Neurocutaneous melanosis is an extremely rare disease characterized by large or multiple congenital melanocytic nevi and benign or malignant proliferation of melanocytes in the central nervous ...system. Neurological manifestations usually develop during the first three years of life and the prognosis of patients with NCM who manifest neurological symptoms is very poor. Here we describe a 9‐year‐old girl who manifested neurological symptoms caused by communicating hydrocephalus and died of proliferation of melanocytes in the central nervous system 11 months after the initial symptoms. Serum and cerebrospinal fluid 5‐S‐CD levels could be a useful marker of disease progression, even in patients with NCM without apparent malignant findings at initial biopsy.
The endogenous neurotoxin 5-S-cysteinyl-dopamine (CysDA) has been linked to the degeneration of dopaminergic neurons in the Substantia nigra. Sulforaphane (SFN) is an isothiocyanate derived from ...cruciferous vegetables that has been proposed as a potential chemopreventive agent, although its effects on other cells are less clear. This study was undertaken to investigate the protective effects of SFN against CysDA-induced injury in primary cortical neurons. The results indicate that SFN protects primary cortical neurons against CysDA-induced injury by a mechanism involving the increased nuclear translocation of Nrf2 and the increased activity of phase II enzymes such as glutathione-S-transferase, glutathione reductase, and thioredoxine reductase. Moreover, the protection exerted by SFN appears to be mediated by the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Akt/protein kinase B (PKB) pathways
A decrease in reduced glutathione levels in dopamine containing nigral cells in Parkinson's disease may result from the formation of cysteinyl‐adducts of catecholamines, which in turn exert toxicity ...on nigral cells. We show that exposure of neurons (CSM 14.1) to 5‐S‐cysteinyl conjugates of dopamine, l‐DOPA, DOPAC or DHMA causes neuronal damage, increases in oxidative DNA base modification and an elevation of caspase‐3 activity in cells. Damage to neurons was apparent 12–48 h of post‐exposure and there were increases in caspase‐3 activity in neurons after 6 h. These changes were paralleled by large increases in pyrimidine and purine base oxidation products, such as 8‐OH‐guanine suggesting that 5‐S‐cysteinyl conjugates of catecholamines are capable of diffusing into cells and stimulating the formation of reactive oxygen species (ROS), which may then lead to a mechanism of cell damage involving caspase‐3. Indeed, intracellular ROS were observed to rise sharply on exposure to the conjugates. These results suggest one mechanism by which oxidative stress may occur in the substantia nigra in Parkinson's disease.
The incidence of malignant melanona has increased over the past decades, particularly in Caucasian population. This disease presents defavourable prognosis in terms of survey, especially when ...detection occurs at the metastatic phase. Reliable analytical methods for biomarker determination are thus an interesting tool in pathology detection and follow-up. In this context, a method using SPE-LC–ESI–MS–MS for the determination of 5-S-cysteinyldopa (5-SCD) in human plasma was optimized. The presence of matrix effect was investigated in details while 5-SCD stability was studied according to FDA requirements for the validation of bioanalytical methods. Pre-study and in-study validations of the entire method were then successfully performed by applying the approach based on total measurement error and accuracy profiles over a concentration ranges from 1.6 to 200ng/ml. Good results with respect to accuracy, trueness and precision were obtained. The maximum risk of observing future measurements falling outside the acceptance limits during routine analysis was also estimated.
Lean Manufacturing Implementation: An Approach To Reduce Production Cost. Opportunities to improve production processes and reduce production cost through the implementation of lean manufacturing in ...small medium garment manufacturing are presented in this research. This research shows that there is a possibility of decrease in production cost and increase in return on sales. Lean manufacturing implementation can eliminate waste in the production process. This is a set of techniques for identification and elimination of waste gathered from The Ford Production, Statistical Process Control and other techniques. Improvement of quality could be carried out while time and cost of production are being reduced.
Abstract N -β-Alanyl-5- S -glutathionyl-3,4-dihydroxyphenylalanine (5- S -GAD), an antibacterial substance isolated from flesh fly, has been described as having multipotential biological activities ...toward various tissues. However, there has been no report testing its action on neural cells. In the present study, we investigate whether 5- S -GAD is neurotoxic or neuroprotective to the rat retina. 5- S -GAD at high doses (more than 200 pmol) induced apoptosis of retinal neurons 7 days after intraocular injection. 5- S -GAD at low doses (2–20 pmol) significantly attenuated the loss of retinal ganglion cells (RGCs) and the thinning of inner retina induced by NMDA in a dose-dependent manner. To understand the protective mechanism of 5- S -GAD, we investigated the influence of 5- S -GAD on the cell survival molecules, phospho-Akt and Bcl-2. 5- S -GAD (2–20 pmol) rapidly increased phospho-Akt expression 1–7 days and Bcl-2 expression 3–7 days after injection. The cellular localization of this increase was both in bipolar cells and RGCs. This neurosurvival effect of 5- S -GAD was further tested using another model of optic nerve injury. 5- S -GAD significantly blocked the apoptosis of RGCs 7 days after optic nerve crush. These results show that 5- S -GAD (2–20 pmol) protects against the NMDA- and optic nerve crush-induced apoptosis of RGCs. The neuroprotective action of 5- S -GAD in the retina might be mediated by the cell survival phospho-Akt/Bcl-2 system and offers a therapeutic option to rescue RGCs from various types of excitotoxic disease, such as glaucoma.
The ability of
N-β-alanyl-5-
S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD)—a novel catechol derivative isolated from an insect as an antibacterial substance—to scavenge free radicals and ...prevent cataract progression was examined. 5-S-GAD scavenged 1,1-diphenylpicrylhydrazyl (DPPH) and superoxide anions (O
2
−
), and inhibited lipid peroxidation. It also significantly inhibited the onset of glucocorticoid-induced lens opacification in chick embryos. These effects of 5-S-GAD were stronger than those of
N-acetylcarnosine and TEMPOL, which are reported to be effective radical scavengers in the prevention of cataract progression. 5-S-GAD clearly delayed the maturation of cataracts induced by diamide in cultured lenses of rats. Daily instillation of 5-S-GAD retarded the development of lens opacity in galactose-fed rats. Biochemical analysis of the lenses revealed that 20-kDa proteins, presumably consisting of α-crystallin, were the most susceptible to oxidative stress, which leads to the carbonylation of the side chains of these proteins. α-Crystallin carbonylation induced by diamide or galactose was notably inhibited by 5-S-GAD in a dose-dependent manner. Our results show that 5-S-GAD prevents acute lens opacification in these short-term experimental models, possibly in part by virtue of its antioxidative property, and 5-S-GAD is expected to have long-term pharmaceutical effects.
We reported the case of a 92‐year‐old woman with a pigmented and non‐pigmented surface of the pedunculated nodule on her lower leg. Microscopic examination revealed that this nodule consisted of a ...component of small, dark, homogenous, poroid cells and cuticular cells in the dermis. The histopathological features of the lesion were consistent with poroid neoplasm. Immunohistochemistry showed that HMB‐45 and Melan‐A were positive in malanocytes and melanophages of the pigmented areas. Unlike most poroid neoplasms, this case showed pigmented lesion mimicked nodular melanoma.
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