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2.
Scand J Med Sci Sports ; 34(6): e14681, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38881390

RESUMO

BACKGROUND: Neuromuscular function is considered as a determinant factor of endurance performance during adulthood. However, whether endurance training triggers further neuromuscular adaptations exceeding those of growth and maturation alone over the rapid adolescent growth period is yet to be determined. OBJECTIVE: The present study investigated the concurrent role of growth, maturation, and endurance training on neuromuscular function through a 9-month training period in adolescent triathletes. METHODS: Thirty-eight 13- to 15-year-old males (23 triathletes [~6 h/week endurance training] and 15 untrained [<2 h/week endurance activity]) were evaluated before and after a 9-month triathlon training season. Maximal oxygen uptake (V̇O2max) and power at V̇O2max were assessed during incremental cycling. Knee extensor maximal voluntary isometric contraction torque (MVCISO) was measured and the voluntary activation level (VAL) was determined using the twitch interpolation technique. Knee extensor doublet peak torque (T100Hz) and normalized vastus lateralis (VL) electromyographic activity (EMG/M-wave) were also determined. VL and rectus femoris (RF) muscle architecture was assessed using ultrasonography. RESULTS: Absolute V̇O2max increased similarly in both groups but power at V̇O2max only significantly increased in triathletes (+13.8%). MVCISO (+14.4%), VL (+4.4%), and RF (+15.8%) muscle thicknesses and RF pennation angle (+22.1%) increased over the 9-month period in both groups similarly (p < 0.01), although no changes were observed in T100Hz, VAL, or VL EMG/M-wave. No changes were detected in any neuromuscular variables, except for coactivation. CONCLUSION: Endurance training did not induce detectible, additional neuromuscular adaptations. However, the training-specific cycling power improvement in triathletes may reflect continued skill enhancement over the training period.


Assuntos
Adaptação Fisiológica , Eletromiografia , Treino Aeróbico , Contração Isométrica , Consumo de Oxigênio , Torque , Humanos , Masculino , Adolescente , Estudos Longitudinais , Consumo de Oxigênio/fisiologia , Contração Isométrica/fisiologia , Músculo Quadríceps/fisiologia , Músculo Quadríceps/diagnóstico por imagem , Resistência Física/fisiologia , Ciclismo/fisiologia , Músculo Esquelético/fisiologia , Joelho/fisiologia , Ultrassonografia , Força Muscular/fisiologia , Atletas , Natação/fisiologia
3.
Rheumatology (Oxford) ; 63(3): 665-671, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37255329

RESUMO

OBJECTIVE: To validate the predictive value of the DAS28 γ-glutamyl transferase (DAS28-γGT) for the occurrence of major cardiovascular (CV) events (MACE) in the 'Etude et Suivi des Polyarthrites Indifférenciées Récentes' ESPOIR cohort. METHODS: Analysis of 13-year outcome from the ESPOIR cohort. RA patients with missing data for baseline γGT activity and those not followed-up to 1 year were excluded. Baseline DAS28-γGT was calculated using the following formula: 0.56*√TJ-28 + 0.28 * √SJ-28 + 2*ln(γGT) + 0.014 * GH. Our primary outcome was the merit of the DAS28-γGT in predicting the occurrence of MACE. RESULTS: Among the 696 patients [536 women, mean (s.d.) age of 49 (12) years], 34 MACE were recorded, with a mean time to event of 71 (44) months. Receiver operating characteristic curve analysis indicated that a DAS28-γGT >9.4 had the best sensitivity and specificity for the diagnosis of MACE during the observation period. DAS28-γGT >9.4 was predictive of the occurrence of MACE, with a hazard ratio (HR) of 3.11 (95% CI 1.41, 5.43). Multivariate Cox analyses confirmed higher DAS28-γGT (HR 2.44, 95% CI 1.05, 5.64) together with age (HR 1.04, 95% CI 1.01, 1.07) and diabetes mellitus (HR 4.12, 95% CI 1.55, 10.95) as independent predictors of MACE. There was a dose effect of the DAS28-γGT for MACE-risk prediction, which was in line with the application of the Framingham risk score. CONCLUSION: The DAS28-γGT was identified in this large prospective cohort as an independent predictor of MACE in patients with RA. The DAS28-γGT is a simple and useful tool to evaluate CV risk in routine and warn the clinician about the CV risk burden in patients with RA.


Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Humanos , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Estudos Prospectivos , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Fatores de Risco , Doenças Cardiovasculares/etiologia
4.
Small Methods ; 8(3): e2301343, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38032133

RESUMO

Owing to their high porosity and tunability, porous solids such as metal-organic frameworks (MOFs), zeolites, or activated carbons (ACs) are of great interest in the fields of air purification, gas separation, and catalysis, among others. Nonetheless, these materials are usually synthetized as powders and need to be shaped in a more practical way that does not modify their intrinsic property (i.e., porosity). Elaborating porous, freestanding and flexible sheets is a relevant shaping strategy. However, when high loadings (>70 wt.%) are achieved the mechanical properties are challenged. A new straightforward and green method involving the combination softwood bleached kraft pulp fibers (S) and nano-fibrillated cellulose (NFC) is reported, where S provides flexibility while NFC acts as a micro-structuring and mechanical reinforcement agent to form high loadings porous solids paper sheets (>70 wt.%). The composite has unobstructed porosity and good mechanical strength. The sheets prepared with various fillers (MOFs, ACs, and zeolites) can be rolled, handled, and adapted to different uses, such as air purification. As an example of potential application, a MOF paper composite has been considered for the capture of polar volatile organic compounds exhibiting better performance than beads and granules.

5.
Acta Neurochir (Wien) ; 165(10): 3003-3010, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37665404

RESUMO

PURPOSE: Sustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors. METHODS: Patients operated for GH-secreting pituitary adenomas between 2005-2020 were included from the local pituitary registry (n = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control. RESULTS: A total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38-59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas (p = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96-0.99), p = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57-1.00), p = 0.053). CONCLUSION: In unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.


Assuntos
Acromegalia , Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Hormônio do Crescimento Humano , Neoplasias Hipofisárias , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Acromegalia/cirurgia , Fator de Crescimento Insulin-Like I/metabolismo , Hipófise/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Neoplasias Hipofisárias/cirurgia , Adenoma/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Hormônio do Crescimento Humano/metabolismo
6.
Pharmaceuticals (Basel) ; 16(8)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37631042

RESUMO

The metabotropic glutamate receptor subtype 5 (mGluR5) is a class C G-protein-coupled receptor (GPCR) that has been implicated in various neuronal processes and, consequently, in several neuropsychiatric or neurodevelopmental disorders. Over the past few decades, mGluR5 has become a major focus for pharmaceutical companies, as an attractive target for drug development, particularly through the therapeutic potential of its modulators. In particular, allosteric binding sites have been targeted for better specificity and efficacy. In this context, Positron Emission Tomography (PET) appears as a useful tool for making decisions along a drug candidate's development process, saving time and money. Thus, PET provides quantitative information about a potential drug candidate and its target at the molecular level. However, in this area, particular attention has to be given to the interpretation of the PET signal and its conclusions. Indeed, the complex pharmacology of both mGluR5 and radioligands, allosterism, the influence of endogenous glutamate and the choice of pharmacokinetic model are all factors that may influence the PET signal. This review focuses on mGluR5 PET radioligands used at several stages of central nervous system drug development, highlighting advances and setbacks related to the complex pharmacology of these radiotracers.

7.
Carbohydr Polym ; 310: 120727, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36925252

RESUMO

In order to investigate a synergetic role of water and oxygen in the degradation of permanent paper in archiving climate, accelerated ageing in three different conditions was conducted: humid air, humid nitrogen and dry air. This allowed to decouple acid-catalysed hydrolysis versus oxidation of cellulose. After ensuring the reliability of the ageing experiment, the degradation state of the paper was assessed. Various techniques (size exclusion chromatography, pH extraction, alkaline reserve, paper colour and water content) were used. It appeared that the cellulose scission rate of the Canson® permanent paper was reduced compared to the Whatman No. 40 acidic cotton paper used as reference, but not in the same proportion for all the ageing conditions. This was attributed to a lower acidification, inhibiting acid-catalysed hydrolysis, due to the presence of the alkaline reserve. The degradation mechanisms are the same for both papers, which exhibited a similar chemical and physical degradation.

8.
Eur J Sport Sci ; 23(7): 1394-1404, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35757854

RESUMO

We investigated the acute cardiac consequences of a long-duration (>5 h) adventure race in adolescent athletes from evaluations of left ventricular (LV) strains and myocardial work. Twenty trained male adolescents (i.e. 8 ± 4 h·week-1 of endurance sports) aged 14-17 years participated in a competitive long-duration adventure race. Blood samples were collected before, immediately and 24 h after the race to determine the time course of troponin I (cTnI) considered a myocardial damage biomarker. Resting echocardiography was conducted before and after the race to assess myocardial regional strains, LV twisting mechanics and myocardial work using speckle tracking echocardiography. The mean completion time of the race was 05:38 ± 00:20 h, with a mean heart rate (HR) of 83 ± 5% of maximal HR. cTnI concentration significantly increased in 16/20 participants after the race (pre: 0.001 ± 0.002 vs. post: 0.244 ± 0.203 ng·dL-1, p < .001) and returned to baseline within 24 h. Stroke volume, ejection fraction and global longitudinal strains remained unchanged after the race, while LV twist and global myocardial work significantly decreased (8.6 ± 3.3 vs. 6.3 ± 3.3 deg and 2080 ± 250 vs. 1781 ± 334 mmHg%, p < .05). Diastolic function, indexes of myocardial relaxation and LV untwisting rate (-91.0 ± 19.0 vs. -56.4 ± 29.1 deg·s-1, p < .001) were affected after the race. We demonstrated that in trained adolescents, a high-intensity endurance exercise of several hours induced an increase of the cTnI concentration associated with an alteration of myocardial function.HighlightsThis is the first study to explore the acute cardiac consequences of a very-long duration and high-intensity race in trained adolescentsThe cardiac evaluations before and immediately after the race were conducted using up-to-date advances in echocardiography, including not only regional left ventricular strains, rotations and twists, but also global myocardial work to consider changes in loading conditions that occur after such exercises.We observed exercise-induced cardiac fatigue in the adolescents, characterized by a drop in myocardial work, associated with an increase of cardiac troponin I in 16/20 participants.The cardiac alterations were principally observed at the apical level of the heart: the apical strains and rotations were decreased and delayed. Consequently, left ventricular twist and twisting rates were also delayed, which probably affected the diastolic function after the race.


Assuntos
Ventrículos do Coração , Troponina I , Humanos , Masculino , Adolescente , Ventrículos do Coração/diagnóstico por imagem , Coração , Ecocardiografia , Miocárdio , Volume Sistólico
9.
Mol Psychiatry ; 28(2): 801-809, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36434055

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of ASD. Recently, studies proposed the implication of elevated mGluR5 densities in brain areas in the pathophysiology of ASD. Thus, our objective was to characterize glutamate dysfunctions in adult subjects with ASD by quantifying (1) glutamate levels in the cingulate cortex and periphery using proton magnetic resonance spectroscopy and metabolomics, and (2) mGluR5 brain density in this population and in a validated animal model of ASD (prenatal exposure to valproate) at developmental stages corresponding to childhood and adolescence in humans using positron emission tomography. No modifications in cingulate Glu levels were observed between individuals with ASD and controls further supporting the difficulty to evaluate modifications in excitatory transmission using spectroscopy in this population, and the complexity of its glutamate-related changes. Our imaging results showed an overall increased density in mGluR5 in adults with ASD, that was only observed mostly subcortically in adolescent male rats prenatally exposed to valproic acid, and not detected in the stage corresponding to childhood in the same animals. This suggest that clinical changes in mGluR5 density could reflect the adaptation of the glutamatergic dysfunctions occurring earlier rather than being key to the pathophysiology of ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Gravidez , Feminino , Adolescente , Adulto , Masculino , Ratos , Animais , Criança , Ácido Glutâmico , Encéfalo , Ácido Valproico , Sinapses
10.
Med Sci Sports Exerc ; 54(12): 2064-2072, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35881931

RESUMO

PURPOSE: This study aimed at assessing the prevalence of adverse cardiac events, as identified in the media, in world-class athletes according to their sex and sports discipline. METHODS: All female and male athletes from 30 individual Olympic sports who ranked in the international yearly top 10 between 2006 and 2018 were included. The name of each of them was associated in a Google search with selected key terms related to heart disease and/or acute cardiac events after their inclusion date. Global and sex-specific adverse cardiac event hazard function λ were calculated for each sport. Global and sex-specific prevalences of cardiac events were calculated, then compared (Fisher's exact test) between all sports. RESULTS: From the 2471 athletes included, 15 cases of cardiac events (prevalence of 0.61%) were reported; 2 sudden cardiac deaths (0.08%) occurred in male athletes. The other events were related to arrhythmic events ( n = 13), mainly supraventricular arrhythmias ( n = 9). All surviving athletes were able to continue their career, mostly after ablation procedure. Male endurance athletes accounted for seven events, among which three events occurred among short-distance triathletes. Events among women were comparatively rare ( n = 4), and all were observed among short-distance triathletes. CONCLUSIONS: A relatively unexpected high prevalence of cardiac events in endurance elite athletes was observed as compared with other sports, mainly, in short-distance male and female triathletes. This raises the question of particular cardiovascular constraints in this discipline and underlines the urge of international longitudinal follow-up studies in these kinds of athletes.


Assuntos
Atletas , Esportes , Humanos , Feminino , Masculino , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Coração , Internet
11.
J Sports Med Phys Fitness ; 62(11): 1552-1559, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35179331

RESUMO

BACKGROUND: Little is known about the biochemical consequences of endurance activities in adolescents. The present study aimed to examine the impact of a long-duration adventure race (>5 h) on hydration status, blood electrolytes and biomarkers of kidney function in adolescent athletes. METHODS: Twenty male adolescents aged 14 to 17 y (mean±SD; body mass: 59.7±9.1 kg and maximal O2 uptake: 56.2±4.6 mL∙kg-1∙min-1) volunteered to participate in a competitive adventure race of 68.5 km. Volunteers could drink ad libitum and fluid intake was monitored throughout the race. Blood samples were collected before, within 15 minutes after, and 24 hours after the race to monitor blood electrolytes (sodium, potassium, chloride), creatinine and blood urea nitrogen (BUN). Body mass and urine specific gravity (USG) were also measured across the same time points. RESULTS: The race was completed on average in 05:38±00:20 h:min under cold and rainy conditions (10-15 °C and 83-93% of relative humidity). Fluid intake was 1.45±0.66 L and body mass decreased by 1.2% compared to before the race (P<0.001). Blood sodium concentrations remained stable after the race (140.4±2.1 mmol∙L-1) despite an expansion in the plasma volume of 8.9±15.6%. No significant variations in BUN or BUN-to-creatinine ratio occurred. A significant increase in creatinine (+13.5%, P=0.003) was observed immediately after the race but remained within the reference range. CONCLUSIONS: The long-duration race completed under cold and humid conditions seems not to have exposed adolescents to hypohydration, hyponatremia or clinically significant alterations in kidney function.


Assuntos
Atletas , Cloretos , Adolescente , Humanos , Masculino , Creatinina , Ingestão de Líquidos , Resistência Física , Sódio , Biomarcadores , Rim , Potássio
12.
Int J Sports Med ; 43(8): 687-693, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34875701

RESUMO

The present study investigated the acute effects of a mixed-modality, long-duration adventure race on pulmonary function in adolescent athletes. Twenty male adolescents aged 14 to 17 years volunteered to participate in a wilderness adventure race of 68.5-km. Expiratory function was evaluated before, immediately after, and 24 h after race completion. Measurements included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF). Maximal inspiratory and expiratory mouth static pressures (MIP and MEP, respectively) were also measured using a portable hand-held mouth pressure meter across the same time points. The mean completion time of the race was 05:38±00:20 hours. A significant post-race decrease in FVC was observed immediately after the race (-5.2%, p=0.01). However, no significant changes were observed for FEV1, PEF and the FEV1/FVC and FEV1/PEF ratios. In addition, estimates of respiratory muscle strength (MIP and MEP) were unaffected by the race. The long-duration adventure race induced no marked reduction in expiratory pulmonary function and this response was associated with no apparent respiratory muscle fatigue. Therefore, the pulmonary system of trained adolescent athletes was sufficiently robust to sustain the mixed-modality, long-duration adventure race of ~ 5-6 h.


Assuntos
Pulmão , Músculos Respiratórios , Adolescente , Atletas , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Músculos Respiratórios/fisiologia , Capacidade Vital/fisiologia
13.
Pediatr Exerc Sci ; 33(3): 103-111, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958502

RESUMO

PURPOSE: To characterize the acute effects of a long-duration adventure race on knee extensor (KE) fatigue and the knee functional ratio in adolescent athletes. METHODS: Twenty trained male adolescents (aged 14-17 y) performed an adventure race of 68.5 km. Maximal voluntary isometric contraction (MVIC) KE and knee flexor torques were measured before and immediately after the race. Central and peripheral components of neuromuscular fatigue were quantified from the maximal voluntary activation level and the doublet peak torque (Tw100), respectively. The peak eccentric knee flexor torque to concentric KE torque ratio was also measured to determine functional ratio. RESULTS: The race completion time was 05:38 (00:20) hours. Significant reductions in MVICKE (-14.7%, P < .001) and MVICKF (-17.0%, P < .01) were observed after the race. Voluntary activation level decreased by 8.3% (P < .001) while Tw100 remained unchanged. Peak eccentric knee flexor torque decreased 16.0% (P < .001) while peak concentric KE torque did not change. This resulted in a significant reduction in functional ratio (-12.0%, P < .01). CONCLUSION: The adventure race induced a moderate fatigue, which was mainly explained by central factors without significant peripheral fatigue. However, particular attention should be paid to the knee muscular imbalance incurred by the race, which could increase the risk of ligament injury in adolescent athletes.


Assuntos
Contração Isométrica , Fadiga Muscular , Adolescente , Atletas , Eletromiografia , Humanos , Joelho , Masculino , Contração Muscular , Músculo Esquelético , Torque
14.
Transl Psychiatry ; 11(1): 66, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33473111

RESUMO

Altered glutamate signaling is thought to be involved in a myriad of psychiatric disorders. Positron emission tomography (PET) imaging with [18F]FPEB allows assessing dynamic changes in metabotropic glutamate receptor 5 (mGluR5) availability underlying neuropathological conditions. The influence of endogenous glutamatergic levels into receptor binding has not been well established yet. The purpose of this study was to explore the [18F]FPEB binding regarding to physiological fluctuations or acute changes of glutamate synaptic concentrations by a translational approach; a PET/MRS imaging study in 12 healthy human volunteers combined to a PET imaging after an N-acetylcysteine (NAc) pharmacological challenge in rodents. No significant differences were observed with small-animal PET in the test and retest conditions on the one hand and the NAc condition on the other hand for any regions. To test for an interaction of mGuR5 density and glutamatergic concentrations in healthy subjects, we correlated the [18F]FPEB BPND with Glu/Cr, Gln/Cr, Glx/Cr ratios in the anterior cingulate cortex VOI; respectively, no significance correlation has been revealed (Glu/Cr: r = 0.51, p = 0.09; Gln/Cr: r = -0.46, p = 0.13; Glx/Cr: r = -0.035, p = 0.92).These data suggest that the in vivo binding of [18F]FPEB to an allosteric site of the mGluR5 is not modulated by endogenous glutamate in vivo. Thus, [18F]FPEB appears unable to measure acute fluctuations in endogenous levels of glutamate.


Assuntos
Acetilcisteína , Receptor de Glutamato Metabotrópico 5 , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Voluntários Saudáveis , Humanos , Tomografia por Emissão de Pósitrons , Piridinas , Compostos Radiofarmacêuticos , Ratos , Receptor de Glutamato Metabotrópico 5/metabolismo
15.
Clin Nucl Med ; 46(2): 164-165, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33234939

RESUMO

ABSTRACT: 68Ga-DOTATOC PET/CT of a patient with metastatic neuroendocrine tumor reveals an abnormal biodistribution of the tracer with a vascular binding and a very low fixation on the known lesions despite the temporary discontinuation of "cold" somatostatin analogs. A possible interaction with a high intake of turmeric may be suspected by inhibition of hepatic uptake process.


Assuntos
Octreotida/análogos & derivados , Compostos Organometálicos/farmacocinética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Octreotida/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distribuição Tecidual
16.
EJNMMI Radiopharm Chem ; 5(1): 26, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33196944

RESUMO

BACKGROUND: Fluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3ß-p-tolyl-8-aza-bicyclo[3.2.1]octane-2ß-carboxylic acid methyl ester ([18F]LBT999) is a selective radioligand for the in vivo neuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET). [18F]LBT999 was produced on a TRACERlab FXFN for the Phase I study but for Phase III and a potent industrial production transfer, production was also implemented on an AllinOne (AIO) system requiring a single use cassette. Both production methods are reported herein. RESULTS: Automation of [18F]LBT999 radiosynthesis on FXFN was carried out in 35% yield (decay-corrected) in 65 min (n = 16), with a radiochemical purity higher than 99% and a molar activity of 158 GBq/µmol at the end of synthesis. The transfer to the AIO platform followed by optimizations allowed the production of [18F]LBT999 in 32.7% yield (decay-corrected) within 48 min (n = 5), with a radiochemical purity better than 98% and a molar activity above 154 GBq/µmol on average at the end of synthesis. Quality controls of both methods met the specification for clinical application. CONCLUSION: Both modules allow efficient and reproducible radiosynthesis of [18F]LBT999 with good radiochemical yields and a reasonable synthesis time. The developments made on AIO, such as its ability to meet pharmaceutical criteria and to more easily comply with GMP requirements, make it an optimal approach for the potent industrial production of [18F]LBT999 and future wider use.

17.
Biomacromolecules ; 21(7): 2795-2807, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32539350

RESUMO

X-ray analytical techniques are increasingly being used to study manuscripts and works of art on paper, whether with laboratory equipment or synchrotron sources. However, it is difficult to anticipate the impact of X-ray photons on paper- and cellulose-based artifacts, particularly due to the large variety of their constituents and degradation levels, and the subsequent material multiscale heterogeneity. In this context, this work aims at developing an analytical approach to study the modifications in paper upon synchrotron radiation (SR) X-ray radiation using analytical techniques, which are fully complementary and highly sensitive, yet not frequently used together. At the molecular scale, cellulose chain scissions and hydroxyl free radicals were measured using chromatographic separation techniques (size-exclusion chromatography-multiangle laser light scattering-differential refractive index (SEC-MALS-DRI) and reversed-phase high-performance liquid chromatography-fluorescence detector-diode array detector (RP-HPLC-FLD-DAD)), while the optical properties of paper were characterized using spectroscopy (UV luminescence and diffuse reflectance). These techniques showed different sensitivities toward the detection of changes. The modifications in the cellulosic material were monitored in real time, within a few days, and up to 2 years following the irradiation to define a lowest observed adverse effect dose (LOAED). As paper is a hygroscopic material, the impact of the humidity in the environment was studied using this approach. Three levels of moisture content in the paper, achieved by conditioning the samples and irradiating them at different relative humidities (RHs), were studied (0, 50, 80% RH). It was shown that very low moisture content accelerated molecular and optical modifications.


Assuntos
Síncrotrons , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Radiografia , Raios X
18.
Front Physiol ; 11: 10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116738

RESUMO

The aim of the present study was to examine the effect of 1- and 2-day adventure races on cardiac muscle damage and skeletal muscle soreness and function in young athletes. Twelve male trained adolescents (14-15 years) completed both 1-day (48.2 km) and 2-day (66.0 km) races that included trail running, mountain biking, kayaking, and in-line skating separated by 10 weeks. Myocardial damage biomarker concentrations (cTnI and CK-MB), maximal voluntary isometric contraction (MVIC) torque, perceived knee extensor (KE) muscle soreness (PMS), and drop and squat jump heights were measured before and after each race. Heart rate was also monitored throughout. Mean heart rate (% cardiac reserve) was higher during the 1-day (66.6 ± 6.4%) than 2-day (62.6 ± 7.8%, p = 0.038) race. The amplitude of cardiac damage biomarker release was also higher following the 1-day than the 2-day race (peak cTnI: 0.14 vs. 0.03 ng/mL, p = 0.045; peak CK-MB: 20.30 vs. 11.98 ng/mL, p = 0.020). However, cardiac biomarker concentrations returned to baseline at 24-48 h post-exercise, except for CK-MB after the 2-day race (p = 0.017). Eight and three participants exceeded the cTnI cut-off for myocardial injury in 1- and 2-day races, respectively, but none exceeded the cut-off for acute myocardial infarction. While there was a significant decrease in drop jump height (-5.9%, p = 0.003), MVIC torque and squat jump height remained unchanged after both races. PMS was increased at 24 h after both races (p < 0.001) but returned to baseline levels by 72 h post-race. In conclusion, the shorter, more intense race produced more cardiac damage, although this probably represents a standard exercise intensity-dependent response rather than pathological response. Skeletal muscle functional and soreness responses were moderate and similar between races.

19.
Q J Nucl Med Mol Imaging ; 63(4): 371-378, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28478665

RESUMO

BACKGROUND: Leucocytes scintigraphy (LS) is an in-vivo imaging technique investigating infectious foci, performed in our nuclear medicine department after a 99mTc-bisphophonates bone scintigraphy (BS) or an 18F-FDG-PET, in osteoarticular or vascular localizations, respectively. The aim of this study was to reassert the relevance of LS in the diagnostic of occult infections and its impact in therapeutic management. METHODS: A 45-month retrospective study (2012-2015), including 34 patients, was conducted. Patients who underwent LS were identified and classified according to the location of the suspected infection and the feature of first-line imaging exploration. The final diagnosis (infected or non-infected lesion) was established regarding patients' follow-up care, including clinical, biological biomarkers and therapeutic interventions. Sensitivity and specificity were calculated for each imaging modality. RESULTS: LS were conducted for exploration of joint prosthesis (N.=14), vascular prosthesis (N.=7), bone infection or osteitis (N.=8), algoneurodystrophia (N.=2), symphisis infection (N.=1), acute infection on chronicle inflammation (N.=1), and cancer (N.=1). All patients underwent a previous imaging exploration: BS (N.=20, 59%), 18FDG-PET (N.=10, 29%), or another exploration (N.=4, 12%). The sensitivity and specificity of BS were 67% and 36%, respectively, and 100% and 50% for 18FDG-PET, evidencing the lack of specificity of these approaches. Fourteen LS were positive (41%), with sensitivity, specificity and diagnostic accuracy of 85%, 86% and 85%, respectively. CONCLUSIONS: Despite a long, delicate, and costly radiopharmaceutical and nuclear imaging process, the high specificity of LS supports its qualitative added value in the diagnosis of infectious foci, by improving clinical and therapeutic patient's outcomes.


Assuntos
Infecções/diagnóstico por imagem , Infecções/imunologia , Leucócitos/metabolismo , Tecnécio Tc 99m Exametazima , Estudos de Coortes , Feminino , Humanos , Marcação por Isótopo , Masculino , Cintilografia , Estudos Retrospectivos
20.
Carbohydr Polym ; 202: 172-185, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30286990

RESUMO

Complex cellulosic samples are often difficult to analyse with size-exclusion chromatography. The strong molecular associations of hemicelluloses and lignin with cellulose produce multimodal molar mass distributions (MMD) that are difficult to interpret. More reliable ways of calculating the molar masses of cellulose are thus necessary. This is particularly relevant when studying the kinetics of paper degradation, as the number average molar mass is the most precise indicator. In this study various data handling methods based on the deconvolution of bimodal and multimodal MMDs of complex cellulosic samples after SEC-MALS-DRI analysis are examined in order to propose more accurate paper degradation rates. Two deconvolution methods, which do or do not rely on polymer calibration curves were developed and were applied to several kraft and groundwood pulp papers unaged and hygrothermally aged. The deconvolution methods are discussed and evaluated in light of calculated cellulose activation energies, degradation rates and paper usable lifetime predictions.

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