The influence of uric acid treatments on liver glutathione system prevent oxidative damages in experimental autoimmune encephalomyelitis mice

Recently we reported that antioxidant system in brain and spinal cord in experimental autoimmune encephalomyelitis (EAE) mice is mainly affected at early stages of the disease [M. Zargari, A. Allameh, M.H. Sanati, T. Tiraihi, S.H. Lavasani, O. Emadyan, Relationship between the clinical scoring and demyelination in central nervous system with total antioxidant capacity of plasma during experimental autoimmune encephalomyelitis development in mice, Neurosci. Lett. 412 (2007), 24–28]. The aim of the present study was to investigate the role of uric acid (UA) on antioxidant system in liver and plasma of EAE mice. EAE was induced in C57/BL6 mice (n = 60), followed by i.p. administration of UA (10 mg/kg BW) in 30 mice at three distinct clinical stages (A: prior to onset, B: after onset, C: after development of EAE). Livers were removed and processed for measurement of lipid peroxidation products, reduced glutathione (GSH), and glutathione S-transferase (GST) and total antioxidant capacity of plasma (FRAP). The results showed that lipid peroxidation products in liver of EAE mice was increased significantly (∼85%) as compared to normal. UA administration to EAE mice caused a significant suppression of liver lipid peroxidation products (∼45%) at early stages (A and B). There was an inverse relationship between lipid peroxidation and cellular GSH in liver. GSH was significantly depleted in mice liver during the EAE progression, but it was recovered (∼29%) when UA was injected before the onset of the disease (groups A and B). Plasma total antioxidant capacity was significantly decreased during the development of EAE, however it was subsided in mice treated with UA as compared to the corresponding controls (21%) in groups A and B. Elevated liver GST as a result of EAE induction was reversed in mice treated with UA particularly in groups A and B. These results indicate that hepatic glutathione system, particularly GST plays a major role in modulation of oxidative damages to central nervous system (CNS) during EAE induction. The positive response of antioxidant system to UA administration in EAE mice was corroborated with improvement of clinical manifestation of the animals.     

Vasopressin and oxytocin in the rat spinal cord: distribution and origins in comparison to [Met]enkephalin, dynorphin and related opioids and their irresponsiveness to stimuli modulating neurohypophyseal secretion

Immunoreactive-vasopressin, -oxytocin, -dynorphin, -dynorphin-(1-8), -alpha-neo-endorphin and -[Met]enkephalin were, in each case, present in greater concentrations in dorsal as compared to ventral, and lumbo-sacral as compared to cervico-thoracic, spinal cord. These differences were significantly more pronounced for vasopressin and oxytocin than for the other peptides. Lesions of the hypothalamic paraventricular nucleus depleted levels of immunoreactive-vasopressin and -oxytocin throughout the cord whereas levels of the opioid peptides therein were unaffected. In contrast, destruction of either the supraoptic or suprachiasmatic nucleus failed to change the content of immunoreactive-vasopressin, -oxytocin or any of the opioid peptides in the cord. Dehydration for 3 days depressed levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate lobe of the pituitary. In distinction, the levels of these were not modified in the spinal cord. Further, treatment with the synthetic corticosteroid, dexamethasone, elevated levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate pituitary whereas these were unaffected in the spinal cord. It is concluded that vasopressin and oxytocin in the spinal cord are predominantly derived from the paraventricular nucleus, localized in dorsal lumbo-sacral regions of the cord and insensitive to endocrinological manipulations. These pools may, thus, be modulated differently from their counterparts in the neurohypophysis and have a differing role, possibly in the control of the primary processing, autonomic or motor junctions. Further, there is no evidence from these or our prior studies for a close interrelationship of spinal cord vasopressin with dynorphin-related peptides (or oxytocin with [Met]enkephalin), likewise in contrast to the neurohypophysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanical and Tribological Behavior of Mechanically Alloyed Ni-TiC Composites Processed via Spark Plasma Sintering

Titanium carbide (TiC) reinforced nickel (Ni) matrix composites were processed via mechanical alloying (MA) followed by spark plasma sintering (SPS) process. Mechanical alloying has gained special attention as a powerful non-equilibrium process for fabricating amorphous and nanocrystalline materials, whereas spark plasma sintering (SPS) is a unique technique for processing dense and near net shape bulk alloys with homogenous microstructure. TiC reinforcement varied from 5 to 50 wt.% into nickel matrix to investigate its effect on the microstructure and mechanical behavior of Ni-TiC composites. All Ni-TiC composites powder was mechanically alloyed using planetary high energy ball mill with 400 rpm and ball to powder ratio (BPR) 15:1 for 24 h. Bulk Ni-TiC composites were then sintered via SPS process at 50 MPa pressure and 900–1200 °C temperature. All Ni-TiC composites exhibited higher microhardness and compressive strength than pure nickel due to the presence of homogeneously distributed TiC particles within the nickel matrix, matrix grain refinement, and excellent interfacial bonding between nickel and TiC reinforcement. There is an increase in Ni-TiC composites microhardness with an increase in TiC reinforcement from 5 to 50 wt.%, and it reaches the maximum value of 900 HV for Ni-50TiC composites.     

Lipopolysaccharides,but not Angiotensin ll,lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Angiotensin II (Ang II) might induce pro‐inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro‐inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance‐sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24‐hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL‐6 or MCP‐1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine. In support, 24‐hr organ culture of mouse MRA significantly suppressed Agtr1a mRNA and augmented Tlr4 mRNA along with attenuated vasomotor responses to Ang II. Moreover, contrary to LPS and TNF‐α, Ang II and [Sar1]‐Ang II had no concentration‐ or time‐dependent effects on IL‐6 and MCP‐1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression was undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary to previous studies and the observed effects of LPS, we could not demonstrate direct vascular pro‐inflammatory effects of Ang II ex vivo or in vitro. As indicated by our results, down‐regulation or desensitization of AT₁R during culture may explain our findings.     

Nonarteritic anterior ischemic optic neuropathy and ‘visual field defects’ following vitrectomy: could they be related?

Background Visual field defects after uncomplicated vitrectomy have been reported but poorly explained. We describe two cases of nonarteritic anterior ischemic optic neuropathy (NAION) observed following vitrectomy. We also reviewed the literature for cases of post-vitrectomy visual field defects for evidence of optic nerve damage. Methods Two patients developed optic disc edema and features of an optic neuropathy after uncomplicated vitrectomy for macular hole and epiretinal membrane. A systematic literature search was conducted to obtain prior reports of visual field defects or ischemic optic neuropathy following vitrectomy. Additional studies were identified from the bibliographies of the retrieved articles. Results The incidence of visual field defects following vitrectomy has varied from 1–71% across all studies. Overall, we found 160 (14.5%) cases of unexplained visual field defects following vitrectomy out of 1,104 patients. Of these, 31 eyes (19.4%) have shown some sign of optic nerve damage following vitrectomy, including pallor in 29 eyes, relative afferent pupillary defect in eight eyes, and intrapapillary hemorrhage in two eyes. Conclusions NAION may develop following vitrectomy. “Visual field defects” following vitrectomy are common and many of the involved eyes demonstrate evidence of optic nerve damage, some of which may have represented NAION. Presented in part at the Association for Research in Vision and Ophthalmology Annual Meeting, April 30, 2006, Ft Lauderdale, FL, USA. Grant Support: Supported in part by an nnrestricted grant from Research to Prevent Blindness, New York, NY (MSL). Proprietary Interest: None.     

Anterior ischemic optic neuropathy after uncomplicated scleral buckling surgery

Background To report a case of non-arteritic anterior ischemic optic neuropathy (NAION) observed after uncomplicated scleral buckle placement.Methods A 57-year-old man presented with a rhegmatogenous retinal detachment of the left eye. He underwent uncomplicated scleral buckle placement and C₃F₈ injection. Perioperative intraocular pressures were normal.Results On postoperative day 24, fundus examination revealed swelling of the left optic nerve and features of an optic neuropathy (visual field defect, relative afferent pupillary defect). Fluorescein angiography did not reveal delayed choroidal filling. Review of systems and laboratory investigations were not consistent with giant cell arteritis.Conclusions Non-arteritic anterior ischemic optic neuropathy may develop after uncomplicated scleral buckling surgery.     

Viability of limbal epithelium after anterior lamellar harvesting using a microkeratome

OBJECTIVE: To determine the viability in cold eye bank storage of different layers of central and limbal corneal epithelium, including the limbal basal stem cell population, on days 0, 3, 6, and 9 after harvest using a large diameter microkeratome system. METHODS: Twenty-two human whole globes not suitable for transplantation were obtained from an eye bank (San Diego Eye Bank, San Diego, California) and used for study. Large-diameter anterior corneal discs were prepared using a large diameter microkeratome and stained with calcein AM and an ethidium homodimer to differentiate live from dead cells, respectively. A laser confocal microscope and digital imaging were used to distinguish live (green) from dead (red) cells. Central and limbal epithelial regions were isolated and the middle and basal epithelial sections were cell counted by 3 independent observers. These sections were stored up to 9 days at 4 degrees C in an eye bank corneal storage medium. Differences were tested using nonparametric methods. MAIN OUTCOME MEASURES: The percentage of live cells in each of these epithelial layers was determined for up to 9 days in cold eye bank corneal storage medium. RESULTS: At all time points studied, the better protected basal epithelial layers displayed greater mean viability than the overlying middle epithelial layers. However, the difference was not statistically significant on all days. When comparing the basal epithelial viability of the limbal and central regions, after day 0 in 4 degrees C cold organ culture, the observed viability of the limbal basal epithelium, the purported location of the limbal epithelial stem cell region, was significantly greater than that of the central epithelium. On day 0, median limbal basal versus central basal epithelial viability were 100% (range, 71.7-100%) versus 98.4% (range, 88.9-100%) (P>0.05); on day 3, 100% (range, 64.3-100%) versus 63.4% (range, 13.6-95.5%) (P<0.0005); on day 6, 95.0% (range, 35.0-100%) versus 28.0% (range, 0-92.0%) (P<0.0005); and on day 9, 95.0% (range, 3.7-100%) versus 68.6% (range, 0-100%) (P<0.0005). CONCLUSIONS: After microkeratome harvesting, the limbal basal epithelium is significantly longer lived in cold eye bank storage than central basal epithelium and the middle layers of limbal and central epithelium. This longevity not only bodes well for organ storage of limbal grafts, but also confirms the hardiness of the stem cell region.     

Histopathology and ultrastructural examination of optic nerve sheath biopsies after optic nerve sheath decompression with and without mitomycin

PURPOSE: We chose to compare histologically and ultrastructurally changes in the optic nerve sheath after optic nerve sheath decompression, initially after a second surgery and after treatment with mitomycin-C. The mechanism by which optic nerve sheath decompression alleviates papilledema can be further understood in consideration of the results. METHODS: Tissue was obtained by biopsy from 3 first-time surgical and 4 reoperative cases with and without mitomycin-C in patients with idiopathic intracranial hypertension. The sheaths were fixed in a mixture of 2% paraformaldehyde and 2% glutaraldehyde, osmicated and dehydrated in a series of ethanol, and finally embedded in epon. Tissue blocks were sectioned at 1 microm and stained with both PPD and toluidine blue. Thin sections were examined by transmission electron microscopy. RESULTS: Normal meningeal tissue obtained at the time at optic nerve sheath decompression consisted mainly of collagen, closely packed and roughly parallel to the axis of the optic nerve. Collagen deposition seen in scar tissue after secondary optic nerve sheath decompression was extremely disorganized and irregular, with the individual fibers laid down seemingly at random. There was little sense of layering or of parallel arrays. Mitomycin-C appeared to influence collagen deposition in such a way that the collagen was more regularly packed and more closely resembled unoperated tissue. CONCLUSIONS: The regular well-organized collagen packing seen in normal sheath tissue is disrupted and replaced by less organized but compact scar tissue after optic nerve sheath decompression. With mitomycin use, more regular collagen packing closely approximating that found in unoperated sheath occurs. This configuration of fibers lends support for the filtration mechanism of optic nerve sheath decompression in treating papilledema.