Oxytocin alleviates hepatic ischemia-reperfusion injury in rats

Various mechanisms have been proposed for the pathogenesis of postischemic hepatic injury, including the generation of reactive oxygen metabolites. Oxytocin (OT) possesses antisecretory, antiulcer effects, facilitates wound healing and has anti-inflammatory properties. Hepatic ischemia-reperfusion (I/R)-injury was induced by inflow occlusion to median and left liver lobes ( approximately 70%) for 30 min of ischemia followed by 1h reperfusion in female Sprague-Dawley rats under anesthesia. I/R group (n=8) was administered intraperitoneally either OT (500 microg/kg) or saline at 24 and 12 h before I/R and immediately before reperfusion. Sham-operated group that underwent laparotomy without hepatic ischemia served as the control. Rats were decapitated at the end of reperfusion period. Hepatic samples were obtained for the measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH) and collagen levels and histopathological analysis. Tumor necrosis factor-alfa (TNF-alpha) and transaminases (SGOT, SGPT) were assayed in serum samples. I/R injury caused significant increases in hepatic microscopic damage scores, MPO activity, collagen levels, transaminase, serum TNF-alpha levels. Oxytocin treatment significantly reversed the I/R-induced elevations in serum transaminase and TNF-alpha levels and in hepatic MPO and collagen levels, and reduced the hepatic damage scores. OT treatment had tendency to abolish I/R-induced increase in MDA levels, while GSH levels were not altered. These results suggest that OT has a protective role in hepatic I/R injury and its protective effect in the liver appears to be dependent on its inhibitory effect on neutrophil infiltration.     

Time of Flight-Secondary Ion Mass Spectrometry on isolated extracellular fractions and intact biofilms of three species of benthic diatoms

Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS) was used to study compositional characteristics of Extracellular Polymeric Substances (EPS) and compared these to characteristics of the EPS-matrix of intact diatom biofilms. Three benthic diatoms species were investigated, Cylindrotheca closterium, Navicula mutica and Nitzschia cf. brevissima. Comparison of the ToF-SIMS spectra of sequentially extracted EPS-fractions by cluster analysis and multidimensional scaling analysis (MDS) indicated that soluble and bound EPS were not distinguishable based on their ion spectra. On the contrary the water insoluble bicarbonate soluble (WIBS)-EPS-fraction formed a distinct cluster showing that this material was compositionally different from the other EPS-fractions. Ion spectra of the EPS-fractions were dissimilar to results obtained from intact biofilms. This suggested that during the extraction procedure, the structure of the EPS irreversibly changed, which alters the fragmentation patterns of the extracellular surface layer. Furthermore, from the examination of the positive ion spectra it was shown that the overall composition of EPS in the intact biofilms was different between diatom species. In spite of these differences, several common peak patterns were shared between different species. This suggests the presence of common structural components in the EPS of these diatoms that may play a role in building the surface EPS-layer.     

A Strong Relationship Between Oral Squamous Cell Carcinoma and DNA Repair Genes

Single nucleotide polymorphisms of DNA repair genes alter protein function and modulate DNA repair efficiency in various cancers. The X-ray repair cross-complementing group (XRCC) is responsible for the repair of DNA base damage and single-strand breaks. The aim of our study was to investigate the association of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms with the susceptibility to develop oral squamous cell carcinoma (OSCC) in Turkish subjects. One hundred eleven patients with OSCC and 148 healthy controls were recruited for the study. Genetic analysis was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). We found that the XRCC1 Arg399Gln Gln/Gln genotype and Gln allele were risk factors for OSCC. Also, Arg/Arg genotype and Arg allele had protective effects against OSCC. Relative to XRCC3 Thr241Met polymorphism, carrying homozygote variants (Thr/Thr and Met/Met) was related with elevated OSCC risk. However, the heterozygote genotype and Thr allele variants were shown to be protective against OSCC. We suggest that XRCC1 Arg399Gln Gln/Gln genotype, Gln allele, and homozygote variants of XRCC3 Thr241Met polymorphism may be a risk factor for predisposition of OSCC in Turkish. In addition, XRCC3 Thr241Met genotype could be associated with tumor size and level of daily smoking.     

Carbonic anhydrase from Apis mellifera: purification and inhibition by pesticides

Carbonic anhydrase (CA) enzymes have been shown to play an important role in ion transport and in pH regulation in several organisms. Despite this information and the wealth of knowledge regarding the significance of CA enzymes, few studies have been reported about bee CA enzymes and the hazardous effects of chemicals. Using Apis mellifera as a model, this study aimed to determine the risk of pesticides on Apis mellifera Carbonic anhydrase enzyme (Am CA). CA was initially purified from Apis mellifera spermatheca for the first time in the literature. The enzyme was purified with an overall purification of ～35-fold with a molecular weight of ～32?kDa. The enzyme was then exposed to pesticides, including tebuconazole, propoxur, carbaryl, carbofuran, simazine and atrazine. The six pesticides dose-dependently inhibited in vitro AmCA activity at low micromolar concentrations. IC₅₀ values for the pesticides were 0.0030, 0.0321, 0.0031, 0.0087, 0.0273 and 0.0165?μM, respectively. The AmCA inhibition mechanism of these compounds is unknown at this moment.     

Alpine–Himalayan orogeny drove correlated morphological,molecular, and ecological diversification in the Persian dwarf snake (Squamata: Serpentes: Eirenis persicus)

The Persian dwarf snake Eirenis (Pseudocyclophis) persicus (Anderson, 1872) has a wide distribution range in south‐western Asia. This species group was comprehensively studied here using traditional biometry, geometric morphometrics, ecological niche modelling, and genetics. Our analyses revealed that E. persicus is split into two clades. A western clade, bearing at least two different species: E. persicus, distributed in south‐western Iran, and an undescribed species from south‐eastern Turkey and western Iran. The eastern clade consists of at least three species: Eirenis nigrofasciatus, distributed across north‐eastern Iraq, and western and southern Iran; Eirenis walteri, distributed across eastern Iran, southern Turkmenistan, and western and southern Pakistan, and Eirenis angusticeps, distributed in north‐eastern Pakistan. Ecological niche modelling revealed that the distribution of the species in the western clade are mainly affected by winter precipitation, and those in the eastern clade are mainly affected by the minimum temperature of the coldest month. A molecular clock analysis revealed that the divergence and diversification of the E. persicus species group mainly correspond to Eocene to Pliocene orogeny events subsequent to the Arabia–Eurasia collision. This study confirms that specimens with the unique morphology of having 13 dorsal scale rows on the anterior dorsum, occurring in the Suleiman Mountains in central Pakistan, can be referred to Eirenis mcmahoni (Wall, 1911). However, at this moment we have insufficient data to evaluate the taxonomy of this species.     

Oxidant and antioxidant status of Turkish marasmic children: A single center study

The aim of this study was to investigate plasma oxidant and antioxidant status in Turkish marasmic children. The study population consisted of 38 marasmic children (group I) and 28 age-matched children (group II) who were apparently well, with weight-forage >80% of the standards in the same region. After overnight fasting, venous blood samples were drawn and immediately transferred to heparinized and normal tubes. Plasma antioxidant potential (AOP), and malondialdehyde (MDA) levels were measured in both groups. The plasma MDA levels were found to be higher in group I than in group II. However, plasma AOP values were lower in group I than in group II. The present study suggests that AOP is reduced due to an impaired antioxidant system in the plasma of malnourished patients. This oxidant stress causes significant peroxidation. Also, the antioxidant defense system of the patients is deteriorated in marasmus.     

Iloprost (ZK 36374) modulates the responses to beta-adrenoceptor agonists in guinea-pig airways and pulmonary vasculature

The effect of iloprost on airway smooth muscles and its influence on the actions of beta-agonists and histamine were studied in the isolated perfused lung and isolated tracheal strips from guinea-pigs. Bolus injection of iloprost into the pulmonary artery elicited a concentration-dependent decrease in pulmonary perfusion pressure and an increase in airway resistance. These effects are not mediated through cholinergic, serotoninergic and histaminergic receptors. A rapid tachyphylaxis affected the effect of iloprost in airway resistance but not in pulmonary perfusion pressure. Iloprost did not induce a response in the isolated tracheal strips and did not alter the effect of histamine in both tracheal strips and airway resistance. This compound, however, caused an inhibition in the airway resistance-reducing effect of adrenaline and isoprenaline in the isolated perfused lung and a potentiation in the perfusion pressure-increasing effect of adrenaline. Iloprost also inhibited the relaxing effect of adrenaline and isoprenaline in the isolated tracheal strips precontracted with histamine and potentiated the inhibitory effect of propranolol against adrenaline and isoprenaline. From these results it was concluded that: Iloprost, a stable analogue of prostacyclin, modulates the beta-adrenoceptor blocking effect of propranolol in both airway smooth muscles and pulmonary vasculature.     

Identification of major ERK-related phosphorylation sites in Gab1

Gab1 (Grb2-associated binder1) belongs to a family of multifunctional docking proteins that play a central role in the integration of receptor tyrosine kinase (RTK) signaling, i.e., mediating cellular growth response, transformation, and apoptosis. In addition to RTK-specific tyrosine phosphorylation, these docking proteins also can be phosphorylated on serine/threonine residues affecting signal transduction. Since serine and threonine phosphorylation are capable of modulating the initial signal one major task to elucidate signal transduction via Gab1 is to determine the exact localization of distinct phosphorylation sites. To address this question in this report we examined extracellular signal-regulated kinases 1/2 (ERK) specific serine/threonine phosphorylation of the entire Gab1 engaged in insulin signaling in more detail in vitro. To elucidate the ERK1/2-specific phosphorylation pattern of Gab1, we used phosphopeptide mapping by two-dimensional HPLC analysis. Subsequently, phosphorylated serine/threonine residues were identified by sequencing the separated phosphopeptides using matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) and Edman degradation. Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. Serine residues S454, S581, S597, and threonine residue T476 represent nearly 80% of overall incorporated phosphate. These sites are located adjacent to src homology region-2 (SH2) binding motifs (YVPM-motif: Y447, Y472, Y619) specific for the phosphatidylinositol 3kinase (PI3K). The biological role of identified phosphorylation sites was proven by PI3K and Akt activity in intact cells. These data demonstrate that ERK1/2 modulate insulin action via Gab1 by targeting serine and threonine residues beside YXXM motifs. Accordingly, insulin signaling is blocked at the level of PI3K.