Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.152
Filtrar
1.
No Shinkei Geka ; 47(8): 869-875, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31477630

RESUMO

A 41-year-old woman underwent coil embolization for subarachnoid hemorrhage associated with a ruptured anterior cerebral artery(A1)aneurysm. Approximately 3 weeks later, MRI revealed right cerebral white matter changes with extensive edema and enhancement lesions. Even though she was asymptomatic, we suspected an allergic reaction to the hydrophilic coating polymer and initiated steroid treatment. After tapering and discontinuing the steroid treatment, follow-up MRI revealed development of white matter lesions;thus, steroid treatment was reinitiated. Progression and regression of the lesions occurred repeatedly, and she was radiologically stable at almost 1 year after coiling. We speculated that these white matter lesions were foreign body granulomas that reacted to the hydrophilic coating of the endovascular device. Overall, an allergic reaction to hydrophilic coating polymer could occur as a delayed complication after coil embolization and that progression and regression of the lesions could repeatedly occur in rare cases.


Assuntos
Aneurisma Roto , Edema Encefálico , Embolização Terapêutica , Hipersensibilidade , Aneurisma Intracraniano , Polímeros , Adulto , Prótese Vascular , Edema Encefálico/etiologia , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Polímeros/efeitos adversos , Hemorragia Subaracnóidea/terapia
2.
AIDS Rev ; 21(3): 126-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532397

RESUMO

Persistent coinfection with the hepatitis B/D viruses (HDV) represents the most severe form of viral hepatitis. Hepatitis D often leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. The current treatment options are limited as only pegylated interferon-alpha (PEG-IFNa) has efficacy against HDV. However, treatment response is still unsatisfactory with 25-40% HDV RNA suppression after 1-2 years. In addition, late HDV RNA relapses have been described during long-term follow-up. Fortunately, new treatment options for patients with chronic hepatitis delta are now on the horizon. The hepatocyte entry inhibitor bulevirtide (formerly myrcludex B) and the farnesyl transferase inhibitor lonafarnib are currently explored in patients with chronic hepatitis delta in Phase 3 clinical studies. The nucleic acid inhibitor REP-2139-Ca and PEG-IFN-lambda are studied in Phase 2 trials. We here summarize data on the efficacy of these new antiviral drugs and the existing safety data on the treatment of HDV infection.


Assuntos
Antivirais/administração & dosagem , Hepatite D/tratamento farmacológico , Interferon-alfa/administração & dosagem , Lipopeptídeos/administração & dosagem , Ácidos Nucleicos/administração & dosagem , Piperidinas/administração & dosagem , Polímeros/administração & dosagem , Piridinas/administração & dosagem , Antivirais/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Coinfecção/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Hepatite B Crônica/tratamento farmacológico , Vírus Delta da Hepatite/efeitos dos fármacos , Humanos , Interferon-alfa/efeitos adversos , Lipopeptídeos/efeitos adversos , Ácidos Nucleicos/efeitos adversos , Piperidinas/efeitos adversos , Polímeros/efeitos adversos , Piridinas/efeitos adversos , Recidiva , Resultado do Tratamento
3.
Int J Nanomedicine ; 14: 4383-4395, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354267

RESUMO

Background: The bioactive compounds glycyrrhizin (GL) and thymoquinone (TQ) have been reported for antidiabetic activity in pure and nanoformulation (NF) form. However, the antidiabetic effect of a combined nanoformulation of these two has not been reported in the literature. Here, a combinational nanomedicine approach was investigated to enhance the antidiabetic effects of the two bioactive compounds of GL and TQ (GT), in type 2 diabetic rats in reference to metformin. Methods: Two separately prepared NFs of GL (using polymeric nanoparticles) and TQ (using polymeric nanocapsules) were mixed to obtain a therapeutic cargo of nanomedicine and then characterized with respect to particle size, stability, morphology, chemical interaction, and in vivo behavior. Additionally, NFs were evaluated for their cytotoxic effect on Vero cell lines compared to the pure form. This nanomedicine was administered orally, both independently and in combination (pure form or NF) for 21 successive days to type 2 diabetic rats and the effect assessed in term of body weight, fasting blood-glucose level, and various biochemical parameters (such as lipid-profile parameters and HbA1c). Results: When these nanomedicines were applied in combined rather than individual forms, significant decreases in blood glucose and HbA1c and significant improvements in body weight and lipid profile were observed, despite them containing lower amounts than the pure forms. The treatment of diabetic rats with GL and TQ, when administered independently in either pure or NF forms, did not lead to favorable trends in any studied parameters. Conclusion: The administration of combined GT NFs exhibited significant improvement in studied parameters. Improvements in antidiabetic activity could have been due to a synergistic effect of combined NFs, leading to enhanced absorption of NFs and lesser cytotoxic effects compared to pure bioactive compounds. Therefore, GT NFs demonstrated potential as a new medicinal agent for the management of diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Composição de Medicamentos , Hipoglicemiantes/uso terapêutico , Nanopartículas/química , Polímeros/química , Animais , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Feminino , Hemoglobina A Glicada/metabolismo , Ácido Glicirrízico/uso terapêutico , Hipoglicemiantes/administração & dosagem , Lipídeos/química , Nanopartículas/ultraestrutura , Niacinamida , Polímeros/efeitos adversos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Estreptozocina
4.
Vasc Endovascular Surg ; 53(7): 606-608, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31272303

RESUMO

Hydrophilic polymer coatings are now widely applied to catheters and other intravascular devices used in neurovascular, cardiovascular, and peripheral vascular procedures. Emboli consisting of these materials have been previously identified in biopsies and autopsies following pulmonary infarction, stroke, gangrene, or death. We report a case involving a nonhealing foot ulcer that appeared following cardiac catheterization, stenting, and automatic implanted cardiac defibrillator (AICD) implantation in a patient without other evidence of significant peripheral artery disease. An 85-year-old woman with chronic atrial fibrillation, aortic valve stenosis, and coronary artery disease underwent coronary stenting and AICD implantation for ventricular tachycardia and syncope. She developed a toe ulcer shortly thereafter, which did not respond to standard treatment. A histological examination following amputation of the toe found amorphous basophilic material in capillaries adjacent to the edge of the ulcer, which was similar to material associated with hydrophilic polymer coatings. Ischemia and infarcts following endovascular procedures should not be presumed to result from thrombus or vascular disease, even if intravascular devices appear intact or properly placed after the procedure. To help establish the incidence of ischemia caused by hydrophilic polymer device coatings, if excision of ischemic or infarcted tissue after endovascular procedures using coated devices becomes necessary, the tissue should be evaluated microscopically. Surgeons should also consider the tolerance of distal organs to infarct or ischemia when selecting coated intravascular devices.


Assuntos
Materiais Revestidos Biocompatíveis/efeitos adversos , Embolia/etiologia , Úlcera do Pé/etiologia , Migração de Corpo Estranho/etiologia , Isquemia/etiologia , Polímeros/efeitos adversos , Dedos do Pé/irrigação sanguínea , Idoso de 80 Anos ou mais , Amputação , Angiografia , Biópsia , Embolia/diagnóstico por imagem , Embolia/cirurgia , Feminino , Úlcera do Pé/diagnóstico por imagem , Úlcera do Pé/fisiopatologia , Úlcera do Pé/cirurgia , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/cirurgia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Isquemia/cirurgia , Fluxo Sanguíneo Regional , Dedos do Pé/cirurgia , Resultado do Tratamento
5.
Lancet ; 394(10196): 396-406, 2019 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-31248662

RESUMO

BACKGROUND: Metabolic acidosis, a complication of chronic kidney disease, causes protein catabolism and bone demineralisation and is associated with adverse kidney outcomes and mortality. Veverimer, a non-absorbed, counterion-free, polymeric drug candidate selectively binds and removes hydrochloric acid from the gastrointestinal lumen. METHODS: We did a multicentre, randomised, blinded, placebo-controlled, 40-week extension of a 12-week parent study at 29 sites (hospitals and specialty clinics) in seven countries (Bulgaria, Georgia, Hungary, Serbia, Slovenia, Ukraine, and the USA). Eligible patients were those with chronic kidney disease (estimated glomerular filtration rate 20-40 mL/min per 1·73 m2) and metabolic acidosis (serum bicarbonate 12-20 mmol/L), who had completed the 12-week parent study, for which they were randomly assigned (4:3) to veverimer (6 g/day) or placebo as oral suspensions in water with food. Participants in the extension continued with the same treatment assignment as in the parent study. The primary endpoint was safety; the four secondary endpoints assessed the long-term effects of veverimer on serum bicarbonate concentration and physical functioning. The safety analysis set was defined as all patients who received any amount of study drug. This trial is registered at ClinicalTrials.gov, number NCT03390842, and has now completed. FINDINGS: Participants entered the study between Dec 20, 2017, and May 4, 2018. Of the 217 patients randomly assigned to treatment in the parent study (124 to veverimer and 93 to placebo), 196 patients (114 veverimer and 82 placebo) continued on their blinded randomised treatment assignment into this 40-week extension study. Compared with placebo, fewer patients on veverimer discontinued treatment prematurely (3% vs 10%, respectively), and no patients on veverimer discontinued because of an adverse event. Serious adverse events occurred in 2% of veverimer-treated patients and in 5% of placebo patients (two of whom died). Renal system adverse events were reported in 8% and 15% in the veverimer and placebo groups, respectively. More patients on veverimer than placebo had an increase in bicarbonate (≥4 mmol/L or normalisation) at week 52 (63% vs 38%, p=0·0015) and higher bicarbonate concentrations were observed with veverimer than placebo at all timepoints starting at week 1 (p<0·001). Veverimer resulted in improved patient-reported physical functioning (Kidney Disease and Quality of Life-Physical Function Domain) versus placebo with a mean placebo-subtracted change at end of treatment of 12·1 points (SE 3·3; p<0·0001). Time to do the repeat chair stand test improved by 4·3 s (1·2) on veverimer versus 1·4 s (1·2) on placebo (p<0·0001). INTERPRETATION: In patients with chronic kidney disease and metabolic acidosis, veverimer safely and effectively corrected metabolic acidosis and improved subjective and objective measures of physical function. FUNDING: Tricida.


Assuntos
Acidose/tratamento farmacológico , Polímeros/administração & dosagem , Insuficiência Renal Crônica/complicações , Acidose/etiologia , Acidose/metabolismo , Administração Oral , Idoso , Bicarbonatos/metabolismo , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polímeros/efeitos adversos , Insuficiência Renal Crônica/metabolismo , Resultado do Tratamento
6.
J Cardiovasc Surg (Torino) ; 60(5): 599-611, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31089086

RESUMO

BACKGROUND: Synthetic vascular material use, particularly polytetrafluoroethylene- (PTFE) -based, can be associated with bleeding, which may increase operative time and blood loss. None of the commercially available sealants designed to ensure hemostasis combine bioresorption, high viscosity, hydrophobicity, and compliance with the underlying tissue and on-demand activation. METHODS: A study was designed to assess the biocompatibility and in-vivo performance and bioresorption of a new synthetic on-demand light-activated poly(glycerol-sebacate) acrylate- (PGSA) -based SETALIUM™ Vascular Sealant (TISSIUM, Paris, France) in three large animal studies of open vascular carotid and aortic surgery. The pre-clinical results were then translated into a clinical setting in a prospective, single-arm multicenter study in patients requiring carotid endarterectomy using an ePTFE patch. RESULTS: The biocompatibility testing showed that the PGSA-based SETALIUM™ Vascular Sealant did not induce any significant toxic reaction at a standard clinical dose nor at doses up to 40 times the equivalent intended clinical dose. The PGSA-based sealant was shown to be non-pyrogenic, non-sensitizing, non-irritant, non-clastogenic, and non-mutagenic. The animal studies showed excellent performance and safety results, with clinically significant hemostasis achieved in 100% of the animals in both carotid and aorta studies and excellent local tolerance. Histopathology and morphometric analyses showed surface-based gradual and sustained bioresorption of the PGSA-based sealant up to 86% at 12 months. In the clinical study, the application of the PGSA-based sealant resulted in good performance and safety, with immediate hemostasis achieved in 84% of the cases and no adverse event related to the sealant reported through the one-year follow-up. CONCLUSIONS: The new synthetic on-demand light activated PGSA-based SETALIUM™ Vascular Sealant investigated in our studies demonstrated good biocompatibility, sustained and gradual surface based bioresorption, and acceptable safety profile in animal studies. In addition, the first in-human use showed that the sealant is a safe and effective alternative to achieve fast and controlled hemostasis in vascular carotid reconstructions. A larger randomized controlled study will allow further validation of these encouraging preliminary results.


Assuntos
Acrilatos/administração & dosagem , Angioplastia/efeitos adversos , Aorta Torácica/cirurgia , Artérias Carótidas/cirurgia , Decanoatos/administração & dosagem , Endarterectomia das Carótidas/efeitos adversos , Glicerol/análogos & derivados , Hemorragia/prevenção & controle , Técnicas Hemostáticas , Polímeros/administração & dosagem , Adesivos Teciduais/administração & dosagem , Acrilatos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Angioplastia/instrumentação , Animais , Decanoatos/efeitos adversos , Endarterectomia das Carótidas/instrumentação , Feminino , Glicerol/administração & dosagem , Glicerol/efeitos adversos , Técnicas Hemostáticas/efeitos adversos , Humanos , Masculino , Teste de Materiais , Pessoa de Meia-Idade , Modelos Animais , Polímeros/efeitos adversos , Estudos Prospectivos , Carneiro Doméstico , Fatores de Tempo , Adesivos Teciduais/efeitos adversos , Resultado do Tratamento
7.
Colloids Surf B Biointerfaces ; 178: 488-499, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30925372

RESUMO

Usnic acid (UA) is a lichenic secondary metabolite useful for the treatment of burn wounds thanks to its antimicrobial activity, particularly toward strains responsible for their infections. However, the poor solubility is the main factor limiting the activity and thus its use in health care products. Adhesive polymeric films were designed to improve UA use by enhancing its bioavailability in the wounded tissues. Three different NaCMC hydrogel films, NaCMC 2% alone (F1), mixed to PVP K90 0.1% (F2) or to Carbopol 971 P 0.1% (F3), were prepared by casting method. Ex vivo experiments performed on pig skin samples showed their suitable adhesion capacity. in vitro release test, performed using the extraction cell, showed that film F2 provides the highest UA concentrations. Differential scanning calorimetry and X-ray analyses performed on the three films highlighted that UA is present in a more soluble form in F2. The in vitro antibacterial activity studies demonstrated that F2 is the most effective film against UA sensitive bacteria S. Epidermidis, E. Faecalis, B. Cereus and S. Pyogenes. In vitro cytotoxicity assays on human keratinocytes and fibroblasts showed that cells viability is not compromised.


Assuntos
Benzofuranos/química , Benzofuranos/farmacologia , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Polímeros/química , Polímeros/farmacologia , Animais , Antibacterianos/efeitos adversos , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacillus cereus/efeitos dos fármacos , Benzofuranos/efeitos adversos , Benzofuranos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Polímeros/efeitos adversos , Polímeros/uso terapêutico , Staphylococcus epidermidis/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Suínos , Cicatrização/efeitos dos fármacos
8.
Interv Neuroradiol ; 25(4): 447-453, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30922199

RESUMO

The use of flow diverting stents for wide based, intracranial aneurysms has become an invaluable treatment option. While intracranial hemorrhage and ischemic stroke from dislodged atherosclerotic emboli are common adverse events, the potential for delayed granulomatous inflammation from possible hydrophilic polymer emboli is rarely recognized. We present a unique case in which visible chipping of the pusher wire for stent placement was observed, followed by clinical and radiographic evidence suggestive of a delayed foreign body reaction to intracranial hydrophilic polymer emboli. A 55-year-old woman underwent placement of a Pipeline embolization device for a left-sided, broad-based aneurysm at the base of the internal carotid artery and posterior communicating artery. Two months later she developed right-sided focal neurological deficits. Imaging showed ipsilateral focal edema and enhancing lesions with contrast. Although not confirmed with biopsy and histopathology, clinical and radiographic evidence suggests that this patient probably experienced a delayed foreign body reaction to hydrophilic polymer emboli from compromised procedural equipment during flow diverting stent placement. Although previously described, this is the first instance to our knowledge in whichvisible chipping of the pusher wire was observed on a Pipeline embolization device.


Assuntos
Prótese Vascular , Encéfalo , Embolização Terapêutica/métodos , Reação a Corpo Estranho/etiologia , Aneurisma Intracraniano/cirurgia , Polímeros/efeitos adversos , Stents , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Pessoa de Meia-Idade
9.
Mater Sci Eng C Mater Biol Appl ; 98: 737-745, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30813078

RESUMO

Controlled release of incorporated foreign DNA from multilayered films plays an important role in surface-mediated gene delivery. Herein, multilayered polyelectrolyte complex thin films, composed of dendrimer-grafted bio-reducible cationic poly(disulfide amine) and plasmid DNA, were fabricated via layer-by-layer (LBL) assembly for in vitro localized gene delivery. The UV absorbance and thickness of the LBL films were found to have linear correlation with the numbers of poly(disulfide amine)/DNA bilayers. Although LBL films were stable in PBS buffer, their degradation could be triggered by reducing agents (i.e. glutathione, GSH). The degradation rate of the films is directly proportional to the GSH concentration, which in turn affected the corresponding gene expression. All poly(disulfide amine)/DNA films exhibited lower cytotoxicity and higher transfection activity in comparison with PEI/DNA multilayered films. Moreover, LBL films showed the highest transfection efficiency in the presence of 2.5 mM GSH when cultured with 293T cells, with ~36% GFP-positive 293T cells after 5-days of co-culture. These DNA-containing reducible films could potentially be useful in gene therapy and tissue engineering by controlling the release of incorporated DNA.


Assuntos
DNA/química , Dendrímeros/química , Poliaminas/química , Polímeros/química , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Células HEK293 , Humanos , Poliaminas/efeitos adversos , Polímeros/efeitos adversos
10.
Biomater Sci ; 7(5): 1919-1932, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30773580

RESUMO

Accumulation of nano-scale contrast agents in body tissues potentially induces adverse effects associated with free Gd(iii) ion release from the nano-scale system, such as nephrogenic systemic fibrosis and gadolinium deposition in the brain tissue. A novel formulation strategy was proposed herein for Gd-based macromolecular MRI contrast agents (Gd-mCAs), which may significantly reduce Gd(iii) retention but maintain sufficient imaging contrast. Biodegradable poly[N-(1,3-dihydroxypropyl)methacrylamide] copolymers (pDHPMA) were synthesized from N-(1,3-dihydroxypropyl)methacrylamide (DHPMA) as a monomer and enzyme-responsive short peptide (GFLG) as a chain transfer agent. Small molecular Gd-chelate (Gd-DOTA) was conjugated onto the copolymer backbone through a sulfide bond or a GSH-sensitive cleavable disulfide bond to produce two novel Gd-mCAs (pDHPMA-Cy5.5-DOTA-Gd or pDHPMA-Cy5.5-SS-DOTA-Gd) for tumor diagnosis. Their relaxivities were 10.49 and 10.24 mM-1 s-1 respectively, which were significantly higher than that of DTPA-Gd (3.97 mM-1 s-1). Compared with pDHPMA-Cy5.5-DOTA-Gd, pDHPMA-Cy5.5-SS-DOTA-Gd had a shorter Gd(iii) retention time but maintained a sufficient contrast efficacy. We have demonstrated that the conjugation of small molecular Gd-chelate to biodegradable macromolecular carriers through a ROX-sensitive biocleavable disulfide bond may be an efficient strategy for formulating safe biodegradable Gd-based pDHPMA copolymers as MRI contrast agents.


Assuntos
Meios de Contraste/efeitos adversos , Meios de Contraste/química , Gadolínio/química , Imagem por Ressonância Magnética , Polímeros/efeitos adversos , Polímeros/química , Segurança , Animais , Meios de Contraste/farmacocinética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Imagem Óptica , Oxirredução , Polímeros/farmacocinética , Distribuição Tecidual
11.
Skin Res Technol ; 25(4): 415-423, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30767275

RESUMO

BACKGROUND: The work is aimed at the development of a methodology to characterize the tactile properties of topical products during application. Specific attention was paid to the study of the residual properties left at the surface of the skin. This approach was interestingly used to better understand the formulation factors governing the skinfeel of topical preparations. MATERIALS AND METHODS: Cosmetic and pharmaceutical topical products were selected based on their various texture, galenic form (gel or emulsion), and composition (polymer used as texturing agent). Key texture attributes namely Firmness, Stickiness, Spreadability, and Amount of residue were objectively evaluated using sensory analysis. Additionally, texture analysis (compression test), rheology (flow test), and tribology (in vivo friction test) were carried out. RESULTS: Sensory evaluations highlighted a great diversity of tactile properties among products when applied to skin. For example, assessors perceived an important amount of residue left by emulsions whereas gels were not leaving any residue after application to the skin. These results were confirmed by in vivo tactile friction measurements with two distinct evolutions in time of the residual film properties. CONCLUSION: The present investigation shows how the tactile properties of topical gels and emulsions are studied using complementary tests in order to understand and improve the skinfeel of topical preparations.


Assuntos
Cosméticos/administração & dosagem , Resíduos de Drogas/efeitos adversos , Sensação/efeitos dos fármacos , Pele/efeitos dos fármacos , Administração Tópica , Adulto , Cosméticos/efeitos adversos , Cosméticos/química , Resíduos de Drogas/química , Emulsões/efeitos adversos , Emulsões/química , Feminino , Fricção/fisiologia , Géis/efeitos adversos , Géis/química , Humanos , Pessoa de Meia-Idade , Polímeros/efeitos adversos , Reologia/métodos , Pele/fisiopatologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Propriedades de Superfície/efeitos dos fármacos , Percepção do Tato/efeitos dos fármacos
12.
Cardiovasc Pathol ; 40: 12-18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30769235

RESUMO

INTRODUCTION: Iatrogenic embolization following cardiac investigative procedures may result from hydrophilic polymer emboli (HPE) from catheter valve and vessel wall calcifications, and air embolism from open heart surgery. This retrospective clinical pathologic analysis was undertaken to ascertain the frequency and extent of these potentially fatal complications. METHODS: This retrospective clinical pathologic autopsy analysis with premortem diagnostic imaging correlation identified 110 individuals who had undergone endovascular procedures between 2010 and 2016 within 90 days of death and followed by hospital autopsy. Clinical outcomes, radiologic studies, and autopsy materials were reviewed. RESULTS: Iatrogenic emboli were assessed as causing death in 9/110 autopsy cases (8.2%) and 9/34 (26.5%) cases with proven iatrogenic emboli. Iatrogenic emboli caused strokes in 10/110 (9.1%) autopsy cases including calcified emboli (CE, n=6), HPE (n=2), cardiac valvular tissue (n=1), and air embolism (n=1). Seven cases of calcified emboli complicating endovascular procedures were identified: four of the CE were thought to be the cause of death due to fatal strokes (n=2) and fatal myocardial (n=1) and colonic infarction (n=1). The CE likely originated from calcified aortic valves and atherosclerotic aortic plaques. Histologic evidence of HPE was found in 23% (25/110) of cases; 54% (26/48) showed evidence of infarction in postprocedural imaging, with radiologic evidence of infarction in 32% (8/25) of cases with HPE histology. Endovascular aortic repair was associated with the greatest density/distribution of HPE. HPE material showed degradation with time and was often associated with an inflammatory response. HPE directly contributed to death in three cases. One fatal air embolism followed open heart surgery, and one cardiac tissue embolus resulted in a major stroke. CONCLUSIONS: We advocate for greater awareness of these underrecognized and occasionally fatal complications of endovascular procedures. Targeted postprocedural imaging has a role in the identification of iatrogenic embolic infarcts.


Assuntos
Cateterismo Cardíaco/efeitos adversos , Embolia/etiologia , Procedimentos Endovasculares/efeitos adversos , Migração de Corpo Estranho/etiologia , Doença Iatrogênica , Polímeros/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/complicações , Autopsia , Calcinose/complicações , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/mortalidade , Causas de Morte , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Embolia/diagnóstico por imagem , Embolia/mortalidade , Embolia/patologia , Embolia Aérea/etiologia , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/mortalidade , Feminino , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/mortalidade , Migração de Corpo Estranho/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
13.
Cornea ; 38(4): 502-503, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30702469

RESUMO

PURPOSE: To report a case of polyquaternium-1 (Polyquad, PQ-1)-associated dendritiform keratopathy that developed after exposure to the tear substitute Systane (Alcon Laboratories, Inc, Fort Worth, TX). METHODS: A retrospective review of the case was performed. RESULTS: Dendritiform keratopathy developed in the patient after an increase in the use of topical Systane from 4 times per day to every hour. Keratopathy resolved with discontinuation of Systane. CONCLUSIONS: Polyquaternium-1-associated dendritiform keratopathy can occur in patients who have previously tolerated the preservative. Because keratopathy seems to have developed and improved because of dose-dependent factors, the mechanism is more likely toxicity than hypersensitivity.


Assuntos
Doenças da Córnea/induzido quimicamente , Polímeros/efeitos adversos , Conservantes Farmacêuticos/efeitos adversos , Idoso , Humanos , Masculino , Soluções Oftálmicas/efeitos adversos , Estudos Retrospectivos
14.
Nanomedicine ; 17: 266-275, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30794962

RESUMO

The complement system plays an essential role in both innate and adaptive immunity. The traditional understanding of this system comes from studies investigating complement proteins produced by the liver and present in plasma to "complement" the immune cell-mediated response to invading pathogens. Recently, it has been reported that immune cells including, but not limited to, T-cells and monocytes, express complement proteins. This complement is referred to as intracellular (IC) and implicated in the regulation of T-cell activation. The mechanisms and the structure-activity relationship between nanomaterials and IC, however, are currently unknown. Herein, we describe a structure-activity relationship study demonstrating that under in vitro conditions, only polymeric materials with cationic surfaces activate IC in T-cells. The effect also depends on particle size and occurs through a mechanism involving membrane damage, thereby IC on the cell surface serves as a self-opsonization marker in response to the nanoparticle-triggered danger affecting the cell integrity.


Assuntos
Ativação do Complemento , Ativação Linfocitária , Nanopartículas/efeitos adversos , Polímeros/efeitos adversos , Linfócitos T/imunologia , Cátions/efeitos adversos , Cátions/química , Células Cultivadas , Ativação do Complemento/efeitos dos fármacos , Humanos , Células Jurkat , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Nanopartículas/química , Polímeros/química , Linfócitos T/efeitos dos fármacos
15.
PLoS One ; 14(1): e0209841, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30629613

RESUMO

Current drug-eluting stents have abluminal polymer coating; however, thrombus formation in these compared with that in uniformly coated stents remains controversial. We evaluated thrombus formation and early endothelialization after using abluminal biodegradable polymer-coated sirolimus- (BP-SES), and everolimus-eluting stents (BP-EES) versus a durable polymer-coated everolimus-eluting stent (DP-EES) in an in vivo setting. BP-SES, BP-EES, and DP-EES (n = 6 each) were implanted in coronary arteries of 12 mini-pigs that were then sacrificed after 7 and 10 days. Stents were stained with hematoxylin and eosin, and a combined Verhoeff and Masson trichrome stain. Areas of fibrin deposition were digitally detected and measured with off-line morphometric software. Stents were investigated for re-endothelialization by transmission electron microscopy. At 7 days, histological analysis revealed the lowest area of fibrin deposition in BP-SES (BP-SES vs. BP-EES vs. DP-EES; 0.10 ± 0.06 mm2 vs. 0.15 ± 0.07 mm2 vs. 0.19 ± 0.06 mm2, p = 0.0004). At 10 days, the area of fibrin deposition was significantly greater in DP-EES (0.13 ± 0.04 mm2 vs. 0.14 ± 0.05 mm2 vs. 0.19 ± 0.08 mm2, p = 0.007). Endothelial cells in BP-SES demonstrated a significantly greater number of tight junctions than those in DP-EES according to by transmission electron microscopy for both days (p<0.05). Various parameters, including an inflammatory reaction and neointimal formation, were comparable among the groups at 7 and 10 days. An abluminal biodegradable polymer-coated SES showed the least fibrin deposition and greatest endothelial cell recovery at an early stage following implantation in the coronary arteries of mini-pigs.


Assuntos
Implantes Absorvíveis , Vasos Coronários/cirurgia , Stents Farmacológicos , Polímeros/química , Animais , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/química , Angiografia Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Células Endoteliais/metabolismo , Everolimo/administração & dosagem , Everolimo/química , Fibrina/metabolismo , Modelos Animais , Intervenção Coronária Percutânea , Polímeros/administração & dosagem , Polímeros/efeitos adversos , Desenho de Prótese , Sirolimo/administração & dosagem , Sirolimo/química , Suínos , Porco Miniatura , Trombose/etiologia , Trombose/metabolismo , Resultado do Tratamento
17.
J Prosthodont ; 28(1): e304-e309, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29323779

RESUMO

PURPOSE: To see whether applying four different liners under short fiber-reinforced composite (SFRC), everX Posterior, compared to conventional composite resin, Z250, affected their strengthening property in premolar MOD cavities. MATERIALS AND METHODS: Mesio-occluso-distal (MOD) cavities were prepared in 120 sound maxillary premolars divided into 10 groups (n = 12) in terms of two composite resin types and 4 liners or no liner. For each composite resin, in 5 groups no liner, resin-modified glass ionomer (RMGI), conventional flowable composite (COFL), self-adhesive flowable composite resin (SAFL), and self-adhesive resin cement (SARC) were applied prior to restoring incrementally. After water storage and thermocycling, static fracture resistance was tested. Data (in Newtons) were analyzed using two-way ANOVA (α = 0.05). RESULTS: Fracture resistance was significantly affected by composite resin type (p = 0.02), but not by the liner (p > 0.05). The interaction of the two factors was not statistically significant (p > 0.05). SFRC exhibited higher fracture strength (1470 ± 200 N) compared to conventional composite resin (1350 ± 290), irrespective of the application of liners. Application of SARC and SAFL liners led to a higher number of restorable fractures for both composite resins. CONCLUSIONS: The four liners can be used without interfering with the higher efficacy of SFRC, compared to conventional composite resins, to improve the fracture strength of premolar MOD cavities.


Assuntos
Dente Pré-Molar/cirurgia , Resinas Compostas/uso terapêutico , Forramento da Cavidade Dentária , Restauração Dentária Permanente , Resinas Compostas/efeitos adversos , Forramento da Cavidade Dentária/efeitos adversos , Falha de Restauração Dentária , Restauração Dentária Permanente/efeitos adversos , Restauração Dentária Permanente/métodos , Análise do Estresse Dentário , Vidro , Humanos , Polímeros/efeitos adversos , Polímeros/uso terapêutico
18.
Cardiovasc Interv Ther ; 34(1): 25-33, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29349686

RESUMO

Percutaneous coronary intervention (PCI) in coronary artery disease (CAD) with very small vessels remains challenging. The aim of this study is to evaluate the safety and effectiveness of the 2.25-mm diameter Ultimaster sirolimus-eluting stent in the treatment of Japanese patients with CAD due to lesions in very small vessels. The CENTURY JSV study is a prospective, multicentre, single-arm study. Seventy patients with lesions deemed suitable for implantation of a 2.25-mm diameter stent were enrolled at seven hospitals in Japan. Patients underwent clinical follow-up at 1-, 9-month, 1-, and 2-year after the PCI procedure. The primary endpoint was the major adverse cardiac event (MACE), a composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization (TLR) free rate at 9-month following the procedure. The MACE-free rate was 97.1%, and the lower limit of the two-sided 95% confidence interval (CI) was 90.1%, which exceeded the threshold of 80% set as the performance goal. Angiographic in-stent and in-segment late loss at 9-month were 0.22 ± 0.31 and - 0.02 ± 0.34 mm, respectively. Between 9 months and 2 years, two additional TLRs occurred. Stent thrombosis, bleeding and vascular complication did not occur throughout 2 years. The 2.25-mm diameter Ultimaster® bioresorbable-polymer sirolimus-eluting stent is safe and effective for treating lesions in very small coronary arteries throughout 2 years after stent implantation.Clinical trial registration: UMIN000012928.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Sirolimo/administração & dosagem , Implantes Absorvíveis/efeitos adversos , Idoso , Fármacos Cardiovasculares/efeitos adversos , Angiografia Coronária/métodos , Vasos Coronários/cirurgia , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Polímeros/administração & dosagem , Polímeros/efeitos adversos , Estudos Prospectivos , Sirolimo/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
19.
J Neurointerv Surg ; 11(1): 80-83, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30026256

RESUMO

We report two serial neuroendovascular cases of hydrophilic polymer embolic complications, and highlight a unique case of a routine diagnostic cerebral angiogram that was complicated by delayed intracranial hemorrhage requiring surgical decompression. Histopathology specimens revealed organized intravascular thrombi with foci of non-polarizable, basophilic foreign material. Shavings from the hydrophilic coatings of a standard diagnostic catheter and guidewire share histologic characteristics with this intravascular foreign material, confirming the diagnosis of hydrophilic polymer emboli. While this phenomenon has been described for complex neurointerventional procedures, it is rare with routine diagnostic cerebral angiography. Along with a detailed literature review, these cases provides further evidence that even basic hydrophilic coated catheters and/or wires may contribute to the etiology of iatrogenic emboli in the neurovasculature with the potential for acute and subacute complications, requiring further investigation.


Assuntos
Cateterismo/efeitos adversos , Cateteres/efeitos adversos , Angiografia Cerebral/efeitos adversos , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/etiologia , Polímeros/efeitos adversos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Feminino , Corpos Estranhos , Humanos , Hemorragias Intracranianas/terapia , Masculino , Polímeros/administração & dosagem
20.
Nagoya J Med Sci ; 80(4): 597-604, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30587874

RESUMO

Carbon nanotubes (CNTs) have attracted much business interest in industrial applications due to their high electrical and heat conductivities while being both durable and versatile. However, multiwall CNTs (MWCNTs) of ~50 nm diameter (NT50) have been shown to cause mesothelioma in rodents after direct exposure to mesothelial cells, and thus were classified as a Group 2B carcinogen to humans, which requires considerable regulations for use. In contrast, tangled MWCNTs of ~15 nm diameter (NTtngl) are not carcinogenic to rats, indicating that the physical dimension linked with mesothelial cellular uptake is an important factor for human environmental risk. In the present study, hypothesizing that dustability is another distinct risk factor, for the first time, we evaluated the toxicity of CNT granules (Durobeads) that were generated with a polymer coating to mesothelial cells. Polymer coating induced prominent agglomeration and significantly suppressed the dustability of CNTs in a dose-dependent manner, with a 10% polymer coating resulting in 730 times less dustability. These CNT granules revealed significantly lower mesothelial uptake and cytotoxicity in comparison to NT50 in in vitro assays. Similarly, in in vivo analyses, CNT granules induced limited peritoneal inflammation 4 weeks after intraperitoneal injection, whereas NT50 caused severe fibrosing inflammation. Previously, we demonstrated that the severity of inflammation by intraperitoneal injection in the subacute studies are in agreement with the mesothelial carcinogenicity by CNTs. Therefore, we suggest that adding a polymer coating to CNTs provides another smart strategy for the safe use of CNTs.


Assuntos
Nanotubos de Carbono/efeitos adversos , Nanotubos de Carbono/química , Polímeros/efeitos adversos , Polímeros/química , Animais , Linhagem Celular , Humanos , Masculino , Mesotelioma/induzido quimicamente , Microscopia Eletrônica de Varredura , Nanotubos de Carbono/ultraestrutura , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA