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Monoclonal antibodies (mAbs) blocking immune checkpoints such as programmed death ligand 1 (PD-L1) have yielded strong clinical benefits in many cancer types. Still, the current limitations are the lack of clinical response in a majority of patients and the development of immune-related adverse events in some. As an alternative to PD-L1-specific antibody injection, we have developed an approach based on the engineering of tumor-targeting T cells to deliver intratumorally an anti-PD-L1 nanobody. In the MC38-OVA model, our strategy enhanced tumor control as compared with injection of PD-L1-specific antibody combined with adoptive transfer of tumor-targeting T cells. As a possible explanation for this, we demonstrated that PD-L1-specific antibody massively occupied PD-L1 in the periphery but failed to penetrate to PD-L1-expressing cells at the tumor site. In sharp contrast, locally delivered anti-PD-L1 nanobody improved PD-L1 blocking at the tumor site while avoiding systemic exposure. Our approach appears promising to overcome the limitations of immunotherapy based on PD-L1-specific antibodies.
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Antígeno B7-H1 , Neoplasias , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Humanos , Imunoterapia , Neoplasias/tratamento farmacológico , Linfócitos TRESUMO
PURPOSE: To evaluate the impact of preemptive inferior mesenteric artery (IMA) embolization on outcomes of endovascular abdominal aortic aneurysm (AAA) repair (EVAR). MATERIALS AND METHODS: From January 2015 to July 2017, all patients undergoing elective EVAR or fenestrated EVAR (F-EVAR) for asymptomatic AAA in a single tertiary hospital were retrospectively included. Three groups of patients were defined: patients with a patent IMA who underwent embolization during EVAR/F-EVAR (group 1), those with a patent IMA who did not undergo embolization during EVAR/F-EVAR (group 2), and those with a chronically occluded IMA (group 3). Preoperative aortic morphology, demographics, and procedural details were recorded. Aneurysmal growth (≥5 mm), reintervention, and overall mortality rates were analyzed using multivariate proportional hazard multivariate modeling. Propensity scores were constructed, and inverse probability weighting was applied to a new set of multivariate analyses to perform a sensitivity analysis. RESULTS: A total of 266 patients (male, 95% [n = 249]) with a median age of 70 (65-77) years were included, with F-EVAR procedures comprising 87 (32.7%) of the interventions. There were 52, 142, and 72 patients in groups 1, 2, and 3, respectively. Changes in aneurysmal sac size did not differ between groups, nor did overall survival or reintervention rates at 24 months. IMA embolization was not identified as an independently protective factor for aneurysmal growth during follow-up (relative risk [RR] = 2.82/mm [0.96-8.28], P = .060), whereas accessory renal arteries (RR = 5.07/mm [1.72-14.96], P = .003) and a larger preoperative aneurysmal diameter (RR = 1.09/mm [1.03-1.15], P = .004) were independent risk factors for sac enlargement. CONCLUSIONS: Preventive embolization of the IMA during EVAR or F-EVAR did not promote aneurysmal sac shrinking or decrease the reintervention rate at 2-year follow-up.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Endoleak , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Artéria Mesentérica Inferior/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
As industrialized countries race to install and deploy 5G networks, some countries have taken the lead and already have operational 5G networks in place. South Korea is among these. In this study, we measured exposure to electromagnetic fields in South Korea to evaluate the relative contribution of 5G as compared with other frequencies such as 2G, 3G, and 4G. Results show that the emission of 5G contributes about 15% to total telecommunications emissions. The highest levels were observed in the vicinity of 5G antennas and remain below the limits set by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). © 2021 Bioelectromagnetics Society.
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Telefone Celular , Ondas de Rádio , Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/análise , Ondas de Rádio/efeitos adversos , República da CoreiaRESUMO
BACKGROUND: Tranexamic acid (TA) use in lowerlimb arthroplasty has been valued in these surgeries highrisk hemorrhagic due to its antifibrinolytic action. The objective of the present study was to determine the effectiveness of the combined intravenous (IV) and intraarticular (IA) administration of TA in lowerlimb arthroplasty. METHODS: We conduct a prospective observational study between January 1, 2014, and December 31, 2017, including all programmed lowerlimb arthroplasties. Patients were divided into four groups: no TA, 15 mg/kg IV TA, 3 g IA TA, and 15 mg/kg IV and 3 g IA. The effect on calculated total blood loss (milliliter of red blood cell [RBC]), hemoglobin, transfusion, and duration of hospitalization was studied after adjustment on age, American Society of Anesthesiologists, surgery, and postoperative curative anticoagulation. Complications related to TA administration were systematically reported. RESULTS: A total of 1909 patients were included - "no TA," n = 184; "IV," n = 1137; "IA," n = 214; and "IV + IA," n = 374. In the IV + IA group, a decrease in blood loss was observed compared to the no TA group (+ 220 ml 95% confidence interval [CI] [184; 255] of RBC P < 0.001) and in the IA group (+ 65 ml 95% CI [30; 99] of RBC P < 0.001). The length of hospital stay of the IV + IA group was shorter compared to the no TA group (hazard ratio [HR] 0.35, 95% CI [0.29; 0.43], P < 0.001) to the IA group (HR 0.57, 95% CI [0.48; 0.69], P < 0.001) and the IV group (HR 0.45, 95% CI [0.39; 0.50], P < 0.001). One case of deep vein thrombosis occurred in the group without TA. CONCLUSION: Administration of combined TA appears effective and safe; further studies are needed in order to establish a consensual protocol.
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The design of glycogen phosphorylase (GP) inhibitors targeting the catalytic site of the enzyme is a promising strategy for a better control of hyperglycaemia in the context of type 2 diabetes. Glucopyranosylidene-spiro-heterocycles have been demonstrated as potent GP inhibitors, and more specifically spiro-oxathiazoles. A new synthetic route has now been elaborated through 1,3-dipolar cycloaddition of an aryl nitrile oxide to a glucono-thionolactone affording in one step the spiro-oxathiazole moiety. The thionolactone was obtained from the thermal rearrangement of a thiosulfinate precursor according to Fairbanks' protocols, although with a revisited outcome and also rationalised with DFT calculations. The 2-naphthyl substituted glucose-based spiro-oxathiazole 5h, identified as one of the most potent GP inhibitors (Ki = 160 nM against RMGPb) could be produced on the gram-scale from this strategy. Further evaluation in vitro using rat and human hepatocytes demonstrated that compound 5h is a anti-hyperglycaemic drug candidates performing slightly better than DAB used as a positive control. Investigation in Zucker fa/fa rat model in acute and subchronic assays further confirmed the potency of compound 5h since it lowered blood glucose levels by â¼36% at 30 mg kg-1 and â¼43% at 60 mg kg-1. The present study is one of the few in vivo investigations for glucose-based GP inhibitors and provides data in animal models for such drug candidates.
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Inibidores Enzimáticos/farmacologia , Glucose/metabolismo , Glicogênio Fosforilase/antagonistas & inibidores , Hipoglicemiantes/farmacologia , Compostos de Espiro/farmacologia , Tiazóis/farmacologia , Animais , Glicemia/metabolismo , Ciclização , Teoria da Densidade Funcional , Glicogênio/metabolismo , Glicogênio Fosforilase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Concentração Inibidora 50 , Cinética , Lactonas/síntese química , Lactonas/química , Oxirredução , Ratos Zucker , Compostos de Espiro/síntese química , Compostos de Espiro/química , Estereoisomerismo , Temperatura , Tiazóis/síntese química , Tiazóis/químicaRESUMO
BACKGROUND: Tranexamic acid (TA) use in lower-limb arthroplasty has been valued in these surgeries high-risk hemorrhagic due to its antifibrinolytic action. The objective of the present study was to determine the effectiveness of the combined intravenous (IV) and intraarticular (IA) administration of TA in lower-limb arthroplasty. METHODS: We conduct a prospective observational study between January 1, 2014, and December 31, 2017, including all programmed lower-limb arthroplasties. Patients were divided into four groups: no TA, 15 mg/kg IV TA, 3 g IA TA, and 15 mg/kg IV and 3 g IA. The effect on calculated total blood loss (milliliter of red blood cell [RBC]), hemoglobin, transfusion, and duration of hospitalization was studied after adjustment on age, American Society of Anesthesiologists, surgery, and postoperative curative anticoagulation. Complications related to TA administration were systematically reported. RESULTS: A total of 1909 patients were included - "no TA," n = 184; "IV," n = 1137; "IA," n = 214; and "IV + IA," n = 374. In the IV + IA group, a decrease in blood loss was observed compared to the no TA group (+220 ml 95% confidence interval [CI] [184; 255] of RBC P < 0.001) and in the IA group (+65 ml 95% CI [30; 99] of RBC P < 0.001). The length of hospital stay of the IV + IA group was shorter compared to the no TA group (hazard ratio [HR] 0.35, 95% CI [0.29; 0.43], P < 0.001) to the IA group (HR 0.57, 95% CI [0.48; 0.69], P < 0.001) and the IV group (HR 0.45, 95% CI [0.39; 0.50], P < 0.001). One case of deep vein thrombosis occurred in the group without TA. CONCLUSION: Administration of combined TA appears effective and safe; further studies are needed in order to establish a consensual protocol.
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Here, we report a study of white-ochre powders with targeted composition MnWO4 prepared via a coprecipitation method. Through X-ray total scattering combined with pair distribution function analysis and Rietveld refinement of X-ray diffraction data, we find that their crystal structure is similar to that of bulk-MnWO4, despite a mean crystallite size of 1.0-1.6 nm and a significant deviation of the average chemical composition from MnWO4. The chemical formula derived from elemental and thermogravimetric analyses is Mn0.8WO3.6(OH)0.4·3H2O. X-ray absorption and magnetic susceptibility measurements show that Mn and W have the same oxidation states as in MnWO4. No magnetic ordering or spin glass or superparamagnetic behavior is observed above 2 K, unlike in the case of MnWO4 nanocrystals having a mean size higher than 10 nm.
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It has been claimed that Nigella sativa seeds (NSS), also known as black cumin, have antidiabetic and lipid-lowering properties. Our pilot study investigated the effects of powdered NSS on insulin secretion and lipid profile in healthy male volunteers. We conducted a double-blind, randomized, placebo-controlled 4-week trial in 30 subjects, receiving NSS powder (1 g/day) or placebo orally (15 subjects/group). Insulin secretion as determined by the hyperglycaemic clamp technique, insulin sensitivity as well as cholesterol and triglycerides serum concentrations, were measured before and after treatment. NSS powder administration was clinically well tolerated. It did not modify fasting glycaemia and insulinaemia, and was ineffective on glucose-induced insulin secretion and insulin sensitivity. No significant changes on serum lipids were observed after treatment in any treatment groups, nor between the two treatment groups. However, in the treated group only, there was a significant correlation between total cholesterol change after treatment and its baseline level (r = -0.71, P = 0.006, n = 13), and between low-density lipoprotein (LDL) cholesterol change after treatment and its baseline level (r = -0.74, P = 0.004, n = 13). No such correlations were found for high-density lipoprotein (HDL) cholesterol, and for triglycerides. These results do not confirm any NSS effect on glucose regulation; however, they suggest that NSS powder may be of interest in lowering lipid concentrations in hyperlipidaemic subjects.
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Secreção de Insulina/efeitos dos fármacos , Lipídeos/sangue , Nigella sativa/química , Extratos Vegetais/farmacologia , Adulto , Método Duplo-Cego , Glucose/metabolismo , Humanos , Hipolipemiantes/efeitos adversos , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/farmacologia , Masculino , Projetos Piloto , Extratos Vegetais/efeitos adversos , Sementes , Adulto JovemRESUMO
Immunotherapy based on checkpoint inhibitors is providing substantial clinical benefit, but only to a minority of cancer patients. The current priority is to understand why the majority of patients fail to respond. Besides T-cell dysfunction, T-cell apoptosis was reported in several recent studies as a relevant mechanism of tumoral immune resistance. Several death receptors (Fas, DR3, DR4, DR5, TNFR1) can trigger apoptosis when activated by their respective ligands. In this review, we discuss the immunomodulatory role of the main death receptors and how these are shaping the tumor microenvironment, with a focus on Fas and its ligand. Fas-mediated apoptosis of T cells has long been known as a mechanism allowing the contraction of T-cell responses to prevent immunopathology, a phenomenon known as activation-induced cell death, which is triggered by induction of Fas ligand (FasL) expression on T cells themselves and qualifies as an immune checkpoint mechanism. Recent evidence indicates that other cells in the tumor microenvironment can express FasL and trigger apoptosis of tumor-infiltrating lymphocytes (TIL), including endothelial cells and myeloid-derived suppressor cells. The resulting disappearance of TIL prevents anti-tumor immunity and may in fact contribute to the absence of TIL that is typical of "cold" tumors that fail to respond to immunotherapy. Interfering with the Fas-FasL pathway in the tumor microenvironment has the potential to increase the efficacy of cancer immunotherapy.
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Anticorpos Monoclonais/uso terapêutico , Receptores Coestimuladores e Inibidores de Linfócitos T/metabolismo , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/terapia , Linfócitos T/imunologia , Animais , Apoptose , Receptores Coestimuladores e Inibidores de Linfócitos T/imunologia , Proteína Ligante Fas/metabolismo , Humanos , Neoplasias/imunologia , Transdução de Sinais , Receptor fas/metabolismoAssuntos
Compostos de Benzalcônio/efeitos adversos , Fludrocortisona/análogos & derivados , Hiperaldosteronismo/induzido quimicamente , Hipopotassemia/etiologia , Lidocaína/efeitos adversos , Neomicina/efeitos adversos , Úlceras Orais/tratamento farmacológico , Polimixina B/efeitos adversos , Síncope/etiologia , Administração Tópica , Idoso de 80 Anos ou mais , Compostos de Benzalcônio/administração & dosagem , Combinação de Medicamentos , Eletrocardiografia , Feminino , Fludrocortisona/administração & dosagem , Fludrocortisona/efeitos adversos , Humanos , Hidrocortisona/sangue , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hipopotassemia/diagnóstico , Lidocaína/administração & dosagem , Neomicina/administração & dosagem , Polimixina B/administração & dosagem , Síncope/diagnósticoRESUMO
Direct collection of extracellular fluid (ECF) plays a central role in the monitoring of neurological disorders. Current approaches using microdialysis catheters are however drastically limited in term of temporal resolution. Here we show a functional in vivo validation of a droplet collection system included at the tip of a neural probe. The system comprises an advanced droplet formation mechanism which enables the collection of neurochemicals present in the brain ECF at high-temporal resolution. The probe was implanted in a rat brain and could successfully collect fluid samples organized in a train of droplets. A microfabricated target plate compatible with most of the surface-based detection methods was specifically developed for sample analysis. The time-resolved brain-fluid samples are analyzed using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The results provide a time evolution picture of the cerebral tissues neurochemical composition for selected elements known for their involvement in neurodegenerative diseases.
Assuntos
Cérebro/química , Líquido Extracelular/química , Microdiálise/métodos , Animais , Encéfalo , Química Encefálica , Cálcio/análise , Feminino , Magnésio/análise , Espectrometria de Massas , Mercúrio/análise , Potássio/análise , Ratos , Ratos Sprague-Dawley , Sódio/análise , Fatores de TempoRESUMO
PURPOSE: The objective of this cross-sectional study was to describe and estimate the prevalence of antipsychotics (AP) in a cohort of addicted patients, and to compare the profiles of addictive patients receiving AP or not. METHODS: We included all adult patients seen at the addiction care center of Montpellier University Hospital, between January 1, 2015, and March 31, 2015. Demographic, clinical, and therapeutic data were collected from the patients' medical records. RESULTS: During the study period, 415 patients were included, with a mean age of 38 ± 10 years. They were mostly men (73.3%), French (54.9%), and unemployed (61.8%). Among the study population, 93 patients (patients treated with AP [trAP], 22.4%) were treated by 111 different AP, mainly cyamemazine (29.0% of treated patients), aripiprazole (20.4%), olanzapine (17.2%), and quetiapine (16.1%), mostly in monotherapy (80.6%) and by oral route (93.2% of AP). Psychiatric history was more frequent in trAP than in those without AP (untrAP) (55.9% vs 35.4% respectively; P < 0.001). Professional activity tended to be less frequent in patients with AP (25.3% vs 38.9%, P = 0.08).When compared with untrAP, trAP consumed more amphetamine (10.8% vs 4.4%; P = 0.02) and tended to consume less opiates (7.5% vs 14.9%; P = 0.06); the consumptions of cannabis (43.0% vs 35.7%; P = 0.20) and cocaine (22.6% vs 16.8%; P = 0.20) were not statistically different.Opiate maintenance therapy was reported in 63.7% of trAP and 68.4% of untrAP (P = 0.41): it consisted of methadone (trAP, 60.3% vs untrAP, 56.5%) and buprenorphine (trAP, 39.7% vs untrAP, 43.5%). CONCLUSIONS: The concomitant management of psychiatric and substance use disorders in the same center may explain the high prevalence of trAP in this study. Cannabis and psychostimulants may have been used in these patients as self-medication for mental disease-related symptoms or adverse effects of APs.
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Antipsicóticos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Substâncias/terapia , Adulto , Instituições de Assistência Ambulatorial , Estudos de Coortes , Comorbidade , Estudos Transversais , Diagnóstico Duplo (Psiquiatria) , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Prevalência , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
We report the success of tardive electroconvulsive therapy in a case of loxapine malignant syndrome with catatonia. Loxapine and its metabolites were measured in biological samples by liquid chromatography coupled to tandem mass spectrometry. Genes were studied by sequencing and quantitative polymerase chain reaction (PCR). Plasmatic drug concentrations showed a supratherapeutic concentration of loxapine with a very low 8-hydroxyloxapine/loxapine ratio (range from 0.32 to 0.66, normal value>2 for 100mg) and a very long elimination half-life of loxapine (half-life>140h, normal value from 1 to 4hours). We tried to explain this kinetics by exploring the main pharmacogenes implicated in the metabolism of loxapine. No genetic abnormality for CYP1A2 was observed. The study of associated treatments showed the potential contribution of valproate. Pharmacokinetics and pharmacogenetics investigations revealed a blockade of the CYP1A2 metabolic pathway without genetic abnormalities, probably due to valproate co-medication. Toxicological monitoring of loxapine and its metabolites helped to explain the persistence of symptoms and to adapt the therapeutic management.
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Antipsicóticos/efeitos adversos , Eletroconvulsoterapia/métodos , Loxapina/efeitos adversos , Síndrome Maligna Neuroléptica/terapia , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacocinética , Cromatografia Líquida/métodos , Citocromo P-450 CYP1A2/genética , Feminino , Meia-Vida , Humanos , Loxapina/administração & dosagem , Loxapina/farmacocinética , Pessoa de Meia-Idade , Síndrome Maligna Neuroléptica/etiologia , Farmacogenética , Reação em Cadeia da Polimerase , Espectrometria de Massas em Tandem/métodos , Resultado do TratamentoRESUMO
The understanding of the interactions between the different components of supported metal doped gold catalysts is of crucial importance for selecting and designing efficient gold catalysts for reactions such as CO oxidation. To progress in this direction, a unique supported nano gold catalyst Au/SS was prepared, and three doped samples (Au/SS@M) were elaborated. The samples before and after test were characterized by Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). It is found that the doping metal species prefer to be located on the surface of gold nanoparticles and that a small amount of additional reductive metal leads to more efficient reaction. During the catalytic test, the nano-structure of the metal species transforms depending on its chemical nature. This study allows one to identify and address the contribution of each metal on the CO reaction in regard to oxidative species of gold, silica and dopants. Metal doping leads to different exposure of interface sites between Au and metal oxide, which is one of the key factors for the change of the catalytic activity. The metal oxides help the activation of oxygen by two actions: mobility inside the metal bulk and transfer of water species onto of gold nanoparticles.
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DUF89 family proteins occur widely in both prokaryotes and eukaryotes, but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), with subfamily II being split into stand-alone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metal-dependent phosphatase activity against reactive phosphoesters or their damaged forms, notably sugar phosphates (subfamilies II and III), phosphopantetheine and its S-sulfonate or sulfonate (subfamily II-PanK fusions), and nucleotides (subfamily I). Genetic and comparative genomic data strongly associated DUF89 genes with phosphoester metabolism. The crystal structure of the yeast (Saccharomyces cerevisiae) subfamily III protein YMR027W revealed a novel phosphatase active site with fructose 6-phosphate and Mg(2+) bound near conserved signature residues Asp254 and Asn255 that are critical for activity. These findings indicate that DUF89 proteins are previously unrecognized hydrolases whose characteristic in vivo function is to limit potentially harmful buildups of normal or damaged phosphometabolites.
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Metais/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/metabolismo , Domínio Catalítico , Modelos Moleculares , Monoéster Fosfórico Hidrolases/química , Monoéster Fosfórico Hidrolases/genética , Hidrolases de Triester Fosfórico/química , Hidrolases de Triester Fosfórico/genética , Hidrolases de Triester Fosfórico/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
RATIONALE: Several case-reports suggest that the use of quinolones may increase the risk of psychiatric adverse reactions such as suicidal behaviors. OBJECTIVES: The aim of this study is to investigate whether there is a safety signal for quinolone-related suicidal behaviors in a global adverse drug reactions database. METHODS: All antibiotic-related adverse reactions were extracted from VigiBase, the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database. Disproportionality analyses were performed to investigate the association between reports of suicidal behavior and exposure to quinolones, in comparison with other antibiotics. RESULTS: From December 1970 through January 2015, we identified 992,097 antibiotic-related adverse reactions. Among them, 608 were quinolone-related suicidal behaviors including 97 cases of completed suicides. There was increased reporting of suicidal behavior (adjusted reporting odds ratios [ROR] 2.78, 95 % CI 2.51-3.08) with quinolones as compared to other antibiotics. Candidate mechanisms for quinolone-induced suicidal behaviors include GABAA antagonism, activation of NMDA receptors, decreased serotonin levels, oxidative stress, and altered microRNA expressions. CONCLUSIONS: We found a strong safety signal suggesting an increased risk of suicidal behaviors associated with quinolone use. Plausible psychopharmacological mechanisms could underlie this association. Further investigations are urgent to confirm and better understand these findings.
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Antibacterianos/efeitos adversos , Quinolonas/efeitos adversos , Suicídio/estatística & dados numéricos , Adulto , Bases de Dados Factuais , Feminino , Humanos , Masculino , MicroRNAs , Pessoa de Meia-Idade , Razão de Chances , SegurançaRESUMO
INTRODUCTION: In order to evaluate whether cardiologists follow guidelines, we studied patients who were seen for a preoperative cardiologic consultation prior to surgery. METHODS: This retrospective study took place in two surgical units (Vascular and Orthopaedic) in two different university hospitals in 2013. The patient eligibility criteria were: planned elective surgery, cardiologic consultation prior to anaesthesiology consultation and lack of any unstable cardiac condition. The primary endpoint was determination of appropriate use of preoperative cardiac stress exams (CSE). RESULTS: The study included 238 patients who were seen by 131 different cardiologists. Of 238 patients, 60 had a CSE before surgery, but only 7/60 (12%) were deemed to be necessary. Seven out 15 (47%) patients with an indication for a CSE actually underwent said exam. Sixty-six percent of patients (156/238) had a resting trans-thoracic echocardiography before surgery, while only 27/156 (17%) were considered of appropriate use. Among patients with known coronary arterial disease, 59/73 (81%) received a statin, 60/73 (82%) received an antiplatelet agent, and 38/73 (52%) received a beta-blocker. Among patients with planned arterial surgery, 86/137 (63%) received a statin and 100/137 (73%) patients received an antiplatelet agent. Of the 159 consultation reports that were examined, only 5 (3%) mentioned the Lee score and 117 (74%) were concluded with "no contraindication" or a similar phrase. DISCUSSION: In this study, we found that guidelines were generally not used when cardiologists evaluated patients for non-cardiac surgery. This is evidenced by the number of inappropriate exams performed, the lack of true perioperative risk stratification, and incomplete optimization of long-term treatment regimens.
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Cardiologistas , Fidelidade a Diretrizes/estatística & dados numéricos , Cuidados Pré-Operatórios/normas , Procedimentos Cirúrgicos Operatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Anestesiologistas , Determinação de Ponto Final , Feminino , França , Cardiopatias/complicações , Cardiopatias/terapia , Testes de Função Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Encaminhamento e Consulta , Estudos Retrospectivos , Medição de Risco , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
We propose a novel neural probe which combines microfluidic channels with recording and stimulation electrodes. The developed microfabrication approach enables the concentration of every active element such as electrodes and the sampling inlet in close proximity on the same surface. As a first approach, full functional validation is presented in this work (in vivo testing will be presented in the next study). Electrical characterization by impedance spectroscopy is performed in order to assess the electrode properties. An advanced experimental setup enabling the validation of the fluidic functions of the neural probe is also presented. It allowed the achievement of a high temporal resolution (170 ms) during sampling as a result of the integration of a T-junction droplet generator inside the probe. The droplets reached a volume of 0.84 nL and are separated by a non-aqueous phase (perfluoromethyldecalin, PFD). This probe represents an innovative tool for neuroscientists as it can be implanted in precise brain structures while combining electrical stimulation with sampling at a high temporal resolution.
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Microdiálise , Técnicas Analíticas Microfluídicas , Eletrodos , Microdiálise/instrumentação , Microdiálise/métodos , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodosRESUMO
Pulsed lasers are widely used in capillary electrophoresis (CE) studies to provide laser induced fluorescence (LIF) detection. Unfortunately pulsed lasers do not give linear calibration curves over a wide range of concentrations. While this does not prevent their use in CE/LIF studies, the non-linear behavior must be understood. Using 7-hydroxycoumarin (7-HC) (10-5000 nM), Tamra (10-5000 nM) and tryptophan (1-200 µM) as dyes, we observe that continuous lasers and LEDs result in linear calibration curves, while pulsed lasers give polynomial ones. The effect is seen with both visible light (530 nm) and with UV light (355 nm, 266 nm). In this work we point out the formation of byproducts induced by pulsed laser upon irradiation of 7-HC. Their separation by CE using two Zeta LIF detectors clearly shows that this process is related to the first laser detection. All of these photodegradation products can be identified by an ESI-/MS investigation and correspond to at least two 7HC dimers. By using the photodegradation model proposed by Heywood and Farnsworth (2010) and by taking into account the 7-HC results and the fact that in our system we do not have a constant concentration of fluorophore, it is possible to propose a new photochemical model of fluorescence in LIF detection. The model, like the experiment, shows that it is difficult to obtain linear quantitation curves with pulsed lasers while UV-LEDs used in continuous mode have this advantage. They are a good alternative to UV pulsed lasers. An application involving the separation and linear quantification of oligosaccharides labeled with 2-aminobezoic acid is presented using HILIC and LED (365 nm) induced fluorescence.
Assuntos
Eletroforese Capilar/métodos , Lasers , Luz , Processos Fotoquímicos , Espectrometria de Fluorescência/métodos , Modelos Químicos , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
Glycogen phosphorylase (GP) is a target for the treatment of hyperglycaemia in the context of type 2 diabetes. This enzyme is responsible for the depolymerization of glycogen into glucose thereby affecting the levels of glucose in the blood stream. Twelve new d-glucopyranosylidene-spiro-isoxazolines have been prepared from O-peracylated exo-D-glucals by regio- and stereoselective 1,3-dipolar cycloaddition of nitrile oxides generated in situ by treatment of the corresponding oximes with bleach. This mild and direct procedure appeared to be applicable to a broad range of substrates. The corresponding O-unprotected spiro-isoxazolines were evaluated as glycogen phosphorylase (GP) inhibitors and exhibited IC50 values ranging from 1 to 800 µM. Selected inhibitors were further evaluated in vitro using rat and human hepatocytes and exhibited significant inhibitory properties in the primary cell culture. Interestingly, when tested with human hepatocytes, the tetra-O-acetylated spiro-isoxazoline bearing a 2-naphthyl residue showed a much lower IC50 value (2.5 µM), compared to that of the O-unprotected analog (19.95 µM). The most promising compounds were investigated in Zucker fa/fa rat model in acute and sub-chronic assays and decreased hepatic glucose production, which is known to be elevated in type 2 diabetes. This indicates that glucose-based spiro-isoxazolines can be considered as anti-hyperglycemic agents in the context of type 2 diabetes.