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Wu Xu, Yan Zhi, Yongsheng Yuan, Bingfeng Zhang, Yuting Shen, Hui Zhang, Kezhong Zhang, Yun Xu
Despite a growing body of evidence suggests that abnormal iron metabolism plays an important role in the pathogenesis of Parkinson's disease (PD), few studies explored its role in non-motor symptoms (NMS) of PD. The present study aimed to investigate the relationship between abnormal iron metabolism and NMS of PD. Seventy PD patients and 64 healthy controls were consecutively recruited to compare serum iron, ceruloplasmin, ferritin, and transferrin levels. We evaluated five classic NMS, including depression, anxiety, pain, sleep disorder, and autonomic dysfunction in PD patients using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms, respectively...
May 10, 2018: Journal of Neural Transmission
E T Zakharova, A V Sokolov, N N Pavlichenko, V A Kostevich, I N Abdurasulova, A V Chechushkov, I V Voynova, A Yu Elizarova, N N Kolmakov, M G Bass, I V Semak, A I Budevich, P M Kozhin, N K Zenkov, V M Klimenko, O V Kirik, D E Korzhevskii, E B Menshchikova, V B Vasilyev
Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs...
May 10, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Bo Wang, Xiao-Ping Wang
Ceruloplasmin (CP) is the major copper transport protein in plasma, mainly produced by the liver. Glycosylphosphatidylinositol-linked CP (GPI-CP) is the predominant form expressed in astrocytes of the brain. A growing body of evidence has demonstrated that CP is an essential protein in body with multiple functions such as regulating the homeostasis of copper and iron ions, ferroxidase activity, oxidizing organic amines, and preventing the formation of free radicals. In addition, as an acute-phase protein, CP is induced during inflammation and infection...
May 7, 2018: Current Neuropharmacology
Xuemei Zhao, Ziqiang Shao, Yu Zhang, Fang Liu, Zhibo Liu, Zunjing Liu
OBJECTIVES: To investigate the relationship between ceruloplasmin (CP) and Parkinson's disease (PD), and the correlation between CP level and the time difference between nonmotor symptoms and motor symptoms and the diagnosis were also mentioned. MATERIALS AND METHODS: Sixty-six patients diagnosed with PD for the first time were included in the study. They were divided into CP reduction group (31 cases) and CP normal group (35 cases) according to their CP level. The estimated time difference between nonmotor symptoms and motor symptoms and the diagnosis were recorded respectively...
May 7, 2018: Brain and Behavior
Maki Watanabe, Ken Ohyama, Masashi Suzuki, Yasunobu Nosaki, Takashi Hara, Katsushige Iwai, Satoshi Kono, Hiroaki Miyajima, Kenji Mokuno
Aceruloplasminemia is an autosomal recessive inherited disorder caused by ceruloplasmin gene mutations. The loss of ferroxidase activity of ceruloplasmin due to gene mutations causes a disturbance in cellular iron transport. We herein describe a patient with aceruloplasminemia, who presented with diabetes mellitus that was treated by insulin injections, liver hemosiderosis treated by phlebotomy therapy, and neurological impairment. A genetic analysis of the ceruloplasmin gene revealed novel compound heterozygous mutations of c...
April 27, 2018: Internal Medicine
Keiko Ueda, Hye Jin Kim, Jin Zhao, Ying Song, Joshua L Dunaief, Janet R Sparrow
Intracellular Fe plays a key role in redox active energy and electron transfer. We sought to understand how Fe levels impact the retina, given that retinal pigment epithelial (RPE) cells are also challenged by accumulations of vitamin A aldehyde adducts (bisretinoid lipofuscin) that photogenerate reactive oxygen species and photodecompose into damaging aldehyde- and dicarbonyl-bearing species. In mice treated with the Fe chelator deferiprone (DFP), intracellular Fe levels, as reflected in transferrin receptor mRNA expression, were reduced...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
Z Chang, H Zhang, H Dong, K Mehmood, M Ijaz, H I Ahmad, M A Naeem, Q Wu, F Nabi, H Zhu
Copper is the most essential trace element in the animal body. Nano-sized copper particles have been widely used in a number of different animal species in modern medicinal practice. The present study was designed to examine the effect of dietary copper sulfate/(CuSO4) and nano copper supplementation on serum antioxidant capacity of weaning piglets. A total of 28 Duroc piglets (21 days, and weighing ~7 kg) were randomly divided into three equal groups. The control group (n=4) was administered with a normal standard diet; however the CuSO4 (n=12) and nano copper (n=12) groups were treated with 50, 100 and 200 mg/kg/day body weight, respectively...
March 2018: Journal of Biological Regulators and Homeostatic Agents
Xudong Wang, Sai Yin, Zhihao Yang, Bing Zhou
Multicopper oxidases (MCOs) are a specific group of enzymes that contain multiple copper centers through which different substrates are oxidized. Main members of MCO family include ferroxidases, ascorbate oxidases, and laccases. MCO type of ferroxidases is key to iron transport across the plasma membrane. In Drosophila, there are four potential multiple oxidases, MCO1-4. No convincing evidence has been presented so far to indicate any of these, or even any insect multicopper oxidase, to be a ferroxidase. Here we show Drosophila MCO3 (dMCO3) is highly likely a bona fide ferroxidase...
April 20, 2018: Biochimica et Biophysica Acta
Jiashuo Zheng, Ruiwei Jiang, Min Chen, Zaitunamu Maimaitiming, Junzhuo Wang, Gregory J Anderson, Chris D Vulpe, Joshua L Dunaief, Huijun Chen
Background: The accumulation of iron occurs in the central nervous system (CNS) in several neurodegenerative diseases. Although multi-copper ferroxidases (MCFs) play an important role in cellular iron metabolism and homeostasis, the mechanism of MCFs in the CNS remains unclear. Objective: The aim was to study the role of MCFs in CNS iron metabolism and homeostasis by using hephaestin/ceruloplasmin (Heph/Cp) double knockout (KO) mice. Methods: Heph/Cp double KO male mice were generated by crossing both single KO mice...
April 1, 2018: Journal of Nutrition
Gang Liu, Dingyuan Ma, Jian Cheng, Jingjing Zhang, Chunyu Luo, Yun Sun, Ping Hu, Yuguo Wang, Tao Jiang, Zhengfeng Xu
BACKGROUND: Wilson's disease (WD) is an autosomal recessive disorder characterized by copper accumulation. ATP7B gene mutations lead to ATP7B protein dysfunction, which in turn causes Wilson's disease. CASE PRESENTATION: We describe a male case of Wilson's disease diagnosed at 10 years after routine biochemical test that showed low serum ceruloplasmin levels and Kayser-Fleischer rings in both corneas. Analysis of the ATP7B gene revealed compound heterozygous mutations in the proband, including the reported c...
April 12, 2018: BMC Medical Genetics
Talal El Imad, Hassan Al Moussawi, Fady G Haddad, Richard Felix, Stephen M Mulrooney
A 64-year-old woman, presented with abdominal distention, jaundice and resting tremor, was found to have liver injury and abnormal liver enzymes. A computed tomography (CT) scan of the abdomen and pelvis showed abdominopelvic ascites and signs of liver cirrhosis. An extensive liver disease workup was performed and came back negative; therefore, a liver biopsy was obtained and showed evidence of cirrhosis with elevated liver copper consistent with Wilson's disease (WD). We report a unique case of late-onset WD in which the ceruloplasmin level and 24-h urinary copper excretion were all normal...
February 8, 2018: Curēus
Aurélia Poujois, France Woimant
Wilson's disease (WD) is characterised by a deleterious accumulation of copper in the liver and brain. It is one of those rare genetic disorders that benefits from effective and lifelong treatments that have dramatically transformed the prognosis of the disease. In Europe, its clinical prevalence is estimated at between 1.2 and 2/100,000 but the genetic prevalence is higher, at around 1/7000. Incomplete penetrance of the gene or the presence of modifier genes may account for the difference between the calculated genetic prevalence and the number of patients diagnosed with WD...
April 3, 2018: Clinics and Research in Hepatology and Gastroenterology
Go Hun Seo, Yoon-Myung Kim, Seak Hee Oh, Sun Ju Chung, In Hee Choi, Gu-Hwan Kim, Mi-Sun Yum, Jin-Ho Choi, Kyung Mo Kim, Tae-Sung Ko, Beom Hee Lee, Han-Wook Yoo
BACKGROUND: To identify biochemical and genetic features that characterise neurological Wilson disease as a distinct disease subgroup. METHODS: Detailed biochemical profiles and genotypic characteristics of neurological (86 patients) and hepatic subgroups (233 patients) from 368 unrelated Korean families were analysed. RESULTS: Compared with patients in the hepatic subgroup, patients in the neurological subgroup had a later age at onset, a higher proportion with Kayser-Fleischer rings and higher serum creatinine levels, and a lower proportion with favourable outcome (62% vs 80%, P<0...
April 4, 2018: Journal of Medical Genetics
Michael Maes, Andre F Carvalho
Here, we review a novel concept namely the compensatory immune-regulatory reflex system (CIRS) as applied to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). There is evidence that a substantial subset of individuals with MDD and BD exhibit an activation of the immune-inflammatory response system (IRS), as indicated by an increased production of macrophagic M1 and T helper (Th)-1 pro-inflammatory cytokines, interleukin (IL)-6 trans-signaling, positive acute phase proteins (APPs), and complement factors...
April 2, 2018: Molecular Neurobiology
Bogdan Bernevic, Ahmed H El-Khatib, Norbert Jakubowski, Michael G Weller
OBJECTIVE: The human copper-protein ceruloplasmin (Cp) is the major copper-containing protein in the human body. The accurate determination of Cp is mandatory for the reliable diagnosis of several diseases. However, the analysis of Cp has proven to be difficult. The aim of our work was a proof of concept for the determination of a metalloprotein-based on online immunocapture ICP-MS. The immuno-affinity step is responsible for the enrichment and isolation of the analyte from serum, whereas the compound-independent quantitation with ICP-MS delivers the sensitivity, precision, and large dynamic range...
April 2, 2018: BMC Research Notes
T Tomasi, A Volpato, W A B Pereira, L H Debastiani, N B Bottari, V M Morsch, M R C Schetinger, M L R Leal, G Machado, A S Da Silva
The aim of this study was to evaluate whether injectable zinc and copper affect host immune responses and antioxidant status of newborn calves. For this study, 19 newborn calves were divided into two groups. The control group consisted of 10 animals; and the treated group consisted of nine animals that received copper edetate (Cu-ed) and zinc edetate (Zn-ed) subcutaneously at the first day of life at doses of 0.3 mg/kg and 1.0 mg/kg respectively. Blood and faecal samples were collected for laboratory analyses (seric biochemistry, proteinogram, antioxidant enzymes and parasitological examination) on days 10, 20 and 30 after birth...
March 30, 2018: Journal of Animal Physiology and Animal Nutrition
M N Karpenko, E Yu Ilyicheva, Z M Muruzheva, I V Milyukhina, Yu A Orlov, L V Puchkova
Serum concentration of copper, immunoreactive polypeptides of ceruloplasmin and its oxidase activity, and the number of copper atoms per ceruloplasmin molecule were decreased in patients with Parkinson's disease in comparison with the corresponding parameters in age-matched healthy individuals, but the ratio of apoceruloplasmin to holoceruloplasmin in patients with Parkinson's disease was similar in both groups. Treatment of blood serum with Helex 100, a high-affinity copper chelator, revealed reduced content of labile copper atoms per ceruloplasmin molecule in patients with Parkinson's disease in comparison with that in healthy controls...
March 26, 2018: Bulletin of Experimental Biology and Medicine
Ryota Matsuoka, Aya Shiba-Ishii, Noriyuki Nakano, Akira Togayachi, Shingo Sakashita, Yukio Sato, Yuko Minami, Masayuki Noguchi
OBJECTIVES: Ceruloplasmin (CP) is a well-known copper binding protein synthesized mainly in the liver, but its expression is known to be elevated in the serum of cancer patients and in malignant tumor cells. Lung cancer is the leading cause of cancer-related death worldwide, and adenocarcinoma is the main histological type of lung cancer. However, the role of CP in lung adenocarcinoma is still unclear. Here we examined and compared the expression of CP in various histological subtypes of lung adenocarcinoma and its correlation with clinicopathological parameters...
April 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Yu Huang, Mitsuhisa Takatsuki, Akihiko Soyama, Masaaki Hidaka, Shinichiro Ono, Tomohiko Adachi, Takanobu Hara, Satomi Okada, Takashi Hamada, Susumu Eguchi
BACKGROUND Liver transplantation is indicated for patients with Wilson's disease (WD) who present either with acute liver failure or with end-stage liver disease and severe hepatic insufficiency as the first sign of disease. However, almost all reported cases have been treated with death donor liver transplantation. Here we report the case of a patient with WD associated with fulminant hepatic failure (WD-FHF) who underwent living donor liver transplantation (LDLT). CASE REPORT A 17-year-old female was diagnosed with WD-FHF based on high uric copper (10 603 μg/day, normal <100 μg/day), low serum ceruloplasmin (15 mg/dL, normal >20 mg/dL) and Kayser-Fleischer (K-F) corneal ring, and acute liver failure (ALF), acute renal failure (ARF) and grade 2 hepatic encephalopathy (HE)...
March 17, 2018: American Journal of Case Reports
Jung-Heun Ha, Caglar Doguer, Shireen R L Flores, Tao Wang, James F Collins
Background: Consumption of a high-iron diet causes copper deficiency in weanling rodents; however, the minimum amount of dietary iron that disrupts copper homeostasis has not been established. Objective: We tested the hypothesis that dietary iron at only several-fold above physiologic requirements would cause copper depletion. Methods: Weanling male Sprague-Dawley rats (n = 6/group) were fed AIN-93G-based diets with adequate (88 µg Fe/g = 1×), or excessive (4×, 9...
March 1, 2018: Journal of Nutrition
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