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1.
J Interv Card Electrophysiol ; 66(1): 27-38, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35072829

RESUMO

BACKGROUND: Arrhythmic death is very common among patients with structural heart disease, and it is estimated that in European countries, 1 per 1000 inhabitants yearly dies for sudden cardiac death (SCD), mainly as a result of ventricular arrhythmias (VA). The scar is the result of cardiac remodelling process that occurs in several cardiomyopathies, both ischemic and non-ischemic, and is considered the perfect substrate for re-entrant and non-re-entrant arrhythmias. METHODS: Our aim was to review published evidence on the histological and electrophysiological properties of myocardial scar and to review the central role of cardiac magnetic resonance (CMR) in assessing ventricular arrhythmias substrate and its potential implication in risk stratification of SCD. RESULTS: Scarring process affects both structural and electrical myocardial properties and paves the background for enhanced arrhythmogenicity. Non-uniform anisotropic conduction, gap junctions remodelling, source to sink mismatch and refractoriness dispersion are some of the underlining mechanisms contributing to arrhythmic potential of the scar. All these mechanisms lead to the initiation and maintenance of VA. CMR has a crucial role in the evaluation of patients suffering from VA, as it is considered the gold standard imaging test for scar characterization. Mounting evidences support the use of CMR not only for the definition of gross scar features, as size, localization and transmurality, but also for the identification of possible conducting channels suitable of discrete ablation. Moreover, several studies call out the CMR-based scar characterization as a stratification tool useful in selecting patients at risk of SCD and amenable to implantable cardioverter-defibrillator (ICD) implantation. CONCLUSIONS: Scar represents the substrate of ventricular arrhythmias. CMR, defining scar presence and its features, may be a useful tool for guiding ablation procedures and for identifying patients at risk of SCD amenable to ICD therapy.


Assuntos
Cardiomiopatias , Desfibriladores Implantáveis , Humanos , Cicatriz/diagnóstico por imagem , Cicatriz/patologia , Vento , Arritmias Cardíacas/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/terapia , Morte Súbita Cardíaca/prevenção & controle , Fatores de Risco
2.
Sci Total Environ ; 838(Pt 4): 156592, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35690195

RESUMO

The intense rainfall associated with the Intertropical Convergence Zone (ITCZ), a narrow zone of confluence of the northeast and southeast trades, can significantly alter sea surface salinity, the chemistry of inorganic C and the resulting sea-air CO2 exchange in the tropics. We have analyzed extensive underway data collected from 2008 until 2014 and recorded by an autonomous CO2 system installed on a commercial ship that crosses the central tropical Atlantic (5°S to 15°N, 18°W to 36°W) to disentangle the effects of the ITCZ over the carbonate system there. Based on statistically significant linear co-variance of sea surface fugacity of CO2 (fCO2sw) and sea surface salinity in the areas affected by the ITCZ, we calculated CO2 drawdown rates associated with the impact of the ITCZ in the central tropical Atlantic ranging from 0.11 ± 0.02 to 2.35 ± 0.08 mmol m-2 d-1. These were calculated by comparing the observed fCO2sw with that expected without surface seawater carbonate system dilution and increase in gas transfer caused by the ITCZ. The observed decrease in fCO2sw associated with the freshening caused by the ITCZ is much larger than expected from thermodynamics alone. 59.1 ± 4.1 % of the total observed CO2 drawdown associated with the ITCZ cannot be explained by abiotic processes. Instead, we found significant negative correlations between underway sea surface salinity and remote-sensed chlorophyll a in the areas affected by the ITCZ. Different to other tropical oceanic basins, the tropical Atlantic receives large amounts of continental dust originated from Africa. Wet dust deposition driven by the ITCZ appears associated with the interannual variability of the CO2 drawdown associated with the ITCZ. Fertilization driven by the ITCZ seems to enhance primary production in the otherwise oligotrophic tropical Atlantic, thus significantly lowering CO2 emissions to the atmosphere.


Assuntos
Atmosfera , Dióxido de Carbono , Clorofila A , Poeira , Água do Mar
3.
Front Neurosci ; 15: 661569, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248478

RESUMO

Stroke survivors can be affected by motor deficits in the hand. Robotic equipment associated with brain-machine interfaces (BMI) may aid the motor rehabilitation of these patients. BMIs involving orthotic control by motor imagery practices have been successful in restoring stroke patients' movements. However, there is still little acceptance of the robotic devices available, either by patients and clinicians, mainly because of the high costs involved. Motivated by this context, this work aims to design and construct the Hand Exoskeleton for Rehabilitation Objectives (HERO) to recover extension and flexion movements of the fingers. A three-dimensional (3D) printing technique in association with textiles was used to produce a lightweight and wearable device. 3D-printed actuators have also been designed to reduce equipment costs. The actuator transforms the torque of DC motors into linear force transmitted by Bowden cables to move the fingers passively. The exoskeleton was controlled by neuroelectric signal-electroencephalography (EEG). Concept tests were performed to evaluate control performance. A healthy volunteer was submitted to a training session with the exoskeleton, according to the Graz-BCI protocol. Ergonomy was evaluated with a two-dimensional (2D) tracking software and correlation analysis. HERO can be compared to ordinary clothing. The weight over the hand was around 102 g. The participant was able to control the exoskeleton with a classification accuracy of 91.5%. HERO project resulted in a lightweight, simple, portable, ergonomic, and low-cost device. Its use is not restricted to a clinical setting. Thus, users will be able to execute motor training with the HERO at hospitals, rehabilitation clinics, and at home, increasing the rehabilitation intervention time. This may support motor rehabilitation and improve stroke survivors life quality.

4.
Front Neurosci ; 15: 660141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025344

RESUMO

Introduction: Adaptive algorithms for controlling orthosis emerged to overcome significant problems with automatic biosignal classification and personalized rehabilitation. Smart orthoses are evolving fast and need a better human-machine interaction performance since biosignals, feedback, and motor control dynamically change and must be adaptive. This manuscript outlines a scoping review protocol to systematically review the smart upper limb (UL) orthoses based on adaptive algorithms and feasibility tests. Materials and Methods: This protocol was developed based on the York framework. A field-specific structure was defined to achieve each phase. Eleven scientific databases (PubMed, Web of Science, SciELO, Koreamed, Jstage, AMED, CENTRAL, PEDro, IEEE, Scopus, and Arxiv) and five patent databases (Patentscope, Patentlens, Google Patents, Kripis, J-platpat) were searched. The developed framework will extract data (i.e., orthosis description, adaptive algorithms, tools used in the usability test, and benefits to the general population) from the selected studies using a rigorous approach. Data will be described quantitatively using frequency and trend analysis methods. Heterogeneity between the included studies will be assessed using the Chi-test and I-statistic. The risk of bias will be summarized using the latest Prediction Model Study Risk of Bias Assessment Tool. Discussion: This review will identify, map, and synthesize the advances about the description of adaptive algorithms for control strategies of smart UL orthosis using data extracted from patents and articles.

5.
Pharm Dev Technol ; 26(1): 92-100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33074769

RESUMO

Isradipine is a dihydropyridine calcium channel blocker (CCB) commonly used as vasodilator with antihypertensive properties. A remote-controlled release formulation for isradipine would substantially improve the clinical outcomes of the patients requiring chronic long-term treatment. In this work, sustained release (SR) tablets of isradipine, composed of hydroxypropylmethyl cellulose (HPMC), have been produced by wet granulation and their in vitro and in vivo characterization was compared to a conventional tablet dosage form of immediate release (IR) as preliminary assessment. Tablets composed of 15.0% (wt/wt) HPMC exhibited a SR profile over a period of 24 hours. The release of isradipine followed a Fickian diffusion pattern obeying to the first order kinetics and the extent of absorption was even higher in comparison to the developed conventional tablets, which showed immediate drug release. In vivo studies were carried out in rabbits, showing that the extent of isradipine absorption from the developed tablets was higher in comparison to IR tablets due to the modified release profile obtained for the former (p < 0.05). Our results suggest that SR tablets of isradipine are an efficient solid dosage form to overcome the limitations encountered in conventional IR tablets.


Assuntos
Anti-Hipertensivos/síntese química , Anti-Hipertensivos/farmacocinética , Fenômenos Químicos , Isradipino/síntese química , Isradipino/farmacocinética , Animais , Anti-Hipertensivos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Isradipino/administração & dosagem , Coelhos , Comprimidos
6.
Int J Pharm ; 591: 120001, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33141086

RESUMO

The aim of this study was to develop and characterize a double layer biomembrane for dual drug delivery to be used for the treatment of wounds. The membrane was composed of chitosan, hydroxypropyl methylcellulose and lidocaine chloride (anesthetic drug) in the first layer, and of sodium alginate-polymyxin B sulphate (antibiotic) nanoparticles as the second layer. A product with excellent thickness (0.01-0.02 mm), adequate mechanical properties with respect to elasticity, stiffness, tension, and compatible pH for lesion application has been successfully obtained. The incorporation of the drugs was confirmed analysing the membrane cross-sections by scanning electron microscopy. A strong interaction between the drugs and the functional groups of respective polymers was confirmed by Fourier-Transform Infrared Spectroscopy, thermal analysis and X-ray diffraction. Microbiological assays showed a high antimicrobial activity when polymyxin B was present to act against the Staphylococcus aureus and Pseudomonas aeruginosa strains. Low cytotoxicity observed in a cell viability colorimetric assay and SEM analysis suggest biocompatibility between the developed biomembrane and the cell culture. The in vivo assay allowed visualizing the healing potential by calculating the wound retraction index and by histological analysis. Our results confirm the effectiveness of the developed innovative biomaterial for tissue repair and regeneration in an animal model.


Assuntos
Quitosana , Nanopartículas , Alginatos , Animais , Bandagens , Lidocaína , Polimixinas , Espectroscopia de Infravermelho com Transformada de Fourier , Cicatrização
7.
Pharmazie ; 75(2): 75-81, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32213238

RESUMO

In this study we developed a mucoadhesive polymeric membrane wound dressing incorporating red propolis extract (HERP). Membranes were made using a casting method employing collagen, chitosan, polyethylene glycol (15, 20, and 30v%), and hydroethanolic extract of EtOH-H2O 70v% - 30v% (v/v) of HERP (0.5, 1.0, and 1.5%). Membranes were extensively characterized to assess the thickness, pH, morphology using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), mechanical properties, swelling, in vitro mucoadhesion, cytotoxicity, and minimum inhibitory concentration (MIC). Assessment of the thickness and mechanical properties of the membranes containing HERP revealed that the most significant thickness obtained was 40.7 µm; thermal analysis suggests suggesting the hydrogen bonds between hydroxyl groups of isoflavones and the free amine present in the region of chitosan. Cell viability decreased as the amount of HERP increased. Finally, the MICs were 7.8 and 1.9 µg.mL-1 for Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853, respectively. These results were suggesting that the 0.5 % HERP membrane has the potential for future studies for wound application.


Assuntos
Própole/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Quitosana/farmacologia , Colágeno/farmacologia , Testes de Sensibilidade Microbiana
8.
Nanomaterials (Basel) ; 10(2)2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32102229

RESUMO

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430-450 nm in the ultraviolet-visible (UV-Vis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FT-IR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm-1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.

9.
Environ Sci Pollut Res Int ; 25(11): 10654-10667, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29392604

RESUMO

Seepage faces, the outer rim of subterranean estuaries, are an important reaction node for SGD-borne nitrate (NO3-) on a global scale. Labile dissolved organic matter (DOM) has been suggested to be a key factor constraining the NO3- removal rate in aquifer systems. To determine whether and to what extent the availability of labile DOM affects benthic NO3- reduction in seepage faces, a series of flow-through reactor (FTR) experiments with sandy sediment collected from a seepage face was conducted under oxic conditions. Experimental results revealed that the addition of labile DOM (glucose) to porewater did not trigger a significant enhancement in NO3- reduction rate. In contrast, the aerobic respiration was boosted from ca. 50 to 90 µmol dm-3 sediment h-1 by glucose amendments, accounting for approximately 70% consumption of the labile DOM pool. This rapid consumption may increase the NO3- reducing capability within the sediment, but only indirectly. Together with fluorescent DOM (FDOM) analyses, it can be inferred that NO3- reducers tend to choose sediment organic matter the prime electron donor under the experimental conditions. As a result, enrichment of DOM in seepage faces, depending on composition, might only stimulate aerobic respiration and nitrification, thus promoting the increase of ensuing NO3- fluxes to adjacent coastal waters.

10.
Saudi Pharm J ; 25(2): 231-235, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28344473

RESUMO

The aim of this study was the assessment of the physicochemical stability of d-α-tocopherol formulated in medium chain triglyceride nanoemulsions, stabilized with Tween®80 and Lipoid®S75 as surfactant and co-surfactant, respectively. d-α-tocopherol was selected as active ingredient because of its well-recognized interesting anti-oxidant properties (such as radical scavenger) for food and pharmaceutical industries. A series of nanoemulsions of mean droplet size below 90 nm (polydispersity index < 0.15) have been produced by high-pressure homogenization, and their surface electrical charge (zeta potential), pH, surface tension, osmolarity, and rheological behavior, were characterized as a function of the d-α-tocopherol loading. In vitro studies in Caco-2 cell lines confirmed the safety profile of the developed nanoemulsions with percentage of cell viability above 90% for all formulations.

11.
Saudi Pharm J ; 25(1): 99-103, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28223869

RESUMO

Paracetamol (PAR), phenylephrine hydrochloride (PHE) and chlorpheniramine maleate (CPM) are commonly used in clinical practice as antipyretic and analgesic drugs to ameliorate pain and fever in cold and flu conditions. The present work describes the use of thermal analysis for the characterization of the physicochemical compatibility between drugs and excipients during the development of solid dosage forms. Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC) were used to study the thermal stability of the drug and of the physical mixture (drug/excipients) in solid binary mixtures (1:1). DSC thermograms demonstrated reproducible melting event of the prepared physical mixture. Starch, mannitol, lactose and magnesium stearate influence thermal parameters. Information recorded from the derivative thermogravimetric (DTG) and TGA curves demonstrated the decomposition of drugs in well-defined thermal events, translating the suitability of these techniques for the characterization of the drug/excipients interactions.

12.
Sci Rep ; 7: 41694, 2017 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-28134309

RESUMO

Following the 2009 Pacific El Niño, a warm event developed in the tropical and subtropical North Atlantic during boreal spring of 2010 promoted a significant increase in the CO2 fugacity of surface waters. This, together with the relaxation of the prevailing wind fields, resulted in the reversal of the atmospheric CO2 absorption capacity of the tropical and subtropical North Atlantic. In the region 0-30°N, 62-10°W, this climatic event led to the reversal of the climatological CO2 sink of -29.3 Tg C to a source of CO2 to the atmosphere of 1.6 Tg C from February to May. The highest impact of this event is verified in the region of the North Equatorial Current, where the climatological CO2 uptake of -22.4 Tg for that period ceased during 2010 (1.2 Tg C). This estimate is higher than current assessments of the multidecadal variability of the sea-air CO2 exchange for the entire North Atlantic (20 Tg year-1), and highlights the potential impact of the increasing occurrence of extreme climate events over the oceanic CO2 sink and atmospheric CO2 composition.

13.
Pharm Dev Technol ; 22(3): 360-369, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27050395

RESUMO

Elastic liposomes are capable to improve drug transport through the skin by acting as penetration enhancers due to the high fluidity and elasticity of the liposome membranes. Therefore, elastic liposomes were prepared and characterized to facilitate the transdermal transport of bioactive molecules. Liposomes consisted of dimyristoylphosphatidylcholine (DMPC) as the structural component, with different surfactants derived from lauric acid as elastic components: C12E5 (polyoxyethylene-5-lauryl ether), PEG4L (polyethyleneglycol-4-lauryl ester), PEG4DL (polyethylene glycol-4-dilauryl ester), PEG8L (polyethylene glycol-8-lauryl ester) and PEG8DL (polyethylene glycol-8-dilauryl ester). The elastic liposomes were characterized in terms of their phospholipid content, mean diameter, size distribution, elasticity and stability during storage, as well as their ability to incorporate surfactant and permeate through 50 nm pore size membranes. The results showed that the phospholipid phase transition temperature, the fluidity of the lipid bilayer resulting from incorporation of the surfactant and the preservation of particle integrity were factors determining the performance of the elastic liposomes in permeating through nanoporous membranes. The best results were obtained using DMPC combined with the surfactants PEG8L or PEG8DL. The findings demonstrate the potential of using elastic liposomes for transdermal administration of drugs.


Assuntos
Dimiristoilfosfatidilcolina/química , Portadores de Fármacos/química , Bicamadas Lipídicas/química , Tensoativos/química , Tecnologia Farmacêutica/métodos , Elasticidade , Lipossomos , Tamanho da Partícula , Propriedades de Superfície , Temperatura de Transição
14.
Int J Cardiol ; 199: 337-41, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26241640

RESUMO

INTRODUCTION: Heart failure places a significant economic burden on health care. Acute heart failure requires hospitalization and often frequent re-hospitalization in expensive wards where vasoactive rescue therapy is often added on top of standard medications. In these lean times, there is a growing need for cost-effective therapeutic options that supply superior support and in addition shorten the length of stay in hospital and reduce re-hospitalization rates. The inodilator levosimendan represents the latest addition to the vasoactive treatments of acute heart failure patients, and it appears to meet these expectations. Our aim was to answer the question whether the treatment efficacy of levosimendan - when selected as therapy for patients hospitalized for acute heart failure - brings savings to hospitals in various European countries representing different economies. METHODS AND RESULTS: We took a conservative approach and selected some a fortiori arguments to simplify the calculations. We selected seven European countries to represent different economies: Italy, Spain, Greece, Germany, Sweden, Finland and Israel. Data on the costs of medications and on the cost per day were collected and fed in a simple algorithm to detect savings. These saving varied from country to country, from a minimum of €0.50 in Germany to a maximum of €354.64 in Sweden. CONCLUSIONS: The use of levosimendan as a therapy for patients hospitalized for acute heart failure provides a net saving to hospitals driven by a reduction in the length of hospital stay. This finding is true in each of the countries considered in this study.


Assuntos
Cardiotônicos/economia , Cardiotônicos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Hidrazonas/economia , Hidrazonas/farmacologia , Piridazinas/economia , Piridazinas/farmacologia , Doença Aguda , Algoritmos , Cardiologia , Análise Custo-Benefício , Farmacoeconomia , Europa (Continente)/epidemiologia , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/mortalidade , Hospitalização/economia , Humanos , Tempo de Internação/economia , Modelos Econômicos , Mortalidade , Qualidade de Vida , Simendana
15.
Neurotox Res ; 27(2): 118-28, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25367806

RESUMO

The search for new therapeutic strategies through modulation of glutamatergic transmission using effective neuroprotective agents is essential. Glutamatergic excitotoxicity is a major factor common to neurodegenerative diseases and in acute events such as cerebral ischemia, traumatic brain injury and epilepsy. We have previously demonstrated that N-methyl-D-aspartate (NMDA) preconditioning in mice showed 50 % of protection against seizures and full protection against damage to neuronal tissue induced by quinolinic acid (QA). In this study, cellular and molecular mechanisms involved on NMDA preconditioning and neuroprotection were investigated in mice treated with NMDA 24 h before QA insult. Calcium uptake and D-aspartate release from hippocampal slices obtained from mice treated with NMDA plus QA and not displaying seizures (protected mice) were similar to control (saline) or NMDA preconditioned mice. Increased calcium uptake and glutamate release is evidenced in unprotected (convulsed) mice as well as QA control, demonstrating that calcium and glutamate are involved in NMDA-induced preconditioning. Increased glutamate release evoked by QA was blocked by MK-801, whereas increased calcium uptake was abolished by voltage-dependent calcium channels inhibitors, but not MK-801. NMDA preconditioning is effective in normalizing the deregulation of glutamate transport and calcium homeostasis evoked by QA due to aberrant NMDA receptors activation that culminates in seizures and hippocampal cells damage.


Assuntos
Cálcio/metabolismo , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/efeitos dos fármacos , Homeostase/efeitos dos fármacos , N-Metilaspartato/farmacologia , Animais , Ácido D-Aspártico/metabolismo , Agonistas de Aminoácidos Excitatórios/administração & dosagem , Hipocampo/metabolismo , Masculino , Camundongos , N-Metilaspartato/administração & dosagem , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Ácido Quinolínico/administração & dosagem , Convulsões/induzido quimicamente , Convulsões/metabolismo
16.
Pharmazie ; 70(11): 693-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26790184

RESUMO

Polymyxins are efficient antibiotic drugs used for the treatment of Gram-negative bacterial infections. These compounds are not absorbed in the gastrointestinal tract and are responsible for serious toxicological effects. In order to enhance their therapeutic effectiveness, decrease the adverse/toxic side effects and promote a sustained release profile, a derivative--polymyxin B sulphate--has been formulated in solid lipid nanoparticles (SLNs) intended for buccal administration. To quantify polymyxin B in the formulation, UV spectrophotometry analysis was applied, validating the analytical methodology by assessing the selectivity, accuracy, precision, linearity, and repeatability. Analyses were performed at 210 nm keeping the samples at 25 degrees C. Results showed that lipid composition of SLNs did not interfere with the polymyxin B spectra. The linearity showed a correlation coefficient of 0.9977 in the range of 5-90 µg/mL. Quantification of polymyxin B by UV spectrophotometry, at 210 nm in SLN formulations, was approved in all analyzed parameters, validating the methodology proposed in this work.


Assuntos
Antibacterianos/análise , Nanopartículas/análise , Polimixina B/análise , Algoritmos , Preparações de Ação Retardada , Composição de Medicamentos , Lipídeos/análise , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta
17.
Br J Cancer ; 109(8): 2106-14, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24064971

RESUMO

BACKGROUND: High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.


Assuntos
Antígenos Glicosídicos Associados a Tumores/biossíntese , Vacina BCG/uso terapêutico , Mucinas/biossíntese , Recidiva Local de Neoplasia/imunologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Idoso , Antígenos Glicosídicos Associados a Tumores/imunologia , Vacina BCG/farmacocinética , Biomarcadores Tumorais/biossíntese , Adesão Celular/imunologia , Linhagem Celular Tumoral , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/imunologia , Análise Multivariada , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
18.
Clin Transl Oncol ; 15(6): 417-24, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23344664

RESUMO

Basal cell carcinomas and squamous cell carcinomas are non-melanoma skin cancers reported to be among the most common malignancies, being responsible for high human morbidity. Conventional chemotherapy applied to these conditions shows non-specific targeting, thus severe adverse side effects are also commonly reported. New therapeutic strategies based on nanoparticulates technology have emerged as alternatives for site specific chemotherapy. Among the different types of nanoparticulates, lipid nanoemulsions and nanoparticles have several advantages for topical delivery of poorly soluble chemotherapeutics. These particles show sustained drug release and protection of loaded drugs from chemical degradation. This technology is promising to enhance the intracellular concentration of drugs and consequently reduce the cytotoxicity of skin chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Portadores de Fármacos , Lipídeos/química , Nanopartículas , Neoplasias Cutâneas/tratamento farmacológico , Emulsões , Humanos
19.
Pharm Dev Technol ; 18(2): 428-33, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22519303

RESUMO

Nevirapine is the first antiretroviral member of non-nucleoside reverse transcriptase inhibitor used in active antiretroviral therapy (HAART). The aim of this work was the evaluation of the dissolution profile of nevirapine tablets by means of the Disk Intrinsic Dissolution Rate (DIDR) using a 2(3) factorial design. This study used a triplicate in central point and was based on three independent variables: the rotational speed of the apparatus, the compression force of nevirapine disk, and the distance of the tank dissolution. The dependent variable was set as intrinsic dissolution speed (IDS). IDS was strongly dependent on the rotational speed, compression force, and distance of the apparatus, analyzed by Student's t test with 95% confidence, and confirmed by ANOVA. The rotational speed of nevirapine disks was the main factor contributing to the IDS, whereas the compression force and the distance of disks on the dissolution apparatus revealed no effects.


Assuntos
Fármacos Anti-HIV/química , Nevirapina/química , Comprimidos/química , Terapia Antirretroviral de Alta Atividade/métodos , Composição de Medicamentos/métodos , Solubilidade
20.
Mater Sci Eng C Mater Biol Appl ; 33(2): 596-602, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25427461

RESUMO

Nevirapine is a hydrophobic non-nucleoside reverse transcriptase inhibitor, used in first line regimens of highly active antiretroviral therapy (HAART). The drug has more than one crystalline form, which may have implications for its behaviour during production and also for its in vivo performance. This study was aimed at exploring the suitability of thermoanalytical methods for the solid-state characterization of commercial crystalline forms of nevirapine. The drug powder was characterized by ultraviolet spectrophotometry, stereoscopy, scanning electron microscopy, wide-angle X-ray diffraction, measurements of density, flowability, solubility and intrinsic dissolution rate (IDR), differential scanning calorimetry, thermogravimetric analysis, and photostability measurements. The results showed that nevirapine has high stability and is not susceptible to degradation under light exposure. The drug showed compatibility with the excipients tested (lactose, microcrystalline cellulose, polyvinylpyrrolidone and polyvinyl acetate copolymer (PVP/PVA), and hydroxypropylmethylcellulose (HPMC)). Nevirapine has low solubility, an acid medium being the most appropriate medium for assessing the release of the drug from dosage forms. However, the data obtained from IDR testing indicate that dissolution is the critical factor for the bioavailability of this drug.


Assuntos
Antirretrovirais/química , Excipientes/química , Nevirapina/química , Administração Oral , Antirretrovirais/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Varredura Diferencial de Calorimetria , Estabilidade de Medicamentos , Nevirapina/administração & dosagem , Solubilidade , Termodinâmica , Termogravimetria
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