Zeitschriftenartikel zum Thema „Bimol Kar“

<p>This research is entitled Analysis of the Effect of Location and Price on the Purchase Decision of Cooking Oil at the Sulawesi Shop, Kab. Majene and the formulation of the problem expressed in this study is how the influence of location on the decision to purchase Bimoli cooking oil at the Sulawesi shop, Kab. Majene, How is the Price of Bimoli Cooking Oil Purchase Decision at the Sulawesi Shop, Kab. Majene and which variable has a more dominant influence on the Purchase Decision of Bimoli Cooking Oil at the Sulawesi Shop, Kab. Majene while the purpose of this study is to analyze the influence of location on the decision to purchase Bimoli cooking oil at the Sulawesi shop, Kab. Majene, to analyze the effect of price on the decision to purchase Bimoli cooking oil at the Sulawesi shop, Kab. Majene and To analyze which variable has a more dominant influence on the Purchase Decision of Bimoli Cooking Oil at the Sulawesi Shop, Kab. Majene. The population in this study are consumers of Sulawesi Stores, Kab. Majene with infinite population. The number of variables is 2, then the minimum number of samples is 50 people while the analytical method used in this study is to use Validity Value Testing and Reliability Value Testing, Multiple Regression Equation Results, t-value testing and F-value testing. While the results found in this study is Location (X1) has a significant effect on the Dependent Variable of Bimoli Cooking Oil Purchase Decision (Y) at the Sulawesi Shop, Kab. Majene, Price (X2) has a significant effect on the Dependent Variable Purchase Decision of Bimoli Cooking Oil (Y) at the Sulawesi Shop, Kab. Majene and (X1) have a more significant effect on the Purchase Decision of Bimoli Cooking Oil (Y) at the Sulawesi Shop, Kab. Majene.</p><p><strong>Keywords: </strong>Location, Price, Purchase Decision</p>

ABSTRACT Nat4, also designated NatD, was previously shown to acetylate the N termini of histones H2A and H4, which have SGGKG and SGRGK N termini (O. K. Song, X. Wang, J. H. Waterborg, and R. Sternglanz, J. Biol. Chem. 278:38109-38112, 2003). The analysis of chimeric proteins with various N-terminal segments of histone H4 fused to iso-1-cytochrome c revealed that efficient acetylation by NatD required at least 30 to 50 amino acid residues of the N terminus of histone H4. This requirement for an extended N terminus is in marked contrast with the major N-terminal acetyl transferases (NATs), i.e., NatA, NatB, and NatC, which require as few as two specific residues and usually no more than four or five. However, similar to the other NATs, NatD is associated with ribosomes. The nat4-Δ strain showed several minor phenotypes, including sensitivity to 3-aminotriazole, benomyl, and thiabendazole. Moreover, these nat4-Δ phenotypes were enhanced in the strain containing K5R K8R K12R replacements in the N-tail of histone H4, suggesting that the lack of N-terminal serine acetylation is synergistic to the lack of acetylation of the H4 N-tail lysines. Thus, N-terminal serine acetylation of histone H4 may be a part of an essential charge patch first described for the histone H2A.Z variant in Tetrahymena species.

Schwann cells are remarkably plastic cells that can both form and stably maintain myelin sheaths around axons and also rapidly dedifferentiate upon injury. New findings (Parkinson, D.B., A. Bhaskaran, P. Arthur-Farraj, L.A. Noon, A. Woodhoo, A.C. Lloyd, M.L. Feltri, L. Wrabetz, A. Behrens, R. Mirsky, and K.R. Jessen. 2008. J. Cell Biol. 181:625–637) indicate that the transition between these distinct states of differentiation is directed by the transcription factor Krox-20, which promotes and maintains myelination, and c-Jun, which antagonizes it. Cross-inhibition of these transcription factors serves to switch Schwann cells between the myelinated and dedifferentiated phenotypes, respectively.

ABSTRACT TraP is a triply phosphorylated staphylococcal protein that has been hypothesized to be the mediator of a second Staphylococcus aureus quorum-sensing system, “SQS1,” that controls expression of the agr system and therefore is essential for the organism's virulence. This hypothesis was based on the loss of agr expression and virulence by a traP mutant of strain 8325-4 and was supported by full complementation of both phenotypic defects by the cloned traP gene in strain NB8 (Y. Gov, I. Borovok, M. Korem, V. K. Singh, R. K. Jayaswal, B. J. Wilkinson, S. M. Rich, and N. Balaban, J. Biol. Chem. 279:14665-14672, 2004), in which the wild-type traP gene was expressed in trans in the 8325-4 traP mutant. We initiated a study of the mechanism by which TraP activates agr and found that the traP mutant strain used for this and other recently published studies has a second mutation, an adventitious stop codon in the middle of agrA, the agr response regulator. The traP mutation, once separated from the agrA defect by outcrossing, had no effect on agr expression or virulence, indicating that the agrA defect accounts fully for the lack of agr expression and for the loss of virulence attributed to the traP mutation. In addition, DNA sequencing showed that the agrA gene in strain NB8 (Gov et al., J. Biol. Chem., 2004), in contrast to that in the agr-defective 8325-4 traP mutant strain, had the wild-type sequence; further, the traP mutation in that strain, when outcrossed, also had no effect on agr expression.

Glucocorticoid hormones can regulate the posttranslational maturation of mouse mammary tumor virus (MTV) precursor polyproteins in M1.54, a stably infected rat hepatoma cell line. We have used complement-mediated cytolysis to recover variants of M1.54 that fail to express MTV cell surface glycoproteins in a hormone-regulated manner (Firestone, G.L., and K.R. Yamamoto, 1983, Mol. Cell. Biol., 3:149-160). One such clonal isolate, CR4, is similar to wild-type with respect to synthesis of MTV mRNAs, production of the MTV glycoprotein precursor (gPr74env) and a glycosylated maturation product (gp51), and hormone-induced processing of two MTV phosphoproteins. In contrast, three viral cell surface glycoproteins (gp78, gp70, and gp32) and one extracellular species (gp70s), which derive from gPr74env in glucocorticoid-treated wild-type cells, fail to appear in CR4. CR4 showed no apparent alterations in proliferation rate, cell shape, or expression of total functional mRNA and bulk glycoproteins. We conclude that the genetic lesion in CR4 defines a highly selective hormone-regulated glycoprotein maturation pathway that alters the fate of a restricted subset of precursor species.

Several biologically important examples of posttranscriptionally regulated genes have recently been described (T. Gerster, D. Picard, and W. Schaffner, Cell 45:45-52, 1986; R. Reeves, T.S. Elton, M.S. Nissen, D. Lehn, and K.R. Johnson, Proc. Natl. Acad. Sci. USA 84:6531-6535, 1987; H.A. Young, L. Varesio, and P. Hwu, Mol. Cell. Biol. 6:2253-2256, 1986). Little is known, however, regarding sequences that mediate posttranscriptional RNA stability. Characterization in our laboratory of a mutant murine B lymphoma, M12.C3, revealed a posttranscriptional defect affecting the synthesis of a major histocompatibility complex class II gene (A beta d) whose product normally controls both the specificity and magnitude of the immune response. Molecular studies revealed that the mutation responsible for diminished A beta d gene expression was an intronic deletion of 10 base pairs (bp) located 99 bp 5' of the third exon. This deletion lies in a region not known to be critical for accurate and efficient splicing. Furthermore, sequence analysis of amplified A beta-specific cDNA demonstrated that the small number of A beta d transcripts produced in the mutant cells was correctly spliced. It appears that the mechanism by which this intronic 10-bp deletion acts to decrease RNA stability is unlikely to be at the level of RNA splicing.

Several biologically important examples of posttranscriptionally regulated genes have recently been described (T. Gerster, D. Picard, and W. Schaffner, Cell 45:45-52, 1986; R. Reeves, T.S. Elton, M.S. Nissen, D. Lehn, and K.R. Johnson, Proc. Natl. Acad. Sci. USA 84:6531-6535, 1987; H.A. Young, L. Varesio, and P. Hwu, Mol. Cell. Biol. 6:2253-2256, 1986). Little is known, however, regarding sequences that mediate posttranscriptional RNA stability. Characterization in our laboratory of a mutant murine B lymphoma, M12.C3, revealed a posttranscriptional defect affecting the synthesis of a major histocompatibility complex class II gene (A beta d) whose product normally controls both the specificity and magnitude of the immune response. Molecular studies revealed that the mutation responsible for diminished A beta d gene expression was an intronic deletion of 10 base pairs (bp) located 99 bp 5' of the third exon. This deletion lies in a region not known to be critical for accurate and efficient splicing. Furthermore, sequence analysis of amplified A beta-specific cDNA demonstrated that the small number of A beta d transcripts produced in the mutant cells was correctly spliced. It appears that the mechanism by which this intronic 10-bp deletion acts to decrease RNA stability is unlikely to be at the level of RNA splicing.

Cytoplasmic dynein is a microtubule minus-end–directed motor that is thought to power the transport of vesicles from the TGN to the apical cortex in polarized epithelial cells. Trans-Golgi enriched membranes, which were isolated from primary polarized intestinal epithelial cells, contain both the actin-based motor myosin-I and dynein, whereas isolated Golgi stacks lack dynein but contain myosin-I (Fath, K.R., G.M. Trimbur, and D.R. Burgess. 1994. J. Cell Biol. 126:661–675). We show now that Golgi stacks in vitro bind dynein supplied from cytosol in the absence of ATP, and bud small membranes when incubated with cytosol and ATP. Cytosolic dynein binds to regions of stacks that are destined to bud because dynein is present in budded membranes, but absent from stacks after budding. Budded membranes move exclusively towards microtubule minus-ends in in vitro motility assays. Extraction studies suggest that dynein binds to a Golgi peripheral membrane protein(s) that resists extraction by ice-cold Triton X-100. In the presence of cytosol, these membrane ghosts can move towards the minus-ends of microtubules. Detergent-extracted Golgi stacks and TGN-containing membranes are closely associated with an amorphous matrix composed in part of spectrin and ankyrin. Although spectrin has been proposed to help link dynein to organellar membranes, we found that functional dynein may bind to extracted membranes independently of spectrin and ankyrin.

The characteristic shapes and positions of each individual body muscle are established during the process of muscle morphogenesis in response to patterning information from the surrounding mesenchyme. Throughout muscle morphogenesis, primary myotubes are arranged in small parallel bundles, each myotube spanning the forming muscles from end to end. This unique arrangement potentially assigns a crucial role to primary myotube end regions for muscle morphogenesis. We have cloned muscle ankyrin repeat protein (MARP) as a gene induced in adult rat skeletal muscle by denervation. MARP is the rodent homologue of human C-193 (Chu, W., D.K. Burns, R.A. Swerick, and D.H. Presky. 1995. J. Biol. Chem. 270:10236–10245) and is identical to rat cardiac ankyrin repeat protein. (Zou, Y., S. Evans, J. Chen, H.-C. Kuo, R.P. Harvey, and K.R. Chien. 1997. Development. 124:793–804). In denervated muscle fibers, MARP transcript accumulated in a unique perisynaptic pattern. MARP was also expressed in large blood vessels and in cardiac muscle, where it was further induced by cardiac hypertrophy. During embryonic development, MARP was expressed in forming skeletal muscle. In situ hybridization analysis in mouse embryos revealed that MARP transcript exclusively accumulates at the end regions of primary myotubes during muscle morphogenesis. This closely coincided with the expression of thrombospondin-4 in adjacent prospective tendon mesenchyme, suggesting that these two compartments may constitute a functional unit involved in muscle morphogenesis. Transfection experiments established that MARP protein accumulates in the nucleus and that the levels of both MARP mRNA and protein are controlled by rapid degradation mechanisms characteristic of regulatory early response genes. The results establish the existence of novel regulatory muscle fiber subcompartments associated with muscle morphogenesis and denervation and suggest that MARP may be a crucial nuclear cofactor in local signaling pathways from prospective tendon mesenchyme to forming muscle and from activated muscle interstitial cells to denervated muscle fibers.

Previous studies have shown that polymorphonuclear leukocyte (PMN) adherence to endothelial cells (EC) induces transient increases in EC cytosolic free calcium concentration ([Ca2+]i) that are required for PMN transit across the EC barrier (Huang, A.J., J.E. Manning, T.M. Bandak, M.C. Ratau, K.R. Hanser, and S.C. Silverstein. 1993. J. Cell Biol. 120:1371–1380). To determine whether stimulation of [Ca2+]i changes in EC by leukocytes was induced by the same molecules that mediate leukocyte adherence to EC, [Ca2+]i was measured in Fura2-loaded human EC monolayers. Expression of adhesion molecules by EC was induced by a pretreatment of the cells with histamine or with Escherichia coli lipopolysaccharide (LPS), and [Ca2+]i was measured in single EC after the addition of mAbs directed against the EC adhesion proteins P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), or platelet/endothelial cell adhesion molecule-1 (PECAM-1). Both anti–P- and anti–E-selectin mAb, as well as anti–VCAM-1 mAb, induced transient increases in EC [Ca2+]i that were comparable to those induced by 200 μM histamine. In contrast, no effect was obtained by mAbs directed against the endothelial ICAM-1 or PECAM-1. PMN adherence directly stimulated increases in [Ca2+]i in histamine- or LPS-treated EC. mAbs directed against leukocyte CD18 or PECAM-1, the leukocyte counter-receptors for endothelial ICAM-1 and PECAM-1, respectively, did not inhibit PMN-induced EC activation. In contrast, mAb directed against sialyl Lewis x (sLex), a PMN ligand for endothelial P- and E-selectin, completely inhibited EC stimulation by adherent PMN. Changes in EC [Ca2+]i were also observed after adherence of peripheral blood monocytes to EC treated with LPS for 5 or 24 h. In these experiments, the combined addition of mAbs to sLex and VLA-4, the leukocyte counter-receptor for endothelial VCAM-1, inhibited [Ca2+]i changes in the 5 h–treated EC, whereas the anti–VLA-4 mAb alone was sufficient to inhibit [Ca2+]i changes in the 24 h-treated EC. Again, no inhibitory effect was observed with an anti-CD18 or anti–PECAM-1 mAb. Of note, the conditions that induced changes in EC [Ca2+]i, i.e., mAbs directed against endothelial selectins or VCAM-1, and PMN or monocyte adhesion to EC via selectins or VCAM-1, but not via ICAM-1 or PECAM-1, also induced a rearrangement of EC cytoskeletal microfilaments from a circumferential ring to stress fibers. We conclude that, in addition to their role as adhesion receptors, endothelial selectins and VCAM-1 mediate endothelial stimulation by adhering leukocytes.

Background:Granulomatosis with polyangiitis (GPA) is characterized by extravascular necrotizing granulomatous inflammation and systemic ANCA – associated (AAV) vasculitis with neutrophils as a key player in the pathogenesis (1). We and others have shown that neutrophil-related cell death mechanisms contribute to chronic inflammatory processes in AAV (2, 3). Recently, another form of inflammatory cell death primarily described in monocytes called pyroptosis was also discovered in neutrophils (4). A cardinal feature of pyroptosis is the activation of the NLRP3 inflammasome, a sensor of different pathogen- and damage-associated molecular patterns (PAMP, DAMP), following caspase-1-mediated processing and secretion of IL-1beta (5).Objectives:The aim of this study was to investigate, if neutrophils from GPA patients express pyroptosis-related components NLRP3, active caspase 1 and cleaved IL-1beta.Methods:Polymorphonuclear leukocytes (PMN) were isolated from peripheral blood of GPA patients and healthy controls (HC) (n = 10 each). Expression of NLRP3, inactive/active caspase 1 and active IL-1beta was determined by western blot. In addition, peripheral blood mononuclear cells (PBMC) were isolated from GPA and HC. mRNA expression ofnlrp3andil1bwas determined by qPCR. To exclude false-positive results by contamination with monocytes we performed flow cytometry analysis of whole blood samples with markers CD3, CD14, CD15, CD66b and NLRP3.Results:PMN from GPA patients showed markedly increased expression of NLRP3, active caspase 1 and active IL-1beta compared to HC. In contrast, there was no difference between GPA and HC on the mRNA level of neithernlrp3noril1bin PBMC. In addition, we confirmed by flow cytometry increased expression of NLRP3 in PMN from GPA, but not in monocytes.Conclusion:Here we provide evidence, that neutrophils from GPA undergo pyroptosis, demonstrated by increased NLRP3, active caspase 1 expression as well as IL-1beta processing. Neutrophils are present in high numbers at the site of granulomatous lesions of inflamed tissue in GPA and IL-1beta is increased in GPA sera (2). Therefore, neutrophils represent a potential source of IL-1beta in GPA. Given the fact that GPA-associated features such as massive release of necrosis-related DAMP or microbial agents such asStaphylococcus aureus(6) can activate the NLRP3-inflammasome, we identified here a potential relevant mechanism of neutrophils contributing to chronic inflammation of GPA.References:[1]Jennette, J.C., and Falk, R.J. (2014). Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat. Rev. Rheumatol.10, 463–473.[2]Millet, A., Martin, K.R., Bonnefoy, F., Saas, P., Mocek, J., Alkan, M., Terrier, B.,Kerstein,A., Tamassia, N., Satyanarayanan, S.K., et al. (2015). Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis. J. Clin. Invest. 125, 4107–4121.[3]Schreiber, A., Rousselle, A., Becker, J.U., von Mässenhausen, A., Linkermann, A., and Kettritz, R. (2017). Necroptosis controls NET generation and mediates complement activation, endothelial damage, and autoimmune vasculitis. Proc. Natl. Acad. Sci. 201708247.[4]Tourneur, L., and Witko-Sarsat, V. (2019). Inflammasome activation: Neutrophils go their own way. J. Leukoc. Biol.105, 433–436.[5]Bergsbaken, T., Fink, S.L., and Cookson, B.T. (2009). Pyroptosis: Host cell death and inflammation. Nat. Rev. Microbiol.7, 99–109.[6]Lamprecht, P.,Kerstein, A., Klapa, S., Schinke, S., Karsten, C.M., Yu, X., Ehlers, M., Epplen, J.T., Holl-Ulrich, K., Wiech, T., et al. (2018). Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides. Front. Immunol.9, 1–10.Disclosure of Interests:Anja Kerstein-Staehle: None declared, Nadja Leinung: None declared, Jannik Meyer: None declared, Silke Pitann: None declared, Antje Müller: None declared, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Peter Lamprecht: None declared

Abstract Introduction Thrombosis is a common pathology underlying ischemic heart disease, stroke, and venous thromboembolism. D-dimer is a global indicator of blood coagulation activation and fibrinolysis and, therefore, an indirect marker of thrombotic activity. D-dimers half-life is 48 hours. D-dimer determination is the standard procedure in the treatment of thrombosis. Serine protease thrombin plays pivotal roles in thrombosis and hemostasis, blood coagulation and platelet activation. Thrombin has a short half-life and naturally occurring inhibitors, such as antithrombin, rapidly bind thrombin, which makes the direct measurements of in vivo active thrombin difficult. Thrombin binds to fibrin where it is quite efficiently protected from inhibition by heparin-antithrombin but susceptible to inactivation by different antithrombin-independent inhibitors. There are two low affinity non-substrate thrombin binding sites, one in each half of the dimeric fibrinogen E region, and one high affinity thrombin non-substrate binding site on fibrinogen gamma' chains inside the D region (Meh DA, Siebenlist KR, Mosesson MW, J Biol Chem. 1996, 23121-5). We have shown that thrombin bound to fibrin promotes further fibrin growth in the presence of fibrinogen and absence of free thrombin in solution (Riedel T, Brynda E, Dyr JE, Houska, M, J. Biomed. Mater. Res. Part A 2009, 437-447). The aim of this project was to look for any thrombin activity on isolated D-dimers using several commercial D-dimer kits in groups of patients with elevated D-dimers. Methods Three D-dimers kits were used (ELISA kits CEA506Hu, USCN and D-Dimer (D2D), BioAssay™; and immunoturbidimetric assay D-Dimer KAI-090, K-ASSAY). To detect thrombin activity on captured D-dimers one chromogenic (S-2238, Chromogenix) and two fluorogenic (SN-59, Haematologic Technologies, Inc.; (p-tosyl-Gly-Pro-Arg)2-R110, Thermo Fisher Scientific, Inc.) specific substrates and specific inhibitors (hirudine and PPACK) were used. Independently, bound proteins were removed from immobilized antibodies in 8 M urea and after treatment with trypsin analyzed by mass spectrometry (TripleTOF 5600, Sciex). 34 patients with high, moderate, and low levels of D-dimers and with different diagnosis were analyzed. Results Out of 18 patients with main diagnosis linked with thrombosis 61 % exhibited active thrombin on D-dimers. In these patients we found active thrombin bound to D-dimers captured by antibodies in all applied D-dimer kits. Using mass spectrometry thrombin bound to isolated D-dimers was detected. Specificity of thrombin activity related to D-dimers was determined by combination of several specific thrombin substrates and inhibitors. The activity of bound thrombin was remarkably stable over the period of more than 24 hours. It showed that precise measurement of even very low activity of thrombin was possible. In the group of 16 non-thrombotic patients with elevated D-dimers only 19 % exhibited thrombin activity. Interestingly, differences in values of thrombin activity were up to five orders of magnitude and differences in the activities related to the value of captured D-dimers were even greater. Conclusion This, to our knowledge, is the first report showing the presence of active thrombin bound to circulating D-dimers. Although the group of patients we were so far able to evaluate is too small to being statistically tested, the results are highly encouraging. The amount of bound active thrombin on fibrin degradation products reflects the way of thrombus formation and its degradation (times, durations and rates of relevant reactions and especially the rate of thrombin generation). The thrombin concentration present at the time of fibrin gelation plays an important role in formation of fibrin clot structure, including its mechanical and fibrinolytic stability. It remains to be seen in further studies with much larger cohorts of patients if the presence of active thrombin has any impact on pathophysiology of thrombosis and if its determination may be of importance for the improvement of diagnosis of thrombotic events. Supported by the project of the Ministry of Health of the Czech Republic for conceptual development of the research organization 00023736, by Grant from the Academy of Sciences, Czech Republic (P205/12/G118), and by ERDF OPPK CZ.2.1.16/3.1.00/28007. Disclosures No relevant conflicts of interest to declare.

In 1986, a paper in the Lancet was the first to collate hematology, molecular findings, and clinical features of homozygous sickle cell (SS) disease in India. The paper came from the group organized by Professor Bimal Kar in Burla Medical College, Sambalpur University, in western Odisha. Although widely quoted, few readers will be aware of the history of this work that is now attached in an informal summary.

Abstract Ischemic stroke remains a major cause of disability and death. Kaempferol (Kae) is a neuroprotective flavonoid compound. Thus, this study aimed to explore the impact of Kae on cerebral infarction. We generated the middle cerebral artery occlusion (MCAO) mouse model to study the effects of Kae on infarction volume and neurological function. The oxygen and glucose deprivation (OGD)/reoxygenation (R) model of neural stem cells (NSCs) was established to study the effects of Kae on cell viability, migration, and apoptosis. Cell processes were assessed by cell counting kit-8, Transwell assay, flow cytometry, and TUNEL analysis. The molecular mechanism was assessed using the Western blot. The results indicated that Kae attenuated MCAO-induced cerebral infarction and neurological injury. Besides, Kae promoted cell viability and migration and inhibited apoptosis of OGD/R-treated NSCs. Moreover, OGD/R suppressed total O‐GlcNAcylation level and O‐GlcNAcylation of β-catenin, thereby suppressing the Wnt/β-catenin pathway, whereas Kae reversed the suppression. Inactivation of the Wnt/β-catenin pathway abrogated the biological functions of NSCs mediated by Kae. In conclusion, Kae suppressed cerebral infarction by facilitating NSC viability, migration, and inhibiting apoptosis. Mechanically, Kae promoted O‐GlcNAcylation of β-catenin to activate the Wnt/β-catenin pathway. Kae may have a lessening effect on ischemic stroke.

Sredinom prošloga stoljeća pojavljuje se u razvoju slovenske književnosti novela Martin Krpan z Vrha, koju je god. 1858. objavio Fran Levstik i koju bismo mogli nazvati »uzornom novelom«, ako upotre- bimo Cervantesov izraz. Ujedno je isti autor u literarnom putopisu Popotovanje iz Litije do Čateža teoretski obrazložio svoj nazor o noveli, njezinu sadržaju i obliku, kao i prozi općenito.

Abstract Background Ovarian and adnexal torsions are gynecologic emergencies [Li Q, Li X, Zhang P. Ovarian torsion caused by hyperreactio luteinalis in the third trimester of pregnancy: a case report. Int J Clin Exp Med. 2015;8:19612–5; Ssi-Yan-Kai G, Rivain AL, Trichot C, Morcelet MC, Prevot S, Deffieux X. What every radiologist should know about adnexal torsion. Emerg Radiol. 2018;25:51–9; Huchon C, Fauconnier A. Adnexal torsion: a literature review. Eur J Obstet Gynecol Reprod Biol. 2010;150:8–12]. Case presentation Though rare in pregnancy, this case report describes a 32-year-old G0 at 39 + 3/7 weeks with a history of kidney stones and a simple ovarian cyst that presented to the labor floor with left lower quadrant pain. She underwent an induction of labor for persistent pain and had a subsequent primary section for a category II tracing. Conclusion During the section, a torsion x3 of the left infundibular ligament was noted. The pathology indicated an acute infarct – only one other case of a full-term torsion was found in the literature (Li Q, Li X, Zhang P. Ovarian torsion caused by hyperreactio luteinalis in the third trimester of pregnancy: a case report. Int J Clin Exp Med. 2015;8:19612–5).

Abstract: The study aims to provide evidence of double nutritional burden (including malnutrition and overweight/obesity) as well as the impact of eating habits on nutritional status of preschool children at Nam Hong commune, Dong Anh district, Hanoi. Subjects of study: children aged from 24 to 60 months old at 2 preschools of Nam Hong commune. The study is divided into 2 phases: at the phase 1: a cross sectional study was applied to 1593 children; at the phase 2: a matched case-control study was applied in order to analyze effects of eating habits to nutritional status of children (1 malnourished child / 5 normal children and 1 obese overweight child / 5 normal children, matched pairs in age, sex, class). Research results: the percentage of children with normal nutritional status is 86.8%, however, Nam Hong still suffer a double burden of nutrition when the rate of malnourished children is still high (accounting for 4.2%) and overweight/obesity children is 9.0%, in which the rate of overweight and obesity children in boys is higher than girls (10.9% compared with 6.7%, respectively). Eating characteristics affect malnutrition status of children including: loss appetite (OR=4.3), slowness in eating (OR=2.23), enjoyment of food score (OR=0.69), desire to drink score (OR=0.82). Eating characteristics affect the overweight/obesity child’s include: appetite characteristics (OR=4.24), loss appetite (OR=0.43), fast eating (OR=2.56), slowness eating (OR=0.43), eating more (OR=6.78), eating less (OR=0.31), prefer fat (OR=2.18), food responsiveness score (OR=1.59), enjoyment of food score (OR=1.8), satiety responsiveness score (OR=0.51), slowness in eating score (OR=0.05), emotional under eating score (OR=0.67), food fussioness score (OR=0.72). Keywords Double burdens, malnutrition, overweight/obesity, Nam Hong commune, Dong Anh. References [1] L.T. Huong, N.T. Linh, N.T.T. Ha, Nutritional status and cognitive development of children under 6 in urban, rural and mountainous area of the north in 2012, Journal of Food and Nutrition Sciences 10 (2014) 67-74 (in Vietnamese). http://viendinhduong.vn/research/detail?id=620&catName=cac-de-tai-va-xuat-ban-pham&lang=vi[2] N.T.T. Thu, L.T. Tuyet, Anthropometric characteristics and nutritional status in 24 - 59 months children in Hanoi city, Thanh Hoa province and Phu Tho province in 2018, HNUE Journal of Science, Natural Sciences 3 (2018) 150-157. (in Vietnamese). https://doi.org/10.18173/2354-1059.2018-0016. http://stdb.hnue.edu.vn/portal/journals.php?articleid=5149.[3] N.T.T. Thu, L.T.T. Dung, L.T Tuyet, Nutritional status: the trends of preschool children aged 10–60 months in the north of Vietnam, Health Risk Analysis 4 (2018). https://doi.org/10.21668/health.risk/2018.4.06.eng[4] N.H. Trang, T.K. Hong, M.J. Dibley, Cohort profile: Ho Chi Minh City Youth Cohortdchanges in diet, physical activity, sedentary behaviour and relationship with overweight/obesity in adolescents, BMJ Open 2 (2012) e000362. https://doi.org/10.1136/bmjopen-2011-000362. http://dx.doi.org/10.1136/bmjopen-2011-000362[5] WHO, fact sheet, 2019. Infant and young child feeding, http://www.who.int/mediacentre/factsheets/fs342/en/ (accessed 6/2019). [6] WHO, Childhood overweight and obesity, 2019. https://www.who.int/dietphysicalactivity/childhood/en/ (accessed 6/2019).[7] J.M. Braun, H.J. Kalkwarf, G.D. Papandonatos, A. Chen, B.P. Lanphear, Patterns of early life body mass index and childhood overweight and obesity status at eight years of age, BMC Pediatr 18 (2018) 161. https://doi.org/10.1186/s12887-018-1124-9.[8] L.T. Tuyet, B.T. Nhung, T.Q. Binh, Association of neonatal, breastfeeding, eating behavior characteristics with obesity in primary school children in Hanoi urban areas, VNU Journal of Science: Natural Sciences and Technology 30 (2014) 275-281. (in Vietnamese). [9] L. Webber, C. Hill, J. Saxton, C.H. Van Jaarsveld, J. Wardle, Eating behaviour and weight in children, Int J Obes (Lond). 33 (2009) 21-28. https://doi.org/10.1038/ijo.2008.219.[10] A. Meule, A.P. Lutz, C. Vogele, A. Kubler, Impulsive reactions to food-cues predict subsequent food craving. Eat Behav 14 (2014) 99-105. https://doi.org/10.1016/j.eatbeh.2013.10.023.[11] WHO, Anthro Plus for Personal Computers Manual: Software for Assessing Growth of the World’s Children and Adolescents. Geneva, Switzerland: World Health Organization. http://www.who.int/growthref/tools/en/ (accessed 3/2019).[12] J. Wardle, C.A. Guthrie, S. Sanderson, L. Rapopor, Development of the Children's Eating Behaviour Questionnaire. J Child Psychol Psychiatry 42 (2001) 963-970. https://doi.org/10.1111/1469-7610.00792.[13] Vietnam National Institute of Nutrition, UNICEF, Alive and Thrive, Nutrition monitoring information 2013, Hanoi, Vietnam (2014).[14] UNICEF. Undernutrition contributes to nearly half of all deaths in children under 5 and is widespread in Asia and Africa 2019. 2019. https://data.unicef.org/topic/nutrition/malnutrition/# (accessed 3/2019).[15] M. de Onis, E. Borghi, M. Arimond, P. Webb, T. Croft, K. Saha, et al., Prevalence thresholds for wasting, overweight and stunting in children under 5 years, Public Health Nutr 22 (2019) 175-179. https://doi.org/10.1017/S1368980018002434.[16] A. Ek, K. Sorjonen, K. Eli, L. Lindberg, J. Nyman, C. Marcus, P. Nowicka, Associations between Parental Concerns about Preschoolers' Weight and Eating and Parental Feeding Practices: Results from Analyses of the Child Eating Behavior Questionnaire, the Child Feeding Questionnaire, and the Lifestyle Behavior Checklist, PLoS One 22 (2016) e0147257. https://doi.org/10.1371/journal.pone.0147257.[17] J. Zhang, Y. Zhai, X.Q. Feng, W.R. Li, Y.B. Lyu, T. Astell-Burt, P.Y. Zhao, X.M. Shi, Gender differences in the prevalence of overweight and obesity, associated behaviors, and weight-related perceptions in a National Survey of Primary School Children in China, Biomed Environ Sci 31 (2018) 1-11. https://doi.org/10.3967/bes2018.001.[18] V.H.C. Wang, J. Min, H. Xue, S. Du, F. Xu, H. Wang, Y. Wang, Factors contributing to sex differences in childhood obesity prevalence in China, Public Health Nutr 21 (2018) 2056-2064. https://doi.org/10.1017/S1368980018000290.[19] H. Ochiai, T. Shirasawa, R. Nishimura, A. Morimoto, N. Shimada, T. Ohtsu, M. Hashimoto, H. Hoshino, N. Tajima, A. Kokaze, Eating behavior and childhood overweight among population-based elementary school children in Japan, Int J Environ Res Public Health 9 (2012) 1398-1410. https://doi.org/10.3390/ijerph9041398.[20] L.T. Tuyet, B.T Nhung, T.Q Binh, Association of some eating behaviour characteristics and sedentary lifestyle with obesity among Hanoi primary school boy in 2012, VNU Journal of Science: Natural Sciences and Technology 31 (2), 60-66 (in Vietnamese). https://js.vnu.edu.vn/NST/article/view/76.[21] W. Labree W., D. van de Mheen, F. Rutten, G. Rodenburg, G. Koopmans, M. Foets, Differences in Overweight and Obesity among Children from Migrant and Native Origin: The Role of Physical Activity, Dietary Intake, and Sleep Duration, PLoS One 10 (2015) e0123672. https://doi.org/10.1371/journal.pone.0123672.[22] S. Kar, B. Khandelwal, Fast foods and physical inactivity are risk factors for obesity and hypertension among adolescent school children in east district of Sikkim, India, J Nat Sci Biol Med 6 (2015) 356-359. https://doi.org/10.4103/0976-9668.160004.[23] J.L. Santos, J.A. Ho-Urriola, A. Gonzalez, S.V. Smalley, P. Dominguez-Vasquez, R. Cataldo, Association between eating behavior scores and obesity in Chilean children, Nutr J. 10 (2011) 108. https://doi.org/10.1186/1475-2891-10-108.[24] J.C. Spence, V. Carson, L. Casey, N. Boule, Examining behavioural susceptibility to obesity among Canadian pre-school children: the role of eating behaviours, Int J Pediatr Obes 6 (2011) e501–7. https://doi.org/10.3109/17477166.2010.512087.[25] Y.T. Cao, V. Svensson, C. 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Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus. Methodology: Twenty-eight Wistar Albino rats were randomised into four groups as control (C), diabetic (DC), diabetic with hepatic ischemia-reperfusion injury (DIR), and diabetic but administered dexmedetomidine followed by hepatic IRI (DIRD) groups. Hepatic tissue samples were evaluated histopathologically by semiquantitative methods. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathion s-transpherase (GST), and catalase (CAT) enzyme levels were investigated in liver and kidney tissues as oxidative state parameters. Results: In Group DIR; hepatocyte degeneration, sinusoidal dilatation, pycnotic nucleus, and necrotic cells were found to be more in rat hepatic tissue; while mononuclear cell infiltration was higher in the parenchyme. MDA levels were significantly lower; but SOD levels were significantly higher in Group DIRD with regard to Group DIR. In the IRI induced diabetic rats’ hepatic and nephrotic tissues MDA levels, showing oxidative injury, were found to be lower. SOD levels, showing early antioxidant activity, were higher. Conclusion: The enzymatic findings of our study together with the hepatic histopathology indicate that dexmedetomidine has a potential role to decrease IRI. Key words: Hepatic ischemia reperfusion injury; Diabetes mellitus; Dexmedetomidine; Rat; MDA; SOD Citation: Sezen SC, Işık B, Bilge M, Arslan M, Çomu FM, Öztürk L, Kesimci E, Kavutçu M. Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats. Anaesth Pain & Intensive Care 2016;20(2):143-149 Received: 21 November 2015; Reviewed: 10, 24 December 2015, 9, 10 June 2016; Corrected: 12 December 2015; Accepted: 10 June 2016 INTRODUCTİON Perioperative acute tissue injury induced by ischemia-reperfusion is a comman clinical event caused by reduced blood supply to the tissue being compromised during major surgery. Ischemia leads to cellular injury by depleting cellular energy deposits and resulting in accumulation of toxic metabolites. The reperfusion of tissues that have remained in ischemic conditions causes even more damage.1 Furthermore hepatic ischemia-reperfusion injury (IRI) demonstrates a strong relationship with peri-operative acute kidney injury.2 The etiology of diabetic complications is strongly associated with increased oxidative stress (OS). Diabetic patients are known to have a high risk of developing OS or IRI which results with tissue failure.3 The most important role in ischemia and reperfusion is played by free oxygen radicals.1 In diabetes, characterized by hyperglycemia, even more free oxygen radicals are produced due to oxidation of glucose and glycosylation of proteins.3 The structures which are most sensitive to free oxygen radicals in the cells are membrane lipids, proteins, nucleic acids and deoxyribonucleic acids.1 It has been reported that endogenous antioxidant enzymes [superoxide dismutase (SOD), glutathion s-transpherase (GST), catalase (CAT)] play an important role to alleviate IRI.4-8 Also some pharmacological agents have certain effects on IRI.1 The anesthetic agents influence endogenous antioxidant systems and free oxygen radical formation.9-12 Dexmedetomidine is a selective α-2 adrenoceptor agonist agent. It has been described as a useful and safe adjunct in many clinical applications. It has been found that it may increase urine output by considerably redistributing cardiac output, inhibiting vasopressin secretion and maintaining renal blood flow and glomerular filtration. Previous studies demonstrated that dexmedetomidine provides protection against renal, focal cerebral, cardiac, testicular, and tourniquet-induced IRI.13-18 Arslan et al observed that dexmedetomidine protected against lipid peroxidation and cellular membrane alterations in hepatic IRI, when given before induction of ischemia.17 Si et al18 demonstrated that dexmedetomidine treatment results in a partial but significant attenuation of renal demage induced by IRI through the inactivation of JAK/STAT signaling pathway in an in vivo model. The efficacy of the dexmedetomidine for IRI in diabetic patient is not resarched yet. The purpose of this experimental study was to evaluate the biochemical and histological effects of dexmedetomidine on hepatic IRI in diabetic rat’s hepatic and renal tissue. METHODOLOGY Animals and Experimental Protocol: This study was conducted in the Physiology Laboratory of Kirikkale University upon the consent of the Experimental Animals Ethics Committee of Kirikkale University. All of the procedures were performed according to the accepted standards of the Guide for the Care and Use of Laboratory Animals. In the study, 28 male Wistar Albino rats, weighing between 250 and 300 g, raised under the same environmental conditions, were used. The rats were kept under 20-21 oC at cycles of 12-hour daylight and 12-hour darkness and had free access to food until 2 hours before the anesthesia procedure. The animals were randomly separated into four groups, each containing 7 rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (Sigma Chemical, St. Louis, MO, USA) at a dose of 65 mg/kg body weight. The blood glucose levels were measured at 72 hrs following this injection. Rats were classified as diabetic if their fasting blood glucose (FBG) levels exceeded 250 mg/dl, and only animals with FBGs of > 250 mg/dl were included in the diabetic groups (dia­betes only, diabetes plus ischemia-reperfusion and diabetes plus dexmedetomidine-ischemia-reperfusion). The rats were kept alive 4 weeks after streptozotocin injection to allow development of chronic dia­betes before they were exposed to ischemia-reperfusion.(19) The rats were weighed before the study. Rats were anesthetized with intraperitoneal ketamine 100 mg/kg. The chest and abdomen were shaved and each animal was fixed in a supine position on the operating table. The abdomen was cleaned with 1% polyvinyl iodine and when dry, the operating field was covered with a sterile drape and median laparotomy was performed. There were four experimental groups (Group C (sham-control; n = 7), (Group DC (diabetes-sham-control; n = 7), Group DIR (diabetes-ischemia-reperfusion; n = 7), and Group DIRD (diabetes-ischemia-reperfusion-dexmedetomidine; n = 7). Sham operation was performed on the rats in Group C and Group DC. The sham operation consisted of mobilization of the hepatic pedicle only. The rats in this group were sacrificed 90 min after the procedure. Hepatic I/R injury was induced in Groups DIR and DIRD respectively with hepatic pedicle clamping using a vascular clamp as in the previous study of Arslan et al.(17) After an ischemic period of 45 min, the vascular clamp was removed. A reperfusion period was maintained for 45 min. In Group DIRD, dexmedetomidine hydrochloride 100 μg/kg, (Precedex 100 μg/2 ml, Abbott®, Abbott Laboratory, North Chicago, Illinois, USA) was administrated via intraperitoneal route 30 minutes before surgery. All the rats were given ketamine 100 mg/kg intraperitoneally and intracardiac blood samples were obtained. Preserving the tissue integrity by avoiding trauma, liver and renal biopsy samples were obtained. Biochemical Analysis: The liver and renal tissues were first washed with cold deionized water to discard blood contamination and then homogenized in a homogenizer. Measurements on cell contest require an initial preparation of the tissues. The preparation procedure may involve grinding of the tissue in a ground glass tissue blender using a rotor driven by a simple electric motor. The homogenizer as a tissue blender similar to the typical kitchen blender is used to emulsify and pulverize the tissue (Heidolph Instruments GMBH & CO KGDiax 900 Germany®) at 1000 U for about 3 min. After centrifugation at 10,000 g for about 60 min, the upper clear layer was taken. MDA levels were determined using the method of Van Ye et al,(20) based on the reaction of MDA with thiobarbituric acid (TBA). In the TBA test reaction, MDA and TBA react in acid pH to form a pink pigment with an absorption maximum at 532 nm. Arbitrary values obtained were compared with a series of standard solutions (1,1,3,3-tetraethoxypropane). Results were expressed as nmol/mg.protein. Part of the homogenate was extracted in ethanol/chloroform mixture (5/3 v/v) to discard the lipid fraction, which caused interferences in the activity measurements of T-SOD, CAT and GST activities. After centrifugation at 10.000 x g for 60 min, the upper clear layer was removed and used for the T-SOD, CAT, GST enzyme activity measurement by methods as described by Durak et al21, Aebi22 and Habig et al23 respectively. One unit of SOD activity was defined as the enzyme protein amount causing 50% inhibition in NBTH2 reduction rate and result were expressed in U/mg protein. The CAT activity method is based on the measurement of absorbance decrease due to H2O2 consumption at 240 nm. The GST activity method is based on the measurement of absorbance changes at 340 nm due to formation of GSH-CDNB complex. Histological determinations: Semiquantitative evaluation technique used by Abdel-Wahhab et al(24) was applied for interpreting the structural changes investigated in hepatic tissues of control and research groups. According to this, (-) (negative point) represents no structural change, while (+) (one positive point) represents mild, (++) (two positive points) medium and (+++) (three positive points) represents severe structural changes. Statistical analysis: The Statistical Package for the Social Sciences (SPSS, Chicago, IL, USA) 20.0 softwre was used for the statistical analysis. Variations in oxidative state parameters, and histopathological examination between study groups were assessed using the Kruskal-Wallis test. The Bonferroni-adjusted Mann-Whitney U-test was used after significant Kruskal-Wallis to determine which groups differed from the others. Results were expressed as mean ± standard deviation (Mean ± SD). Statistical significance was set at a p value < 0.05 for all analyses. RESULTS There was statistically significant difference observed between the groups with respect to findings from the histological changes in the rat liver tissue (hepatocyte degeneration, sinüsoidal dilatation, pycnotic nucleus, prenecrotic cell) determined by light microscopy according to semiquantitative evaluation techniques (p < 0.0001). In Group DIR, hepatocyte degeneration was significantly high compared to Group C, Group DC and Group DIRD (p < 0.0001, p < 0.0001, p = 0.002, respectively), (Table 1, Figure 1-4). Similarly, sinüsoidal dilatation was significantly higher in Group DIR (p < 0.0001, p = 0.004, p = 0.015, respectively). Although, pcynotic nucleus was decreased in Group DIRD, it did not make a significant difference in comparison to Group DIR (p = 0.053), (Table 1, Figure 1-4). The prenecrotic cells were significantly increased in Group DIR, with respect to Group C, Group DC and Group DIRD (p < 0.0001, p = 0.004, p < 0.0001, respectively), (Table 1, Figure 1-4). Table 1. The comparison of histological changes in rat hepatic tissue [Mean ± SD)] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR Figure 1: Light microscopic view of hepatic tissue of Group C (control). VC: vena centralis, *: sinusoids. ®: hepatocytes, k: Kupffer cells, G: glycogen granules, mc: minimal cellular changes, Hematoxilen & Eosin x 40 Figure 2: Light-microscopic view of hepatic tissue of Group DC (diabetes mellitus control) (G: Glycogen granules increased in number, (VC: vena centralis, *:sinusoids. ®:hepatocytes, k:Kupffer cells, G: glycogen granules, mc: minimal cellular changes; Hematoxylin & Eosin x 40) Figure 3: Light-microscopic view of hepatic tissue of Group DIR (Diabetes Mellitus and ischemia-reperfusion) (VC: vena centralis, (H) degenerative and hydrophic hepatocytes, (dej) vena centralis degeneration (centrolobar injury) (*): sinusoid dilatation. (←) pycnotic and hyperchromatic nuclei, MNL: mononuclear cell infiltration, (¯) congestion, K: Kupffer cell hyperplasia, (­) vacuolar degeneration (Hematoxylin & Eosin x 40) Figure 4: Light-microscopic view of hepatic tissue of Group DIRD (Diabetes Mellitus and ischemia-reperfusion together with dexmedetomidine applied group) (VC: vena centralis, (MNL) mononuclear cell infiltration, (dej) hydrophilic degeneration in hepatocytes around vena centralis, (conj) congestion, G: glycogen granules, (←) pycnotic and hyperchromatic nuclei, sinusoid dilatation (*) (Hematoxylin & Eosin x 40) Besides, in liver tissue parenchyma, MN cellular infiltration was a light microscopic finding; and showed significant changes among the groups (p < 0.0001). This was significantly higher in Group DIR, compared to Group C, DC, and DIRD (p < 0.0001, p=0.007, p = 0.007, respectively), (Table 1, Figure 1-4). The enzymatic activity of MDA, SOD and GST in hepatic tissues showed significant differences among the groups [(p = 0.019), (p = 0.034). (p = 0.008) respectively]. MDA enzyme activity was significantly incresed in Group DIR, according to Group C and Group DIRD (p = 0.011, p = 0.016, respectively), (Table 2). In Group DIR SOD enzyme activity was lower with respect to Group C and Group DIRD (p = 0.010, p = 0.038, respectively), (Table 2). The GST enzyme activity was significantly higher in Group DIR, when compared to Group C, DC and DIRD (p = 0.007, p = 0.038, p = 0.039, respectively), (Table 2). Table 2. Oxidative state parameters in rat hepatic tissue [Mean ± SD] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR The enzymatic activity of MDA, SOD in renal tissues, showed significant differences among the groups [(p < 0.0001), (p = 0.008) respectively ]. MDA enzyme activity was significantly incresed in Group DIR, according to Group C and Group DIRD (p < 0.0001, p < 0.0001, respectively). Also MDA enzyme activity level was significantly increased in Group DC, in comparison to Group C and Group DIRD (p = 0.003, p = 0.001, respectively), (Table 3). In Group DIR SOD enzyme activity was lower with respect to Group C and Group DIRD (p = 0.032, p = 0.013, respectively), (Table 3). The GST enzyme activity was significantly higher in Group DIR than the other three groups, however; CAT levels were similar among the groups (Table 3). Table 3: Oxidative state parameters in rat nephrotic tissue [Mean ± SD)] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR DISCUSSION In this study, we have reported the protective effect of dexmedetomidine in experimental hepatic and renal IRI model in the rat by investigating the MDA and SOD levels biochemically. Besides, hepatic histopathological findings also supported our report. Ischemic damage may occur with trauma, hemorrhagic shock, and some surgical interventions, mainly hepatic and renal resections. Reperfusion following ischemia results in even more injury than ischemia itself. IRI is an inflammatory response accompanied by free radical formation, leucocyte migration and activation, sinusoidal endothelial cellular damage, deteoriated microcirculation and coagulation and complement system activation.1 We also detected injury in hepatic and renal tissue caused by reperfusion following ischemia in liver. Experimental and clinical evidence indicates that OS is involved in both the pathogenesis and the complications of diabetes mellitus.25,26 Diabetes mellitus is a serious risk factor for the development of renal and cardiovascular disease. It is also related to fatty changes in the liver.27 Diabetes-related organ damage seems to be the result of multiple mechanisms. Diabetes has been associated with increased free radical reactions and oxidant tissue damage in STZ-induced diabetic rats and also in patients.26Oxidative stress has been implicated in the destruction of pancreatic β-cells28 and could largely contribute to the oxidant tissue damage associated with chronic hyperglycemia.29 A number of reports have shown that antioxidants can attenuate the complications of diabetes in patients30 and in experimental models.28,31 This study demonstrated that diabetes causes a tendency to increase the IRI. There is a lot of investigations related to the pharmacological agents or food supplements applied for decreasing OS and IRI. Antioxidant agents paly an important role in IRI by effecting antioxidant system or lessening the formation of ROS. It has been reported that anesthetic agents too, are effective in oxidative stress.1 During surgical interventions, it seems rational to get benefit from anesthetic agents in prevention of OS caused by IRI instead of using other agents. It has been declared that; dexmedetomidine; as an α-2 agonist with sedative, hypnotic properties; is important in prevention of renal, focal, cerebral, cardiac, testicular and tourniquet-induced IRI.13-18 On the other hand Bostankolu et al. concluded that dexmedetomidine did not have an additional protective role for tournique induced IRI during routine general anesthesia.32 In this study; we have shown that dexmedetomidine has a reducing effect in IRI in diabetic rats. Some biochemical tests and histopathological evaluations are applied for bringing up oxidative stress and IRI in the tissues. Reactive oxygen species (ROS) that appear with reperfusion injury damage cellular structures through the process of the lipid peroxidation of cellular membranes and yield toxic metabolites such as MDA.33 As an important intermidiate product in lipid peroxidation, MDA is used as a sensitive marker of IRI.34 ROS-induced tissue injury is triggered by various defense mechanisms.35 The first defence mechanisms include the antioxidant enzymes of SOD, CAT, and GPx. These endogenous antioxidants are the first lines of defence against oxidative stres and act by scavenging potentially damaging free radical moieties.36 There is a balance between ROS and the scavenging capacity of antioxidant enzymes.1-8 In this study, for evaluation of oxidative damage and antioxidant activity, MDS, SOD, GST and CAT levels were determined in liver and kidney tissues. MDA levels in hepatic and renal tissues were higher in Group DIR compared to Group C and Group DIRD. GST levels were higher in Group DIR compared to all the other three groups. When the groups were arranged from highest to lowest order, with respect to CAT levels, the order was; Group DIR, Group DIRD, Group DC and Group C. However, the difference was not significant. The acute phase reactant MDA, as a marker of OS, was found to be high in Group DIR and low in Group DIRD. This could be interpreted as the presence of protective effect of dexmedetomidine in IRI. IRI developing in splanchnic area causes injury also in the other organs.35 Leithead et al showed that clinically significant hepatic IRI demonstrates a strong relationship with peri-operative acute kidney injury.2 In our experimental research that showed correlation to that of research by Leithead et al. After hepatic IRI in diabetic rats renal OS marker MDA levels were significantly more in Group DIR than Group DIRD. In our study, we observed histopathological changes in the ischemic liver tissue and alterations in the level of MDA, SOD, GST and CAT levels which are OS markers. Histopathological changes of the liver tissues are hepatocyt degeneration, sinusoidal dilatation, nuclear picnosis, celluler necrosis, mononuclear cell infiltrationat paranchimal tissue. These histopathological injury scores were significantly lower in the Group DIRD than those in group DIR. LIMITATION Study limitation is there was no negative control group, as this type of surgical intervention is not possible in rats without anesthesia. CONCLUSION The enzymatic findings of our study together with the hepatic histopathology indicate that dexmedetomidine has a potential role to decrease ischemia-reperfusion injury. Conflict of interest and funding: The authors have not received any funding or benefits from industry or elsewhere to conduct this study. 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