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1.
Nanomaterials (Basel) ; 13(22)2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-37999287

RESUMO

This study focuses on the dissolution process and surface characterization of amosite fibres following interaction with a mimicked Gamble's solution at a pH of 4.5 and T = 37 °C, up to 720 h. To achieve this, a multi-analytical approach was adopted, and the results were compared to those previously obtained on a sample of asbestos tremolite and UICC crocidolite, which were investigated under the same experimental conditions. Combining surface chemical data obtained by XPS with cation release quantified by ICP-OES, an incongruent behaviour of the fibre dissolution was highlighted for amosite fibres, similarly to asbestos tremolite and UICC crocidolite. In particular, a preferential release of Mg and Ca from the amphibole structure was observed, in agreement with their Madelung site energies. Notably, no Fe release from amosite fibres was detected in our experimental conditions (pH of 4.5 and atmospheric pO2), despite the occurrence of Fe(II) at the M(4) site of the amphibole structure, where cations are expected to be rapidly leached out during mineral dissolution. Moreover, the oxidation of both the Fe centres initially present on the fibre surface and those promoted from the bulk, because of the erosion of the outmost layers, was observed. Since biodurability (i.e., the resistance to dissolution) is one of the most important toxicity parameters, the knowledge of the surface alteration of asbestos possibly occurring in vivo may help to understand the mechanisms at the basis of its long-term toxicity.

2.
Front Endocrinol (Lausanne) ; 14: 1234237, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37766685

RESUMO

Background: Conventional glucocorticoids (C-GC) replacement regimens have a detrimental effect on skeletal health in patients with adrenal insufficiency (AI), ultimately leading to an increased fracture risk. The novel dual-release hydrocortisone (DR-HC) formulations are characterized by a more favourable safety profile on various clinical endpoints. Data comparing the impact of C-GC and DR-HC on bone, however, are scarce. Methods: Twenty-seven patients with autoimmune primary AI (PAI; 13 treated with C-GC and 14 treated with DR-HC) were evaluated to compare bone-related parameters between the two treatment groups. Results: No significant differences between the two treatments groups were observed with respect to bone turnover markers. Patients treated with C-GC showed a lower bone mineral density (BMD) at lumbar spine (LS; 0.791 ± 0.195 vs. 0.942 ± 0.124 g/cm2, p=0.025) and at femoral neck (FN; 0.633 ± 0.114 vs. 0.716 ± 0.088 g/cm2, p=0.045). Moreover, they were characterized by a lower trabecular bone score (TBS; 1.236 ± 0.035 vs. 1.383 ± 0.030, p=0.004) and by a higher mean number of vertebral fractures per patient (0.75 vs. 0 fractures, p=0.002). TBS was the best predictor of fracture risk, with a pseudo-R2 of 0.593; moreover, at mediation analysis, it was able to fully explain the observed detrimental effect of C-GC, compared to DR-HC, on fracture risk. Conclusions: These results suggest that DR-HC is associated with less bone-related complications compared to C-GC in patients with PAI. Moreover, TBS seems to play a pivotal role in the mediation of the relationship between glucocorticoid treatment regimens and fracture risk.

3.
Sci Rep ; 12(1): 14913, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050396

RESUMO

Several studies argued that cardiovascular evaluation of patients with nonfunctioning adrenal incidentaloma is of particular importance. Therefore, we aimed to evaluate the possibility of stratifying the cardiometabolic risk using metanephrine levels in this setting of patients. A retrospective cross-sectional study was designed, collecting data of metanephrine values in 828 patients with nonfunctioning adrenal incidentaloma, referred to our Division within the University of Turin between 2007 and 2021. The univariate analysis showed associations between urine metanephrines and cardiometabolic variables/parameters, particularly considering the noradrenaline metabolite. At the univariate regression, normetanephrine was associated with metabolic syndrome (OR = 1.13, p = 0.002), hypertensive cardiomyopathy (OR = 1.09, p = 0.026), microalbuminuria (OR = 1.14, p = 0.024), and eGFR < 60 mL/min/1.73 m2 (OR = 1.11, p = 0.013), while metanephrine was associated with microalbuminuria (OR = 1.50, p = 0.008). At multivariate regression, considering all major cardiovascular risk factors as possible confounders, normetanephrine retained a significant association with metabolic syndrome (OR = 1.10, p = 0.037). Moreover, metanephrine retained a significant association with the presence of microalbuminuria (OR = 1.66, p = 0.003). The present study showed a further role for metanephrines in the cardiovascular risk stratification of patients with nonfunctioning adrenal incidentaloma. Individuals with high levels of these indirect markers of sympathetic activity should be carefully monitored and may benefit from an aggressive treatment to reduce their additional cardiometabolic burden.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Síndrome Metabólica , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/epidemiologia , Estudos Transversais , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Metanefrina , Normetanefrina , Feocromocitoma/complicações , Feocromocitoma/epidemiologia , Estudos Retrospectivos
4.
G Ital Nefrol ; 39(3)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35819039

RESUMO

Introduction: The term incremental haemodialysis (HD) means that both dialysis dose and frequency can be low at dialysis inception but should be progressively increased, to compensate for any subsequent reduction in residual kidney function. Policy of the Matera Dialysis Center is to attempt an incremental start of HD without a strict low-protein diet in all patients choosing HD and with urine output (UO) >500 ml/day. The present study aimed at analyzing the results of this policy over the last 20 years. Subjects and methods: The dataset of all patients starting HD between January 1st, 2000 and December 31st, 2019 was retrieved from the local electronic database. Exclusion criteria were: urine output <500 ml/day or follow-up <3 months after the start of the dialysis treatment. Results: A total of 266 patients were retrieved; 64 of them were excluded from the study. The remaining 202 patients were enrolled into the study and subdivided into 3 groups (G1, G2 and G3) according to the frequency of treatment at the start of dialysis: 117 patients (57.9%) started with once-a-week (1HD/wk) (G1); 46 (22.8%) with twice-a-week (2HD/wk) (G2); 39 (19.3%) with thrice-a-week (3HD/wk) dialysis regimen (G3). Patients of G1 remained on 1HD/wk for 11.9 ±14.8 months and then transferred to 2HD/wk for further 13.0 ±20.3 months. Patients of G2 remained on 2HD/wk for 16.7 ±23.2 months. Altogether, 25943 sessions were administered during the less frequent treatment periods instead of 47988, that would have been delivered if the patients had been on 3HD/wk, thus saving 22045 sessions (45.9%). Gross mortality of the entire group was 12.6%, comparable to the mean mortality of the Italian dialysis population (16.2%). Survival at 1 and 5 years was not significantly different among the 3 groups: 94% and 61% (G1); 83% and 39% (G2); 84% and 46% (G3). Conclusions: Our long-term observational study suggests that incremental HD is a valuable option for incident patients. For most of them (80.7%) it is viable for about 1-2 years, with obvious socio-economic benefits and survival rates comparable to that of the Italian dialysis population. However, randomized controlled trials are lacking and therefore urgently needed. If they will confirm observational data, incremental HD will be a new standard of care.


Assuntos
Falência Renal Crônica , Humanos , Rim , Falência Renal Crônica/terapia , Diálise Renal/métodos , Padrão de Cuidado , Taxa de Sobrevida
5.
Front Endocrinol (Lausanne) ; 13: 801529, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250861

RESUMO

OBJECTIVE: This study aimed to evaluate the reliability of simple and corrected aldosterone indices for assessing the selectivity and lateralization of adrenal vein sampling (AVS) in patients with primary aldosteronism. METHODS: Data of all consecutive patients with primary aldosteronism who underwent AVS for subtype diagnosis, followed at two Italian referral centers, were analyzed retrospectively. RESULTS: AVS achieved bilateral selectivity in 112/144 patients. Unilateral disease was diagnosed in 60 cases (53.6%) and idiopathic hyperaldosteronism in 52 individuals (46.4%). The aldosterone index (aldosterone ratio between an adrenal vein and the inferior vena cava) showed a high accuracy in predicting selectivity, compared to a cortisol selectivity index of 1.1, and a moderate accuracy, compared to cortisol cut-offs of 2 and 3. The simple aldosterone index showed a moderate accuracy in predicting ipsi/contralateral aldosterone hypersecretion, while lesion side- and hypokalemia-corrected aldosterone index revealed a significant improvement in predicting ipsi/contralateral disease. Moreover, the comparative aldosterone index (aldosterone ratio in the dominant vs the non-dominant adrenal vein) revealed a high accuracy in predicting unilateral primary aldosteronism. For an immediate clinical application of our results, the adjusted cut-offs were calculated, according to the Youden's criterion and to a pre-established specificity of 90%, for all possible combinations of lesion side at imaging and presence/absence of hypokalemia. CONCLUSIONS: This study demonstrated the diagnostic accuracy of simple and clinical-/imaging-corrected aldosterone indices for adrenal vein sampling in subtype diagnosis of primary aldosteronism and suggests the potential application of these tools to select patients for adrenalectomy when standard indices cannot be performed.


Assuntos
Hiperaldosteronismo , Hipopotassemia , Aldosterona , Humanos , Hidrocortisona , Hiperaldosteronismo/diagnóstico , Hiperplasia , Reprodutibilidade dos Testes , Estudos Retrospectivos
6.
J Matern Fetal Neonatal Med ; 35(25): 8317-8326, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34496692

RESUMO

BACKGROUND: During pregnancy metabolic disorders that affect differently the fetus, are known. These could be early or late disorders. OBJECTIVES: To analyze different biochemical parameters in umbilical cord blood (UCB) of healthy and pathological newborns from mothers with metabolic disorders. MATERIALS AND METHODS: Samples from UCB (121) were analyzed of newborn from mothers with metabolic disorders who attended at Obstetrics Division. Patients were consecutive, prospective and transversally studied. Newborn were classified as healthy (n = 65) and pathological (n = 56). The maternal metabolic disorders were gestational or non-gestational diabetes, glucose intolerance, insulin resistance and/or obesity).The disorders of the pathological newborns were intrauterine growth restriction (IUGR) and/or fetal distress. Glucose (Glu), urea, creatinine, uric acid (UA), total bilirubin (TB), total proteins (TP), albumin (Alb), transaminases (ALT/AST), alkaline-phosphatase (ALP), gammaglutamyltranspeptidase (GGT), creatinkinasa (CK), lactatedehydrogenase, amylase (amy), pseudocholinesterase, iron, calcium, phosphorus, magnesium (Mg), sodium, potassium, chlorine, cholesterol (Chol), HDL-Chol, LDL-Chol, triglycerides (TG), high sensitivity C reactive protein (hsCRP) were determined by recommended methods. T-Student's and Mann Withney tests were applied, p < .05. RESULTS: Pathological neonates (n: 56) showed a significant decrease in maternal gestation weeks (GW) and in newborn weight (NW) with respect to healthy newborns (n: 65) from mothers with metabolic disorders (p < .0001). Pathological neonates from mothers with metabolic pathologies (n: 56) showed significant increases in Chol, TG, TB (p < .01), LDL-Chol, UA, Mg, hsCRP, ALP levels (p < .05) and significant decreases in TP, Alb (p < .0001) and Glu, ALT, CK, GGT, amy (p < .05) in UCB with respect to healthy newborns. CONCLUSIONS: In pathological newborn, the decrease in GW and NW would be related to IUGR that accompany these metabolic disorders. The increases observed of the analyzed parameters would be related to cellular destruction associated to maternal pathology and decreases of the parameters to IUGR with hepatic immaturity.


Assuntos
Doenças Metabólicas , Complicações na Gravidez , Gravidez , Feminino , Recém-Nascido , Humanos , Sangue Fetal/metabolismo , Proteína C-Reativa/metabolismo , Estudos Prospectivos , Triglicerídeos , LDL-Colesterol , Retardo do Crescimento Fetal , Colesterol , Ácido Úrico , gama-Glutamiltransferase , Complicações na Gravidez/metabolismo
7.
Clin Res Hepatol Gastroenterol ; 45(6): 101624, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33676282

RESUMO

AIM: Hereditary hemochromatosis (HH) is a group of inherited disorders that causes a slow and progressive iron deposition in diverse organs, particularly in the liver. Iron overload induces oxidative stress and tissue damage. Coenzyme Q10 (CoQ10) is a cofactor in the electron-transport chain of the mitochondria, but it is also a potent endogenous antioxidant. CoQ10 interest has recently grown since various studies show that CoQ10 supplementation may provide protective and safe benefits in mitochondrial diseases and oxidative stress disorders. In the present study we sought to determine CoQ10 plasma level in patients recently diagnosed with HH and to correlate it with biochemical, genetic, and histological features of the disease. METHODS: Plasma levels of CoQ10, iron, ferritin, transferrin and vitamins (A, C and E), liver tests (transaminases, alkaline phosphatase and bilirubin), and histology, as well as three HFE gene mutations (H63D, S654C and C282Y), were assessed in thirty-eight patients (32 males, 6 females) newly diagnosed with HH without treatment and in twenty-five age-matched normolipidemic healthy subjects with no HFE gene mutations (22 males, 3 females) and without clinical or biochemical signs of iron overload or liver diseases. RESULTS: Patients with HH showed a significant decrease in CoQ10 levels respect to control subjects (0.31 ±â€¯0.03 µM vs 0.70 ±â€¯0.06 µM, p < 0.001, respectively) independently of the genetic mutation, cirrhosis, transferrin saturation, ferritin level or markers of hepatic dysfunction. Although a decreasing trend in CoQ10 levels was observed in patients with elevated iron levels, no correlation was found between both parameters in patients with HH. Vitamins C and A levels showed no changes in HH patients. Vitamin E was significantly decreased in HH patients (21.1 ±â€¯1.3 µM vs 29.9 ±â€¯2.5 µM, p < 0.001, respectively), but no correlation was observed with CoQ10 levels. CONCLUSION: The decrease in CoQ10 levels found in HH patients suggests that CoQ10 supplementation could be a safe intervention strategy complementary to the traditional therapy to ameliorate oxidative stress and further tissue damage induced by iron overload.


Assuntos
Ataxia , Hemocromatose , Doenças Mitocondriais , Debilidade Muscular , Ubiquinona/deficiência , Ataxia/epidemiologia , Estudos de Casos e Controles , Feminino , Hemocromatose/sangue , Hemocromatose/epidemiologia , Hemocromatose/genética , Humanos , Masculino , Doenças Mitocondriais/epidemiologia , Debilidade Muscular/epidemiologia , Ubiquinona/análogos & derivados , Ubiquinona/sangue
8.
Clin Res Hepatol Gastroenterol ; 44(3): 368-374, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31477533

RESUMO

AIM: Intrahepatic cholestasis of pregnancy (ICP) is considered a high-risk condition because it may have serious consequences for the fetus health. ICP is characterized by the accumulation of bile acids in maternal serum which contribute to an imbalance between the production of reactive oxygen species and the antioxidant defenses increasing the oxidative stress experienced by the fetus. Previously, it was reported a significant decrease in plasma coenzyme Q10 (CoQ10) in women with ICP. CoQ10 is a redox substance integrated in the mitochondrial respiratory chain and is recognized as a potent antioxidant playing an intrinsic role against oxidative damage. The objective of the present study was to investigate the levels of CoQ10 in umbilical cord blood during normal pregnancy and in those complicated with ICP, all of them compared to the maternal ones. METHODS: CoQ10 levels and bile acid levels in maternal and umbilical cord blood levels during normal pregnancies (n=23) and in those complicated with ICP (n=13), were investigated. RESULTS: A significant decrease in neonate CoQ10 levels corrected by cholesterol (0.105±0.010 vs. 0.069±0.011, P<0.05, normal pregnancy vs. ICP, respectively), together with an increase of total serum bile acids (2.10±0.02 vs. 7.60±2.30, P<0.05, normal pregnancy vs. ICP, respectively) was observed. CONCLUSIONS: A fetus from an ICP mother is exposed to a greater risk derived from oxidative damage. The recognition of CoQ10 deficiency is important since it could be the starting point for a new and safe intervention strategy which can establish CoQ10 as a promising candidate to prevent the risk of oxidative stress.


Assuntos
Ataxia/sangue , Ácidos e Sais Biliares/sangue , Colestase Intra-Hepática/sangue , Sangue Fetal/química , Doenças Mitocondriais/sangue , Debilidade Muscular/sangue , Complicações na Gravidez/sangue , Ubiquinona/análogos & derivados , Ubiquinona/deficiência , Adulto , Ataxia/diagnóstico , Biomarcadores/sangue , Peso ao Nascer , Colesterol/sangue , Ácido Cólico/sangue , Estudos Transversais , Feminino , Feto/metabolismo , Idade Gestacional , Humanos , Recém-Nascido , Doenças Mitocondriais/diagnóstico , Debilidade Muscular/diagnóstico , Oxirredução , Estresse Oxidativo , Gravidez , Estudos Prospectivos , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/sangue , Adulto Jovem
9.
J Nephrol ; 33(1): 137-146, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31392658

RESUMO

INTRODUCTION: Urea distribution volume (V) can be assessed in different ways, among them the anthropometric Watson Volume (VW). However, many studies have shown that VW does not coincide with V and that the latter can be more accurately estimated with other methods. The present multicentre study was designed to answer the question: what V to choose to assess online Kt/V? MATERIALS AND METHODS: Pre- and postdialysis blood urea nitrogen concentrations and the usual input data set for urea kinetic modelling were obtained for a single dialysis session in 201 Caucasian patients treated in 9 Italian dialysis units. Only dialysis machines measuring ionic dialysance (ID) were utilized. ID reflects very accurately the mean effective dialyser urea clearance (Kd). Six different V values were obtained: the first one was VW; the second one was computed from the equation established by the HEMO Study to predict the single pool-adjusted modelled V from VW (VH) (Daugirdas JT et al. KI 64: 1108, 2003); the others were estimated kinetically as: 1. V_ID, in which ID is direct input in the in the double pool variable volume (dpVV) calculation by means of the Solute-solver software; 2. V_Kd, in which the estimated Kd is direct input in the dpVV calculation by means of the Solute-solver software; 3. V_KTV, in which V is calculated by means of the second generation Daugirdas equation; 4. V_SPEEDY, in which ID is direct input in the dpVV calculation by means of the SPEEDY software able to provide results quite similar to those provided by Solute-solver. RESULTS: Mean± SD of the main data are reported: measured ID was 190.6 ± 29.6 mL/min, estimated Kd was 211.6 ± 29.0 mL/min. The relationship between paired data was poor (R2 = 0.34) and their difference at the Bland-Altman plot was large (21 ± 27 mL/min). VW was 35.3 ± 6.3 L, VH 29.5 ± 5.5, V_ID 28.99 ± 7.6 L, V_SPEEDY 29.4 ± 7.6 L, V_KTV 29.7 ± 7.0 L. The mean ratio VW/V_ID was 1.22, (i.e. VW overestimated V_ID by about 22%). The mean ratio VH/V_ID was 1.02 (i.e. VH overestimated V_ID by only 2%). The relationship between paired data of V_ID and VW was poor (R2 = 0.48) and their mean difference at the Bland-Altman plot was very large (- 6.39 ± 5.59 L). The relationship between paired data of V_ID and VH was poor (R2 = 47) and their mean difference was small but with a large SD (- 0.59 ± 5.53 L). The relationship between paired data of V_ID and V_SPEEDY was excellent (R2 = 0.993) and their mean difference at the Bland-Altman plot was very small (- 0.54 ± 0.64 L). The relationship between paired data of V_ID and V_KTV was excellent (R2 = 0.985) and their mean difference at the Bland-Altman plot was small (- 0.85 ± 1.06 L). CONCLUSIONS: V_ID can be considered the reference method to estimate the modelled V and then the first choice to assess Kt/V. V_SPEEDY is a valuable alternative to V_ID. V_KTV can be utilized in the daily practice, taking also into account its simple way of calculation. VW is not advisable because it leads to underestimation of Kt/V by about 20%.


Assuntos
Soluções para Hemodiálise , Diálise Renal , Insuficiência Renal/terapia , Ureia/metabolismo , Idoso , Nitrogênio da Ureia Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/metabolismo , Fatores de Tempo
10.
Biochem Pharmacol ; 170: 113662, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606411

RESUMO

Acetaminophen (APAP) administration at therapeutic doses is safe, however overdosing produces hepatocellular injury via a multifactorial mechanism(s) that involves generation of reactive oxygen species (ROS), being the most common cause of acute liver failure (ALF) in the northern hemisphere. Brain alterations induced by APAP intoxication are usually considered secondary to hepatic encephalopathy development due to ALF. Although APAP is primarily metabolized in the liver, it is also distributed and metabolized homogeneously in the brain, affecting brain redox status. Nevertheless, comprehensive studies on the potential of APAP intoxication to produce brain toxicity are scarce. The aim of this study was to characterize the direct toxic effects of APAP in different regions of the brain and on behavior in rats where the magnitude of hepatotoxicity produced is not associated with ALF. The present work demonstrates that APAP intoxication producing hepatotoxicity, but not ALF in rats, is associated with marked hypolocomotion. Our studies also suggest that selective downregulation in dopamine levels in brain areas that regulate motor activity may be responsible, in part, for the decreased locomotion observed with APAP treatment. Furthermore, we observed that the brain histoarchitecture is conserved and that edema is not present. However, an increase in oxidative stress, reactive astrogliosis and a decrease in neuron processes are the main features observed in APAP-intoxicated animals. These effects might be partly due to direct toxic effects of APAP in brain, since the same reactive astrogliosis observed in rats was also observed in rat primary astrocyte cultures exposed to APAP.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Encéfalo/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Gliose/induzido quimicamente , Locomoção/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Células Cultivadas , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Feminino , Gliose/metabolismo , Locomoção/fisiologia , Masculino , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar
11.
Biophys Chem ; 216: 23-30, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27372900

RESUMO

The conversion of proteins into amyloid fibrils and other amyloid-like aggregates is closely connected to the onset of a series of age-related pathologies. Upon changes in environmental conditions, amyloid-like aggregates may also undergo disassembly into oligomeric aggregates, the latter being recognized as key effectors in toxicity. This indicates new possible routes for in vivo accumulation of toxic species. In the light of the recognized implication of α-Synuclein (αSN) in Parkinson's disease, we present an experimental study on supramolecular assembly of αSN with a focus on stability and disassembly paths of such supramolecular aggregate species. Using spectroscopic techniques, two-photon microscopy, small-angle X-ray scattering and atomic force microscopy, we report evidences on how the stability of αSN amyloid-like aggregates can be altered by changing solution conditions. We show that amyloid-like aggregate formation can be induced at high temperature in the presence of trifluoroethanol (TFE). Moreover, sudden disassembly or further structural reorganisation toward higher hierarchical species can be induced by varying TFE concentration. Our results may contribute in deciphering fundamental mechanisms and interactions underlying supramolecular clustering/dissolution of αSN oligomers in cells.


Assuntos
Agregados Proteicos/efeitos dos fármacos , Trifluoretanol/farmacologia , alfa-Sinucleína/química , Amiloide/química , Humanos , Estabilidade Proteica , Análise Espectral , Temperatura , alfa-Sinucleína/efeitos dos fármacos
12.
Biophys Chem ; 206: 1-11, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26100600

RESUMO

Aß(1-40) peptide supramolecular assembly and fibril formation processes are widely recognized to have direct implications in the progression of Alzheimer's disease. The molecular basis of this biological process is still unknown and there is a strong need of developing effective strategies to control the occurring events. To this purpose the exploitation of small molecules interacting with Aß aggregation represents one of the possible routes. Moreover, the use specific labeling has represented so far one of the most common and effective methods to investigate such a process. This possibility in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effect of Thioflavin T (ThT), a worldwide used fluorescent dye to monitor amyloid growth, on the Aß(1-40) conformation, stability and aggregation. By combining experimental information and Molecular Dynamics simulation results, we show that the presence of ThT in solution affects peptide conformation inducing peculiar supramolecular association. In particular ThT interactions with specific Aß(1-40) residues promote a rigid partially-folded conformation which shifts the balance between different species in solution toward a more aggregation-prone ensemble of peptides, leading to aggregation. Our findings suggest ways for developing strategies to reverse and block aggregation or to stimulate supramolecular assembly and consequently reduce the presence of transient oligomers. This investigation underlines the need of developing label-free techniques for unbiased quantitative studies of Aß(1-40) aggregation processes.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Corantes Fluorescentes/metabolismo , Fragmentos de Peptídeos/metabolismo , Agregados Proteicos/efeitos dos fármacos , Tiazóis/metabolismo , Doença de Alzheimer/metabolismo , Sequência de Aminoácidos , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/ultraestrutura , Benzotiazóis , Recuperação de Fluorescência Após Fotodegradação , Corantes Fluorescentes/análise , Humanos , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/ultraestrutura , Agregação Patológica de Proteínas/metabolismo , Conformação Proteica/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína/efeitos dos fármacos , Tiazóis/análise
14.
Acta bioquím. clín. latinoam ; 47(1): 101-111, mar. 2013.
Artigo em Espanhol | LILACS | ID: lil-727418

RESUMO

El deporte exige de quienes lo practican una adaptación, entrenamiento y buen estado físico. El objetivo del trabajo fue estudiar en suero/plasma de individuos jugadores de fútbol de élite (n=32) y no entrenados (n=16), los perfiles hematológico, endocrinológico y de química clínica, relacionar los hallazgos bioquímicos con la fisiopatología deportiva y evaluar la probable implicancia clínica de los resultados. De acuerdo con los resultados obtenidos se observó disminución significativa en: hematocrito, hierro, plaquetas y bilirrubina (expansión plasmática fisiológica); magnesio (consumo enzimático); y proteínas y glucemia (incremento del metabolismo energético y recambio proteico). No se detectaron cambios significativos en el perfil endocrinológico (TSH disminuida, mayor eficacia de la hormona) y perfil lipídico (aumento de HDL y disminución de LDL; efecto protector de las lipoproteínas). Se observó un aumento significativo en: calcio (mayor disponibilidad); urea (metabolismo proteico aumentado); y aldolasa y creatinquinasa (lisis fibra muscular entrenada). Se concluye que la creatinquinasa es el marcador de pertenencia al grupo de élite; se debería implementar un valor de referencia diferente para esta población de deportistas ya que el deporte es objeto de estudio del laboratorio bioquímico; y la implementación de los conocimientos científicos en forma práctica y adecuada permite ayudar al profesional médico deportólogo a tomar decisiones oportunas y acertadas.


Assuntos
Humanos , Bioquímica , Medicina Esportiva , Atletas , Creatina Quinase , Futebol
15.
Acta bioquím. clín. latinoam ; 47(1): 53-59, mar. 2013. graf
Artigo em Espanhol | LILACS | ID: lil-727423

RESUMO

La ceruloplasmina (CP) es una proteína que participa en el metabolismo del hierro y transporta el 95% del cobre plasmático. Se considera un inhibidor fisiológico de la mieloperoxidasa (MPO), enzima leucocitaria que forma parte del sistema inmune innato. Ambas se postulan como biomarcadores de la enfermedad cardiovascular. El objetivo del presente trabajo fue determinar la actividad de CP y la concentración de MPO en pacientes con enfermedad coronaria crónica (ECC) y analizar su asociación con otros parámetros de inflamación. Se estudiaron 22 pacientes con ECC y 22 controles sanos. La actividad de CP fue determinada por el método de Ozcan Erel y las concentraciones de MPO, proteína C- reactiva ultrasensible (PCR-us) e Interleuquina 6 (IL-6) por métodos estandarizados. La concentración de MPO y la actividad de CP fueron mayores en pacientes con ECC que en sujetos sanos; (417±295 vs. 179±145 ng/mL, p=0,0018); (891±179 vs. 630±115 IU/L, p< 0,0001) respectivamente y la asociación entre las variables fue estadísticamente significativa (r=0,47, p=0,0272). La liberación sistémica de MPO que conduce a valores incrementados de su concentración sérica, y la hiperceruloplasminemia podrían considerarse un rasgo característico de ECC asintomática e indicarían aterosclerosis en pacientes que eventualmente desarrollen ECC.


Assuntos
Humanos , Ceruloplasmina , Peroxidase , Aterosclerose , Inflamação
17.
Acta bioquím. clín. latinoam ; 47(1): 101-111, mar. 2013. ilus, tab
Artigo em Espanhol | BINACIS | ID: bin-130987

RESUMO

El deporte exige de quienes lo practican una adaptación, entrenamiento y buen estado físico. El objetivo del trabajo fue estudiar en suero/plasma de individuos jugadores de fútbol de élite (n=32) y no entrenados (n=16), los perfiles hematológico, endocrinológico y de química clínica, relacionar los hallazgos bioquímicos con la fisiopatología deportiva y evaluar la probable implicancia clínica de los resultados. De acuerdo con los resultados obtenidos se observó disminución significativa en: hematocrito, hierro, plaquetas y bilirrubina (expansión plasmática fisiológica); magnesio (consumo enzimático); y proteínas y glucemia (incremento del metabolismo energético y recambio proteico). No se detectaron cambios significativos en el perfil endocrinológico (TSH disminuida, mayor eficacia de la hormona) y perfil lipídico (aumento de HDL y disminución de LDL; efecto protector de las lipoproteínas). Se observó un aumento significativo en: calcio (mayor disponibilidad); urea (metabolismo proteico aumentado); y aldolasa y creatinquinasa (lisis fibra muscular entrenada). Se concluye que la creatinquinasa es el marcador de pertenencia al grupo de élite; se debería implementar un valor de referencia diferente para esta población de deportistas ya que el deporte es objeto de estudio del laboratorio bioquímico; y la implementación de los conocimientos científicos en forma práctica y adecuada permite ayudar al profesional médico deportólogo a tomar decisiones oportunas y acertadas.(AU)


Sports demand from those who practice it, adaptation, training and a good physical condition. The objective of the work was to study in serum/plasma of trained people (elite football players, n=32) and untrained people (n=16) the clinical laboratory, haematological, and endocrinal profiles; 2) to relate the biochemical findings to sports physiopathology; 3) Assess the probable clinical implication of the results obtained. The results detained showe a significant decrease in hematocrit, iron, platelets and bilirrubin (physiological plasma expansion); magnesium (enzymatic consumption); proteins and glycemia (increase in energy metabolism and protein change). Without significant changes in endocrinological profile (decreased TSH, greater hormone efficiency); and lipid profile (increased HDL and decreased LDL; lipoprotein protector effect).Significant increase: calcium (more availability); urea (increased protein metabolism); and aldolase y creatinkinase (lysis of trained muscle fibre). Creatinkinase is the scoreboard of belonging to the elite group. It should be a different reference value for this group. -Thus, sport is object of study at the clinical laboratory; and implementation of the scientific knowledge in a practical and suitable manner enables the health professional to make relevant and right decisions.(AU)


O esporte exige daqueles que o praticam uma adaptaþÒo, treinamento e bom estado físico. O objetivo do trabalho foi estudar em soro/plasma de indivíduos jogadores de futebol de elite (n=32) e nÒo treinados (n=16), os perfis hematológico, endocrinológico e de química clínica, relacionar os achados bioquímicos com a fisiopatologia esportiva, e avaliar as possíveis implicaþ§es clínicas dos resultados. De acordo com os resultados obtidos se observou diminuiþÒo em hematocrito, ferro, plaquetas e bilirrubina (expansÒo do plasma fisiológico), magnésio (consumo enzimático); e proteína e glicemia (aumento do metabolismo energético e recÔmbio proteico). NÒo foram observadas alteraþ§es significativas no perfil endocrinológico (TSH diminuído, maior eficácia do horm¶nio); e perfil lipídico (aumento de HDL e diminuiþÒo de LDL; efeito protetor das lipoproteínas). Observou-se-aumento significativo em: cálcio (maior disponibilidade); ureia (metabolismo proteico aumentado); e aldolase e creatina-quinase (lise fibra muscular treinada). Conclui-se que a creatina-quinase é o marcador de pertenþa ao grupo de elite. Deveria ser implementado um valor de referÛncia diferente para esta populaþÒo de esportistas visto que o esporte é objeto de estudo do laboratório bioquímico; e a implementaþÒo dos conhecimentos científicos em forma prática e adequada permite ajudar o profissional médico esportólogo a tomar decis§es oportunas e certas.(AU)

18.
Acta bioquím. clín. latinoam ; 47(1): 101-111, mar.2013.
Artigo em Espanhol | BINACIS | ID: bin-129807

RESUMO

El deporte exige de quienes lo practican una adaptación, entrenamiento y buen estado físico. El objetivo del trabajo fue estudiar en suero/plasma de individuos jugadores de fútbol de élite (n=32) y no entrenados (n=16), los perfiles hematológico, endocrinológico y de química clínica, relacionar los hallazgos bioquímicos con la fisiopatología deportiva y evaluar la probable implicancia clínica de los resultados. De acuerdo con los resultados obtenidos se observó disminución significativa en: hematocrito, hierro, plaquetas y bilirrubina (expansión plasmática fisiológica); magnesio (consumo enzimático); y proteínas y glucemia (incremento del metabolismo energético y recambio proteico). No se detectaron cambios significativos en el perfil endocrinológico (TSH disminuida, mayor eficacia de la hormona) y perfil lipídico (aumento de HDL y disminución de LDL; efecto protector de las lipoproteínas). Se observó un aumento significativo en: calcio (mayor disponibilidad); urea (metabolismo proteico aumentado); y aldolasa y creatinquinasa (lisis fibra muscular entrenada). Se concluye que la creatinquinasa es el marcador de pertenencia al grupo de élite; se debería implementar un valor de referencia diferente para esta población de deportistas ya que el deporte es objeto de estudio del laboratorio bioquímico; y la implementación de los conocimientos científicos en forma práctica y adecuada permite ayudar al profesional médico deportólogo a tomar decisiones oportunas y acertadas.(AU)


Assuntos
Humanos , Medicina Esportiva , Bioquímica , Futebol , Atletas , Creatina Quinase
19.
Acta bioquím. clín. latinoam ; 47(1): 53-59, mar.2013. graf
Artigo em Espanhol | BINACIS | ID: bin-129802

RESUMO

La ceruloplasmina (CP) es una proteína que participa en el metabolismo del hierro y transporta el 95% del cobre plasmático. Se considera un inhibidor fisiológico de la mieloperoxidasa (MPO), enzima leucocitaria que forma parte del sistema inmune innato. Ambas se postulan como biomarcadores de la enfermedad cardiovascular. El objetivo del presente trabajo fue determinar la actividad de CP y la concentración de MPO en pacientes con enfermedad coronaria crónica (ECC) y analizar su asociación con otros parámetros de inflamación. Se estudiaron 22 pacientes con ECC y 22 controles sanos. La actividad de CP fue determinada por el método de Ozcan Erel y las concentraciones de MPO, proteína C- reactiva ultrasensible (PCR-us) e Interleuquina 6 (IL-6) por métodos estandarizados. La concentración de MPO y la actividad de CP fueron mayores en pacientes con ECC que en sujetos sanos; (417±295 vs. 179±145 ng/mL, p=0,0018); (891±179 vs. 630±115 IU/L, p< 0,0001) respectivamente y la asociación entre las variables fue estadísticamente significativa (r=0,47, p=0,0272). La liberación sistémica de MPO que conduce a valores incrementados de su concentración sérica, y la hiperceruloplasminemia podrían considerarse un rasgo característico de ECC asintomática e indicarían aterosclerosis en pacientes que eventualmente desarrollen ECC.(AU)


Assuntos
Humanos , Ceruloplasmina , Peroxidase , Inflamação , Aterosclerose
20.
J Phys Chem Lett ; 3(12): 1596-601, 2012 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-26285714

RESUMO

Fibrillogenesis of the small peptide Aß(1-40) is considered to be the hallmark of Alzheimer's disease. Some evidence indicates small oligomers, rather than mature fibrils, as the key cytotoxic agents. The fluorescent dye Thioflavin T (ThT) is often used to detect amyloid deposits in both in vivo and in vitro experiments, and it is used to study kinetic measurements, under the fundamental hypothesis that this probe does not influence the aggregation processes. We report experimental data showing that ThT may promote the Aß(1-40) peptide amyloid aggregation changing solvent-peptide interactions and stabilizing more ordered ß-like conformation. This finding has a two-fold importance: It is a fundamental warning in all fibrillation experiments where ThT is used as fluorescent probe, and it suggests that ThT, accelerating fibril formation, could be used to reduce the presence of transient small oligomers, thus interfering with the pathogenic impact of Aß peptide.

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