Ceruloplasmin/Transferrin Ratio Changes in Alzheimer's Disease

The link between iron and Alzheimer's disease (AD) has been mainly investigated with a focus on the local accumulation of this metal in specific areas of the brain that are critical for AD. In the present study, we have instead looked at systemic variations of markers of iron metabolism. We measured serum levels of iron, ceruloplasmin, and transferrin and calculated the transferrin saturation and the ceruloplasmin to transferrin ratio (Cp/Tf). Cp/Tf and transferrin saturation increased in AD patients. Cp/Tf ratios also correlated positively with peroxide levels and negatively with serum iron concentrations. Elevated values of ceruloplasmin, peroxides, and Cp/Tf inversely correlated with MMSE scores. Isolated medial temporal lobe atrophy positively correlated with Cp/Tf and negatively with serum iron. All these findings indicate that the local iron accumulation found in brain areas critical for AD should be viewed in the frame of iron systemic alterations

ATP7B Variants as Modulators of Copper Dyshomeostasis in Alzheimer's Disease

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Association between the c. 2495 A>G ATP7B Polymorphism and Sporadic Alzheimer's Disease

Nonceruloplasmin-bound copper (“free”) is reported to be elevated in Alzheimer's disease (AD). In Wilson's disease (WD) Cu-ATPase 7B protein tightly controls free copper body levels. To explore whether the ATP7B gene harbours susceptibility loci for AD, we screened 180 AD chromosomes for sequence changes in exons 2, 5, 8, 10, 14, and 16, where most of the Mediterranean WD-causing mutations lie. No WD mutation, but sequence changes corresponding to c.1216 T>G Single-Nucleotide Polymorphism (SNP) and c.2495 A>G SNP were found. Thereafter, we genotyped 190 AD patients and 164 controls for these SNPs frequencies estimation. Logistic regression analyses revealed either a trend for the c.1216 SNP (P = .074) or a higher frequency for c.2495 SNP of the GG genotype in patients, increasing the probability of AD by 74% (P = .028). Presence of the GG genotype in ATP7B c.2495 could account for copper dysfunction in AD which has been shown to raise the probability of the disease

Oxidative Stress Related to Iron Metabolism in Relapsing Remitting Multiple Sclerosis Patients With Low Disability

Oxidative status may play a role in chronic inflammation and neurodegeneration which are considered critical etiopathogenetic factors in Multiple Sclerosis (MS), both in the early phase of the disease and in the progressive one. The aim of this study is to explore oxidative status related to iron metabolism in peripheral blood of stable Relapsing-Remitting MS with low disability. We studied 60 Relapsing-Remitting MS patients (age 37.2 ± 9.06, EDSS median 1.0), and 40 healthy controls (age 40.3 ± 10.86). We measured total hydroperoxides (dROMs test) and Total Antioxidant Status (TAS), along with the iron metabolism biomarkers: Iron (Fe), ferritin (Ferr), transferrin (Tf), transferrin saturation (Tfsat), and ceruloplasmin (Cp) panel biomarkers [concentration (iCp) and enzymatic activity (eCp), copper (Cu), ceruloplasmin specific activity (eCp:iCp), copper to ceruloplasmin ratio (Cu:Cp), non-ceruloplasmin copper (nCp-Cu)]. We computed also the Cp:Tf ratio as an index of oxidative stress related to iron metabolism. We found lower TAS levels in MS patients than in healthy controls (CTRL) and normal reference level and higher dROMs and Cp:Tf ratio in MS than in healthy controls. Cp and Cu were higher in MS while biomarkers of iron metabolism were not different between patients and controls. Both in controls and MS, dROMs correlated with iCp (CTRL r = 0.821, p < 0.001; MS r = 0.775 p < 0.001) and eCp (CTRL r = 0.734, p < 0.001; MS r = 0.820 p < 0.001). Moreover, only in MS group iCp correlated negatively with Tfsat (r = -0.257, p = 0.047). Dividing MS patients in “untreated” group and “treated” group, we found a significant difference in Fe values [F(2, 97) = 10.136, p < 0.001]; in particular “MS untreated” showed higher mean values (mean = 114.5, SD = 39.37 μg/dL) than CTRL (mean 78.6, SD = 27.55 μg/dL p = 0.001) and “MS treated” (mean = 72.4, SD = 38.08 μg/dL; p < 0.001). Moreover, “MS untreated” showed significantly higher values of Cp:Tf (mean = 10.19, SD = 1.77∗10-2; p = 0.015), than CTRL (mean = 9.03, SD = 1.46 ∗10-2). These results suggest that chronic oxidative stress is relevant also in the remitting phase of the disease in patients with low disability and short disease duration. Therefore, treatment with antioxidants may be beneficial also in the early stage of the disease to preserve neuronal reserve

High performance liquid chromatographic analysis of quinolone antibacterial agents.

Eleven quinolone antibacterials have been analyzed by HPLC. The effects of different pH values and organic modifiers on chromatographic behaviour are discussed. Moreover the influence on separation mechanism of different counter-ions at various concentrations in the eluent has been investigated. Two different chromatographic methods have been selected, that allow the simultaneous analysis of quinolones containing or not a piperazinyl moiety, respectively

Degradation of imazosulfuron in soil

Imazosulfuron, 1-(2-chloroimidazo[1,2-alpha]pyridin-3-ylsulfonyl)-3- (4,6-dimethoxypyrimidin-2-yl)urea, is a new post-emergence sulfonylurea herbicide applied once per growing season, highly active at low application levels, used to control most annual and perennial broad-leaf weeds and sedges in paddy rice (75-95 g AI ha-1) and turf (500-1000 g AI ha-1), and characterised by low mammalian toxicity. The degradation of imazosulfuron in a sandy loam soil (10-15 cm depth) has been investigated under aerobic and anaerobic laboratory conditions to evaluate its likely environmental fate. Test soils were treated with imazosulfuron in acetonitrile to give a final concentration of 0.2 mg kg-1 (100 g ha-1). The treated soils were extracted with methylene chloride + acetonitrile + 1 M ammonium hydroxide (4 + 15 + 1 by volume) and analysed by HPLC. Recoveries from spiked soils ranged from 80% to 95% (RSD 0.5-2.5%; n = 3) for imazosulfuron and its metabolites 2-chloroimidazo[1,2-alpha]pyridin-3-sulfonamide (IPSN), 1-(2-chloroimidazo[1,2-alpha]pyridin-3-ylsulfonyl)-3-(4-hydroxy-6- methoxypyrimidin-2-yl)urea (HMS) and 2-amino-4,6-dimethoxypyrimidine (ADPM). The limits of quantitation ranged from 0.001 mg kg-1 to 0.005 mg kg-1. Chemical cleavage of the sulfonylurea bond to give ADPM and IPSN was the main degradation pathway in aerobic conditions, whereas a remarkable production of HMS under anaerobic conditions suggested that degradation was due to micro-organisms which had the ability to demethylate imazosulfuron. In aerobic and anaerobic conditions, imazosulfuron disappeared from the soil with a half-life of approximately 70 (90% CL 62-75; r2 = 0.98) and 4 (90% CL 3.2-4.2; r2 = 0.97) days, respectively

Iron in Alzheimer’s Disease: From Physiology to Disease Disabilities

Reactive oxygen species (ROS) play a key role in the neurodegeneration processes. Increased oxidative stress damages lipids, proteins, and nucleic acids in brain tissue, and it is tied to the loss of biometal homeostasis. For this reason, attention has been focused on transition metals involved in several biochemical reactions producing ROS. Even though a bulk of evidence has uncovered the role of metals in the generation of the toxic pathways at the base of Alzheimer’s disease (AD), this matter has been sidelined by the advent of the Amyloid Cascade Hypothesis. However, the link between metals and AD has been investigated in the last two decades, focusing on their local accumulation in brain areas known to be critical for AD. Recent evidence revealed a relation between iron and AD, particularly in relation to its capacity to increase the risk of the disease through ferroptosis. In this review, we briefly summarize the major points characterizing the function of iron in our body and highlight why, even though it is essential for our life, we have to monitor its dysfunction, particularly if we want to control our risk of AD

Zinc Therapy in Early Alzheimer’s Disease: Safety and Potential Therapeutic Efficacy

Zinc therapy is normally utilized for treatment of Wilson disease (WD), an inherited condition that is characterized by increased levels of non-ceruloplasmin bound (‘free’) copper in serum and urine. A subset of patients with Alzheimer’s disease (AD) or its prodromal form, known as Mild Cognitive Impairment (MCI), fail to maintain a normal copper metabolic balance and exhibit higher than normal values of non-ceruloplasmin copper. Zinc’s action mechanism involves the induction of intestinal cell metallothionein, which blocks copper absorption from the intestinal tract, thus restoring physiological levels of non-ceruloplasmin copper in the body. On this basis, it is employed in WD. Zinc therapy has shown potential beneficial effects in preliminary AD clinical trials, even though the studies have missed their primary endpoints, since they have study design and other important weaknesses. Nevertheless, in the studied AD patients, zinc effectively decreased non-ceruloplasmin copper levels and showed potential for improved cognitive performances with no major side effects. This review discusses zinc therapy safety and the potential therapeutic effects that might be expected on a subset of individuals showing both cognitive complaints and signs of copper imbalance

Serum brain-derived neurotrophic factor levels in different neurological diseases

Consistent evidence indicates the involvement of the brain-derived neurotrophic factor (BDNF) in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In the present study, we compared serum BDNF in 624 subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD), 40 by Lewy body dementia (LBD), 91 by vascular dementia (VAD), 30 by PD, and 169 controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD patients (P < 0.001) and a higher BDNF concentration in patients affected by PD (P = 0.045). Analyses of effects of pharmacological treatments suggested significantly higher BDNF serum levels in patients taking mood stabilizers/antiepileptics (P = 0.009) and L-DOPA (P < 0.001) and significant reductions in patients taking benzodiazepines (P = 0.020). In conclusion, our results support the role of BDNF alterations in neurodegenerative mechanisms common to different forms of neurological disorders and underline the importance of including drug treatment in the analyses to avoid confounding effects