Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver

Drug-induced liver toxicity is a common cause of liver injury. This study was designed to elucidate whether high dose vancomycin (VCM) induces oxidative stress in liver and to investigate the protective effects of erdosteine, an expectorant agent. Twenty-two young Wistar rats were divided into three groups as follows: control group, VCM, and VCM plus erdosteine. VCM was administered intraperitoneally in the dosage of 200 mg/kg twice daily for 7 days. Erdosteine was administered orally administered once a day at a dose of 10 mg/kg body weight. The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the concentration of malondialdehyde, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the liver. VCM administration increased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities. Erdosteine co-administration with VCM injections caused significantly decreased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities in liver tissue when compared with VCM alone. It can be concluded that erdosteine may prevent VCM-induced oxidative changes in liver by reducing reactive oxygen species.     

A novel role of sodium butyrate in the regulation of cancer-associated aromatase promoters I.3 and II by disrupting a transcriptional complex in breast adipose fibroblasts

The aromatase gene encodes the key enzyme for estrogen formation. Aromatase enzyme inhibitors eliminate total body estrogen production and are highly effective therapeutics for postmenopausal breast cancer. A distal promoter (I.4) regulates low levels of aromatase expression in tumor-free breast adipose tissue. Two proximal promoters (I.3/II) strikingly induce in vivo aromatase expression in breast fibroblasts surrounding malignant cells. Treatment of breast fibroblasts with medium conditioned with malignant breast epithelial cells (MCM) or a surrogate hormonal mixture (dibutyryl (Bt2)cAMP plus phorbol diacetate (PDA)) induces promoters I.3/II. The mechanism of promoter-selective expression, however, is not clear. Here we reported that sodium butyrate profoundly decreased MCM- or Bt2cAMP + PDA-induced promoter I.3/II-specific aromatase mRNA. MCM, Bt2cAMP + PDA, or sodium butyrate regulated aromatase mRNA or activity only via promoters I.3/II but not promoters I.1 or I.4 in breast, ovarian, placental, and hepatic cells. Mechanistically, recruitment of phosphorylated ATF-2 by a CRE (-211/-199, promoter I.3/II) conferred inductions by MCM or Bt2cAMP + PDA. Chromatin immunoprecipitation-PCR and immunoprecipitation-immunoblotting assays indicated that MCM or Bt2cAMP + PDA stabilized a complex composed of phosphorylated ATF-2, C/EBPbeta, and cAMP-response element-binding protein (CREB)-binding protein in the common regulatory region of promoters I.3/II. Overall, histone acetylation patterns of promoters I.3/II did not correlate with sodium butyrate-dependent silencing of promoters I.3/II. Sodium butyrate, however, consistently disrupted the activating complex composed of phosphorylated ATF-2, C/EBPbeta, and CREB-binding protein. This was mediated, in part, by decreased ATF-2 phosphorylation. Together, these findings represent a novel mechanism of sodium butyrate action and provide evidence that aromatase activity can be ablated in a signaling pathway- and cell-specific fashion.     

The Interactions of Nitric Oxide and Acetylcholine on Penicillin-Induced Epilepsy in Rats

The aim of this study was to investigate the interaction between nitric oxide (NO) and acetylcholine (ACh) in penicillin-induced experimental epilepsy. Adult male Wistar rats weighing 220 ± 35 g were used in the experiments. The epileptiform activity was induced by microinjection of penicillin (200 IU/1 μl) into the left sensorymotor cortex. Electrocorticogram was recorded by using Ag/AgCl ball electrodes. Sodium nitroprusside (SNP), a NO donor, given intracortically 30 min after penicillin significantly reduced the spike frequency whereas ACh increased the epileptiform activity for 5 min. Atropine, an antagonist for muscarinic receptors, was given intracortically 30 min after penicillin and did not significantly affect epileptiform activity for 30 min. SNP given after atropine significantly suppressed the epileptiform activity. ACh given 10 min after Nω-nitro-L: -arginine methyl ester (L-NAME), a nonspecific nitric oxide synthase inhibitor, did not have a significant effect on spike frequency. When ACh and SNP were administered together, penicillin induced epileptiform activity and spike frequency were significantly suppressed from the 10th minute onwards. It can be concluded that ACh increases the penicillin-induced epileptiform activity while co-administration of ACh and SNP produces a potent anticonvulsant effect as compared to SNP alone.     

Interactions of the antifungal mycosubtilin with ergosterol-containing interfacial monolayers

Mycosubtilin, an antimicrobial lipopeptide produced by Bacillus subtilis, is characterized by strong antifungal activities. The molecular mechanisms of its biological activities on the membranes of the sensitive yeasts or fungi have not yet been clearly elucidated. Our purpose was to mimic the mycosubtilin interactions with these membranes using various Langmuir monolayers. Since the major sterol of yeasts or fungi is ergosterol, the interactions of mycosubtilin with monolayers constituted by ergosterol, DPPC/ergosterol or DPPC/sphingomyelin/ergosterol were examined at different initial surface pressures (Πi). Plotting the mycosubtilin-induced surface pressure increases versus Πi allowed to determine that the exclusion pressures of mycosubtilin from these different monolayers is higher than the surface prevailing within the biological membranes. However, this behavior was lost when mycosubtilin was interacting with ergosteryl acetate-containing monolayers. This suggests the involvement of the sterol alcohol group in the mycosubtilin interactions within membranes. Furthermore, the behavior of mycosubtilin with stigmasterol, similar to that observed with ergosterol, differs from that previously observed with cholesterol, suggesting a role of the alkyl side chain of the sterols. The adsorption of mycosubtilin to ergosterol monolayers induced changes in the lipopeptide orientation at the air-water interface as revealed by polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS). Moreover, imaging the air-water interface by Brewster angle microscopy (BAM) indicates that mycosubtilin induced changes in the organization and morphology of monolayers containing pure ergosterol with the appearance of small condensed dots, suggesting again that the target of mycosubtilin might be the ergosterol present in the membranes of the sensitive yeasts or fungi.     

Electrical detection of biomolecular adsorption on sprayed graphene sheets

The binding affinities of graphite-binding peptides to a graphite surface were electrically characterized using sprayed graphene field effect transistors (SGFETs) fabricated with solution exfoliated graphene. The binding affinities of these peptides were also characterized using atomic force microscopy (AFM) and mechanically exfoliated graphene field effect transistors (GFETs) to confirm the validity of the SGFET platform. Binding constants obtained via GFET and AFM were comparable with those observed using SGFETs. The sprayed graphene film serves as a scalable platform to study biomolecular adsorption to graphitic surfaces.     

Dynamics of microRNAs in bull spermatozoa

Background

Degenerative effects of critical regulators of reproduction, the kisspeptin peptides, on cellular aspects of sexually immature male gonads are known but similar information on accessory sex glands remain elusive.

Methods

Prepubertal laboratory rats were injected kisspeptin-10 at three different dosage concentrations (10 pg, 1 ng and 1 microgram) for a period of continuous 12 days at the rate of two doses per day. Control rats were maintained in parallel. The day following the end of the experimental period, seminal vesicles were removed and processed for light and electron microscopic examination using the standard methods. DNA damage was estimated by DNA ladder assay and DNA fragmentation assay.

Results

The results demonstrated cellular degeneration. Epithelial cell height of seminal vesicles decreased significantly at all doses (P < 0.05). Marked decrease in epithelial folds was readily noticeable, while the lumen was dilated. Ultrastructural changes were characterized by dilatation of endoplasmic reticulum and Golgi complex, heterochromatization of nuclei, invagination of nuclear membranes and a decreased number of secretory granules. Percent DNA damage to the seminal vesicle was 19.54 +/- 1.98, 38.06 +/- 2.09 and 58.18 +/- 2.59 at 10 pg, 1 ng and 1 microgram doses respectively.

Conclusion

The study reveals that continuous administration of kisspeptin does not lead to an early maturation but instead severe degeneration of sexually immature seminal vesicles.     

Fracture resistance and analysis of stress distribution of implant-supported single zirconium ceramic coping combination with abutments made of different materials

The purpose of this study was to compare the fracture resistance and fracture mode of single implant-zirconium coping combinations using zirconium and titanium abutments and to analyze the stress distribution pattern using three-dimensional finite elements analysis. Twenty implants with titanium and zirconium abutments were randomly divided into two groups (n = 10) and into resin blocks. Zirconium copings were cemented onto the abutments. The specimens were loaded with 135° angles to the long axis and the load values at the moment of failure were recorded using a universal test machine. Stress levels were calculated according to the maximum Von Mises criteria. The fracture resistances for titanium and zirconium abutment groups were 525.65 N and 514.05 N, respectively. No significant differences were observed between two groups regarding the fracture resistance levels. The maximum Von Mises equivalent stress concentrated on zirconium copings in both of the groups. Implant-abutment-ZrO2 coping combination has the potential to withstand physiological occlusal forces in the anterior region. Three-dimensional finite elements analysis results of the implant-abutment-ZrO2 coping combination is compatible with the results of fracture resistance.