been achieved so far in opposing political violence in North Caucasus region. This evaluation can then be used in formulating theoretical recommendations for modification of existing and development of new, more effective strategie

Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

Acute ethanol intoxication increases the production of reactive oxygen species (ROS). Hemorrhagic shock with subsequent resuscitation (H/R) also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.). Then, rats were hemorrhaged to a mean arterial blood pressure of 30 ± 2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.). Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE) and nitrosative (3-nitrotyrosine, 3-NT) stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver

Inhibition of Macrophage Migration Inhibitory Factor Activity Attenuates Haemorrhagic Shock-Induced Multiple Organ Dysfunction in Rats

OBJECTIVE: The aim of this study was to investigate (a) macrophage migration inhibitory factor (MIF) levels in polytrauma patients and rats after haemorrhagic shock (HS), (b) the potential of the MIF inhibitor ISO-1 to reduce multiple organ dysfunction syndrome (MODS) in acute (short-term and long-term follow-up) HS rat models and (c) whether treatment with ISO-1 attenuates NF-κB and NLRP3 activation in HS. BACKGROUND: The MODS caused by an excessive systemic inflammatory response following trauma is associated with a high morbidity and mortality. MIF is a pleiotropic cytokine which can modulate the inflammatory response, however, its role in trauma is unknown. METHODS: The MIF levels in plasma of polytrauma patients and serum of rats with HS were measured by ELISA. Acute HS rat models were performed to determine the influence of ISO-1 on MODS. The activation of NF-κB and NLRP3 pathways were analysed by western blot in the kidney and liver. RESULTS: We demonstrated that (a) MIF levels are increased in polytrauma patients on arrival to the emergency room and in rats after HS, (b) HS caused organ injury and/or dysfunction and hypotension (post-resuscitation) in rats, while (c) treatment of HS-rats with ISO-1 attenuated the organ injury and dysfunction in acute HS models and (d) reduced the activation of NF-κB and NLRP3 pathways in the kidney and liver. CONCLUSION: Our results point to a role of MIF in the pathophysiology of trauma-induced organ injury and dysfunction and indicate that MIF inhibitors may be used as a potential therapeutic approach for MODS after trauma and/or haemorrhage

Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides

5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations, revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c) with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM, respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological results are therefore in accordance with the molecular docking simulations thus proving the rational design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new, potential antidepressants

Contributions to the phylogeny of Ixodes (Pholeoixodes) canisuga, I. (Ph.) kaiseri, I. (Ph.) hexagonus and a simple pictorial key for the identification of their females

Background: In Europe, hard ticks of the subgenus Pholeoixodes (Ixodidae: Ixodes) are usually associated with burrow-dwelling mammals and terrestrial birds. Reports of Pholeoixodes spp. from carnivores are frequently contradictory, and their identification is not based on key diagnostic characters. Therefore, the aims of the present study were to identify ticks collected from dogs, foxes and badgers in several European countries, and to reassess their systematic status with molecular analyses using two mitochondrial markers. Results: Between 2003 and 2017, 144 Pholeoixodes spp. ticks were collected in nine European countries. From accurate descriptions and comparison with type-materials, a simple illustrated identification key was compiled for adult females, by focusing on the shape of the anterior surface of basis capituli. Based on this key, 71 female ticks were identified as I. canisuga, 21 as I. kaiseri and 21 as I. hexagonus. DNA was extracted from these 113 female ticks, and from further 31 specimens. Fragments of two mitochondrial genes, cox1 (cytochrome c oxidase subunit 1) and 16S rRNA, were amplified and sequenced. Ixodes kaiseri had nine unique cox1 haplotypes, which showed 99.2-100% sequence identity, whereas I. canisuga and I. hexagonus had eleven and five cox1 haplotypes, respectively, with 99.5-100% sequence identity. The distribution of cox1 haplotypes reflected a geographical pattern. Pholeoixodes spp. ticks had fewer 16S rRNA haplotypes, with a lower degree of intraspecific divergence (99.5-100% sequence identity) and no geographical clustering. Phylogenetic analyses were in agreement with morphology: I. kaiseri and I. hexagonus (with the similar shape of the anterior surface of basis capituli) were genetically more closely related to each other than to I. canisuga. Phylogenetic analyses also showed that the subgenus Eschatocephalus (bat ticks) clustered within the subgenus Pholeoixodes. Conclusions: A simple, illustrated identification key is provided for female Pholeoixodes ticks of carnivores (including I. hexagonus and I. rugicollis) to prevent future misidentification of these species. It is also shown that I. kaiseri is more widespread in Europe than previously thought. Phylogenetic analyses suggest that the subgenus Pholeoixodes is not monophyletic: either the subgenus Eschatocephalus should be included in Pholeoixodes, or the latter subgenus should be divided, which is a task for future studies

Valproic acid inhibits adhesion of vincristine- and cisplatin-resistant neuroblastoma tumour cells to endothelium

Drug resistance to chemotherapy is often associated with increased malignancy in neuroblastoma (NB). In pursuit of alternative treatments for chemoresistant tumour cells, we tested the response of multidrug-resistant SKNSH and of vincristine (VCR)-, doxorubicin (DOX)-, or cisplatin (CDDP)-resistant UKF-NB-2, UKF-NB-3 or UKF-NB-6 NB tumour cell lines to valproic acid (VPA), a differentiation inducer currently in clinical trials. Drug resistance caused elevated NB adhesion (UKF-NB-2VCR, UKF-NB-2DOX, UKF-NB-2CDDP, UKF-NB-3VCR, UKF-NB-3CDDP, UKF-NB-6VCR, UKF-NB-6CDDP) to an endothelial cell monolayer, accompanied by downregulation of the adhesion receptor neural cell adhesion molecule (NCAM). Based on the UKF-NB-3 model, N-myc proteins were enhanced in UKF-NB-3VCR and UKF-NB-3CDDP, compared to the drug naïve controls. p73 was diminished, whereas the p73 isoform deltaNp73 was upregulated in UKF-NB-3VCR and UKF-NB-3CDDP. Valproic acid blocked adhesion of UKF-NB-3VCR and UKF-NB-3CDDP, but not of UKF-NB-3DOX, and induced the upregulation of NCAM surface expression, NCAM protein content and NCAM coding mRNA. Valproic acid diminished N-myc and enhanced p73 protein level, coupled with downregulation of deltaNp73 in UKF-NB-3VCR and UKF-NB-3CDDP. Valproic acid also reverted enhanced adhesion properties of drug-resistant UKF-NB-2, UKF-NB-6 and SKNSH cells, and therefore may provide an alternative approach to the treatment of drug-resistant NB by blocking invasive processes

Evidence That Lipopolisaccharide May Contribute to the Cytokine Storm and Cellular Activation in Patients with Visceral Leishmaniasis

Visceral leishmaniasis (VL) affects organs rich in lymphocytes, being characterized by intense Leishmania-induced T-cell depletion and reduction in other hematopoietic cells. In other infectious and non-infectious diseases in which the immune system is affected, such as HIV-AIDS and inflammatory bowel disease, damage to gut-associated lymphocyte tissues occurs, enabling luminal bacteria to enter into the circulation. Lipopolisaccharide (LPS) is a bacterial product that stimulates macrophages, leading to the production of pro-inflammatory cytokines and other soluble factors such as MIF, which in turn activate lymphocytes. Continuous and exaggerated stimulation causes exhaustion of the T-cell compartment, contributing to immunosuppression