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1.
Nat Commun ; 13(1): 5089, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042203

RESUMO

Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, in a range from transient to diet-induced obesity, could result in the transition of ATMs from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is a key regulator of macrophage oxidative capacity in response to caloric excess. ATMs from mice with genetic-deficiency of Irf5 are characterised by increased oxidative respiration and mitochondrial membrane potential. Transient inhibition of IRF5 activity leads to a similar respiratory phenotype as genomic deletion, and is reversible by reconstitution of IRF5 expression. We find that the highly oxidative nature of Irf5-deficient macrophages results from transcriptional de-repression of the mitochondrial matrix component Growth Hormone Inducible Transmembrane Protein (GHITM) gene. The Irf5-deficiency-associated high oxygen consumption could be alleviated by experimental suppression of Ghitm expression. ATMs and monocytes from patients with obesity or with type-2 diabetes retain the reciprocal regulatory relationship between Irf5 and Ghitm. Thus, our study provides insights into the mechanism of how the inflammatory transcription factor IRF5 controls physiological adaptation to diet-induced obesity via regulating mitochondrial architecture in macrophages.


Assuntos
Fatores Reguladores de Interferon , Macrófagos , Tecido Adiposo/metabolismo , Animais , Fatores Reguladores de Interferon/metabolismo , Macrófagos/metabolismo , Camundongos , Monócitos/metabolismo , Obesidade/genética , Obesidade/metabolismo
2.
J Nutr Health Aging ; 25(10): 1140-1144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34866140

RESUMO

The objective of this cohort study was to determine whether hypercalcemia in early COVID-19 was associated with 3-month mortality in frail elderly patients. Circulating calcium and albumin concentrations at hospital admission and 3-month mortality were assessed in geriatric patients hospitalized for COVID-19 with normal-to-high calcium concentrations. Hypercalcemia was defined as corrected calcium >2.5mmol/L. Covariables were age, sex, functional abilities, malignancies, hypertension, cardiomyopathy, number of acute health issues, use antibiotics and respiratory treatments. In total, 94 participants (mean±SD 88.0±5.5years; 47.9% women; 22.3% hypercalcemia; 0% hypocalcemia) were included. Sixty-five participants who survived at 3months exhibited less often hypercalcemia at baseline than the others (13.9% versus 41.4%, P=0.003). Hypercalcemia was associated with 3-month mortality (fully-adjusted HR=3.03, P=0.009) with specificity=0.86 and sensitivity=0.41. Those with hypercalcemia had shorter survival time than those with normocalcemia (log-rank P=0.002). In conclusion, hypercalcemia was associated with poorer survival in hospitalized frail elderly COVID-19 patients.


Assuntos
COVID-19 , Hipercalcemia , Idoso , Biomarcadores , Estudos de Coortes , Feminino , Idoso Fragilizado , Humanos , Hipercalcemia/complicações , Masculino , Prognóstico , SARS-CoV-2
3.
Phys Rev Lett ; 124(13): 133902, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32302194

RESUMO

We report evidence of strong lasing on the 4p-4s transition at 62.7 nm in nickel-like krypton occurring simultaneously with the usual 4d-4p lasing at 32.8 nm. The gain dynamics of both transitions were experimentally and numerically investigated and found comparable. The two-color amplifier was seeded by the same harmonic pulse, therefore producing a short-duration coherent two-color soft x-ray laser pulse. Both transitions offer similar prospects of pulse energy and duration and could lead to the delivery of intense and ultrashort two-color coherent soft x-ray pulses with a controllable delay.

4.
Br J Dermatol ; 182(2): 477-480, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31077337

RESUMO

Immune checkpoint inhibitors are now the standard of care in the treatment of several types of cancer. Cutaneous immune-related adverse events (irAEs) are usually of low grade and reversible, while endocrine irAEs are generally irreversible and managed with hormone replacement therapy. We report a 47-year-old patient, treated with the anti-programmed cell death (PD)1 antibody pembrolizumab for a metastatic melanoma, who developed severe lipodystrophy after 10 months of treatment, characterized by the loss of subcutaneous fat tissue, central obesity and insulin resistance with a decreased leptin level. Histological analysis of a cutaneous biopsy revealed subcutaneous fat cell destruction associated with oedema, the presence of lipophages, and a CD3+ lymphocytic infiltrate involving the panniculus. This led to the diagnosis of anti-PD-1-induced acquired generalized lipodystrophy, after ruling out differential diagnoses (i.e. genetic and systemic autoimmune diseases). No corticosteroids were introduced considering the high risk of inducing severe metabolic complications, and pembrolizumab was discontinued as complete response of the melanoma was achieved. However, after 12 months of follow-up, lipodystrophy and its severe metabolic complications are still ongoing. What's already known about this topic? Anti-programmed cell death (PD)1 agents are now a standard of care in the treatment of several cancers, including melanoma. Endocrine and cutaneous immune-related adverse events (irAEs) are among the most frequent irAEs (14-30% and 30-40%, respectively) in patients treated with immune checkpoint inhibitors. What does this study add? Acquired generalized lipodystrophy can occur during anti-PD1 therapy and is associated with severe metabolic complications. With the increase in anti-PD1 prescription in several cancer types, clinicians must be aware of the whole range of irAEs that may occur.


Assuntos
Lipodistrofia Generalizada Congênita , Melanoma , Anticorpos Monoclonais Humanizados , Humanos , Inibidores de Checkpoint Imunológico , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1
5.
Diabetes Metab ; 46(5): 370-376, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31783142

RESUMO

BACKGROUND: Cardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin. METHODS: Included were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated. RESULTS: Using LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2. CONCLUSION: Our results reveal that 'aspirin resistance' is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.


Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus Tipo 2/sangue , Resistência a Medicamentos , Ativação Plaquetária , Inibidores da Agregação Plaquetária/uso terapêutico , Calcificação Vascular/diagnóstico por imagem , Idoso , Ácido Araquidônico , Proteína C-Reativa/metabolismo , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/sangue , Inflamação/metabolismo , Resistência à Insulina , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária , Testes de Função Plaquetária , Índice de Gravidade de Doença , Trombopoetina/sangue , Tromboxano B2/sangue , Fator de Necrose Tumoral alfa/sangue
6.
Sci Rep ; 9(1): 19020, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836730

RESUMO

Undulator based synchrotron light sources and Free Electron Lasers (FELs) are valuable modern probes of matter with high temporal and spatial resolution. Laser Plasma Accelerators (LPAs), delivering GeV electron beams in few centimeters, are good candidates for future compact light sources. However the barriers set by the large energy spread, divergence and shot-to-shot fluctuations require a specific transport line, to shape the electron beam phase space for achieving ultrashort undulator synchrotron radiation suitable for users and even for achieving FEL amplification. Proof-of-principle LPA based undulator emission, with strong electron focusing or transport, does not yet exhibit the full specific radiation properties. We report on the generation of undulator radiation with an LPA beam based manipulation in a dedicated transport line with versatile properties. After evidencing the specific spatio-spectral signature, we tune the resonant wavelength within 200-300 nm by modification of the electron beam energy and the undulator field. We achieve a wavelength stability of 2.6%. We demonstrate that we can control the spatio-spectral purity and spectral brightness by reducing the energy range inside the chicane. We have also observed the second harmonic emission of the undulator.

7.
Eur J Paediatr Neurol ; 23(4): 560-570, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31182404

RESUMO

It is increasingly accepted that survival alone is an inadequate measure of the success of childhood brain tumour treatments. Consequently, there is growing emphasis on capturing quality of survival. Ependymomas are the third most frequently occurring brain tumours in childhood and present significant clinical challenges. European Society of Paediatric Oncology Ependymoma II is a comprehensive international program aiming to evaluate outcomes under different treatment regimens and improve diagnostic accuracy. Importantly, there has been agreement to lower the age at which children with posterior fossa ependymoma undergo focal irradiation from three years to either eighteen months or one year of age. Hitherto radiotherapy in Europe had been reserved for children over three years due to concerns over adverse cognitive outcomes following irradiation of the developing brain. There is therefore a duty of care to include longitudinal cognitive follow-up and this has been agreed as an essential trial outcome. Discussions between representatives of 18 participating European countries over 10 years have yielded European consensus for an internationally accepted test battery for follow-up of childhood ependymoma survivors. The 'Core-Plus' model incorporates a two-tier approach to assessment by specifying core tests to establish a minimum dataset where resources are limited, whilst maintaining scope for comprehensive assessment where feasible. The challenges leading to the development of the Core-Plus model are presented alongside learning from the initial stages of the trial. We propose that this model could provide a solution for future international trials addressing both childhood brain tumours and other conditions associated with cognitive morbidity.


Assuntos
Assistência ao Convalescente/métodos , Neoplasias Encefálicas/radioterapia , Ensaios Clínicos como Assunto/métodos , Cognição/efeitos da radiação , Ependimoma/radioterapia , Adolescente , Sobreviventes de Câncer/psicologia , Criança , Pré-Escolar , Irradiação Craniana/efeitos adversos , Europa (Continente) , Feminino , Humanos , Lactente , Masculino , Morbidade
8.
J Viral Hepat ; 25(10): 1132-1138, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29660206

RESUMO

An important requirement for a state-of-the-art hepatitis B surface antigen (HBsAg) screening assay is reliable detection of mutated HBsAg. Currently, there is a striking shortage of data regarding the detection rates of in vivo HBsAg mutations for these clinically important assays. Therefore, we compared the detection rates of four commercial HBsAg screening assays using a global cohort of 1553 patients from four continents with known HBV genotypes. These samples, which represent the broadest spectrum of known and novel HBsAg major hydrophilic region (MHR) mutations to date, were analyzed for the presence of HBsAg using the Roche Elecsys® HBsAg II Qualitative, Siemens ADVIA Centaur XP HBsAg II, Abbott Architect HBsAg Qualitative II and DiaSorin Liaison® HBsAg Qualitative assays, respectively. Of the 1553 samples, 1391 samples could be sequenced; of these, 1013 (72.8%) carried at least one of the 345 currently known amino acid substitutions (distinct HBsAg mutation) in the HBsAg MHR. All 1553 patient samples were positive for HBsAg using the Elecsys® HBsAg II Qual assay, with a sensitivity (95% confidence interval) of 99.94% (99.64%-100%), followed by the Abbott Architect 99.81% (99.44%-99.96%), Siemens ADVIA 99.81% (99.44%-99.96%) and DiaSorin Liaison® 99.36% (98.82%-99.69%) assays, respectively. Our results indicate that the Elecsys® HBsAg II Qual assay exhibits the highest sensitivity among the commercial HBsAg screening assays, and demonstrate that its capacity to detect HBV infection is not compromised by HBsAg MHR mutants.


Assuntos
Testes Diagnósticos de Rotina/normas , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/virologia , Programas de Rastreamento/métodos , Estudos de Coortes , Genótipo , Hepatite B/diagnóstico , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Imunoensaio , Mutação , Sensibilidade e Especificidade
9.
J Nutr Health Aging ; 21(10): 1307-1313, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29188894

RESUMO

OBJECTIVES: To determine i) whether cases of elderly fallers had lower serum 25-hydroxyvitamin D (25OHD) concentration than controls without history of falls; and ii) whether serum 25OHD concentration was associated with specific mechanisms, circumstances and consequences of falls. DESIGN: Case-control study with a 1:2 ratio. SETTING: Geriatric ward of the University Hospital of Angers, France, between February 2012 and March 2014. PARTICIPANTS: 216 inpatients (72 cases and 144 age- and gender-matched controls). MEASUREMENT: Falls were defined as involuntary events causing the person to the ground or other lower level. The main mechanisms, circumstances and consequences of falls were identified using standardized questionnaires. Vitamin D deficiency was defined as serum 25OHD concentration ≤25nmol/L. Age, gender, body mass index, polypharmacy, use antihypertensive drugs, use psychoactive drugs, disability, cognitive performance, serum concentrations of parathyroid hormone, creatinine and albumin, and season of evaluation were used as potential confounders. RESULTS: 216 participants (72 cases and 144 controls) were included in the study. There was no between-group difference in the prevalence of vitamin D deficiency (P=0.176). After adjusting for confounding factors, vitamin D deficiency was positively associated with falls (OR=4.03, P=0.014). Finally, the fallers with vitamin D deficiency exhibited more often orthostatic hypotension (68.8% against 33.3%, P=0.039) and a history of recurrent falls (85% against 50%, P=0.002) than those without vitamin D deficiency. CONCLUSION: This case-control study reported that vitamin D deficiency was associated with falls in older inpatients. There was a greater prevalence of orthostatic hypotension and of the reccurrence of falls among fallers with vitamin D deficiency, suggesting that vitamin D may influence the conditions predisposing to falls rather than the fall by itself.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Vitamina D/análogos & derivados , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , França/epidemiologia , Humanos , Hipotensão Ortostática/epidemiologia , Pacientes Internados/estatística & dados numéricos , Masculino , Prevalência , Recidiva , Vitamina D/sangue , Deficiência de Vitamina D/sangue
10.
Diabetes Metab ; 43(1): 79-82, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27262367

RESUMO

BACKGROUND AND OBJECTIVES: Peripheral tissue resistance to insulin action is a characteristic of type 2 diabetes mellitus (T2DM). It has also been reported that some chronic viral infections can contribute to insulin resistance. Human herpesvirus (HHV)-8 infection has been detected in T2DM patients in previous studies. Our study investigated whether the presence of the virus is associated with insulin resistance in patients with ketosis-prone type 2 diabetes (KPD), as reported with other viruses. RESEARCH DESIGN AND METHODS: A total of 11 insulin-free KPD patients positive (+) and seven patients who were negative (-) for HHV-8 infection were recruited; the latter had KPD that was well controlled (HbA1c=6.2±0.7%). A two-step euglycaemic-hyperinsulinaemic clamp test coupled with deuterated [6,6-2H2]glucose was used to assess insulin sensitivity, non-esterified fatty acid (NEFA) suppression and endogenous glucose production. RESULTS: In KPD patients, whether HHV-8+ or HHV-8-, there were no differences in NEFA release, endogenous glucose production or insulin sensitivity (M value). CONCLUSION: Asymptomatic HHV-8 infection does not appear to be associated with decreased insulin sensitivity in diabetic patients. These results should now be confirmed in a larger sample population.


Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Infecções por Herpesviridae , Herpesvirus Humano 8 , Resistência à Insulina , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/virologia , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/virologia , Feminino , Técnica Clamp de Glucose , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade
11.
Rev Sci Instrum ; 87(7): 073505, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27475557

RESUMO

Recent results on laser wakefield acceleration in tailored plasma channels have underlined the importance of controlling the density profile of the gas target. In particular, it was reported that the appropriate density tailoring can result in improved injection, acceleration, and collimation of laser-accelerated electron beams. To achieve such profiles, innovative target designs are required. For this purpose, we have reviewed the usage of additive layer manufacturing, commonly known as 3D printing, in order to produce gas jet nozzles. Notably we have compared the performance of two industry standard techniques, namely, selective laser sintering (SLS) and stereolithography (SLA). Furthermore we have used the common fused deposition modeling to reproduce basic gas jet designs and used SLA and SLS for more sophisticated nozzle designs. The nozzles are characterized interferometrically and used for electron acceleration experiments with the Salle Jaune terawatt laser at Laboratoire d'Optique Appliquée.

12.
J Biomed Nanotechnol ; 11(1): 177-89, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26301312

RESUMO

In the field of oncology, research is now focused on the development of theranostic nanosystems that combine the functions of drug delivery and imaging for diagnosis/monitoring. In this context, we designed polyethylene glycol (PEG)ylated superparamagnetic iron oxide nanoparticles (SPIONs) for the delivery of doxorubicin (DOX), an antineoplastic agent. These DOX-loaded PEGylated SPIONs, or DLPS, should be useful for the delivery of DOX in vivo, as well as for magnetic drug targeting (MDT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate the potential applications of DLPS in vivo as drug carrier systems for the reduction of xenograft breast tumors induced in nude mice. Prior to the animal model experiments, the main internalization pathways for the nanovectors in MDA-MB435 breast cancer cells were determined to be based on caveolae- and clathrin-mediated endocytosis. The time- and quantity-dependence of the nanoparticle uptake by the cells altered the in vitro cytotoxicity of the DLPS. The in vitro antiproliferative effect of the DLPS was dependent not only on DOX concentration, but also on the efficacy of nanoparticle internalization. Evaluation of the effect of DLPS treatment on xenograft tumors in nude mice showed that DLPS limited tumor growth in a manner comparable to that of free DOX under normal conditions of tumor growth. The application of an external magnetic field on tumors, i.e., MDT, did not improve the efficacy of the DLPS treatment. Nevertheless, the vectorization of DOX with DLPS appears to limit the hematologic side effects usually associated with DOX treatment.


Assuntos
Células Sanguíneas/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Dextranos/química , Dextranos/toxicidade , Doxorrubicina/administração & dosagem , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Nanocápsulas/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Células Sanguíneas/patologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Difusão , Doxorrubicina/química , Doxorrubicina/toxicidade , Feminino , Humanos , Teste de Materiais , Camundongos , Camundongos Nus , Nanocápsulas/toxicidade , Nanocápsulas/ultraestrutura , Resultado do Tratamento
13.
Sci Rep ; 5: 7786, 2015 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-25585715

RESUMO

High harmonic generation in gases is developing rapidly as a soft X-ray femtosecond light-source for applications. This requires control over all the harmonics characteristics and in particular, spatial properties have to be kept very good. In previous literature, measurements have always included several harmonics contrary to applications, especially spectroscopic applications, which usually require a single harmonic. To fill this gap, we present here for the first time a detailed study of completely isolated harmonics. The contribution of the surrounding harmonics has been totally suppressed using interferential filtering which is available for low harmonic orders. In addition, this allows to clearly identify behaviors of standard odd orders from even orders obtained by frequency-mixing of a fundamental laser and of its second harmonic. Comparisons of the spatial intensity profiles, of the spatial coherence and of the wavefront aberration level of 5ω at 160 nm and 6ω at 135 nm have then been performed. We have established that the fundamental laser beam aberrations can cause the appearance of a non-homogenous donut-shape in the 6ω spatial intensity distribution. This undesirable effect can be easily controlled. We finally conclude that the spatial quality of an even harmonic can be as excellent as in standard generation.

14.
Diabetes Obes Metab ; 16(9): 861-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24641271

RESUMO

AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. METHODS: Six randomized, placebo-controlled studies of lixisenatide 20 µg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. RESULTS: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9 mmol/l, p < 0.001) and glucose excursion (LS mean difference vs. placebo: -4.5 mmol/l, p < 0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0 ng/l, p < 0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p < 0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. CONCLUSIONS: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Glucagon/sangue , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Peptídeos/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Esvaziamento Gástrico/efeitos dos fármacos , Glucagon/efeitos dos fármacos , Glucagon/metabolismo , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Secreção de Insulina , Período Pós-Prandial , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Prog Urol ; 23(16): 1389-99, 2013 Dec.
Artigo em Francês | MEDLINE | ID: mdl-24274943

RESUMO

The Lithiasis Committee of the French Association of Urology (CLAFU) aimed to update the current knowledge about urolithiasis. This update will be divided into four parts: 1) general considerations; 2) the management of ureteral stones; 3) the management of kidney stones; 4) metabolic assessment and medical treatment of urolithiasis. Recent technicals advances helped the urologists to improve stones management: new extracorporeal shockwave lithotripsy (ESWL) devices, new flexible ureterorenoscopes, development of laser fragmentation. ESWL, semi-rigid and flexible ureteroscopy and the percutaneous nephrolithotomy (PCNL) remain currently the main therapeutic options. The first part of this update deals with the description and classification of stones, preoperative assessment, post-operative management and clinical follow-up. Main criteria of therapeutic choices are stone location, stone composition and stone size. Stone composition is assessed with infrared spectrophotometry analysis and its hardness is correlated with U.H. density on CT scan assessment. Preoperative assessment consists in urinary cytobacteriological examine, urinary PH, blood creatininemia, hemostasis. Low-dose CT scan is recommended before urological treatment. The result of the treatment must be done 1 or 3 months later with plain abdominal film and ultrasonography. Medical management of urolithiasis will be based on stone composition, metabolic and nutritional evaluation. Treatment success is definited by absence of residual fragments. Annual follow-up is recommended and based either on plain abdominal film and ultrasonography or low-dose CT scan.


Assuntos
Litotripsia a Laser , Nefrolitíase/terapia , Nefrostomia Percutânea , Ureterolitíase/terapia , Ureteroscopia , Urologia , Adulto , Congressos como Assunto , França , Humanos , Litotripsia a Laser/instrumentação , Litotripsia a Laser/métodos , Nefrolitíase/diagnóstico , Nefrostomia Percutânea/instrumentação , Nefrostomia Percutânea/métodos , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios/métodos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Ureterolitíase/diagnóstico , Ureteroscopia/instrumentação , Ureteroscopia/métodos
16.
Nanotechnology ; 24(43): 432002, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24107712

RESUMO

Metallic nanoparticles (MNPs) such as iron oxide and gold nanoparticles are interesting platforms to build theragnostic nanocarriers which combine both therapeutic and diagnostic functions within a single nanostructure. Nevertheless, their surface must be functionalized to be suitable for in vivo applications. Surface functionalization also provides binding sites for targeting ligands, and for drug loading. This review focuses on the materials and surface chemistry used to build hybrid nanocarriers that are inorganic cores functionalized with organic materials. The surface state of the MNPs largely depends on their synthesis routes, and dictates the strategies used for functionalization. Two main strategies can be found in the literature: the design of core-shell nanosystems, or embedding nanoparticles in organic materials. Emerging tendencies such as the use of clusters or alternative coating materials are also described. To present both hydrophilic and lipophilic nanosystems, we chose the doxorubicin anticancer agent as an example, as the molecule presents an affinity for both types of materials.


Assuntos
Nanopartículas Metálicas/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Coloides/síntese química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos , Compostos Férricos/química , Interações Hidrofóbicas e Hidrofílicas , Lipossomos/química , Polímeros/química , Eletricidade Estática , Propriedades de Superfície
17.
J Control Release ; 169(1-2): 48-61, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23567046

RESUMO

Hybrid (organic/inorganic) nanoparticles emerged as a simple solution to build "theranostic" systems. Due to their physical properties, superparamagnetic iron oxide nanoparticles (SPIONs) and plasmonic gold nanoparticles (Au-NPs) are extensively studied as a part of diagnostic and therapeutic strategies in cancer treatments. They can be used as agents for in vitro or in vivo imaging, for magnetic drug targeting and/or thermal therapy. Their functionalization with organic shells enhances their potential performance in tumor targeting and drug delivery. The advances in such hybrid nanocarriers are well illustrated with the example of the anticancer drug doxorubicin (DOX). The aim of this review is to give a multidisciplinary overview of such smart nanosystems loaded with DOX, based on examples taken from recent publications. From a physico-chemical point of view, we discuss the choices for the strategies for loading DOX and the consequences on drug release. From a biological point of view, we analyze the in vitro and in vivo assays concerning tumor imaging, targeted drug delivery and anticancer efficiency. Future opportunities and challenges are also addressed.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Compostos Férricos/química , Ouro/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Portadores de Fármacos/química , Humanos
18.
Prog Urol ; 23(1): 22-8, 2013 Jan.
Artigo em Francês | MEDLINE | ID: mdl-23287480

RESUMO

UNLABELLED: The flexible ureterorenoscopy coupled with photovaporisation LASER (USSR-L) for the treatment of kidney kidney is a modern tool whose place is under evaluation. METHODS: Its place has been assessed in France in 2010 by the Committee of urolithiasis of the French Association of Urology (CLAFU). A practice survey among 27 experts concerned the following decision criteria: comorbid patient's supposed nature of the calculation, anatomy of the urinary tract of the patient. This investigation has been proposed to calculate the size not exceeding 20mm, for a calculation of size greater than 20mm and for multiple calculations kidney. RESULTS: Fourteen experts responded. The criteria for the USSR-The first line were: morbid obesity (BMI>30), anticoagulation or anti platelet aggregation, calculations Hard (UH>1000, cystine stones), calculations within diverticular caliceal calculations below, the failure of a first treatment or the wish of the patient. CONCLUSION: The URS-SL was a first-line treatment validated regardless of size and number of kidney stones, when ESWL and PCNL were contraindicated or when their predictable results were poor (hard stones/morbid obesity/lower pole stones) or when stone access is difficult (intradiverticular). It was also the treatment of choice after the failure of a first treatment (ESWL/PCNL).


Assuntos
Cálculos Renais/terapia , Litotripsia a Laser/métodos , Ureteroscópios , Ureteroscopia/métodos , Idoso , Índice de Massa Corporal , França , Pesquisas sobre Atenção à Saúde , Humanos , Litotripsia a Laser/instrumentação , Obesidade/complicações , Guias de Prática Clínica como Assunto , Reprodutibilidade dos Testes , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento , Ureteroscopia/instrumentação , Urologia
19.
Eur J Pharm Biopharm ; 81(3): 498-505, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22510695

RESUMO

The aim of this work was to elucidate the impact of polyethylene glycol (PEG) polymeric coating on the in vitro and in vivo stealthiness of magnetic nanocarriers loaded or not with the anticancer drug doxorubicin. The comparison was made between aqueous suspensions of superparamagnetic iron oxide nanoparticles (SPIONs) stabilized by either citrate ions (C-SPIONs) or PEG(5000) (P-SPIONs), the latter being loaded or not with doxorubicin via the formation of a DOX-Fe(2+) complex (DLP-SPIONs). After determination of their relevant physico-chemical properties (size and surface charge), nanoparticle (NP) stealthiness was studied in vitro (ability to activate the complement system and uptake by monocytes and macrophage-like cells) and in vivo in mice (blood half-life; t(1/2), and biodistribution in main clearance organs). These aspects were quantitatively assessed by atomic absorption spectrometry (AAS). Complement activation dramatically decreased for sterically stabilized P-SPIONs and DLP-SPIONs in comparison with C-SPIONs stabilized by charge repulsion. Monocyte and macrophage uptake was also largely reduced for pegylated formulations loaded or not with doxorubicin. The t(1/2) in blood for P-SPIONs was estimated to be 76 ± 6 min, with an elimination mainly directed to liver and spleen. Thanks to their small size (<80 nm) and a neutral hydrophilic polymer-extended surface, P-SPIONs exhibit prolonged blood circulation and thus potentially an increased level in tumor delivery suitable for magnetic drug targeting applications.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Nanopartículas de Magnetita/química , Polietilenoglicóis/química , Animais , Antibióticos Antineoplásicos/farmacocinética , Citratos , Ativação do Complemento/efeitos dos fármacos , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Feminino , Meia-Vida , Fígado/metabolismo , Macrófagos/metabolismo , Camundongos , Monócitos/metabolismo , Tamanho da Partícula , Espectrofotometria Atômica , Baço/metabolismo , Fatores de Tempo , Distribuição Tecidual
20.
Int J Pharm ; 423(1): 16-25, 2012 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-21703340

RESUMO

One of the new strategies to improve cancer chemotherapy is based on new drug delivery systems, like the polyethylene glycol-coated superparamagnetic iron oxide nanoparticles (PEG-SPION, thereafter called PS). In this study, PS are loaded with doxorubicin (DOX) anticancer drug, using a pre-formed DOX-Fe(2+) complex reversible at lower pH of tumour tissues and cancer cells. The DOX loaded PS (DLPS, 3% w/w DOX/iron oxide) present a hydrodynamic size around 60nm and a zeta potential near zero at physiological pH, both parameters being favourable for increased colloidal stability in biological media and decreased elimination by the immune system. At physiological pH of 7.4, 60% of the loaded drug is gradually released from the DLPS in ∼2h. The intracellular release and distribution of DOX is followed by means of confocal spectral imaging (CSI) of the drug fluorescence. The in vitro cytotoxicity of the DLPS on MCF-7 breast cancer cells is equivalent to that of a DOX solution. The reversible association of DOX to the SPION surface and the role of polymer coating on the drug loading/release are discussed, both being critical for the design of novel stealth magnetic nanovectors for chemotherapy.


Assuntos
Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Magnetismo/métodos , Nanopartículas de Magnetita/química , Polietilenoglicóis/química , Disponibilidade Biológica , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Cloretos/química , Citoplasma/metabolismo , Doxorrubicina/metabolismo , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Compostos Férricos/química , Compostos Ferrosos/química , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Ponto Isoelétrico , Luz , Nanopartículas de Magnetita/ultraestrutura , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência/métodos , Nitratos/química , Tamanho da Partícula , Propilaminas/química , Espalhamento de Radiação , Silanos/química , Eletricidade Estática , Propriedades de Superfície
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