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1.
Nano Lett ; 19(10): 7210-7216, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31487461

RESUMO

At cryogenic temperature and at the single emitter level, the optical properties of single-wall carbon nanotubes depart drastically from that of a one-dimensional (1D) object. In fact, the (usually unintentional) localization of excitons in local potential wells leads to nearly 0D behaviors such as photon antibunching, spectral diffusion, inhomogeneous broadening, etc. Here, we present a hyperspectral imaging of this spontaneous exciton localization effect at the single nanotube level using a super-resolved optical microscopy approach. We report on the statistical distribution of the trap localization, depth, and width. We use a quasi-resonant photoluminescence excitation approach to probe the confined quantum states. Numerical simulations of the quantum states and exciton diffusion show that the excitonic states are deeply modified by the interface disorder inducing a remarkable discretization of the excitonic absorption spectrum and a quenching of the free 1D exciton absorption.

2.
Int J Obes (Lond) ; 39(11): 1638-43, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26095245

RESUMO

BACKGROUND/OBJECTIVES: Although weight loss has been associated with changes in circulating 25-hydroxyvitamin D (25(OH)D) levels, the quantification of the increase in 25(OH)D levels as a function of adipose tissue volume loss precisely assessed by imaging has not been reported before. The objective of this substudy was to describe the effects of a 1-year lifestyle intervention on plasma 25(OH)D levels. The relationships between changes in 25(OH)D levels and changes in adiposity volume (total and by adipose tissue compartment) were studied. SUBJECTS/METHODS: This intervention study was performed between 2004 and 2006 and participants were recruited from the general community. Sedentary, abdominally obese and dyslipidemic men (n=103) were involved in a 1-year lifestyle modification program. Subjects were individually counseled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500-kcal daily energy deficit and to increase physical activity/exercise habits. Body weight, body composition and fat distribution were assessed by dual-energy X-ray absorptiometry and computed tomography, whereas the 25(OH)D levels were measured with an automated assay. RESULTS: The 1-year intervention resulted in a 26% increase in circulating 25(OH)D (from 48±2 nmol l(-1) or 19±0.8 ng ml(-1) (±s.e.m.) to 58±2 nmol l(-1) or 23±0.8 ng ml(-1), P<0.0001) along with a 26% decrease in visceral adiposity volume (from 1947±458 to 1459±532 cm3). One-year increases in 25(OH)D levels correlated inversely with changes in all adiposity indices, especially Δvisceral (r=-0.36, P<0.0005) and Δtotal abdominal (r=-0.37, P<0.0005) adipose tissue volumes. CONCLUSIONS: These results indicate that there is a linear increase in circulating 25(OH)D levels as a function of adiposity volume loss, and therefore suggest a role of adiposity reduction in the management of obesity-associated vitamin D insufficiency.


Assuntos
Restrição Calórica , Dislipidemias/sangue , Exercício Físico , Obesidade/sangue , Comportamento de Redução do Risco , Vitamina D/análogos & derivados , Redução de Peso , Tecido Adiposo , Adiposidade , Adulto , Biomarcadores/sangue , Dislipidemias/terapia , Comportamento Alimentar , Humanos , Masculino , Saúde do Homem , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/prevenção & controle , Quebeque , Valores de Referência , Resultado do Tratamento , Vitamina D/sangue
3.
Int J Obes (Lond) ; 39(3): 495-501, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25179244

RESUMO

OBJECTIVES: To examine the specific distribution of liver fat content, visceral and subcutaneous adiposity in normal glucose tolerance (NGT/NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined conditions (IFG+IGT), as well as with newly diagnosed type 2 diabetes (nT2D). DESIGN: Multicenter, international observational study: cross-sectional analysis. SUBJECTS: Two thousand five hundred and fifteen patients (50.0% women, 54.5% non-Caucasian) without previously known diabetes were recruited from 29 countries. Abdominal fat distribution was measured by computed tomography (CT). Liver fat was estimated using the CT-liver mean attenuation. RESULTS: Compared with NGT/NGT patients, increased visceral adiposity was found in iIFG, iIGT, IFG+IGT and nT2D; estimated liver fat progressively increased across these conditions. A one-s.d. increase in visceral adiposity was associated with an increased risk of having iIFG (men: odds ratio (OR) 1.41 (95% confidence interval (CI) 1.15-1.74), women: OR 1.62 (1.29-2.04)), iIGT (men: OR 1.59 (1.15-2.01), women: OR 1.30 (0.96-1.76)), IFG+IGT (men: OR 1.64 (1.27-2.13), women: OR 1.83 (1.36-2.48)) and nT2D (men: OR 1.80 (1.35-2.42), women: OR 1.73 (1.25-2.41)). A one-s.d. increase in estimated liver fat was associated with iIGT (men: OR 1.46 (1.12-1.90), women: OR 1.81 (1.41-2.35)), IFG+IGT (men: OR 1.42 (1.14-1.77), women: OR 1.74 (1.35-2.26)) and nT2D (men: OR 1.77 (1.40-2.27), women: OR 2.38 (1.81-3.18)). Subcutaneous abdominal adipose tissue showed an inverse relationship with nT2D in women (OR 0.63 (0.45-0.88)). CONCLUSIONS: Liver fat was associated with iIGT but not with iIFG, whereas visceral adiposity was associated with both. Liver fat and visceral adiposity were associated with nT2D, whereas subcutaneous adiposity showed an inverse relationship with nT2D in women.


Assuntos
Glicemia/metabolismo , Intolerância à Glucose/metabolismo , Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Estado Pré-Diabético/metabolismo , Índice de Massa Corporal , Estudos Transversais , Jejum , Feminino , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Valor Preditivo dos Testes
4.
Eur J Clin Nutr ; 78(7): 651-652, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38802605

RESUMO

Holoprosencephaly is an anomaly in the division of the prosencephalon into cerebral hemispheres during the second month of gestation. Patients can present with early-onset obesity favoured by the cognitive impairment. We present a case of a 24 year-old woman with holoprosencephaly and class III obesity who was treated by 2.4 mg/week SEMAGLUTIDE. Her body weight decreased from 115.3 to 94.3 kg after one-year (18% of total body weight loss). In addition, she presented a marked reduction in self- and hetero-aggressive behaviour when exposed to the sight of food. The treatment was well tolerated, with the exception of a few vomiting when eating palatable food too quickly. GLP1-RAs may be interesting for obesity treatment in the context of neurodevelopmental disorders. They appear to reduce compulsive eating and aggressive behaviour, particularly in relation to exposure to food, and lead to weight loss similar to that seen in people without neurodevelopmental disorders.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1 , Holoprosencefalia , Transtornos do Neurodesenvolvimento , Obesidade , Humanos , Feminino , Holoprosencefalia/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Adulto Jovem , Obesidade/complicações , Transtornos do Neurodesenvolvimento/etiologia , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Redução de Peso
5.
Sci Rep ; 14(1): 20720, 2024 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237521

RESUMO

Liver fibrosis is often undetected whereas it is the determinant of liver-related mortality. We evaluate a pathway based on the systematic calculation of FIB-4 to screen for advanced hepatic fibrosis. Systematic calculation of FIB-4 was implemented in the centralized laboratory of a French University Hospital in 4 pilot departments. If ≥ 2.67, the FIB-4 result was returned to the prescribers, for patients between 18 and 70 years of age, with an incentive to measure liver stiffness by vibration controlled transient elastography. During a 2-years period, a FIB-4 was calculated in 2963 patients and 135 were ≥ 2.67 (4.6%). After exclusion of patients with a known cause of elevated FIB-4, 47 patients (34.8%) were eligible for elastography. Forty patients underwent elastography, but only 15% (7/47) at the spontaneous request of the referring physician. Fifteen patients were identified with significant fibrosis, among which 8 attended the scheduled specialist consultation, all with a confirmed diagnosis of cirrhosis. A sequential pathway based on the systematic calculation of FIB-4 enables the identification of patients with significant unknown liver fibrosis, allowing to refer them to specialized care. Raising awareness is essential to improve the care pathway.


Assuntos
Técnicas de Imagem por Elasticidade , Cirrose Hepática , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Idoso , Técnicas de Imagem por Elasticidade/métodos , Diagnóstico Precoce , Adolescente , Adulto Jovem , Doença Crônica , Programas de Rastreamento/métodos
6.
Diabetes Obes Metab ; 15(7): 629-41, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23356633

RESUMO

AIM: Visceral adipose tissue (VAT) and liver fat (LF) are strongly associated with type 2 diabetes. It is not known, however, how diabetes treatment and/or risk factor management modulates the association between VAT, LF and diabetes. The aim was to determine the level of VAT and LF in patients with type 2 diabetes according to their treatment status and achievement of the American Diabetes Association's (ADA) diabetes management goals. METHODS: We performed a cross-sectional analysis of the baseline data of the International Study of the Prediction of Intra-Abdominal Adiposity and its Relationship with Cardiometabolic risk/Intra-Abdominal Adiposity (INSPIRE ME IAA), a 3-year prospective cardiometabolic imaging study conducted in 29 countries. Patients (n = 3991) were divided into four groups: (i) those without type 2 diabetes (noT2D n = 1003 men, n = 1027 women); (ii) those with type 2 diabetes but not treated with diabetes medications (T2Dnomeds n = 248 men, n = 198 women); (iii) those with type 2 diabetes and treated with diabetes medications but not yet using insulin (T2Dmeds-ins n = 591 men, n = 484 women) and (iv) those with type 2 diabetes and treated with insulin (T2Dmeds+ins n = 233 men, n = 207 women). Abdominal and liver adiposity were measured by computed tomography. RESULTS: Fewer patients with high VAT or LF achieved the ADA's goals for high-density lipoprotein cholesterol (HDL-C) or triglycerides compared to patients with low VAT or LF. Visceral adiposity (p = 0.02 men, p = 0.003 women) and LF (p = 0.0002 men, p = 0.0004 women) increased among patients who met fewer of the ADA treatment criteria, regardless of type 2 diabetes treatment. CONCLUSION: Residual cardiometabolic risk exists among patients with type 2 diabetes characterized by elevated VAT and LF.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Síndrome Metabólica/prevenção & controle , Adiposidade , Adulto , Idoso , Estudos de Coortes , Terapia Combinada , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/terapia , Quimioterapia Combinada , Feminino , Humanos , Hiperlipidemias/etiologia , Hiperlipidemias/prevenção & controle , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/patologia , Metabolismo dos Lipídeos , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Adesão à Medicação , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Radiografia , Fatores de Risco
7.
Obes Surg ; 31(6): 2641-2648, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33665755

RESUMO

BACKGROUND AND AIMS: Bariatric surgery provides a useful opportunity to perform intraoperative liver biopsy to screen for non-alcoholic steatohepatitis (NASH). There is currently no consensus on whether intraoperative liver biopsy should be systematically performed. The aim of this study was to develop and validate a decision tree to guide that choice. APPROACH AND RESULTS: This prospective study included 102 consecutive patients from the severe obesity outcome network (SOON) cohort in whom liver biopsy was systematically performed during bariatric surgery. A classification and regression tree (CART) was created to identify the nodes that best classified patients with and without NASH. External validation was performed. Seventy-one biopsies were of sufficient quality for analysis (median body mass index 43.3 [40.7; 48.0] kg/m2). NASH was diagnosed in 32.4% of cases. None of the patients with no steatosis on ultrasound had NASH. The only CART node that differentiated between a "high-risk" and a "low-risk" of NASH was alanine aminotransferase (ALT). ALT>53IU/L predicted NASH with a positive predictive value (PPV) of 68% and a negative predictive value (NPP) of 89%, a sensitivity of 77%, and a specificity of 84%. In the external cohort (n=258), PPV was 68%, NPV was 62%, sensitivity was 27%, and specificity was 90%. CONCLUSIONS: The present work supports intraoperative liver biopsy to screen for NASH in patients with ALT>53IU/L; however, patients with no steatosis on ultrasound should not undergo biopsy. The CART failed to identify an algorithm with a good sensitivity to screen for NASH in patients with ultrasonography-proven steatosis and ALT≤53IU/L.


Assuntos
Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Biópsia , Árvores de Decisões , Humanos , Fígado/diagnóstico por imagem , Obesidade Mórbida/cirurgia , Estudos Prospectivos
8.
J Clin Pharm Ther ; 34(5): 585-94, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19744014

RESUMO

OBJECTIVE: The pharmacokinetic (PK) and pharmacodynamic (PD) responses to prasugrel were compared in three studies of healthy subjects vs. those with moderate or end-stage renal impairment. METHODS: Two of the three protocols were parallel-design, open-label, single dose (60-mg prasugrel) studies in subjects with end-stage renal disease (ESRD; n = 12) or moderate renal impairment (n = 10) and matched healthy subjects with normal renal function (n = 10). The third protocol was an open-label, single-dose escalation (5, 10, 30 and 60 mg prasugrel) study in subjects with ESRD (n = 16) and matched healthy subjects with normal renal function (n = 16). Plasma concentrations of prasugrel's active metabolite were determined and pharmacokinetic parameter estimates were derived. Maximum platelet aggregation (MPA) was measured by light transmission aggregometry using 20 mum adenosine diphosphate as agonist. RESULTS: Across all studies, prasugrel's C(max) and AUC(0-t) were 51% and 42% lower in subjects with ESRD than in healthy subjects. AUC(0-t) did not differ between healthy subjects and subjects with moderate renal impairment. The magnitude of change and time-course profiles of MPA was similar for healthy subjects compared with subjects with moderate renal impairment and those with ESRD. Prasugrel was well-tolerated in all subjects. CONCLUSION: There was no difference in pharmacokinetics or PD responses between subjects with moderate renal impairment and healthy subjects. Despite significantly lower exposure to prasugrel's active metabolite in subjects with ESRD, MPA did not differ between healthy subjects and those with ESRD.


Assuntos
Nefropatias/metabolismo , Falência Renal Crônica/metabolismo , Piperazinas/farmacocinética , Inibidores da Agregação Plaquetária/farmacocinética , Tiofenos/farmacocinética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Piperazinas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Cloridrato de Prasugrel , Ligação Proteica , Tiofenos/efeitos adversos , Tiofenos/farmacologia
9.
PLoS One ; 14(5): e0216733, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150420

RESUMO

In archaeological assemblages the presence of percussion marks, on the surface of long bones, is an indicator of long bone marrow extraction. The form, quantity and distribution of percussion marks are analysed to gain a better understanding of the marrow extraction process. Patterns of bone percussion damage in archaeological assemblages may highlight standardized actions, possibly related to butchery traditions. However, additional factors could underlie these patterns and should also be considered. In this article we test intuitiveness as a factor in appearance of percussion mark patterns, to see if patterns can appear when bones are being fractured without prior experience with bone fracture properties. To test this hypothesis, for this study we selected a sample of 40 cattle (Bos taurus) long limb bones from a large bone breakage experiment (400 long limb bones), where participants had no previous experience in bone breakage and may thus have broken bones intuitively. We used Geographic Information System (GIS) software to analyse the distribution of percussion marks. Using ArcGIS Spatial Analysts tools, we identified and quantified significant concentrations of percussion marks. Results show that percussion mark patterns emerge for the same bone element, and that specific sides and zones were recurrently selected by experimenters. The distribution of patterns varies among the different long bone elements, and we attribute this variance to an adjustment to bone morphology. In addition, we calculated and identified bone damage patterns resulting from hammerstone percussion. Crossing bone survivorship with percussion mark patterns enabled us to recognise and evaluate the effects of fragmentation and surface visibility in controlled experimental conditions. The GIS method facilitates comparisons between different variables and provides a sophisticated visual representation of results. Enlarging the sample will allow to constitute a more substantial analogous model for fossil assemblages.


Assuntos
Medula Óssea , Fósseis/patologia , Fraturas Ósseas , Sistemas de Informação Geográfica , Matadouros , Animais , Arqueologia/métodos , Medula Óssea/anatomia & histologia , Medula Óssea/diagnóstico por imagem , Carnivoridade , Bovinos , Manipulação de Alimentos/história , Manipulação de Alimentos/métodos , Fósseis/diagnóstico por imagem , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/história , Fraturas Ósseas/patologia , História Antiga , Humanos , Modelos Anatômicos
10.
Diabetes Metab ; 45(2): 91-101, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30189344

RESUMO

AIM: Because type 2 diabetes (T2D) is related to obesity, it is often associated with obstructive sleep apnoea syndrome (OSAS), although OSAS is also frequently diagnosed in patients with type 1 diabetes (T1D) and may promote gestational diabetes. Thus, this systematic review of the scientific evidence aimed to evaluate the epidemiological association between OSAS and all forms of diabetes, the current understanding of the pathophysiological mechanisms behind these associations, the expected benefits and limitations of OSAS treatment in patients with diabetes and, finally, to propose which patients require screening for OSAS. METHODS: A panel comprising French expert endocrinologists and pneumologists was convened. Two of these experts made a search of the relevant literature for each subpart of the present report; all panel experts then critically reviewed the entire report separately as well as collectively. RESULTS: There is little evidence to support the notion that OSAS treatment improves glycated haemoglobin, although it may improve nighttime blood glucose control and insulin sensitivity. However, there is robust evidence that OSAS treatment lowers 24-h blood pressure. CONCLUSION: The high prevalence of OSAS in patients with T1D and T2D justifies screening for the syndrome, which should be based on clinical symptoms, as the benefits of OSAS treatment are mainly improvement of symptoms related to sleep apnoea. There are also several clinical situations wherein screening for OSAS seems justified in patients with diabetes even when they have no symptoms, particularly to optimalize control of blood pressure in cases of resistant hypertension and microvascular complications.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Programas de Rastreamento/métodos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Pressão Positiva Contínua nas Vias Aéreas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Resistência à Insulina/fisiologia , Obesidade/sangue , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/epidemiologia , Seleção de Pacientes , Prevalência , Fatores de Risco , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia
11.
Eur Cell Mater ; 14: 78-90; discussion 90-1, 2007 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-18085506

RESUMO

The present study compares fibroblasts extracted from intact and ruptured human anterior cruciate ligaments (ACL) for creation of a tissue engineered ACL-construct, made of porcine small intestinal submucosal extracellular matrix (SIS-ECM) seeded with these ACL cells. The comparison is based on histological, immunohistochemical and RT-PCR analyses. Differences were observed between cells in a ruptured ACL (rACL) and cells in an intact ACL (iACL), particularly with regard to the expression of integrin subunits and smooth muscle actin (SMA). Despite these differences in the cell source, both cell populations behaved similarly when seeded on an SIS-ECM scaffold, with similar cell morphology, connective tissue organization and composition, SMA and integrin expression. This study shows the usefulness of naturally occurring scaffolds such as SIS-ECM for the study of cell behaviour in vitro, and illustrates the possibility to use autologous cells extracted from ruptured ACL biopsies as a source for tissue engineered ACL constructs.


Assuntos
Ligamento Cruzado Anterior/citologia , Ligamento Cruzado Anterior/fisiopatologia , Fibroblastos/transplante , Regeneração Tecidual Guiada/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais/tendências , Implantes Absorvíveis , Actinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Lesões do Ligamento Cruzado Anterior , Órgãos Bioartificiais , Materiais Biocompatíveis , Adesão Celular , Forma Celular/fisiologia , Células Cultivadas , Colágeno , Tecido Conjuntivo/metabolismo , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Sobrevivência de Enxerto/fisiologia , Humanos , Integrinas/metabolismo , Traumatismos do Joelho/patologia , Traumatismos do Joelho/fisiopatologia , Traumatismos do Joelho/terapia , Masculino , Pessoa de Meia-Idade , Regeneração , Ruptura/patologia , Ruptura/fisiopatologia , Ruptura/terapia , Sus scrofa , Transplante Autólogo/métodos
12.
Med Trop (Mars) ; 67(2): 175-8, 2007 Apr.
Artigo em Francês | MEDLINE | ID: mdl-17691438

RESUMO

The purpose of this report is to describe a case of febrile hypereosinophilic syndrome in a traveler three weeks after returning from a sightseeing trip to Guinea. Laboratory testing demonstrated an inflammatory response syndrome and hepatic cytolysis. Parasite serology led to suspicion of toxocariasis that was treated using albendazole. Follow-up tests at two months showed the presence of Schistosoma mansoni eggs in stools despite negative standard serodiagnostic testing (hemagglutination). Secondarily Western blot testing of serum samples at one, two and 14 months after returning from Guinea continued to show only protein bands specific to toxocariasis with no bands specific to bilhariziasis. These findings provide further evidence of the limitations of serological testing for detection of bilharziasis in travelers and the difficulty of diagnosis. Guinea is a high-risk tourist destination. Intestinal and urinary bilharziasis are endemic over three-fourths of country. Travelers planning even short stays in areas where bilharziasis is endemic should be advised on preventive measures.


Assuntos
Erros de Diagnóstico , Síndrome Hipereosinofílica/parasitologia , Esquistossomose mansoni/diagnóstico , Viagem , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Fezes/parasitologia , Guiné , Testes de Hemaglutinação , Humanos , Masculino , Pessoa de Meia-Idade , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/sangue
13.
Cell Death Discov ; 2: 15072, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27551496

RESUMO

Imeglimin is the first in a new class of oral glucose-lowering agents, having recently completed its phase 2b trial. As Imeglimin did show a full prevention of ß-cell apoptosis, and since angiopathy represents a major complication of diabetes, we studied Imeglimin protective effects on hyperglycemia-induced death of human endothelial cells (HMEC-1). These cells were incubated in several oxidative stress environments (exposure to high glucose and oxidizing agent tert-butylhydroperoxide) which led to mitochondrial permeability transition pore (PTP) opening, cytochrome c release and cell death. These events were fully prevented by Imeglimin treatment. This protective effect on cell death occurred without any effect on oxygen consumption rate, on lactate production and on cytosolic redox or phosphate potentials. Imeglimin also dramatically decreased reactive oxygen species production, inhibiting specifically reverse electron transfer through complex I. We conclude that Imeglimin prevents hyperglycemia-induced cell death in HMEC-1 through inhibition of PTP opening without inhibiting mitochondrial respiration nor affecting cellular energy status. Considering the high prevalence of macrovascular and microvascular complications in type 2 diabetic subjects, these results together suggest a potential benefit of Imeglimin in diabetic angiopathy.

14.
Respir Med ; 112: 119-25, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26847407

RESUMO

BACKGROUND: Insulin resistance, glucose dyshomeostasis and oxidative stress are associated to the cardiovascular consequences of obstructive sleep apnea (OSA). The effects of a long-term continuous positive airway pressure (LT-CPAP) treatment on such mechanisms still remain conflicting. OBJECTIVE: To investigate the effect of LT-CPAP on glucose tolerance, insulin sensitivity, oxidative stress and cardiovascular biomarkers in non-obese non-diabetic OSA patients. PATIENTS & METHODS: Twenty-eight apneic, otherwise healthy, men suffering from OSA (mean age = 48.9 ± 9.4 years; apnea-hypopnea index = 41.1 ± 16.1 events/h; BMI = 26.6 ± 2.8 kg/m(2); fasting glucose = 4.98 ± 0.37 mmol/L) were evaluated before and after LT-CPAP by an oral glucose tolerance test (OGTT), measuring plasma glucose, insulin and proinsulin. Glycated hemoglobin, homeostasis model assessment resistance insulin, blood lipids, oxidative stress, homocysteine and NT-pro-brain natriuretic peptide (NT-proBNP) were also measured. RESULTS: LT-CPAP treatment lasted 13.9 ± 6.5 months. At baseline, the time spent at SaO2<90%, minimal and mean SaO2 were associated with insulin area under the curve during OGTT (r = 0.448, P = 0.011; r = -0.382; P = 0.047 and r = -0.424; P = 0.028, respectively) and most other glucose/insulin homeostasis biomarkers, as well as with homocysteine (r = 0.531, P = 0.006; r = -0.487; P = 0.011 and r = -0.409; P = 0.034, respectively). LT-CPAP had no effect on all the OGTT-related measurements, but increased plasma total antioxidant status (+7.74%; P = 0.035) in a duration-dependent manner (r = 0.607; P < 0.001), and decreased both homocysteine (-15.2%; P = 0.002) and NT-proBNP levels (-39.3%; P = 0.002). CONCLUSIONS: In non-obese non-diabetic OSA patients, nocturnal oxygen desaturation is strongly associated to insulin resistance. LT-CPAP does not improve glucose homeostasis nor insulin sensitivity but has a favorable effect on antioxidant capacity and cardiovascular risk biomarkers.


Assuntos
Glicemia/metabolismo , Doenças Cardiovasculares/metabolismo , Pressão Positiva Contínua nas Vias Aéreas , Resistência à Insulina , Estresse Oxidativo , Apneia Obstrutiva do Sono/terapia , Adulto , Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Homocisteína/metabolismo , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Polissonografia , Proinsulina/metabolismo , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/metabolismo , Resultado do Tratamento , Triglicerídeos/metabolismo
16.
Diabetes Metab ; 41(4): 263-271, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25623152

RESUMO

Sleep duration has been constantly decreasing over the past 50 years. Short sleep duration, sleep quality and, recently, long sleep duration have all been linked to poor health outcomes, increasing the risk of developing metabolic diseases and cardiovascular events. Beyond the duration of sleep, the timing of sleep may also have consequences. Having a tendency to go early to bed (early chronotype) compared with the habit of going to bed later (late chronotype) can interfere considerably with social schedules (school, work). Eventually, a misalignment arises in sleep timing between work days and free days that has been described as 'social jet lag'. The present review looks at how different sleep habits can interfere with diabetes, excluding sleep breathing disorders, and successively looks at the effects of sleep duration, chronotype and social jet lag on the risk of developing diabetes as well as on the metabolic control of both type 1 and type 2 diabetes. Finally, this review addresses the current state of knowledge of physiological mechanisms that could be linking sleep habits and metabolic health.


Assuntos
Diabetes Mellitus/fisiopatologia , Hábitos , Sono/fisiologia , Ritmo Circadiano/fisiologia , Diabetes Mellitus/metabolismo , Humanos , Privação do Sono/metabolismo , Privação do Sono/fisiopatologia , Transtornos do Sono do Ritmo Circadiano/metabolismo , Transtornos do Sono do Ritmo Circadiano/fisiopatologia , Fatores de Tempo
17.
J Fr Ophtalmol ; 38(4): 301-5, 2015 Apr.
Artigo em Francês | MEDLINE | ID: mdl-25842148

RESUMO

INTRODUCTION: Ocular involvement by Candida albicans is rare and may present as endogenous endophthalmitis or choroiditis. It occurs in the context of C. albicans septicemia, in the context of intensive care unit hospitalization or intravenous drug use. We report two cases referred to our department with different characteristics, background, diagnostic modalities and different courses. OBSERVATIONS: A 37-year-old woman, with a history of intravenous drug use, presented with C. albicans endophthalmitis. Intravenous combination antifungal therapy was begun, but vitrectomy and intravitreal amphotericin B were performed due to worsening of the endophthalmitis. The second case was a 53-year-old man who was hospitalized in the intensive care unit for C. albicans septicemia with a left macular chorioretinitis. Intravenous antifungal therapy was initiated and allowed regression of the ocular lesion. DISCUSSION: Our cases illustrate both types of ophthalmic involvement by candidiasis requiring different treatments with well-described recommendations: in the case of endophthalmitis, the use of vitrectomy and intravitreal amphotericin B injection in association with intravenous antifungal treatment, whereas parenteral antifungal treatment is often sufficient in the case of chorioretinitis. CONCLUSION: Early detection, initiation of treatment and ophthalmologic monitoring are difficult but necessary in these populations non-compliant with follow-up or in intensive care units. The management of ocular candidiasis requires good collaboration between the ophthalmology, infectious diseases and intensive care unit departments.


Assuntos
Candidíase , Coriorretinite/microbiologia , Endoftalmite/microbiologia , Infecções Oculares Fúngicas , Adulto , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Coriorretinite/diagnóstico , Coriorretinite/tratamento farmacológico , Endoftalmite/diagnóstico , Endoftalmite/tratamento farmacológico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Thromb Haemost ; 80(6): 919-24, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9869161

RESUMO

A double blind randomized cross-over multi-center study has been conducted to compare the pharmacokinetic and coagulation activation markers of high-purity factor IX concentrate subjected to both solvent/ detergent (SD) treatment and 15 nm-filtration (FIX-SD-15) with the licensed product subjected only to solvent-detergent (FIX-SD). This filtration process allows the elimination of small particles, such as non-enveloped viruses (i.e., hepatitis A and parvovirus B19). Eleven severe hemophilia B patients (FIX coagulant activity <2 IU/dl) received one infusion of 60 IU/kg of FIX-SD and one infusion of 60 IU/kg of FIX-SD-15 at least at 10 days interval. Blood samples were obtained before and at various time up to 72 h after infusion. The decay curves of factor IX (FIX:C and FIX:Ag) were evaluated by a model independent method. Bioequivalence was found between the two concentrates using the Schuirmann test. The mean FIX:C and FIX:Ag recovery of FIX-SD-15 was 1.08 and 0.89 IU/dl/IU/kg respectively with a mean half-life of 33.3 h for FIX:C and 25.6 h for FIX:Ag. Six months after initial enrollment, pharmacokinetic parameters were similar in the 7 patients tested. There was no significant variation of prothrombin fragment 1+2 and thrombin-antithrombin complexes measured up to 6 h after infusion, indicating that there was no activation process after administration of FIX. In conclusion, these data demonstrate that the introduction of a 15 nm filtration does not alter the pharmacokinetic profile of a well characterized SD FIX concentrate while providing additional viral safety.


Assuntos
Fator IX/farmacocinética , Hemofilia B/tratamento farmacológico , Adolescente , Adulto , Antitrombina III/análise , Área Sob a Curva , Biomarcadores , Criança , Estudos Cross-Over , Detergentes , Método Duplo-Cego , Fator IX/isolamento & purificação , Filtração , Meia-Vida , Hemofilia B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Protrombina/análise , Segurança , Solventes , Resultado do Tratamento , Viroses/prevenção & controle
19.
J Gynecol Obstet Biol Reprod (Paris) ; 28(6): 544-9, 1999 Oct.
Artigo em Francês | MEDLINE | ID: mdl-10598348

RESUMO

OBJECTIVE: The utilization, during pregnancy, of low molecular weight heparin (enoxaparine) for obstetric thromboprophylaxis for patients with activated protein C resistance, following Factor V Leiden mutation. STUDY DESIGN: Prospective study enrolling 10 pregnant patients heterozygote or homozygote for Factor V Leiden mutation. They all had familial or personal history of severe thrombotic disease and received 40 mg per day of enoxaparine. RESULTS: No thrombosis or hemorrhage were recorded during pregnancies or deliveries. All the infants were doing well. After birth, low molecular, weight heparin were continued between 6 to 12 weeks accordingly allelic status and history. We reviewed the literature on this subject. CONCLUSION: This series confirmed the efficacy, safety and tolerance of low molecular weight heparins which will probably become the next gold standard for obstetric thromboprophylaxis.


Assuntos
Resistência à Proteína C Ativada/tratamento farmacológico , Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Trombose Venosa/prevenção & controle , Resistência à Proteína C Ativada/genética , Adulto , Fator V/genética , Feminino , Humanos , Mutação Puntual , Gravidez , Resultado da Gravidez
20.
J Fr Ophtalmol ; 37(5): 353-7, 2014 May.
Artigo em Francês | MEDLINE | ID: mdl-24679450

RESUMO

PURPOSE: To compare the results obtained with SLT trabeculoplasty after an initial treatment (SLT-1) and after a second treatment (SLT-2). Subgroup analysis according to trabecular pigmentation and the existence of a high myopia. MATERIALS AND METHODS: Retrospective study of 77 patients, 152 SLT sessions performed in the Ophthalmology Department of Clermont-Ferrand University Medical Center, 118 SLT-1, 34 SLT-2. Three comparable groups of patients were assembled: group 1 (glaucoma patients with normal or subnormal trabecular pigmentation), group 2 (glaucoma patients with high myopia), and group 3 (glaucoma patients with significant trabecular pigmentation). The results were compared between groups, for SLT-1 and SLT-2. RESULTS: Intraocular pressure lowering was consistent with data reported in the literature. Comparison of the results of SLT-1 versus SLT-2 did not find any significant difference in terms of IOP change. However, after SLT-2, the IOP response appears significantly greater (P=0.03) in the group with significant trabecular pigmentation compared to the non-myopic group with normal trabecular pigmentation. DISCUSSION: Our results are consistent with the literature for efficacy, tolerance and reproducibility of SLT. No reduction in SLT efficacy was observed after a second session. Trabecular pigmentation is not a predictor of the response after the first session. In the case of retreatment (SLT-2), the differences observed lead to the hypothesis that it may be appropriate to perform at least two SLT treatments in patients with significant trabecular pigmentation in order to obtain maximal effect. Myopia, a variable not previously studied, does not seem to influence SLT outcomes. CONCLUSION: Trabecular pigmentation and the presence of myopia do not appear to be predictive of a successful first treatment. However, our study leads us to suggest the hypothesis that the maximal response of SLT in patients with significant trabecular pigmentation is not obtained until after at least two sessions. This observation opens an interesting perspective on the therapeutic strategy to adopt in the case of pigmentary glaucoma.


Assuntos
Glaucoma de Ângulo Aberto/cirurgia , Terapia a Laser/métodos , Reoperação/métodos , Trabeculectomia/métodos , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/epidemiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular , Miopia/complicações , Miopia/epidemiologia , Miopia/fisiopatologia , Miopia/cirurgia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Tonometria Ocular , Resultado do Tratamento
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