Secondary structure dependence of amyloid-ß(1-40) on simulation techniques and force field parameters.

Our recent studies revealed that none of the selected widely used force field parameters and molecular dynamics simulation techniques yield structural properties for the intrinsically disordered α-synuclein that are in agreement with various experiments via testing different force field parameters. Here, we extend our studies on the secondary structure properties of the disordered amyloid-ß(1-40) peptide in aqueous solution. For these purposes, we conducted extensive replica exchange molecular dynamics simulations and obtained extensive molecular dynamics simulation trajectories from David E. Shaw group. Specifically, these molecular dynamics simulations were conducted using various force field parameters and obtained results are compared to our replica exchange molecular dynamics simulations and experiments. In this study, we calculated the secondary structure abundances and radius of gyration values for amyloid-ß(1-40) that were simulated using varying force field parameter sets and different simulation techniques. In addition, the intrinsic disorder propensity, as well as sequence-based secondary structure predisposition of amyloid-ß(1-40) and compared the findings with the results obtained from molecular simulations using various force field parameters and different simulation techniques. Our studies clearly show that the epitope region identification of amyloid-ß(1-40) depends on the chosen simulation technique and chosen force field parameters. Based on comparison with experiments, we find that best computational results in agreement with experiments are obtained using the a99sb*-ildn, charmm36m, and a99sb-disp parameters for the amyloid-ß(1-40) peptide in molecular dynamics simulations without parallel tempering or via replica exchange molecular dynamics simulations.

Effects of acute hypoxia on auditory pathway of Wistar albino rats

Background/aim: Ischemia is insufficient blood flow to provide adequate oxygenation. In the present study, we aimed to show whether acute hypoxia has a critical oxygen value that may lead to the deterioration of cochlear function. Materials and methods: Under general anesthesia, prehypoxic signal-to-noise ratios were determined by distortion product otoacoustic emissions (DPOAE). The oxygen saturation (SaO2) values of rats were monitored with an oxygen saturation probe. Rats were injected with an extra dose of anesthetic agent, and SaO2 was reduced. DPOAE values in SaO2 100­90, 90­80, 80­70, and 70­60 posthypoxic values were measured and compared statistically with prehypoxic values. Results: At 3000 and 4000 Hz, SaO2 70­60 values measured after the hypoxia were observed to be statistically significantly lower than the values measured before the hypoxia. At 6000 and 8000 Hz, SaO2 80­70 and 70­60 values measured after the hypoxia were observed to be statistically significantly lower than the values measured before the hypoxia. At 10,000 Hz, all of the values measured after the hypoxia were observed to be statistically significantly lower than the values obtained before the hypoxia. Conclusion: Many studies have been conducted on the effects of hypoxia on the inner ear. It remains unclear how fluctuations in DPOAE levels affect hearing in clinical trials when the SaO2 starts to decrease. Although hypoxia has been implicated in the etiology of sudden hearing loss and tinnitus, the effects of acute hypoxia on the cochlea are still uncertain. Further studies are needed on this subject.

Well-ordered nanoparticle arrays for floating gate memory applications.

A non-volatile floating gate memory device containing well-ordered Au nanoparticles (NPs) is fabricated as a metal-oxide-semiconductor capacitor structure. With superior control on the size, shape and position of nanoparticles, the presented nano-floating gate memory (NFGM) device possesses almost perfect precision of device geometry. The well-ordered Au NPs embedded within the memory device exhibit large memory window at low operation voltages (8.8V @ ± 15V), fast operation time (<10-4 s) and good retention (up to 107 s). In this work, the structural properties of the NFGM device are correlated with the examined electrical properties. The current results are compared with the other studies in the literature to emphasis the advantages of the precise ordering and geometry of the NPs.

Epitope region identification challenges of intrinsically disordered proteins in neurodegenerative diseases: Secondary structure dependence of α-synuclein on simulation techniques and force field parameters.

Due to fast aggregation processes of many disordered proteins in neurodegenerative diseases, it is difficult to study their epitope regions at the monomeric and oligomeric levels. Computer simulations complement experiments and have been used to identify the epitope regions of proteins. Residues that adopt ß-sheet conformation play a central role in the oligomerization and aggregation mechanisms of such proteins, including α-synuclein, which is at the center of Parkinson's and Alzheimer's diseases. In this study, we simulated the monomeric α-synuclein protein in an aqueous environment to evaluate its secondary structure properties, including ß-sheet propensity, and radius of gyration by replica exchange molecular dynamics simulations. We also obtained the molecular dynamics simulation trajectories of α-synuclein that were conducted using various force field parameters by the David E. Shaw group. Using these trajectories, we calculated the impacts of force field parameters on α-synuclein secondary structure properties and radius of gyration values and obtained results are compared with our data from REMD simulations. This study shows that the chosen force field parameters and computer simulation techniques effect the predicted secondary structure properties and radius of gyration values of α-synuclein in water. Herewith, we illustrate the challenges in epitope region identification of intrinsically disordered proteins in neurodegenerative diseases by current computer simulations.

Effects of phenytoin injection on vocal cord healing after mechanical trauma: An experimental study

Background/aim: Phenytoin is an anticonvulsant drug which causes fibroblast proliferation, collagen synthesis, and an increase in epidermal growth factor. Therefore, the aim of the present study is to evaluate the effect of phenytoin injection on the wound healing process in rats with vocal cord injury by histopathological methods. Materials and methods: The vocal cords of 10 albino Wistar rats were damaged bilaterally; the left vocal cord was kept as the control group. Phenytoin was injected in the right vocal cord. Ten rats were sacrificed. The thickness of the lamina propria and density of the fibroblast and collagen were evaluated histopathologically. Results: Thickness of the lamina propria was 18.0 ± 7.1 µm in the control group, 65.5 ± 10.7 µm in the phenytoin group. The density of fibroblast and collagen were statistically lower in the control group compared the phenytoin group (P < 0.05). Conclusion: Phenytoin injection in rats after vocal cord injury significantly increased the thickness of the lamina propria and density of fibroblast and regular and mature collagen in the lamina propria. The findings in our study provide a feasible scientific view for adding phenytoin treatment to vocal cord surgeries in otolaryngology practice, but further studies are needed in order to evaluate the use of phenytoin in preventing the formation of scar tissue and possible effects on vocal cord vibration in humans after vocal cord injury.

Detection and characterization of Distemper virus in a mink (Neovison vison) in Turkey.

In this study a mink showing hard pad disease like symptoms was euthanised. Heart blood and various tissue samples collected during necroscopy and tested by specific RT-PCR were found positive for CDV. H and F gene segments of the CDV strain was also partially sequenced using the appropriate primers, and subsequently the sequences were analysed and compared with same gene fragment sequence of other CDV isolates from different countries. The results of the phylogenetic analysis showed that the Turkish-Mink distemper strain is closely related to European CDV strains of lineage 1. Additionally, the distemper antigen was also detected when the tissue samples were examined by histology or immunohistochemistry.

Study of mouse induced pluripotent stem cell transplantation intoWistar albino rat cochleae after hair cell damage.

BACKGROUND/AIM: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. MATERIALS AND METHODS: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach. Auditory functions were evaluated with auditory brainstem responses (ABRs) before and after the injections. After a final hearing assessment the WARs were sacrificed and cochleae were extracted to see the biologic behavior of IPSCs in the inner ear by light microscopy and immunohistochemistry. RESULTS: There were no significant differences in the click-ABR thresholds in the study group after IPSC transplantation. The mean hearing threshold in the study group after ototoxic agent injection was 53.2 dB (10-90 dB). There was no significant difference between groups (P > 0.05) and no differentiated stem cells were observed immunohistochemically. CONCLUSION: Transplanted IPSCs did not show a therapeutic effect in this trial. We discuss potential pitfalls and factors affecting the therapeutic effect.

Comparison of Etanercept, Etomidate and Erythropoietin and Their Combinations in Experimentally-Induced Spinal Cord Injury.

AIM: The aim of this study was to compare the preventive effects of Etanercept, Etomidate, Erythropoietin and their combination in experimentally induced spinal cord trauma by clinical, histopathological, electrophysiological parameters and biochemical examination. MATERIAL AND METHODS: 85 healthy female Wistar-Albino rats were used in this study. Rats were divided 8 trauma groups that consisted of 10 rats for each, and 5 rats for the sham group. Laminectomy was performed under general anesthesia and the spinal cord was exposed with intact dura mater, and injury was created by the clip compression model. After the spinal cord injury, drugs were administered immediately intraperitoneally or subcutaneously. Except the sham group, all groups received drugs and were observed 24 or 72 hours. At the 72nd hour each group was anesthesized and somatosensorial evoked potentials (SEP) were recorded from the interarcuate ligament from the 2 vertebra proximal to the injured spinal cord and spinal cord tissue samples were taken for histopathological and biochemical evaluation. RESULTS: Etomidate groups showed a lower effect on spinal cord injury than etanercept and erythropoietin in terms of clinical, SEP and TNF-α. Etanercept and erythropoietin's neuroprotective effectiveness was shown alone or in combination treatments. More meaningful results were achieved with the use of erythropoietin and etanercept combination after spinal cord injury (SCI) than using erythropoietin alone. After SCI, highest Basso, Beattie, and Bresnahan (BBB) scores were achieved in the group which Etanercept and Erythropoietin applied together. CONCLUSION: The neuroprotective activity of etomidate was suspect. The neuroprotective effect of etanercept and erythropoietin after SCI was shown in individual and combined applications in this study. However, more experimental studies are needed for clinical use.

Experimental Endoscopic Cordotomy in the Sheep Model.

AIM: Interventional pain therapies are usually based on destruction of the related pain-conducting pathways. Current procedures targeting pain have replaced conventional pain treatment modalities while being less invasive. In this study, we investigated the feasibility of the endoscopic percutaneous cordotomy process on the sheep cervical spinal cord. MATERIAL AND METHODS: Seven male sheep, Akkaraman® genus, were operated on in the study. The guide was introduced at C1 to C2 vertebrae. The interlaminar area was exposed by a dilator, the dura was identified, and then the working cannula was inserted into the subarachnoid space. The target point of cordotomy was defined by endoscopic visualization as the midpoint between the dentate ligament and ventral root entry zone. After determination of the target point, a carbon dioxide laser (CDL) probe was introduced through the cannula. Ablative lesioning was performed by CDL. Hindlimb withdrawal thresholds were measured using the "Sample Pain Scale". The lesion was demonstrated by magnetic resonance imaging and histopathological examination. RESULTS: Three sheep had ipsilateral hemiparesis and the response to firm pressure test was not performed on them. Among the remaining four sheep, the pain tolerance test showed that one sheep was at stage 0, two at stage 1, and the last one at stage 3. CONCLUSION: Cordotomy might be successfully performed with the endoscopic technique in the sheep model and this should encourage future studies regarding minimal invasive procedures for intractable pain.

Imaging and surgical outcomes of spinal tumors in 18 dogs and one cat.

Clinical and magnetic resonance imaging (MRI) findings, histological appearances and surgical outcomes of 18 dogs and one cat with spinal tumors are presented. Medical records of the cases admitted for spinal disorders were reviewed, and cases of spinal tumors that were diagnosed by MRI and confirmed by histological examination were included in this study. T1 weighted, T2 weighted and contrast enhanced T1 weighted images were taken and interpreted to evaluate the spinal tumors. The tumors were diagnosed as: meningioma (n = 6), ependymoma (n = 1), nerve sheath tumor (n = 4), metastatic spinal tumor (n = 3), osteosarcoma (n = 2), osteoma (n = 1), rhabdomyosarcoma (n = 1), and nephroblastoma (n = 1). Thirteen cases underwent surgical operation and the remaining six cases were euthanized at the request of the owners. The neurological status of the surgical cases did not deteriorate, except for one dog that showed ependymoma in the early period after the operation. These results indicate the potential for surgical gross total tumor removal of vertebral tumors to provide better quality of life and surgical collection of histological specimens for definitive diagnosis. For effective case management, dedicated MRI examination is important to accurate evaluation of the spinal tumors, and surgical treatment is useful for extradural and intradural-extramedullary spinal tumors.

Study the effects of zonisamide on fine structure of rabbit basilar artery and hippocampus in rabbit subarachnoid hemorrhage model.

BACKGROUND: In this study, we investigated the effect of a novel antiepileptic drug, zonisamide (ZNS), on the basilar artery and hippocampus in a rabbit subarachnoid hemorrhage (SAH) model. METHODS: Three groups of New Zealand white rabbits were used: a sham (non-SAH) group, an SAH + saline group, and SAH + drug treatment group that received ZNS. In the treatment group, the subjects were given ZNS for 3 days after the SAH. Hippocampal sections were evaluated for neural tissue degeneration. Basilar artery lumen areas and arterial wall thickness were also measured in all groups. RESULTS: The mean luminal area of the SAH + ZNS was significantly greater than the SAH + saline group. In addition, the arterial wall thickness of SAH + ZNS group was significantly thinner than the SAH + saline group. The neuronal degeneration scores of the hippocampal CA1 regions in the SAH + ZNS group were significantly lower than the SAH + saline treatment animals. CONCLUSIONS: These results indicate that ZNS has a vasodilatatory effect on the basilar artery and a neuronal protective effect in the CA1 region of the hippocampus in a rabbit SAH model.

Protective effects of resveratrol on cisplatin-dependent inner-ear damage in rats.

Cisplatin is a common chemotherapeutic agent used in many solid and hematologic malignancies. The main unwanted effect of cisplatin is ototoxicity, for which no standard treatment has been reported. The present study examined the protective efficacy of resveratrol on cisplatin-dependent ototoxicity through an experimental model. Fifteen rats were randomized into three groups. Group 1 (control group) (n = 5) received intraperitoneal (i.p.) 15 mg/kg cisplatin; group 2 (resveratrol group) (n = 5) received i.p. 100 mg/kg resveratrol, followed by i.p. 15 mg/kg cisplatin; group 3 (n = 5) served as a vehicle group and received i.p. 1 ml dimethyl sulfoxide. All rats underwent the auditory brainstem response (ABR) test before and 72 h after the treatment. Pretreatment ABR values of the groups were not significantly different. The pretreatment hearing threshold values of the groups were 30 ± 6.60 and 28.5 ± 5.29 dB in groups 1 and 2, respectively (p > 0.05). The post-ABR-I and post-ABR-IV values were, respectively, 1.41 ± 0.18 and 5.83 ± 0.16 ms in the control subjects and 1.19 ± 0.22 and 4.58 ± 0.27 ms in the study group. The ABR-I and ABR-IV durations in rats treated with resveratrol were significantly shorter (p < 0.01). A comparison of threshold values shows that the resveratrol-treated rats had significantly lower values than the control rats. After cisplatin injection, ABR I-IV intervals were compared among the groups. The ABR I-IV interval duration was 4.42 ± 0.16 ms in the control group, while the resveratrol-treated rats showed a significantly shorter ABR I-IV interval duration of 3.49 ± 0.27 ms (p < 0.001). Resveratrol attenuated cisplatin-dependent inner-ear damage, as shown by the ABR-I, ABR-IV, ABR I-IV interval, and hearing threshold values. Our results suggest that this natural antioxidant may be effectively used in reducing the unwanted effects of cisplatin on the ear physiology of patients, particularly those undergoing chemotherapy.

Methothrexate attenuates early neutrophil infiltration and the associated lipid peroxidation in the injured spinal cord but does not induce neurotoxicity in the uninjured spinal cord in rats.

BACKGROUND: The goal of most acute therapies for spinal cord injury (SCI) in humans include attenuation of the early inflammatory response and may limit the extent of tissue injury and the consequent disability. OBJECTIVE: The purpose of this study was to investigate the early effects of methothrexate (MTX) treatment on myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and ultrastructural findings in the injured and uninjured spinal cords of rats. The effects of MTX treatment were also compared with methylprednisolone sodium succinate (MPSS) treatment. METHODS: Wistar rats were divided into seven groups: control; trauma alone (50 g/cm weight drop trauma); SCI + MPSS (30 mg/kg); SCI + low-dose (0.5 mg/kg) MTX (LDMTX); SCI + higher-dose (1 mg/kg) MTX (HDMTX); non-trauma + LDMTX; non-trauma + HDMTX. RESULTS: Administration of MTX and MPSS treatments significantly decreased MPO activity (p < 0.05) and MDA level (p < 0.05) in the first 24 h. The MTX treatments, particularly HDMTX, were more effective than MPSS in reducing MPO activity, and MTX treatments were also more effective than MPSS in reducing MDA level (p < 0.05). The MTX treatment was more protective on large- and medium-diameter myelinated axons in minimizing ultrastructural changes in the spinal-cord-injured rats, but did not induce neurotoxicity in normal spinal cord. CONCLUSION: The results of this study indicate that MTX treatment has a beneficial effect by reducing early neutrophil infiltration and the associated lipid peroxidation, and has significantly protective effects on the injured spinal cord tissue in the first 24 h after SCI. Given the anti-inflammatory properties of MTX, a single dose of MTX a week is used for non-neoplastic disease in humans, and MTX may have a beneficial role in the immediate management of acute SCI.

Effect of granulocyte-colony stimulating factor on spinal cord tissue after experimental contusion injury.

The purpose of this study was to investigate the early effects of granulocyte-colony stimulating factor (G-CSF) on myeloperoxidase (MPO) activity, lipid peroxidation (LPO) and ultrastructural findings in rats after spinal cord injury (SCI). We also compared the effects of G-CSF and methylprednisolone sodium succinate (MPSS). Wistar rats were divided into four groups: control, SCI alone (50 g/cm weight drop trauma), SCI+MPSS (30 mg/kg), and SCI+G-CSF (50 µg/kg). Administration of G-CSF and MPSS significantly decreased LPO (p < 0.05) and MPO activity (p < 0.05) in the first 24 hours. MPSS was more effective than G-CSF in reducing LPO (p < 0.05) and in minimizing ultrastructure changes. The results of this study indicate that G-CSF exerts a beneficial effect by decreasing MPO activity and LPO and may reduce tissue damage in the first 24 hours after SCI. Our findings do not exclude the possibility that G-CSF has a protective effect on spinal cord ultrastructure after the first 24 hours following SCI.