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1.
Acta Odontol Scand ; 78(5): 321-326, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31909679

RESUMO

Objective: The objective of this study is to evaluate the wall adaptation and apical microleakage values following the application of various irrigation protocols in primary teeth.Material and methods: For the two parts of the study, extracted upper incisor primary teeth were randomly included to the 1% sodium hypochlorite (NaOCl), 10% ethylenediaminetetraacetic acid (EDTA)+1% NaOCl, 6% citric acid (CA)+1% NaOCl and 0.9% physiological saline (PS) groups. Canal wall adaptation and apical microleakage were assessed by scanning electron microscopy (SEM) and stereomicroscope, respectively.Results: 6% CA + 1% NaOCl group was found to be the most successful irrigation protocol in providing strong canal wall adaptation and less apical microleakage, followed by 10% EDTA +1% NaOCl. 6% CA +1% NaOCl was significantly superior regarding apical microleakage (p < .05).Conclusions: Due to the ability to provide appropriate changes in the root canal walls to make a well-adapted and leak-proof canal filling, 6% CA + 1% NaOCl can be recommended as an irrigation protocol in primary teeth.


Assuntos
Infiltração Dentária , Ácido Edético/administração & dosagem , Microscopia Eletrônica de Varredura/métodos , Irrigantes do Canal Radicular/farmacologia , Preparo de Canal Radicular , Camada de Esfregaço , Hipoclorito de Sódio/administração & dosagem , Dente Decíduo/diagnóstico por imagem , Cavidade Pulpar/efeitos dos fármacos , Cavidade Pulpar/ultraestrutura , Humanos , Irrigantes do Canal Radicular/administração & dosagem , Fatores de Tempo
2.
Braz J Otorhinolaryngol ; 86(2): 222-227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30797727

RESUMO

INTRODUCTION: The use of electron microscopy in the study of the inner ear has allowed us to observe minute details of the hair cells, especially in ototoxicity studies; however, the preparation of this material is a difficult and delicate task. In an attempt to simplify the handling of these materials, two agents, toluidine blue and ethylenediamine tetra-acetic acid were tested, in addition to the elimination of osmium tetroxide during the preparation of albino guinea pig cochleae. We also tested the applicability of these methodologies in an ototoxicity protocol. OBJECTIVE: To verify the quality of the images obtained with and without the use of ethylenediamine tetra-acetic acid, toluidine blue and osmium tetroxide in the preparation of cochleae of albino guinea pigs for the scanning electron microscopy. METHODS: Three groups of cochleae were used. In Group 1, 10 cochleae were prepared with the usual methodology, dissecting the optical capsule without decalcification and using osmium tetroxide as a post-fixative agent. In Group 2, we prepared 10 cochleae decalcified with ethylenediamine tetra-acetic acid, injecting toluidine blue in the endolymphatic space to facilitate the identification of the organ of Corti. In Group 3, we used 4 cochleae of guinea pigs that received 3 doses of cisplatin (7.5mg/kg, D1-D5-D6), two prepared according to the methodology used in Group 1 and two with that used in Group 2. Scanning electron microscopy images were obtained from the organ of Corti region of the basal turn of each cochlea. RESULTS: The organ of Corti was more easily identified with the use of toluidine blue. The dissection of the cochlea was more accurate in the decalcified cochleae. The quality of the images and the preservation of the organ of Corti obtained with the two methodologies were similar. CONCLUSION: The proposed modifications resulted in images of similar quality as those observed using the traditional methodology.


Assuntos
Cisplatino/toxicidade , Cóclea/efeitos dos fármacos , Cóclea/ultraestrutura , Animais , Ácido Edético/administração & dosagem , Feminino , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/ultraestrutura , Microscopia Eletrônica de Varredura , Órgão Espiral/efeitos dos fármacos , Órgão Espiral/ultraestrutura , Tetróxido de Ósmio/administração & dosagem , Cloreto de Tolônio/administração & dosagem
3.
Nucl Med Commun ; 41(1): 11-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31764593

RESUMO

OBJECTIVE: Drug quality in medical devices is not evaluated during the marketing authorization of radiopharmaceuticals. Therefore, the extemporaneous change of packaging made for preparation of patient unit doses in a syringe is the responsibility of radiopharmacists. The present study aimed to determine the impact of packaging and storage in a polypropylene syringe on the quality of hydrophilic drugs [Tc]Tc-EDDA/HYNIC-TOC (Tektrotyd) and [Ga]Ga-DOTA-TOC (Somakit-TOC). METHODS: Appearance, pH, radiochemical purity, sterility, and endotoxin tests were performed according the current European Pharmacopoeia. Subvisible and visible particles tests of the European Pharmacopoeia were adapted due to limited preparation volume (<25 ml). Sorption tests were performed according to the literature. RESULTS: After 2 h storage in a syringe, drug sorption of Tektrotyd and Somakit-TOC was of less than 2.5% and similar to other Tc-radiopharmaceuticals (range: from 1.1 ± 0.5% to 4.2 ± 0.6%). For Tektrotyd, this sorption phenomenon was positively influenced by the drug concentration and a short contact with the medical device (4.8 ± 0.2% up to 5 s vs. 2.3 ± 0.2%, n = 4; P < 0.001). For Somakit-TOC, the duration of contact with syringe had no impact (1.6 ± 0.2% up to 5 s vs. 1.7 ± 0.6%; P = 1.000). No drug radiolysis or alteration of microbiological aspects were observed. No impurity from a 3-piece-syringe was observed according to drug aspect, pH, and subvisible and visible particles, which remained within specification of the current European Pharmacopoeia. CONCLUSION: This study found that drug sorption to packaging was compatible with clinical use and absence of drug alteration of Tektrotyd and Somakit-TOC after repackaging in a syringe in polypropylene and prolonged storage during 2 h.


Assuntos
Administração Intravenosa/instrumentação , Ácido Edético/análogos & derivados , Octreotida/análogos & derivados , Compostos Organometálicos/administração & dosagem , Compostos de Organotecnécio/administração & dosagem , Compostos de Organotecnécio/química , Contaminação de Medicamentos , Ácido Edético/administração & dosagem , Ácido Edético/química , Ácidos Nicotínicos/química , Octreotida/administração & dosagem , Controle de Qualidade , Seringas/microbiologia
4.
J Vet Intern Med ; 33(5): 2124-2132, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386229

RESUMO

BACKGROUND: Subcutaneous ureteral bypass (SUB) device placement is an increasingly popular treatment option for decompression of ureteral obstruction in cats. Mineralization occlusion of the device occurs in a minority of cases but is the most common complication. OBJECTIVE: To evaluate a 2% tetrasodium ethylenediaminetetraacetic acid (tEDTA) solution for treatment of mineralization occlusion in cats with SUBs. ANIMALS: Six client-owned cats (8 obstructed devices). METHODS: Case series. Each cat was found to have device occlusion based on a combination of ultrasound examination, SUB irrigation, and failure to identify another cause of device obstruction. Each SUB was drained, irrigated using sterile saline, and infused with 1-2 mL of 2% tEDTA solution. Success was defined as normalization of flow during subsequent ultrasound visualization while irrigating. The volume and frequency of tEDTA instillations, time to achieve device patency, follow-up biochemical and ultrasound findings, and future reobstruction events were recorded. RESULTS: Resolution of mineralization was documented in all 8 SUBs. Reobstruction events occurred in 2 cats, all of which resolved after additional tEDTA infusions, but 1 cat ultimately required device exchange at 356 days from the first tEDTA infusion. In 1 cat, a single infusion was prematurely discontinued because of persistent pelvic dilatation after 1.25 mL of tEDTA had been instilled. No complications were observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Tetrasodium EDTA infusions can be safely considered as a treatment option for mineralized SUB devices in cats. This solution was easily infused, well tolerated, and avoided the need for SUB device exchange in the majority of cats in which it was used.


Assuntos
Doenças do Gato/terapia , Ácido Edético/administração & dosagem , Stents/veterinária , Procedimentos Cirúrgicos Urológicos/veterinária , Animais , Quelantes de Cálcio/administração & dosagem , Doenças do Gato/diagnóstico por imagem , Gatos , Feminino , Masculino , Ultrassonografia/veterinária , Obstrução Ureteral/terapia , Obstrução Ureteral/veterinária , Procedimentos Cirúrgicos Urológicos/instrumentação
5.
World J Gastroenterol ; 25(26): 3370-3379, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341362

RESUMO

BACKGROUND: The treatment of difficult common bile duct stones (CBDS) remains a big challenge around the world. Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography. Fully covered self-expanding metal stent (FCSEMS) has gained increasing attention in the management of difficult CBDS. AIM: To manufacture a drug-eluting FCSEMS, which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS. METHODS: Customized covered nitinol stents were adopted. Sodium cholate (SC) and disodium ethylene diamine tetraacetic acid (EDTA disodium, EDTA for short) were used as stone-dissolving agents. Three different types of drug-eluting stents were manufactured by dip coating (Stent I), coaxial electrospinning (Stent II), and dip coating combined with electrospinning (Stent III), respectively. The drug-release behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method. And the selected stone-dissolving stents were further put into porcine CBD to evaluate their biosecurity. RESULTS: Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d. In still buffer, the final stone mass-loss rate of each group was 5.19% ± 0.69% for naked FCSEMS, 20.37% ± 2.13% for Stent I, 24.57% ± 1.45% for Stent II, and 33.72% ± 0.67% for Stent III. In flowing bile, the final stone mass-loss rate of each group was 5.87% ± 0.25% for naked FCSEMS, 6.36% ± 0.48% for Stent I, 6.38% ± 0.37% for Stent II, and 8.15% ± 0.27% for Stent III. Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile, which was significantly higher than those of other groups (P < 0.05). In vivo, Stent III made no difference from naked FCSEMS in serological analysis (P > 0.05) and histopathological examination (P > 0.05). CONCLUSION: The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro. When conventional endoscopic techniques fail to remove difficult CBDS, SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative.


Assuntos
Stents Farmacológicos , Ácido Edético/administração & dosagem , Cálculos Biliares/terapia , Stents Metálicos Autoexpansíveis , Colato de Sódio/administração & dosagem , Ligas , Animais , Ducto Colédoco , Modelos Animais de Doenças , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ácido Edético/farmacocinética , Humanos , Masculino , Nanofibras , Poliésteres/química , Colato de Sódio/farmacocinética , Suínos , Porco Miniatura , Resultado do Tratamento
6.
Saudi J Kidney Dis Transpl ; 30(3): 587-596, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249222

RESUMO

Estimation of glomerular filtration rate (GFR) in renal transplant patients is often assessed by application of creatinine-based equations. The aim was to correlate the estimated GFR (eGFR) using creatinine-based equations [Cockroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Nankivell] with gold standard 51Cr-EDTA in kidney transplant patients in the Asian population. This is a single-center, cross-sectional study involving adult renal transplant patients. Background demographic data, medications, office blood pressure, and baseline investigations were taken. Correlations between measured GFR and eGFR were analyzed and Pearson's correlation coefficients, bias, and accuracy were assessed. Thirty-seven renal transplant patients with a mean age of 46 ± 13 years were recruited. Majority were Chinese (68%), Malay (24%), and Indian (8%). The median duration of the transplant was 84 (interquartile range 60,132) months. The mean measured GFR was 71 ± 21 mL/min/1.73 m2. Cockroft-Gault and CKD-EPI has the best correlation with 51Cr-EDTA with Pearson correlation coefficients of 0.733 (P <0.001) and 0.711 (P < 0.001), respectively. All formulae showed >80% accuracy with eGFR lies between 30% of the measured value. CKD-EPI and MDRD had the greatest accuracy with 89.2% each. Clinician may use any of these three serum creatinine-based equations to estimate GFR in kidney transplant recipients.


Assuntos
Taxa de Filtração Glomerular , Nefropatias/diagnóstico , Transplante de Rim , Rim/fisiopatologia , Modelos Biológicos , Adulto , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Radioisótopos de Cromo/administração & dosagem , Creatinina/sangue , Estudos Transversais , Ácido Edético/administração & dosagem , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/cirurgia , Nefropatias/etnologia , Nefropatias/fisiopatologia , Transplante de Rim/efeitos adversos , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos/administração & dosagem , Reprodutibilidade dos Testes , Resultado do Tratamento
7.
Int J Mol Sci ; 20(12)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234286

RESUMO

Silk fiber has become a research focus because of its comprehensive mechanical properties. Metal ions can influence the conformational transition of silk fibroin. Current research is mainly focused on the role of a single ion, rather than the whole metal ion environment. Here, we report the effects of the overall metal ion environment on the secondary structure and mechanical properties of silk fibers after direct injection and feeding of silkworms with EDTA. The metal composition of the hemolymph, silk gland, and silk fiber changed significantly post EDTA treatment. Synchrotron FTIR analysis indicated that the secondary structure of silk fiber after EDTA treatment changed dramatically; particularly, the ß-sheets decreased and the ß-turns increased. Post EDTA treatment, the silk fiber had significantly decreased strength, Young's modulus, and toughness as compared with the control groups, while the strain exhibited no obvious change. These changes can be attributed to the change in the metal ion environment in the silk fibroin and sericin in the silk gland. Our investigation provides a new theoretical basis for the natural silk spinning process, and our findings could help develop a method to modify the mechanical properties of silk fiber using metal ions.


Assuntos
Bombyx/metabolismo , Ácido Edético/metabolismo , Metais/metabolismo , Seda/química , Ração Animal/análise , Animais , Fenômenos Biomecânicos , Bombyx/química , Ácido Edético/administração & dosagem , Módulo de Elasticidade , Metais/análise , Conformação Proteica em Folha beta , Seda/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico
8.
Photobiomodul Photomed Laser Surg ; 37(4): 248-253, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31050955

RESUMO

Objective: The aim of this randomized clinical study was to evaluate the effect of laser-activated irrigation using a photon-induced photoacoustic streaming (PIPS) technique on postoperative pain following completion of root canal obturation. Methods: Fifty-six patients were enrolled in this randomized clinical trial. Fifty-six healthy premolars or molars with asymptomatic irreversible pulpitis, symptomatic irreversible pulpitis, or symptomatic pulpal necrosis, with or without apical periodontitis, were mechanically prepared for endodontic treatment and divided into two groups. Patients were randomly allocated to treatment groups. In the positive control group G1, the final irrigation with 2 cc of 5.25% sodium hypochlorite (NaOCl) was achieved using a 27G needle, introduced into the canal to a distance of 5 mm from the predetermined working length. In the experimental group G2, the root canals were irrigated with 17% ethyldiamine tetric acid (EDTA) and 5.25% NaOCl following the PIPS protocol, using an Er:YAG 2940 nm laser (LightWalker ATS®; Fotona, Slovenia) with a 600 µm diameter tip and operating parameters of 20 mJ per pulse, 15 Hz frequency, 0.3 W average power, and a 50-µs pulse duration. Postoperatively, the patients were advised to take a minor analgesic (ibuprofen 400 mg) in the event of pain perception. Postoperative pain levels were assessed after 24, 48, and 72 h and 7 days through the use of a Visual Analogue Scale questionnaire, completed by each patient. Data were analyzed using Kolmogorov-Smirnov, Fisher Exact, Chi square, Mann-Whitney test, and Friedman's test. The level of significance was set at α = 0.05. Results: There was no significant difference between the laser-irradiated group and the control group (p < 0.5). Laser activation of irrigating solutions did not increase postoperative pain. Conclusions: The outcome of this investigation indicated that PIPS was as effective as conventional irrigation in relation to postoperative pain, making this activation technique interesting to use for supplementary root canal disinfection.


Assuntos
Lasers de Estado Sólido/uso terapêutico , Pulpite/terapia , Qualidade de Vida , Tratamento do Canal Radicular/métodos , Irrigação Terapêutica/métodos , Adulto , Idoso , Ácido Edético/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória , Irrigantes do Canal Radicular/administração & dosagem , Preparo de Canal Radicular/métodos , Hipoclorito de Sódio/administração & dosagem
9.
An Acad Bras Cienc ; 91(1): e20171042, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30994751

RESUMO

The aims of this study were to investigate whether treatments with zinc edetate (Zn) and diphenyl diselenide ((PhSe)2) enhance performance, immune responses, protein metabolism, and oxidant/antioxidant status in calf serum and muscle. Animals were divided into four groups (n=6 each): control (without supplementation), and groups supplemented on days 50 and 70 of life with (PhSe)2, Zn, and a combination of (PhSe)2 and Zn. Animals treated with (PhSe)2 gained more weight by experimental day 220 than did the control group, but there was no difference by the end of the experiment (day 300). The absolute number of leukocytes and lymphocytes increased in groups Zn and (PhSe)2+Zn on day 20 of experiment, but decreased on day 40 in groups (PhSe)2, and (PhSe)2+Zn. The number of monocytes decreased in all groups compared with control. One of the principal findings was that (PhSe)2+Zn together had beneficial effects on protein metabolism, represented by increases total protein and globulin levels, compared with the control group. The combination of (PhSe)2 and Zn led to low levels of TBARS and ROS in serum and muscle, and stimulated antioxidant enzyme activities. Thus, supplementation with (PhSe)2+Zn may be a compelling approach to augmenting the calf antioxidant system during weaning.


Assuntos
Derivados de Benzeno/administração & dosagem , Bovinos/fisiologia , Ácido Edético/administração & dosagem , Compostos Organosselênicos/administração & dosagem , Desmame , Zinco/administração & dosagem , Fatores Etários , Animais , Antioxidantes/análise , Peso Corporal , Sistema Imunitário/efeitos dos fármacos , Injeções Subcutâneas/veterinária , Metabolismo dos Lipídeos/efeitos dos fármacos , Malondialdeído/sangue , Músculos/metabolismo , Proteínas/metabolismo , Reprodutibilidade dos Testes , Selênio/administração & dosagem , Fatores de Tempo
10.
Microsc Res Tech ; 82(6): 923-930, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30786090

RESUMO

To compare the smear layer removal ability and mineral content of root canal dentine after initial irrigation with NaOCl and final irrigation with MTAD, QMix, and 17% EDTA. Forty extracted human maxillary incisors before root canal preparation and irrigation with NaOCl were randomly divided into four groups (n = 10) according to the type of final irrigants used: MTAD, QMix, 17% EDTA, and control (sterile distilled water). Scanning electron microscopy (SEM) was used to assess the presence of smear layer. SEM energy-dispersive X-ray spectroscopy was used to quantify dentin mineral composition in MTAD, QMix, 17% EDTA group, and in no-treatment samples (no-treatment group; n = 10). Among the various chelating agents, there were no significant differences in the smear layer removal in the middle and coronal thirds (p > .05). In the apical third, QMix removed significantly more smear layer than 17% EDTA (p < .05), but similarly to MTAD (p > .05). Final irrigation with MTAD resulted in a significant increase in the carbon (C) value compared to EDTA (p < .001). There was no significant difference in the mineral composition between the MTAD and the QMix group, although the values of the mineral elements were significantly altered in the MTAD group. QMix had smear layer removal capability similar to MTAD but better than EDTA in the apical third. MTAD yielded the most pronounced effect on mineral component of root dentin; however, differences were significant only for C level compared to 17% EDTA.


Assuntos
Biguanidas/administração & dosagem , Ácido Cítrico/administração & dosagem , Cavidade Pulpar/efeitos dos fármacos , Dentina/química , Doxiciclina/administração & dosagem , Ácido Edético/administração & dosagem , Minerais/análise , Polímeros/administração & dosagem , Polissorbatos/administração & dosagem , Camada de Esfregaço , Humanos , Microscopia Eletrônica de Varredura , Hipoclorito de Sódio/administração & dosagem , Espectrometria por Raios X , Resultado do Tratamento
11.
PLoS One ; 14(2): e0211973, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730969

RESUMO

BACKGROUND: Intestinal permeability can be assessed by monitoring renal excretion of orally administered radioactively 51Cr-labeled ethylenediaminetetraacetic acid (51Cr-EDTA). Although considered safe, patient participation in using radio-labeled tracers is low. Here, we used orally administered 52Cr-EDTA as non-radioactive alternative to assess intestinal permeability in CD and analyzed the association with disease activity, disease location and gut microbial dysbiosis. MATERIALS AND METHODS: 60 CD patients with low (n = 25) and increased (n = 35) fecal calprotectin levels (cut-off: 100 µg/g feces) ingested 20 mL 52Cr-EDTA (20 mmol/L) solution whereafter 24-h urine was collected. Urinary 52Cr-EDTA concentrations were quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Fecal Enterobacteriaceae and Faecalibacterium prausnitzii were quantified using FISH. Correlations between urinary 52Cr-EDTA excretion and other parameters were established using nonparametric Spearman's correlation coefficients (ρ). RESULTS: CD patients with increased fecal calprotectin levels (> 100 µg/g) demonstrated an elevated urinary 52Cr-EDTA/creatinine ratio (772 vs. 636 µmol/mol, P = 0.132). Patients with primarily colonic disease showed the highest 52Cr-EDTA excretion. Importantly, a positive correlation was observed for the urinary 52Cr-EDTA/creatinine ratio and fecal calprotectin levels (ρ = 0.325, P < 0.05). Finally, urinary 52Cr-EDTA/creatinine ratio negatively correlated with the relative abundance of Faecalibacterium prausnitzii (ρ = -0.221, P = 0.092), while positively correlating with Enterobacteriaceae (ρ = 0.202, P = 0.126). CONCLUSIONS: Orally administered and renal excreted 52Cr-EDTA may be used to assess intestinal permeability in CD and correlates with fecal calprotectin levels and bacterial species relevant to CD. This test may improve non-invasive detection of disease exacerbations and help monitor disease activity.


Assuntos
Doença de Crohn/urina , Disbiose/diagnóstico , Ácido Edético/administração & dosagem , Enterobacteriaceae/isolamento & purificação , Faecalibacterium prausnitzii/isolamento & purificação , Urina/química , Administração Oral , Adulto , Doença de Crohn/complicações , Doença de Crohn/metabolismo , Disbiose/metabolismo , Ácido Edético/química , Ácido Edético/farmacocinética , Enterobacteriaceae/genética , Faecalibacterium prausnitzii/genética , Fezes/química , Feminino , Humanos , Mucosa Intestinal/química , Complexo Antígeno L1 Leucocitário/metabolismo , Espectrometria de Massas , Pessoa de Meia-Idade , Participação do Paciente , Permeabilidade , Adulto Jovem
12.
Trials ; 20(1): 27, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621764

RESUMO

BACKGROUND: Paracetamol (acetaminophen) overdose (POD) is the commonest cause of acute liver failure in Europe and North America. Current treatment involves the use of the antidote N-acetylcysteine (NAC) in patients deemed at risk of liver damage. This regimen was introduced in the 1970s and has remained largely unchanged even though the initial NAC infusion is frequently associated with adverse reactions, in particular nausea, vomiting, and anaphylactoid reactions. NAC has reduced efficacy for preventing liver injury in those patients who present later after overdose. We designed a randomised study investigating the safety and tolerability of a superoxide dismutase (SOD) mimetic, calmangafodipir (PP100-01), co-treatment with a 12-h NAC regimen compared with NAC treatment alone in patients with POD. METHODS/DESIGN: We have designed an open-label, randomised, exploratory, rising dose design, NAC-controlled, phase 1 safety and tolerability study in patients treated with NAC for POD. A total of 24 patients will be assigned into one of three dosing cohorts of eight patients (n = 6 for PP100-01 and NAC; n = 2 for NAC alone). The doses of PP100-01 are 2, 5, and 10 µmol/kg. The primary outcome is the safety and tolerability of PP100-01 when co-administered with a 12-h NAC regimen compared with NAC treatment alone. Furthermore, the study will explore if PP100-01 has potential efficacy for the treatment of paracetamol-induced liver injury by measurement of conventional clinical and exploratory biomarkers. DISCUSSION: The aim of the study is to test the safety and tolerability of a SOD mimetic, PP100-01, in combination with a 12-h NAC regimen in patients presenting within 24 h of POD. This study will provide valuable data regarding the incidence of adverse events caused by the 12-h NAC plus PP100-01 regimen and may provide evidence of PP100-01 efficacy in the treatment of paracetamol-induced liver injury. TRIAL REGISTRATION: EudraCT, 2017-000246-21; ClinicalTrials.gov, NCT03177395 . Registered on 6 June 2017.


Assuntos
Acetaminofen/envenenamento , Acetilcisteína/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ácido Edético/análogos & derivados , Fosfato de Piridoxal/análogos & derivados , Acetilcisteína/administração & dosagem , Comitês de Monitoramento de Dados de Ensaios Clínicos , Ensaios Clínicos Fase I como Assunto , Interpretação Estatística de Dados , Overdose de Drogas , Quimioterapia Combinada , Ácido Edético/administração & dosagem , Ácido Edético/efeitos adversos , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Fosfato de Piridoxal/administração & dosagem , Fosfato de Piridoxal/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
13.
Photodiagnosis Photodyn Ther ; 25: 300-308, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30633998

RESUMO

BACKGROUND: Antibiotic resistance has emerged as one of the most important determinants in diabetic foot infections outcomes. Antimicrobial Photodynamic therapy(A-PDT) or Photodynamic antimicrobial chemotherapy (PACT) has been proposed as an alternative approach for inactivating bacteria, especially resistant bacterial biofilms. This research investigated the synergistic effects of PACT mediated by the photosensitizer indocyanine green (ICG) and ethylenediamine tetraacetate (EDTA) combined with antibiotics against common pathogens of diabetic foot ulcer infection, including Staphylococcus aureus and Pseudomonas aeruginosa, in vitro. METHODS: Planktonic bacteria and biofilms of S. aureus and P. aeruginosa were incubated with ICG and EDTA, and then exposed to laser treatment. Quantitative viable counting estimates the phototoxic effects on S. aureus and P. aeruginosa. The susceptibility of methicillin-resistant S. aureus (MRSA) and multidrug-resistant P. aeruginosa (MRPA) to PACT treatment was detected by disk diffusion and micro-broth dilution methods. Confocal microscopy was used to detect the morphology of biofilms treated with PACT and antibiotics. The resazurin assay was used to quantify the metabolic activity of bacteria in biofilms. RESULTS: PACT mediated by ICG and EDTA led to a more pronounced antibacterial effect in S. aureus and P. aeruginosa compared with ICG alone-mediated PACT. P. aeruginosa was more sensitive to ICG and EDTA-mediated PACT than S. aureus. After PACT treatment, the susceptibility of MRSA and MRPA to antibiotics increased. Furthermore, PACT combined with antibiotic treatment significantly contributed to killing bacteria in the biofilm and disrupting biofilm structure. CONCLUSIONS: ICG and EDTA-mediated PACT combined with antibiotics synergistically enhanced the effects of sterilization and biofilm destruction.


Assuntos
Biofilmes/efeitos dos fármacos , Ácido Edético/farmacologia , Verde de Indocianina/farmacologia , Fotoquimioterapia/métodos , Sobrevivência Celular , Pé Diabético/tratamento farmacológico , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/efeitos dos fármacos , Ácido Edético/administração & dosagem , Verde de Indocianina/administração & dosagem , Lasers Semicondutores , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
14.
Br J Radiol ; 92(1095): 20180667, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30563350

RESUMO

METHODS:: We analysed results of 142 males with staging PSMA prior to radical prostatectomy (RP). Data collected included PSMA PET/CT, bone scan (30/142), mpMRI (112/142), and pathological T stage (pT) stage, Gleason score, surgical margins and lymph node status at RP. Prostate-specific antigen (PSA) was documented at staging scan, and following surgery (median 45 days (interquartile range 38-59). A PSA of < 0.03 ng ml-1 was classified as surgical response (SR). Logistic regression was performed for association of pre-operative clinical variables and SR. RESULTS:: 97.9% (139/142) of males had positive intraprostatic findings on PSMA. 14.1 % (20/142) of males had further sites of extra prostatic disease identified on PSMA PET. In males with disease confined to the prostate, 82.9 % (92/111) achieved an SR, compared to 28.6 % (4/14) in males with extraprostatic disease identified (lymph node positive and distant metastatic disease) (p < 0.001). On binary logistic regression PSMA had a superior predictive value for SR than Gleason score, PSA (at time of imaging) or pT stage. MRI was less sensitive and more specific for SVI, and less sensitive for nodal involvement. CONCLUSION:: Extraprostatic disease identified on staging pre-operative PSMA PET is independently predictive of a poor surgical response to RP, and may indicate a need for a multimodality approach to treatment. ADVANCES IN KNOWLEDGE:: This is one of the first studies to correlate the PSMA PET's staging capacity to prostate cancer patient's outcomes to radical prostatectomy and indicates it's potential in predicting which patients will benefit from radical prostatectomy.


Assuntos
Ácido Edético/análogos & derivados , Recidiva Local de Neoplasia/diagnóstico por imagem , Oligopeptídeos/administração & dosagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Ácido Edético/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Valor Preditivo dos Testes , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
15.
Int J Pharm ; 556: 330-337, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30553004

RESUMO

Poor bioavailability and low residence time limit the efficiency of conventional biguanide-based eye drops against Acanthamoeba keratitis. The aim of this work was to formulate an original anti-amoebic thermoreversible ocular gel combining biguanide and metalloproteases inhibitor - chelating agent. Chlorhexidine digluconate (CHX)-ethylenediaminetetraacetic acid disodium salt (Na2EDTA) were compounded in poloxamer 407 saline solution. 0.02% CHX - 0.1% Na2EDTA loaded thermosensitive ocular gel exhibited appropriate pH (5.73 ±â€¯0.06), iso-osmolality (314 ±â€¯5 mOsm/kg), viscosity (ranged between 15 and 25 mPa.s) and thermal gelation (26.5 °C and 33 °C) properties. Bioadhesion of gel was successfully tested onto isolated bovine eyes as well as the assessment of CHX penetration into the cornea. Intracorneal CHX concentration was found greater than trophozoite minimum amoebicidal concentration and minimal cysticidal concentration after 15-min and 2-h ocular exposure, respectively, while any CHX permeation through the cornea was detected (<51 ng/cm2/h). Improvement of CHX ocular bioavailability was attributed to probable solubilization of tear film lipid layer by poloxamer. In vitro efficiency of CHX-Na2EDTA ocular gel was confirmed from the drastic reduction of trophozoite and cyst survival (to 25% and 2%, respectively), confirming the potential of the multicomponent pharmaceutical material strategy for the treatment of Acanthamoeba keratitis.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Amebicidas/administração & dosagem , Clorexidina/análogos & derivados , Ácido Edético/administração & dosagem , Administração Oftálmica , Amebicidas/farmacocinética , Amebicidas/farmacologia , Animais , Disponibilidade Biológica , Bovinos , Quelantes/administração & dosagem , Quelantes/farmacocinética , Quelantes/farmacologia , Química Farmacêutica/métodos , Clorexidina/administração & dosagem , Clorexidina/farmacocinética , Clorexidina/farmacologia , Córnea/metabolismo , Combinação de Medicamentos , Ácido Edético/farmacocinética , Ácido Edético/farmacologia , Géis , Concentração Osmolar , Temperatura , Trofozoítos/efeitos dos fármacos , Viscosidade
16.
Pest Manag Sci ; 75(2): 537-548, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30094917

RESUMO

BACKGROUND: The Neotropical stink bug Euschistus heros is a major pest in soybean fields. Development of highly species-specific pesticides based on RNA interference (RNAi) could provide a new sustainable and environmentally friendly control strategy. RESULTS: Here, the potential of RNAi as a pest control tool against E. heros was assessed. First, target gene selection using a microinjection approach was performed. Seven of the 15 candidate genes tested exhibited > 95% mortality after hemolymph injection of 27.5 ng dsRNA. Subsequently, dsRNA was administered orally using different formulations: naked dsRNA, liposome-encapsulated-dsRNA and dsRNA formulated with EDTA. Liposome-encapsulated dsRNA targeting vATPase A and muscle actin led to significant mortality after 14 days (45% and 42%, respectively), whereas EDTA-formulated dsRNA did so for only one of the target genes. Ex vivo analysis of the dsRNA stability in collected saliva indicated a strong dsRNA-degrading capacity by E. heros saliva, which could explain the need for dsRNA formulations. CONCLUSION: The results demonstrate that continuous ingestion of dsRNA with EDTA or liposome-encapsulated dsRNA can prevent dsRNA from being degraded enzymatically and suggest great potential for using these formulations in dsRNA delivery to use RNAi as a functional genomics tool or for pest management of stink bugs. © 2018 Society of Chemical Industry.


Assuntos
Ácido Edético/administração & dosagem , Heterópteros/fisiologia , Controle de Insetos/métodos , Lipossomos/administração & dosagem , Ninfa/fisiologia , Interferência de RNA , RNA de Cadeia Dupla/química , Animais , Heterópteros/genética , Heterópteros/crescimento & desenvolvimento , Longevidade , Ninfa/genética , Ninfa/crescimento & desenvolvimento , Saliva/química
17.
Wien Med Wochenschr ; 169(1-2): 3-11, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28577076

RESUMO

Ever since the introduction of 68Ga-prostate-specific membrane antigen 11 positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) a few years ago, it has rapidly achieved great success in the field of prostate cancer imaging. A large number of studies have been published to date, indicating a high potential of 68Ga-PSMA-11 PET/CT in the work-up of prostate cancer patients, including primary diagnosis, staging and biochemical recurrence. The aim of this review is to present the most important data on this novel, highly promising imaging technique, and to formulate recommendations for possible applications of 68Ga-PSMA-11 PET/CT in clinical routine.


Assuntos
Medicina Nuclear , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata , Ácido Edético/administração & dosagem , Ácido Edético/análogos & derivados , Humanos , Masculino , Gradação de Tumores , Oligopeptídeos/administração & dosagem , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos
18.
Eur Urol ; 75(4): 548-551, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30578119

RESUMO

In prostate cancer, disease progression after primary treatment and subsequent androgen deprivation therapy is common. Intensification of systemic treatment is the standard of care. Recently, 68Ga prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging was introduced to identify oligometastatic prostate cancer patients. In this retrospective, exploratory study, we report on the efficacy of PSMA-PET-guided local ablative radiotherapy (aRT) in 15 oligometastatic castration-resistant prostate cancer (CRPC) patients, selected from our prospective institutional database and treated between 2013 and 2016. After multidisciplinary discussion, aRT was delivered with two different schedules. Androgen deprivation therapy remained unchanged. Prostate-specific antigen (PSA) response and time to PSA progression were analysed. For comparison, individual time to PSA progression without aRT was estimated by individual PSA doubling time (PSADT). PSA response was observed in 11 patients (73%). Mean time to PSA progression or last follow-up was 17.9mo, as opposed to 2.9mo estimated from the PSADT without aRT (p<0.001). A relevant subset of CRPC patients had a PSA response with aRT to PET-positive lead metastases. A prospective trial is in preparation. PATIENT SUMMARY: In selected patients with prostate-specific antigen (PSA) increase during androgen deprivation, metastases were detected with prostate-specific membrane antigen positron emission tomography imaging. Fifteen patients with three or fewer metastases were treated with high-dose radiotherapy. Subsequently, PSA values dropped in 11 patients and in six patients no PSA progression was detected for >12mo.


Assuntos
Neoplasias de Próstata Resistentes à Castração/radioterapia , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Bases de Dados Factuais , Progressão da Doença , Fracionamento da Dose de Radiação , Ácido Edético/administração & dosagem , Ácido Edético/análogos & derivados , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Oligopeptídeos/administração & dosagem , Tomografia por Emissão de Pósitrons , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo
19.
Sci Rep ; 8(1): 16171, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30385885

RESUMO

Radio Guided Surgery is a technique helping the surgeon in the resection of tumors: a radiolabeled tracer is administered to the patient before surgery and then the surgeon evaluates the completeness of the resection with a handheld detector sensitive to emitted radiation. Established methods rely on γ emitting tracers coupled with γ detecting probes. The efficacy of this technique is however hindered by the high penetration of γ radiation, limiting its applicability to low background conditions. To overtake such limitations, a novel approach to RGS has been proposed, relying on ß- emitting isotopes together with a dedicated ß probe. This technique has been proved to be effective in first ex-vivo trials. We discuss in this paper the possibility to extend its application cases to 68Ga, a ß+ emitting isotope widely used today in nuclear medicine. To this aim, a retrospective study on 45 prostatic cancer patients was performed, analysing their 68Ga-PSMA PET images to asses if the molecule uptake is enough to apply this technique. Despite the expected variability both in terms of SUV (median 4.1, IQR 3.0-6.1) and TNR (median 9.4, IQR 5.2-14.6), the majority of cases have been found to be compatible with ß-RGS with reasonable injected activity and probing time (5 s).


Assuntos
Partículas beta/uso terapêutico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Cirurgia Assistida por Computador , Ácido Edético/administração & dosagem , Ácido Edético/análogos & derivados , Humanos , Masculino , Oligopeptídeos/administração & dosagem , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos/administração & dosagem
20.
J Contemp Dent Pract ; 19(9): 1087-1094, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30287709

RESUMO

AIM: The purpose of this study was to evaluate the influence of widening the apical root canal preparation (RCP) on the efficiency of different ethylenediaminetetraacetic acid (EDTA) agitation protocols on smear layer removal: EDTA; EDTA + Easy Clean in rotary movement (ECROT); EDTA + Easy Clean in reciprocating movement (ECREC); and EDTA + Passive ultrasonic irrigation (PUI). MATERIALS AND METHODS: A total of 80 mandibular premolars had their crowns sectioned and then were divided into two groups according to widening: size 25 or 40, 0.08 taper. Sequentially they were once again allocated to subgroups according to the agitation protocol performing eight experimental groups (n = 10). Ten additional teeth were prepared for controls (C+/C-). The specimens were then submitted to the cleaning protocols and thereafter cleaved and microphotographed by variable pressure scanning electron microscopy (SEM) at previously determined points along their root thirds (750*). Scores were attributed to the images, and data were analyzed by the Kruskal-Wallis, Student-Newman-Keuls and Friedman tests. RESULTS: A higher widening was observed to have a positive influence on cleaning efficiency offering significant differences in global and apical third evaluations (p < 0.05). Relative to the agitation, significant differences were observed mainly in the apical third, with PUI and ECROT providing the best results (p < 0.05); no difference for C+ was observed when higher widening was employed. CONCLUSION: A greater widening of the apical third provided a significant improvement in the action of the agitation/activation protocols. Moreover, the PUI and ECROT activation methods were shown to be superior to the use of EDTA solely, particularly in the apical third. CLINICAL SIGNIFICANCE: The findings of this study reinforce the need for clinical use of additional methods to complement cleaning. Therefore, it is important for professionals to have knowledge and command of these protocols to obtain more satisfactory results.


Assuntos
Cavidade Pulpar/ultraestrutura , Ácido Edético/administração & dosagem , Microscopia Eletrônica de Varredura , Irrigantes do Canal Radicular/administração & dosagem , Preparo de Canal Radicular/métodos , Irrigação Terapêutica/métodos , Ápice Dentário , Dente Pré-Molar , Humanos , Mandíbula , Camada de Esfregaço , Ultrassom
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