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1.
Photodermatol Photoimmunol Photomed ; 39(6): 648-656, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37776005

RESUMO

BACKGROUND: Ablative carbon dioxide (CO2 ) laser is still a cornerstone in the management of xanthelasma. However, post-laser complications such as post-inflammatory hyperpigmentation or scarring have to be considered. Heparin sodium was recently suggested as an effective therapeutic modality for xanthelasma. OBJECTIVE: The aim of this work was to compare the therapeutic value of ablative CO2 laser versus intradermal heparin sodium in xanthelasma. METHODS: This study was piloted on 30 xanthelasma patients, whose lesions were randomly categorized into two groups. Group A was managed with CO2 laser ablation (2 sessions scheduled every 4 weeks), whereas Group B was managed with intradermal heparin sodium injections (10 sessions scheduled every week). Pre- and post-treatments evaluations were done both clinically and dermoscopically. RESULTS: Significant reduction of xanthelasma lesions was reported in response to both therapeutic interventions. However, the ablative CO2 laser was more significantly effective than intradermal heparin sodium. Interestingly, intradermal injection of heparin sodium was nearly as effective as ablative CO2 laser in early (<2 years duration) grade I and II xanthelasma, with a lower incidence of post-therapy side effects. CONCLUSIONS: Intradermal injection of heparin sodium could be suggested as a safe and cost-effective therapeutic technique for early mild grade I and II xanthelasma. Moreover, it could be recommended as a pre-operative management of grade III and IV xanthelasma to reduce the lesions to be easily ablated with CO2 laser.


Assuntos
Hiperpigmentação , Lasers de Gás , Humanos , Heparina , Lasers de Gás/uso terapêutico , Dióxido de Carbono , Hiperpigmentação/etiologia , Cicatriz , Resultado do Tratamento
2.
BMC Nephrol ; 24(1): 12, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36642717

RESUMO

BACKGROUND: Unfractionated heparin sodium and nafamostat mesylate have long been used as anticoagulants in continuous kidney replacement therapy (CKRT) where citrate is unavailable. This study aimed to determine whether heparin or nafamostat mesylate used during CKRT was associated with a longer filter life. METHODS: In this single-centre observational study, we included adult patients who required CKRT and used heparin or nafamostat mesylate for their first CKRT in the intensive care unit from September 1, 2013, to December 31, 2020. The primary outcome was filter life (from the start to the end of using the first filter). We used propensity score matching to adjust for the imbalance in patients' characteristics and laboratory data at the start of CKRT and compared the outcomes between the two groups. We also performed restricted mean survival time analysis to compare the filter survival times. RESULTS: We included 286 patients, 157 patients on heparin and 129 patients on nafamostat mesylate. After propensity score matching, the mean filter life with heparin was 1.58 days (N = 91, Standard deviation [SD], 1.52) and with nafamostat mesylate was 1.06 days (N = 91, SD, 0.94, p = 0.006). Multivariable regression analysis adjusted for confounding factors supported that heparin was associated with a longer filter life compared with nafamostat mesylate (regression coefficient, days, 0.52 [95% CI, 0.15, 0.89]). The between group difference of the restricted mean filter survival time in the matched cohort was 0.29 (95% CI, 0.07-0.50, p = 0.008). CONCLUSION: Compared to nafamostat mesylate, heparin was associated with one-third to one-half a day longer filter life. TRIAL REGISTRATION: Not applicable.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Adulto , Humanos , Heparina/uso terapêutico , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Ácido Cítrico/uso terapêutico , Injúria Renal Aguda/terapia , Terapia de Substituição Renal
3.
Mar Drugs ; 20(10)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36286469

RESUMO

Excessive inorganic ions in vivo may lead to electrolyte disorders and induce damage to the human body. Therefore, preparation of enhanced bioactivity compounds, composed of activated organic cations and organic anions, is of great interest among researchers. In this work, glucosamine-heparin salt (GHS) was primarily synthesized with positively charged glucosamine hydrochloride (GAH) and negatively charged heparin sodium (Heps) by ion exchange method. Then, the detailed structural information of the GHS was characterized by FTIR, 1H NMR spectroscopy and ICP-MS. In addition, its anticoagulant potency and antioxidant properties were evaluated, respectively. The results demonstrated that GHS salt achieved enhanced antioxidant activities, including 98.78% of O2•- radical scavenging activity, 91.23% of •OH radical scavenging rate and 66.49% of DPPH radical scavenging capacity at 1.6 mg/mL, severally. Meanwhile, anticoagulant potency (ATTP) of GHS strengthened from 153.10 ± 17.14 to 180.03 ± 6.02 at 0.75 µmol/L. Thus, introducing cationic glucosamine residues into GHS could improve its anticoagulant activity. The findings suggest that GHS product with a small amount of inorganic ions can greatly abate the prime cost of antioxidants and anticoagulants, and has significant economic benefits and practical significance.


Assuntos
Anticoagulantes , Heparina , Humanos , Heparina/farmacologia , Heparina/química , Anticoagulantes/farmacologia , Anticoagulantes/química , Antioxidantes/farmacologia , Antioxidantes/química , Glucosamina/farmacologia , Glucosamina/química , Cloreto de Sódio , Íons , Eletrólitos
4.
Ann Pharm Fr ; 80(6): 943-949, 2022 Nov.
Artigo em Francês | MEDLINE | ID: mdl-35248541

RESUMO

OBJECTIVES: Report on the practices of prescribing continuous infusion of heparin sodium by syringe pump in our hospital and shed qualitative light on the protocols used in other French hospitals. METHODS: We interviewed prescribers about the protocol they were using through the computerized provider order entry system. At the same time, we asked hospital pharmacists, particularly through a social network, whether in their hospital one or more protocols were used and which ones. RESULTS: In all, 81 prescribers responded to our request: 22 indicated prescribing the 25,000IU/50mL protocol, 7 the 20,000IU/48mL protocol, 2 the 25,000IU/48mL protocol and 14 indicated that they had no preference for one of them. Ten responded that they did not prescribe any protocols and 26 left the question unanswered. The responses of 42 pharmacists practicing in other establishments allowed us to identify 16 different protocols. Of these 42 establishments, 10 had at least two protocols. CONCLUSIONS: Several protocols for the administration by continuous infusion of heparin sodium with a syringe pump can coexist within a hospital. This diversity is confusing and puts patients and caregivers at risk of medication errors. Among all these protocols, it is not known whether some are riskier than others and research to clarify this unknown is warranted. Defining a national standard concentration of heparin and bringing to the market ready-to-administer solutions are measures to be promoted in order to reduce the risk of errors.


Assuntos
Sistemas de Registro de Ordens Médicas , Seringas , Humanos , Heparina , Erros de Medicação/prevenção & controle , Farmacêuticos
5.
Angiol Sosud Khir ; 25(4): 102-107, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31855206

RESUMO

AIM: The purpose of the study was to assess efficacy and safety of heparin sodium gel 1000 IU/g and Detragel® in decreasing the incidence and treatment of the most common local adverse reactions in patients after endured sclerotherapy of reticular veins and telangiectasias. PATIENTS AND METHODS: Our open prospective observational study included a total of sixty 18-to-35-year-old female patients who after undergoing standardized sclerotherapy of reticular veins and telangiectasias on symmetrical portions of lower limbs were given a tube of heparin sodium gel 1000 IU/g or Detragel® to be applied onto the skin of one (left) lower limb in the projection of the sclerotherapy-exposed vessels 2-3 times daily for 10 days followed by putting on a compression class 2 (RAL standard) stocking. The women were allowed to use only the paired stocking on the contralateral extremity. Efficacy and safety of heparin sodium gel 1000 IU/g and Detragel® were evaluated based on the incidence of typical adverse reactions (ecchymoses, phlebitides, hyperpigmentation and neovasculogenesis), as well as on the patient's subjective perceptions. RESULTS: The use of heparin sodium gel 1000 IU/g and Detragel® in addition to compression after sclerotherapy of reticular veins and telangiectasias significantly and comparably decreased the incidence and accelerated the resolution of ecchymoses and phlebitides associated with phlebosclerosing treatment. The Detragel® group patients were found to develop hyperpigmentation or neovasculogenesis significantly less often as compared with the heparin sodium gel 1000 IU/g group women. What is more, using Detragel® was not accompanied by hyperkeratosis, pruritus or formation of a sticky film, the events, however, observed while applying heparin sodium gel 1000 IU/g. CONCLUSION: The use of Detragel® or heparin sodium gel 1000 IU/g for 10 days additionally to compression significantly decreased the incidence of typical undesirable reactions associated with sclerotherapy of reticular veins and telangiectasias. The Detragel® group women turned out to have lower incidence of hyperpigmentation and neovasculogenesis. Besides, Detragel® demonstrated better organoleptic properties.


Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Soluções Esclerosantes/efeitos adversos , Escleroterapia/efeitos adversos , Telangiectasia/terapia , Varizes/terapia , Administração Tópica , Feminino , Géis/administração & dosagem , Humanos , Hiperpigmentação/etiologia , Hiperpigmentação/prevenção & controle , Incidência , Neovascularização Patológica/etiologia , Neovascularização Patológica/prevenção & controle , Estudos Prospectivos , Meias de Compressão
6.
J Lipid Res ; 57(4): 674-86, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26908829

RESUMO

HDL cholesterol (HDL-C) efflux function may be a more robust biomarker of coronary artery disease risk than HDL-C. To study HDL function, apoB-containing lipoproteins are precipitated from serum. Whether apoB precipitation affects HDL subspecies composition and function has not been thoroughly investigated. We studied the effects of four common apoB precipitation methods [polyethylene glycol (PEG), dextran sulfate/magnesium chloride (MgCl2), heparin sodium/manganese chloride (MnCl2), and LipoSep immunoprecipitation (IP)] on HDL subspecies composition, apolipoproteins, and function (cholesterol efflux and reduction of LDL oxidation). PEG dramatically shifted the size distribution of HDL and apolipoproteins (assessed by two independent methods), while leaving substantial amounts of reagent in the sample. PEG also changed the distribution of cholesterol efflux and LDL oxidation across size fractions, but not overall efflux across the HDL range. Dextran sulfate/MgCl2, heparin sodium/MnCl2, and LipoSep IP did not change the size distribution of HDL subspecies, but altered the quantity of a subset of apolipoproteins. Thus, each of the apoB precipitation methods affected HDL composition and/or size distribution. We conclude that careful evaluation is needed when selecting apoB depletion methods for existing and future bioassays of HDL function.


Assuntos
Apolipoproteínas B/deficiência , Apolipoproteínas B/isolamento & purificação , Precipitação Química , Lipoproteínas LDL/metabolismo , Adulto , Apolipoproteína A-I/metabolismo , Apolipoproteínas B/metabolismo , Transporte Biológico/efeitos dos fármacos , Precipitação Química/efeitos dos fármacos , Cloretos/farmacologia , HDL-Colesterol/química , HDL-Colesterol/metabolismo , Sulfato de Dextrana/farmacologia , Feminino , Heparina/farmacologia , Humanos , Lipoproteínas LDL/química , Compostos de Manganês/farmacologia , Oxirredução/efeitos dos fármacos , Tamanho da Partícula , Polietilenoglicóis/farmacologia
7.
Pharm Res ; 33(11): 2828-43, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27511028

RESUMO

PURPOSE: Heparin sodium (HS)-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (HPTNs) were prepared as a sustained and targeting delivery carrier and combined with emodin (EMO)-loaded PLGA-TPGS nanoparticles (EPTNs), which were investigated previously to form a combination therapy system for the treatment of liver cancer. METHODS: To assess cellular uptake and evaluate the liver-targeting capacity by analyzing the drug concentrations and frozen slices, HS/eosin-loaded PLGA-TPGS nanoparticles, HS/fluorescein- loaded PLGA-TPGS nanoparticles and EMO/C6-loaded PLGA-TPGS nanoparticles, which contained eosin, fluorescein and C6 as fluorescent probes, respectively, were also prepared. All of these nanoparticles were characterized in terms of their size, size distribution, surface charge, drug loading, encapsulation efficiency, in vitro release profile and cellular uptake. The apoptosis of HepG2 cells induced by EPTNs in combination with HPTNs was determined by Annexin V-FITC staining and PI labelling. RESULTS: Transmission electron microscopy indicated that these nanoparticles were stably dispersed spheres with sizes ranging from 100 to 200 nm. The results demonstrated that fluorescent nanoparticles were internalized into HepG2 and HCa-F cells efficiently and had improved liver-targeting properties. The combination of EPTNs and HPTNs effectively inhibited cell growth in vitro and had a remarkable synergistic anticancer effect in vivo. EPTNs combined with HPTNs induced HepG2 cell apoptosis with synergistic effects. The liver H&E slice images of a hepatocarcinogenic mouse model indicated that EPTNs in combination with HPTNs significantly suppressed tumour growth in vivo. CONCLUSIONS: The research suggests that the combination therapy system of EPTNs and HPTNs could be a new direction for liver cancer therapy.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Antineoplásicos/farmacologia , Emodina/farmacologia , Heparina/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Vitamina E/química , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos , Liberação Controlada de Fármacos , Emodina/administração & dosagem , Emodina/química , Corantes Fluorescentes/química , Heparina/administração & dosagem , Heparina/química , Humanos , Masculino , Camundongos , Tamanho da Partícula , Propriedades de Superfície
8.
Cureus ; 16(2): e54436, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38510884

RESUMO

Purpose Thrombophlebitis is a frequent intravenous (IV) therapy consequence. Topical heparin for seven days is used as a treatment for thrombophlebitis. This study was performed to evaluate the clinical safety and effectiveness of the combination of heparin sodium & benzyl nicotinate (Thrombophob Ointment, manufactured by Zydus Healthcare Ltd., Ahmedabad, India) in thrombophlebitis patients in India. Methods A study carried out by 118 Indian doctors examined 2002 thrombophlebitis patients from 2016-2023, prescribing ointment containing heparin sodium and benzyl nicotinate. Patients were followed up on day three and day seven after starting the treatment, and safety and effectiveness were recorded, including adverse events. Result A total of 2002 patients were included in the study and males were predominant (58.15%). IV fluids (60.58%) were the leading cause of thrombophlebitis. The study found notable improvements in key markers of venous health over time. Compared to baseline, patients experienced significantly reduced severity of phlebitis, shorter venous lesion lengths, and lower pain and tenderness scores by both day 3 and day 7 (p<0.001 for all comparisons). Furthermore, these improvements continued between day 3 and day 7, indicating sustained positive effects (p<0.001 for all comparisons). After the application of the ointment, very few patients experienced adverse effects (0.25% on day three and 0.05% on day seven). Treatment effectiveness was excellent in 72% of patients, and treatment safety was excellent in 93% of patients. Conclusion The ointment containing heparin sodium and benzyl nicotinate was well tolerated and efficacious in the treatment of thrombophlebitis in Indian patients.

9.
Biologicals ; 41(6): 355-63, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23827519

RESUMO

Heparin is a sulfated glycosaminoglycan (GAG), which contains N-acetylated or N-sulfated glucosamine (GlcN). Heparin, which is generally obtained from the healthy porcine intestines, is widely used as an anticoagulant during dialysis and treatments of thrombosis such as disseminated intravascular coagulation. Dermatan sulfate (DS) and chondroitin sulfate (CS), which are galactosamine (GalN)-containing GAGs, are major process-related impurities of heparin products. The varying DS and CS contents between heparin products can be responsible for the different anticoagulant activities of heparin. Therefore, a test to determine the concentrations of GalN-containing GAG is essential to ensure the quality and safety of heparin products. In this study, we developed a method for determination of relative content of GalN from GalN-containing GAG in heparin active pharmaceutical ingredients (APIs). The method validation and collaborative study with heparin manufacturers and suppliers showed that our method has enough specificity, sensitivity, linearity, repeatability, reproducibility, and recovery as the limiting test for GalN from GalN-containing GAGs. We believe that our method will be useful for ensuring quality, efficacy, and safety of pharmaceutical heparins. On July 30, 2010, the GalN limiting test based on our method was adopted in the heparin sodium monograph in the Japanese Pharmacopoeia.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Medicamentos/prevenção & controle , Galactosamina/análise , Heparina/análise , Sulfatos de Condroitina/análise , Sulfatos de Condroitina/química , Dermatan Sulfato/análise , Dermatan Sulfato/química , Corantes Fluorescentes/química , Heparina/química , Hidrólise , Modelos Químicos , Reprodutibilidade dos Testes , para-Aminobenzoatos/química
10.
Ann Cardiol Angeiol (Paris) ; 72(4): 101645, 2023 Oct.
Artigo em Francês | MEDLINE | ID: mdl-37660586

RESUMO

OBJECTIVES: Several protocols for administering heparin by electric syringe pump can coexist within the same hospital. This puts patients at risk of medication errors. In our hospital trust, two preparation protocols coexist (20000UI/48mL and 25000UI/50mL). The objective is to relate the work carried out with prescribers and nurses to retain only one protocol. METHODS: We questioned prescribers and nurses about the differences between the two protocols in terms of the simplicity of implementation and the risk of error to which nurses are exposed when preparing the syringe. Contextual information (heparin shortage, waste) was given in order to support the answers. RESULTS: According to the 96 nurses and 82 prescribers who responded, the protocol to use is 25000IU/50mL for 98% and 83% of them respectively. The 20000IU/48mL protocol was considered the riskiest due to the possibility of mistakenly collecting 5mL instead of the required 4mL. Given the heparin shortage, the waste inherent to the 20000IU/48mL protocol reinforced this choice. CONCLUSIONS: The consultation of nurses and prescribers allowed the choice of a protocol with very strong agreement. This work also brought to light what appears to be a medical misconception, namely that the non-concerted choice by physicians of a mode of administration of a drug can put nurses in a situation to make preparation errors more frequently. This emphasizes that nurses must be stakeholders in the decision-making processes that affect their practice.

11.
Carbohydr Polym ; 314: 120956, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37173047

RESUMO

Chlorella is one of the most widely cultivated species of microalgae and has been consumed as a "green healthy food". In this study, a novel polysaccharide (CPP-1) was isolated from Chlorella pyrenoidosa, structurally analyzed, and sulfated as a promising anticoagulant. Structural analyses by chemical and instrumental methods such as monosaccharide composition, methylation-GC-MS and 1D/2D NMR spectroscopy analysis revealed that CPP-1 had a molecular weight of ~13.6 kDa, and mainly consisted of d-mannopyranose (d-Manp), 3-O-methylated d-Manp (3-O-Me-d-Manp), and d-galactopyranose (d-Galp). The molar ratio of d-Manp and d-Galp was 1.0:2.3. CPP-1 consisted of a (1→6)-linked ß-d-Galp backbone substituted at C-3 by the d-Manp and 3-O-Me-d-Manp residues in a molar ratio of 1:1, which was a regular mannogalactan. The sulfated Chlorella mannogalactan (SCM) with sulfated group content of 40.2 % equivalent to that of unfractionated heparin was prepared and analyzed. NMR analysis confirmed its structure, indicating that most free hydroxyl groups in the side chains and partial hydroxyl groups in the backbone were sulfated. Anticoagulant activity assays indicated that SCM exhibited strong anticoagulant activity by inhibiting intrinsic tenase (FXase) with IC50 of 13.65 ng/mL, which may be a safer anticoagulant as an alternative to heparin-like drugs.


Assuntos
Anticoagulantes , Chlorella , Anticoagulantes/farmacologia , Heparina/farmacologia , Sulfatos/química , Polissacarídeos/química
12.
J Cosmet Dermatol ; 21(9): 3888-3895, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34982507

RESUMO

BACKGROUND: Unlike various topical treatment options for acne vulgaris, options for acne scars mostly involve invasive interventions. So far, only a few clinical trials have investigated the effects of topical treatment for acne scars. OBJECTIVES: We evaluated the safety and efficacy of DA-5520, a recently developed topical gel for the treatment of different types of acne scars. METHODS: A 12-week prospective, randomized, active-controlled, evaluator-blind, single-center study involving 36 participants with acne scars was performed. Participants were randomized into four different groups at a 1:1:1:1 ratio: laser resurfacing with DA-5520 application (test 1); laser resurfacing without DA-5520 application (control 1); comedone extraction with DA-5520 application (test 2); and comedone extraction without DA-5520 application (control 2). For 12 weeks, participants in the two test groups applied DA-5520 twice daily, while participants in the control groups applied moisturizers alone. Participants in the test 1 and control 1 groups received a single session of laser resurfacing at visit 1 (week 0). All participants were followed up at 1, 4, 8, and 12 weeks, and objective scar evaluation using the échelle d'évaluation clinique des cicatrices d'acné (ECCA) score was performed at each visit. RESULTS: Clinical improvement of acne scars, confirmed by the ECCA grading scale (1 for atrophic scar and 2 for hypertrophic scar), was observed after using DA-5520 when combined with laser resurfacing or individually, and no associated adverse reactions were noted. CONCLUSIONS: Preliminary results of this study revealed that DA-5520 may be a promising new formulation for treating all type of acne scars.


Assuntos
Acne Vulgar , Cicatriz Hipertrófica , Acne Vulgar/complicações , Atrofia , Cicatriz/terapia , Géis , Humanos , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
13.
Carbohydr Polym ; 298: 120072, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36241268

RESUMO

Stichopus monotuberculatus is a tropical sea cucumber species and used as a folk medicine and tonic food. In this study, a fucosylated glycosaminoglycan (SmFG), the depolymerized SmFG (dSmFG) and its oligosaccharide fractions were prepared. The SmFG and its depolymerized products were comprised of a chondroitin-sulfate-E backbone, and various sulfated fucose side chains, including an unusual disaccharide side chain connected to the C-3 position of D-glucuronic acid (GlcA) or GlcA-ol. A peeling reaction occurred during the deaminative depolymerization process. The dSmFG and its fractions showed strong anticoagulant activity by selectively inhibiting intrinsic tenase complex, and had no anti-factor IIa, Xa and VIIa activity. The anticoagulant activity reduced with the decrease of molecular weight, and the unusual branch and novel reducing end may enhance the anticoagulant activity. These findings can provide significant information for development and utilization of depolymerized products from SmFG in food and pharmaceutical industries.


Assuntos
Glicosaminoglicanos , Pepinos-do-Mar , Animais , Anticoagulantes/química , Anticoagulantes/farmacologia , Sulfatos de Condroitina/química , Dissacarídeos , Fucose/química , Ácido Glucurônico , Glicosaminoglicanos/química , Glicosaminoglicanos/farmacologia , Oligossacarídeos/química , Pepinos-do-Mar/química , Sulfatos
14.
J Drug Target ; 29(1): 60-68, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32649227

RESUMO

The aim of this study was to develop heparin sodium loaded microneedle patches using different compositions of polyvinyl alcohol polymer and sorbitol. A vacuum micromolding technique was used to fabricate microneedle patches while heparin sodium was loaded into needle tips. Physical features of patches were evaluated by measuring thickness, width, folding endurance and swelling percentage. Patches were also characterised by optical microscopy and scanning electron microscopy to determine the microneedle length and surface morphologies. A preliminary assessment of the microneedle performance was studied by examining the in-vitro insertion to the parafilm and recording the in-vitro drug release profile. In-vivo activity of patches was confirmed by measuring activated partial thromboplastin time and histological examination of the micropierced skin tissues. Prepared patches were clear, smooth; uniform in appearance; with sharp pointed microprojections and remained intact after 1000 folding. The microneedles were stiffer in nature, as they reproduce microcavities in the parafilm membrane following hand pushing without any structural loss. Insertion study results showed successful insertion of microneedles into the parafilm. Disrupted stratum corneum evident from histological examination confirmed successful insertion of the microneedle without affecting the vasculature. In-vitro release study confirmed ∼92% release of the loaded drug within 120 min. A significant prolongation of activated partial thromboplastin time (4 folds as compared to negative control) was recorded following the application of heparin sodium loaded microneedle patch onto rabbit skin. In conclusion microneedles are a valuable drug delivery system, benefiting the patients with minimal skin invasion and also allowing self-administration of heparin sodium in a sustained release manner for the management of chronic ailments.


Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Microinjeções/métodos , Agulhas , Pele/efeitos dos fármacos , Adesivo Transdérmico , Administração Cutânea , Animais , Feminino , Heparina/metabolismo , Masculino , Microinjeções/instrumentação , Coelhos , Pele/metabolismo
15.
Carbohydr Polym ; 241: 116284, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32507170

RESUMO

Gradual wear and tear can cause a local inflammatory response in tendons. The trauma and inflammatory reaction eventually impair the biomechanical properties of the tendon. In this study, we prepared lactoferrin-immobilized, heparin-anchored, poly(lactic-co-glycolic acid) nanoparticles (LF/Hep-PLGA NPs) and evaluated their in vitro anti-inflammatory effects on interleukin-1ß (IL-1ß)-treated tenocytes and in vivo tendon healing effects in a rat model of Achilles tendinitis. Long-term LF-deliverable NPs (LF/Hep-PLGA NPs) remarkably decreased mRNA levels of pro-inflammatory factors [cyclooxygenase-2 (COX-2), IL-1ß, matrix metalloproteinase-3 (MMP-3), MMP-13, IL-6, and tumor necrosis factor-α (TNF-α)] and increased mRNA levels of anti-inflammatory cytokines (IL-4 and IL-10) in both IL-1ß-treated tenocytes and the Achilles tendons of a collagenase-induced Achilles tendinitis rat model. Interestingly, anti-inflammatory LF/Hep-PLGA NPs greatly enhanced collagen content, mRNA levels of tenogenic markers [collagen type I (COL1A1), decorin (DCN), tenascin-C (TNC)], and biomechanical properties such as tendon stiffness and tensile strength. These results suggest that anti-inflammatory LF/Hep-PLGA NPs are effective at restoring tendons in Achilles tendinitis.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Anti-Inflamatórios/administração & dosagem , Heparina/administração & dosagem , Lactoferrina/administração & dosagem , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Tendinopatia/tratamento farmacológico , Tendão do Calcâneo/metabolismo , Tendão do Calcâneo/patologia , Tendão do Calcâneo/fisiologia , Animais , Anti-Inflamatórios/química , Colágeno/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Heparina/química , Lactoferrina/química , Masculino , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Sprague-Dawley , Tendinopatia/genética , Tendinopatia/metabolismo , Tendinopatia/patologia , Tenócitos/efeitos dos fármacos , Resistência à Tração
17.
Carbohydr Polym ; 209: 372-381, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30732820

RESUMO

In this study, we prepared the platelet-derived growth factor-containing porous microspheres modified with heparin (PDGF/Hep-PMSs) and investigated their anti-inflammatory and tendon healing effects on rotator cuff (RC) tendinitis rabbit model. PDGF/Hep-PMSs suppressed the mRNA levels of six pro-inflammatory cytokines (i.e., MMP-3, MMP-13, COX-2, ADAMTS-5, IL-6, and TNF-α) in inflamed tenocytes. Long-term local delivery of PDGF/Hep-PMSs into tendon tissues of RC tendinitis decreased the mRNA levels of six pro-inflammatory cytokines and increased the mRNA levels of anti-inflammatory cytokines including IL-4, IL-10, and IL-13. Anti-inflammatory effects of PDGF/Hep-PMSs might have contributed to enhance the collagen content, tenogenic markers, stiffness, and tensile strength of tendons, eventually leading to tendon restoration. Our findings suggest that the long-term local PDGF delivery of PDGF/Hep-PMSs have a great potential to enhance tendon healing of RC tendinitis by suppressing inflammation responses.


Assuntos
Portadores de Fármacos/química , Heparina/química , Microesferas , Fator de Crescimento Derivado de Plaquetas/química , Fator de Crescimento Derivado de Plaquetas/farmacologia , Lesões do Manguito Rotador/tratamento farmacológico , Tendões/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Dopamina/química , Liberação Controlada de Fármacos , Fator de Crescimento Derivado de Plaquetas/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porosidade , Coelhos , Lesões do Manguito Rotador/patologia , Lesões do Manguito Rotador/fisiopatologia , Propriedades de Superfície , Tendões/patologia , Tendões/fisiopatologia , Fatores de Tempo
18.
Adv Mater ; 30(22): e1706924, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29667243

RESUMO

Traps in the photoactive layer or interface can critically influence photovoltaic device characteristics and stabilities. Here, traps passivation and retardation on device degradation for methylammonium lead trihalide (MAPbI3 ) perovskite solar cells enabled by a biopolymer heparin sodium (HS) interfacial layer is investigated. The incorporated HS boosts the power conversion efficiency from 17.2 to 20.1% with suppressed hysteresis and Shockley-Read-Hall recombination, which originates primarily from the passivation of traps near the interface between the perovskites and the TiO2 cathode. The incorporation of an HS interfacial layer also leads to a considerable retardation of device degradation, by which 85% of the initial performance is maintained after 70 d storage in ambient environment. Aided by density functional theory calculations, it is found that the passivation of MAPbI3 and TiO2 surfaces by HS occurs through the interactions of the functional groups (COO- , SO3- , or Na+ ) in HS with undersaturated Pb and I ions in MAPbI3 and Ti4+ in TiO2 . This work demonstrates a highly viable and facile interface strategy using biomaterials to afford high-performance and stable perovskite solar cells.

19.
Clin Chim Acta ; 487: 337-340, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30317021

RESUMO

BACKGROUND: It is known that an immunoglobulin abnormality affects various clinical laboratory measurements and leads to abnormal values. We experienced a case of monoclonal gammopathy of undetermined significance (MGUS) showing a falsely low plasma glycated albumin (GA) level. CASE REPORT: The patient was a 75-y-old male who visited our hospital for thrombocytosis identified during a medical checkup. Based on further examinations, he was diagnosed with MGUS (IgM-κ type). Laboratory examinations revealed that the plasma GA level was significantly low at -1.3% but the serum GA level was reasonable at 15.5%. We investigated the cause of the falsely low plasma GA level. RESULTS: The patient's plasma became turbid after mixing with the first reagent for GA measurement. The plasma GA level was increased by dilution of the plasma. The plasma GA level was falsely decreased only at the time of measurement on a sample collected using a blood-collecting tube with heparin sodium. The GA level was decreased by adding heparin sodium to the patient's serum, whereas the GA level was increased by neutralization of the patient's plasma with protamine sulfate. The GA level was increased after adding polyethylene glycol to the patient's plasma. Serum GA levels in healthy controls were decreased by adding purified M protein from the patient's serum. CONCLUSIONS: We report a patient with MGUS whose plasma GA concentration was falsely decreased by M protein when blood was drawn in a heparin sodium-containing tube.


Assuntos
Imunoglobulina M/sangue , Gamopatia Monoclonal de Significância Indeterminada/sangue , Albumina Sérica/análise , Idoso , Produtos Finais de Glicação Avançada , Humanos , Imunoglobulina M/imunologia , Masculino , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Albumina Sérica/imunologia , Albumina Sérica Glicada
20.
Mater Sci Eng C Mater Biol Appl ; 78: 854-861, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28576059

RESUMO

PCU (polycarbonate polyurethane) is supposed to be an ideal elastomer for manufacturing artificial vessel scaffold with perfect mechanical strength and biocompatibility. Surface grafting by heparin sodium can increase its anticoagulant hemorrhagic, achieving a better application in artificial vessels. Artificial vessels were preliminarily prepared by electrostatic spinning, treated by NH3 plasma and cross-linked with the anticoagulant heparin sodium chemically. Performances of the PCU-Hep (heparin sodium grafted purethane artificial vessels) artificial vessel were calculated through the physical and chemical property tests, evaluation of blood and biocompatibility. Results manifested that heparin sodium was successfully grafted to the vascular surface, porosity, pore diameter and water permeability of the vascular prosthesis fitted the requirements of artificial vessels, the blood test results demonstrated that the vascular material had a low hemolysis, in vitro cytotoxicity experiment and animal experiments proved an excellent biocompatibility. Thus the heparin sodium grafted electrospinning vessels could reduce intravascular thrombus and had potential clinical application.


Assuntos
Heparina/química , Animais , Materiais Biocompatíveis , Substitutos Sanguíneos , Prótese Vascular , Cimento de Policarboxilato , Poliuretanos , Porosidade , Alicerces Teciduais
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