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  • 1
    In: Analytical and Bioanalytical Chemistry, Springer Science and Business Media LLC
    Abstract: Traumatic brain injury (TBI) is an alteration of brain function caused by a sudden transmission of an external force to the head. The biomechanical impact induces acute and chronic metabolic changes that highly contribute to injury evolution and outcome. TBI heterogeneity calls for approaches allowing the mapping of regional molecular and metabolic changes underpinning disease progression, with mass spectrometry imaging (MSI) as an efficient tool to study the spatial distribution of small metabolites. In this study, we applied an innovative targeted atmospheric pressure-MALDI mass spectrometry imaging (AP-MALDI MSI) approach, starting from an extensive list of metabolites, representative of different metabolic pathways, individually validated on the tissue under analysis with original standards using 2,5-dihydroxybenzoic acid (DHB), to characterize the impact of TBI on regional changes to small metabolites in the brain. Brains from sham and TBI mice obtained 21 days post-injury were analyzed to examine the spatial metabolic profile of small metabolites belonging to different metabolic pathways. By a whole brain analysis, we identified four metabolites (alanine, lysine, histidine, and inosine) with higher abundance in TBI than sham mice. Within the TBI group, lysine, histidine, and inosine were higher in the hemisphere ipsilateral to the biomechanical impact vs. the contralateral one. Images showed a major involvement of the ipsilateral thalamus characterized by the increase of arginine, lysine, histidine, and inosine and a significant reduction of glutamic acid, and N-acetylaspartic acid compared to the contralateral thalamus. These findings indicate high-resolution imaging mass spectrometry as a powerful tool to identify region-specific changes after a TBI to understand the metabolic changes underlying brain injury evolution.
    Type of Medium: Online Resource
    ISSN: 1618-2642 , 1618-2650
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
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  • 2
    Online Resource
    Online Resource
    Informa UK Limited ; 2022
    In:  Archives of Physiology and Biochemistry Vol. 128, No. 2 ( 2022-03-04), p. 521-531
    In: Archives of Physiology and Biochemistry, Informa UK Limited, Vol. 128, No. 2 ( 2022-03-04), p. 521-531
    Type of Medium: Online Resource
    ISSN: 1381-3455 , 1744-4160
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2022
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  • 3
    In: Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 106, No. 9S ( 2022-09), p. S274-S274
    Type of Medium: Online Resource
    ISSN: 0041-1337
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 4
    In: Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 106, No. 9S ( 2022-09), p. S622-S622
    Type of Medium: Online Resource
    ISSN: 0041-1337
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 208424-7
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  • 5
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 15 ( 2021-07-26), p. 7938-
    Abstract: Background: exposure to environmental contaminants has been linked to an increased risk of neurological diseases and poor outcomes. Chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Several studies have demonstrated that ATR has the potential to be harmful to the brain’s neuronal circuits. Until today nobody has explored the effect of ATR inhalation on young and aged mice. Methods: young and aged mice were subject to 25 mg of ATR in a vehicle made with saline and 10% of Dimethyl sulfoxide (DMSO) every day for 28 days. At the end of experiment different behavioral test were made and brain was collected. Results: exposure to ATR induced the same response in terms of behavioral alterations and motor and memory impairment in mice but in aged group was more marked. Additionally, in both young and aged mice ATR inhalations induced oxidative stress with impairment in physiological antioxidant response, lipid peroxidation, nuclear factor kappa-light-chain-enhancer of activated B cells (nf-κb) pathways activation with consequences of pro-inflammatory cytokines release and apoptosis. However, the older group was shown to be more sensitive to ATR inhalation. Conclusions: our results showed that aged mice were more susceptible compared to young mice to air pollutants exposure, put in place a minor physiologically response was seen when exposed to it.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 6
    In: The FASEB Journal, Wiley, Vol. 34, No. S1 ( 2020-04), p. 1-1
    Abstract: Diabetes mellitus leads to a number of complications involving brain function, including cognitive decline and depression. Depression is linked to impaired adult neurogenesis in the gyrus dentatus of the hippocampus, but the underlying molecular mechanisms are incompletely understood. The process of neurogenesis consists of the proliferation of neural progenitors and differentiation of new neurons, and the chloride conductance ICl swell , activated after anisosmotic cell swelling during cell volume regulation, is thought to be essential in cell proliferation and differentiation. Diabetes also leads to increase in the post‐translational O‐GlcNAcylation (O‐GlcNAc) of cellular proteins. Recently, the protein ICln, which is crucial in the activation of the current ICl swell , has been found to be O‐GlcNacylated. In the present study, we investigated the characteristic of the current ICl swell following O‐GlcNAc elevation in neuronal‐like SH‐SY5Y and HEK 293 Phoenix cells, with focus on the role of ICln. In parallel to cell viability tests, ICl swell was measured by patch‐clamp in native cells or cells overexpressing either the wild type or non‐glycosilable forms of ICln (IClnT223A, IClnS193X and IClnS67A). O‐GlcNAc elevation significantly reduced the metabolic activity of SH‐SY5Y and HEK 293 Phoenix cells. In SH‐SY5Y cells, O‐GlcNAc elevation significantly suppressed the basally activated ICl swell current. In HEK 293 Phoenix cells, O‐GlcNAc elevation inhibited the ICln‐induced ICl swell current, with no effect on the endogenous ICl swell current, thus indicating that O‐GlcNAc impairs the ICln function. The IClnT223A‐induced current was similar to IClnWT‐induced current and was similarly suppressed after O‐GlcNAc elevation. IClnS193X lost most of its activity, though the residual current was sensitive to O‐GlcNAc elevation. Finally, the IClnS67A‐induced current is similar to the IClnWT‐induced current, but insensitive to O‐GlcNAc elevation. The present work underscores the essential role of O‐GlcNAcylation in governing the ICl swell current through modification of the ICln protein. The results indicate that the O‐GlcNAc modification site responsible for the suppression of the ICln‐induced current should be located upstream the amino acid 193, most likely on Serine 67. We conclude that O‐GlcNAcylation of the ICl swell activator ICln in the context of hyperglycaemic conditions may lead to ICl swell inhibition in brain, which may result in reduced adult neurogenesis and eventually in the depression disorder. We suggest that the protein ICln may represent a novel target in the prevention or treatment of pathological states characterized by chronically elevated O‐GlcNAcylation of cellular proteins, including mood disorders linked to hyperglycaemia
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 7
    In: The FASEB Journal, Wiley, Vol. 34, No. S1 ( 2020-04), p. 1-1
    Abstract: Metabolic dysfunctions continuously expose human erythrocytes to sugars present in plasma during their circulatory life span of 120 days. Hyperglycemia in diabetes mellitus causes glycation of proteins along with oxidative stress in erythrocytes. Moreover, acute systemic administration of D‐galactose was used to artificially induce blood senescence in human models as well to mimic galactosemia. The purpose of this study is to understand the effect of D‐glucose and D‐galactose in human erythrocytes and in particular on the function of Band 3 protein, which is an excellent tool for studying the oxidative events on the erythrocyte membrane. Human erythrocytes in vitro were exposed to increasing concentrations of D‐glucose (5‐15‐35 mM) for 3h or D‐galactose (0.1‐3‐5‐10 mM) for 1h. The rate constant for SO 4 = uptake, accounting for the efficiency of anion exchange through Band 3 protein along with levels of TBARS levels and membrane –SH groups have been measured. When erythrocytes were exposed to high D‐glucose (15–35 mM) for 3 h, TBARS levels and membrane –SH groups were unchanged while the rate constant for SO 4 = uptake was significantly accelerated with respect to control (5 mM). After exposure to high D‐galactose (5–10 mM) for 1 h, TBARS levels were higher and membrane –SH levels were lower than control, while the rate constant for SO 4 = uptake was significantly slower with respect to control (0.1 mM). The present findings show that the measurement of the rate constant for SO 4 = uptake is a suitable tool to monitor the effect of sugars on erythrocytes; hyperglycemia due to high glucose applied for 3 h affects anion exchange capability without producing lipid peroxidation and oxidative protein damage. High concentrations of D‐galactose ( 〉 5 mM) decreased the rate constant for SO 4 = uptake, induced lipid peroxidation and reduced total sulfhydryl content. Based on this evidence, future studies will evaluate if the acceleration of Band 3 protein in presence of high D‐glucose depends on altered Bp3 conformation, affecting crosslink with Hb, or on altered glycosylation or phosphorylation signaling underlying Band 3 protein function. In addition, alterations of parameters of oxidative stress caused by D‐galactose on the erythrocytes membrane open the view to consider a potential therapeutic strategy ameliorating the damage caused by D‐galactose.
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1468876-1
    detail.hit.zdb_id: 639186-2
    SSG: 12
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  • 8
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 575-575
    Abstract: Three short-term randomised clinical trials suggested not difference of Deferiprone (L1) vs Deferoxamine (DFO) in term of iron overload efficacy in thalassemia major (TM) patients. To assess whether L1 (75mg/Kg) alone was comparable to a sequential treatment using L1 (75mg/Kg) for 4 days and DFO (50mg/Kg) for 3 days, we carried ahead a large long-term randomised clinical trial. One-hundred and forty consecutive patients with TM and serum ferritin between 1,500 and 3,000 ng/ml were randomly assigned to L1 (n°69) or sequential L1-DFO (n°71) and treated for 5 years. The main measure of efficacy was the reduction of serum ferritin levels. Secondary outcomes were liver and heart iron contents assessed by T2* magnetic resonance. After one year-treatment the mean serum feritin reduction was −105 ± 90.4 in L1 and −409 ± 64.2 in sequential L1-DFO treatment (p 〈 0.01), respectively. The greater mean serum ferritin reduction of sequential L1- DFO treatment was also confirmed all over the study (2° year L1 106 ± 713, L1-DFO -321 ± 92 (p 〈 0.01); 3° year L1 137 ± 137, L1-DFO -292 ± 117 (p 〈 0.05); 4° year L1 216 ± 200, L1-DFO-230 ± 170 (p 〈 0.01); 5° year L1 336 ± 244, L1-DFO -598 ± 203 (p 〈 0.01)). After one-year treatment this sequential group showed greater efficacy in term of serum ferritin levels reduction (−409 ± 64.2) in comparison with the DFO alone arm (−232 ± 619) of a previous randomised multicenter clinical trial in which a comparable cohort of patients were studied (p 〈 0.05). Reversible leukocytopenia was shown in 8 (11.5%) L1 and in 7 (9.8%) sequential L1-DFO treated patients. No agranulocythosis was reported on sequential L1-DFO treated patients during the 5 years study. Hypertransaminasemia developed in 13 (18.8%) L1 and in 5 (7%) sequential L1-DFO treated patients. No other major side effects have been reported. Discontinuation of treatment was necessary in 55.6% L1 and in 57.7% sequential L1-DFO treated patients (chi2 0.03, p=0.86). The failures of treatment were less in sequential L1-DFO arm (n°2) in comparison to L1 alone arm (n°8), although this difference not so far reached the statistical significance (chi2 3.4, p=0.06). These findings suggest that sequential L1-DFO treatment in a long-term study is more effective than L1 alone with milder and reversible side effects. Moreover, its efficacy is also higher in comparison with DFO alone at short-term evaluation. Fig. 1 VARIATIONS OF THE FERRITIN LEVELS DURING FIVE YEARS TREATMENT BETWEEN THE TWO ARMS OF THE TRIAL Fig. 1. VARIATIONS OF THE FERRITIN LEVELS DURING FIVE YEARS TREATMENT BETWEEN THE TWO ARMS OF THE TRIAL
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-6-16)
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-6-16)
    Abstract: Parkinson's disease (PD) patients frequently engage in rehabilitation to ameliorate symptoms. During the Coronavirus disease 2019 (COVID-19) pandemic, access to rehabilitation programs has been markedly limited, consequently, telerehabilitation gained popularity. In this prospective, open-label, and pilot study, we aimed to investigate feasibility, safety, and efficacy of telerehabilitation in mild-to-moderate PD patients. Materials and Methods Twenty-three PD patients, with Hoehn and Yahr stage & lt;3, without gait disturbances or dementia and capable of using the televisit platform, were recruited for a 5-week telerehabilitation program, consisting of 1 remote visit with a therapist and a minimum of two sessions of & gt;30-min of self-conducted exercises per week. Patients received video tutorials of exercises and were asked to keep a diary of sessions. At baseline (T0), at the end of the intervention (T1), and 1 month after the end of treatment (T2), patients were remotely assessed with MDS-UPDRS part I-III, PDQ-39, Functional Independence Measure (FIM), and Frontal Assessment Battery scales, respectively. Acceptable compliance to the program was defined as & gt;60% matching of frequency and duration of sessions, whereas optimal compliance was set at & gt;80% matching. Results The dropout rate was 0%. Over 85% of patients reached acceptable adherence cut-off and around 70% reached optimal one. No adverse events were reported during sessions. The repeated measure analysis of variance (rANOVA) showed a significant effect of factor “time” for MDS-UPDRS-III ( p & lt; 0.0001) with a mean reduction of 4.217 points between T0 and T1 and return to baseline at T2. No significant effect was found for other outcome measures. Conclusion Our findings demonstrate that telerehabilitation is safe, feasible, and effective on motor symptoms in mild-to-moderate PD patients.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 10
    In: Life, MDPI AG, Vol. 14, No. 7 ( 2024-07-22), p. 915-
    Abstract: Background: Obesity is a global epidemic that affects millions worldwide and can be a deterrent to surgical procedures in the population waiting for kidney transplantation. However, the literature on the topic is controversial. This study evaluates the impact of body mass index (BMI) on complications after renal transplantation, and identifies factors associated with major complications to develop a prognostic risk score. Methods: A correlation analysis between BMI and early and late complications was first performed, followed by a univariate and multivariate logistic regression analysis. The 302 included patients were divided into obese (BMI ≥ 30 kg/m2) and non-obese (BMI ≤ 30 kg/m2) groups. Correlation analysis showed that delayed graft function (DGF) was the only obesity-associated complication (p = 0.044). Logistic regression analysis identified female sex, age ≥ 57 years, BMI ≥ 25 and ≥30 kg/m2, previous abdominal and/or urinary system surgery, and Charlson morbidity Score ≥ 3 as risk factors for significant complications. Based on the analyzed data, we developed a nomogram and a prognostic risk score. Results: The model’s area (AUC) was 0.6457 (95% IC: 0.57; 0.72). The percentage of cases correctly identified by this model retrospectively applied to the entire cohort was 73.61%. Conclusions: A high BMI seems to be associated with an increased risk of DGF, but it does not appear to be a risk factor for other complications. Using an easy-to-use model, identification, and stratification of individualized risk factors could help to identify the need for interventions and, thus, improve patient eligibility and transplant outcomes. This could also contribute to maintaining an approach with high ethical standards.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2662250-6
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