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1.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-34209248

RESUMEN

Starting from indomethacin (IND), one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs), new nitric oxide-releasing indomethacin derivatives with 1,3,4-oxadiazole-2-thiol scaffold (NO-IND-OXDs, 8a-p) have been developed as a safer and more efficient multitarget therapeutic strategy. The successful synthesis of designed compounds (intermediaries and finals) was proved by complete spectroscopic analyses. In order to study the in silico interaction of NO-IND-OXDs with cyclooxygenase isoenzymes, a molecular docking study, using AutoDock 4.2.6 software, was performed. Moreover, their biological characterization, based on in vitro assays, in terms of thermal denaturation of serum proteins, antioxidant effects and the NO releasing capacity, was also performed. Based on docking results, 8k, 8l and 8m proved to be the best interaction for the COX-2 (cyclooxygense-2) target site, with an improved docking score compared with celecoxib. Referring to the thermal denaturation of serum proteins and antioxidant effects, all the tested compounds were more active than IND and aspirin, used as references. In addition, the compounds 8c, 8h, 8i, 8m, 8n and 8o showed increased capacity to release NO, which means they are safer in terms of gastrointestinal side effects.


Asunto(s)
Ciclooxigenasa 2/química , Indometacina , Simulación del Acoplamiento Molecular , Óxido Nítrico/química , Oxadiazoles , Humanos , Indometacina/síntesis química , Indometacina/química , Oxadiazoles/síntesis química , Oxadiazoles/química
2.
Medicina (Kaunas) ; 55(7)2019 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-31269687

RESUMEN

Background and objectives: The etiology of anemia associated with heart failure is not fully understood, but there are data suggesting the involvement of multiple mechanisms, including various drug therapies used in patients with heart failure. Our primary objective was to evaluate the impact of beta blockers, angiotensin-converting enzyme inhibitors, and calcium-channel blockers on iron metabolism in patients with heart failure. Materials and Methods: This was a prospective observational study that included patients diagnosed with heart failure and iron deficiency (defined by ferritin <100 µg/L, or 100-300 µg/L with transferrin saturation <20%). Patients with anemia secondary to a known cause were excluded. Results: We found a statistically significant correlation between beta-blocker treatment and ferritin values (p = 0.02). Iron, hemoglobin, and hematocrit levels were significantly lower in the patients using calcium-channel blockers than those who were not. We also found a statistically significant indirect correlation (p = 0.04) between the use of angiotensin-converting enzyme inhibitors and hematocrit levels. Conclusion: The contribution of our study arises from the additional data regarding the drug-induced etiology of iron deficiency. Practitioners should be aware of the potential impact of therapeutic recommendations and this should imply a close monitoring of the biochemical parameters of iron deficiency in this category of patients.


Asunto(s)
Anemia/etiología , Insuficiencia Cardíaca/tratamiento farmacológico , Trastornos del Metabolismo del Hierro/etiología , Antagonistas Adrenérgicos beta/efectos adversos , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Anemia/sangre , Anemia/complicaciones , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Femenino , Insuficiencia Cardíaca/sangre , Humanos , Hierro/análisis , Hierro/sangre , Trastornos del Metabolismo del Hierro/sangre , Masculino , Persona de Mediana Edad
3.
J Org Chem ; 82(24): 13700-13707, 2017 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-29131628

RESUMEN

This work reports the design of [1,3,4]thiadiazolo[3',2':1,2]imidazo[4,5-c]quinolines using a Pictet-Spengler reaction. The scope of the reaction was achieved from 6-(2-aminophenyl)imidazo[2,1-b][1,3,4]thiadiazole derivatives and available aldehydes. A wide range of aldehydes were employed to examine the scope of the cyclization. In parallel, a mechanism investigation was realized and showed a hydride transfer which led to a dismutation of the intermediate species. To complete this methodological study, a "sequential" oxidation/SNAr procedure was performed to achieve C-2 nucleophilic substitution using several amine types.

4.
Molecules ; 21(7)2016 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-27367664

RESUMEN

The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems.


Asunto(s)
Alendronato/administración & dosificación , Conservadores de la Densidad Ósea/administración & dosificación , Sistemas de Liberación de Medicamentos , Liposomas , Administración Oral , Administración Tópica , Rastreo Diferencial de Calorimetría , Portadores de Fármacos , Liberación de Fármacos , Lípidos/química , Liposomas/química , Liposomas/ultraestructura , Análisis Espectral , Difracción de Rayos X
5.
Int J Mol Sci ; 16(12): 29843-55, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26694354

RESUMEN

The objective of this study was to develop new films based on chitosan functionalized with sulfonamide drugs (sulfametoxydiazine, sulfadiazine, sulfadimetho-xine, sulfamethoxazol, sulfamerazine, sulfizoxazol) in order to enhance the biological effects of chitosan. The morphology and physical properties of functionalized chitosan films as well the antioxidant effects of sulfonamide-chitosan derivatives were investigated. The chitosan-derivative films showed a rough surface and hydrophilic properties, which are very important features for their use as a wound dressing. The film based on chitosan-sulfisoxazol (CS-S6) showed the highest swelling ratio (197%) and the highest biodegradation rate (63.04%) in comparison to chitosan film for which the swelling ratio was 190% and biodegradation rate was only 10%. Referring to the antioxidant effects the most active was chitosan-sulfamerazine (CS-S5) which was 8.3 times more active than chitosan related to DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging ability. This compound showed also a good ferric reducing power and improved total antioxidant capacity.


Asunto(s)
Vendajes , Quitosano/farmacología , Sulfonamidas/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antioxidantes/farmacología , Compuestos de Bifenilo/química , Depuradores de Radicales Libres/química , Procesamiento de Imagen Asistido por Computador , Pruebas de Sensibilidad Microbiana , Microscopía de Fuerza Atómica , Oxidación-Reducción , Picratos/química , Propiedades de Superficie , Agua/química
6.
Molecules ; 19(9): 13824-47, 2014 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-25255761

RESUMEN

New thiazolidine-4-one derivatives based on the 4-aminophenazone (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one) scaffold have been synthesized as potential anti-inflammatory drugs. The pyrazoline derivatives are known especially for their antipyretic, analgesic and anti-inflammatory effects, but recently there were synthesized new compounds with important antioxidant, antiproliferative, anticancer and antidiabetic activities. The beneficial effects of these compounds are explained by nonselective inhibition of cyclooxygenase izoenzymes, but also by their potential scavenging ability for reactive oxygen and nitrogen species. The structure of the new compounds was proved using spectroscopic methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the ferric reducing antioxidant power, phosphomolydenum reducing antioxidant power, DPPH and ABTS radical scavenging assays. The chemical modulation of 4-aminophenazone (6) through linkage to thiazolidine-propanoic acid derivatives 5a-l led to improved antioxidant potential, all derivatives 7a-l being more active than phenazone. The most active compounds are the derivatives 7e, and 7k, which showed the higher antioxidant effect depending on the antioxidant assay considered.


Asunto(s)
Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Pirazoles/química , Tiazolidinas/química , Tiazolidinas/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Espectroscopía de Resonancia Magnética , Tiazolidinas/síntesis química
7.
Molecules ; 19(9): 15005-25, 2014 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-25237755

RESUMEN

New thiazolidine-4-one derivatives of 2-(4-isobutylphenyl)propionic acid (ibuprofen) have been synthesized as potential anti-inflammatory drugs. The structure of the new compounds was proved using spectral methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the total antioxidant activity, the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be involved in many pathological events like diabetes mellitus, neurodegenerative diseases, cancer, infections and more recently, in inflammation. It is known that overproduction of free radicals may initiate and amplify the inflammatory process via upregulation of genes involved in the production of proinflammatory cytokines and adhesion molecules. The chemical modulation of acyl hydrazones of ibuprofen 3a-l through cyclization to the corresponding thiazolidine-4-ones 4a-n led to increased antioxidant potential, as all thiazolidine-4-ones were more active than their parent acyl hydrazones and also ibuprofen. The most active compounds are the thiazolidine-4-ones 4e, m, which showed the highest DPPH radical scavenging ability, their activity being comparable with vitamin E.


Asunto(s)
Propionatos/síntesis química , Propionatos/farmacología , Antioxidantes/farmacología , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Propionatos/química , Espectroscopía Infrarroja por Transformada de Fourier
8.
Polymers (Basel) ; 16(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000680

RESUMEN

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders, with a major involvement of oxidative stress in its onset and progression. Pioglitazone (Pio) is an antidiabetic drug that mainly works by reducing insulin resistance, while curcumin (Cur) is a powerful antioxidant with an important hypoglycemic effect. Both drugs are associated with several drawbacks, such as reduced bioavailability and a short half-life time (Pio), as well as instability and poor water solubility (Cur), which limit their therapeutic use. In order to overcome these disadvantages, new co-delivery (Pio and Cur) chitosan-based nanoparticles (CS-Pio-Cur NPs) were developed and compared with simple NPs (CS-Pio/CS-Cur NPs). The NPs were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). In addition, the entrapment efficiency (EE) and loading capacity (LC), as well as the release profile, of the APIs (Pio and Cur) from the CS-APIs NPs in simulated fluids (SGF, SIF, and SCF) were also assessed. All the CS-APIs NPs presented a small particle size (PS) (211.6-337.4 nm), a proper polydispersity index (PI) (0.104 and 0.289), and a positive zeta potential (ZP) (21.83 mV-32.64 mV). Based on the TEM results, an amorphous state could be attributed to the CA-APIs NPs, and the TEM analysis showed a spherical shape with a nanometric size for the CS-Pio-Cur NPs. The FT-IR spectroscopy supported the successful loading of the APIs into the CS matrix and proved some interactions between the APIs and CS. The CS-Pio-Cur NPs presented increased or similar EE (85.76% ± 4.89 for Cur; 92.16% ± 3.79 for Pio) and LC% (23.40% ± 1.62 for Cur; 10.14% ± 0.98 for Pio) values in comparison with simple NPs, CS-Cur NPs (EE = 82.46% ± 1.74; LC = 22.31% ± 0.94), and CS-Pio NPs (EE = 93.67% ± 0.89; LC = 11.24% ± 0.17), respectively. Finally, based on the release profile results, it can be appreciated that the developed co-delivery nanosystem, CS-Pio-Cur NPs, assures a controlled and prolonged release of Pio and Cur from the polymer matrix along the GI tract.

9.
Molecules ; 18(8): 9684-703, 2013 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-23945643

RESUMEN

Starting from theophylline (1,3-dimethylxanthine) new thiazolidin-4-one derivatives 7a1₋7, 7b1₋7 have been synthesized as potential antidiabetic drugs. The structure of the new derivatives was confirmed using spectral methods (FT-IR, ¹H-NMR, ¹³C-NMR). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the ferric reducing power, the total antioxidant activity and the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be implicated in a variety of pathological events, such as diabetes mellitus and its micro- and macrovascular complications. The results of chemical modulation of the thiazolidin-4-one intermediaries 6a, 6b through condensation with several aromatic aldehydes is the improvement of the antioxidant effect. All benzylidenethiazolidin-4-one derivatives 7a1₋7, 7b1₋7 are more active than their parent thiazolidin-4-ones. The most active compounds are the ones obtained by reaction of condensation with 4-hydroxybenzaldehyde (compounds 7a5, 7a6), 4-dimethylaminobenzaldehyde (compounds 7a6, 7b6) and 2-nitrobenzaldehyde (compounds 7a7, 7b7).


Asunto(s)
Benzaldehídos/síntesis química , Xantina/síntesis química , Antioxidantes/metabolismo , Benzaldehídos/farmacología , Radicales Libres/química , Espectroscopía de Resonancia Magnética , Oxidación-Reducción , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad , Xantina/farmacología
10.
Molecules ; 18(4): 4140-57, 2013 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-23567362

RESUMEN

New series of N-(arylidene)hydrazinoacetyl sulfonamides 4a1-6, 4b1-6 and N-(4-aryl-3-chloro-2-oxoazetidin-1-yl)aminoacetyl sulfonamides 5a1-6, 5b1-6 were synthesized. The structures of the new derivatives was confirmed using spectral methods (FT-IR, 1H-NMR, 13C-NMR). The antibacterial activities of these compounds against Gram positive (Staphylococcus aureus ATCC 6583, Staphylococcus epidermidis ATCC 12228, Enterococcus faecalis ATCC 25912) and Gram negative (Klebsiella pneumoniae CIP 53153, Proteus vulgaris CIP 104989, Citrobacter freundii CIP 5732, Enterobacter cloacae CIP 103475, Escherichia coli ATCC 25922, Pseudomonas aeruginosa CIP 82118) bacterial strains were evaluated using the broth micro-dilution method. Compound 4a2 displayed the highest antibacterial activity, especially against Staphylococcus epidermidis, Enterococcus faecalis and Pseudomonas aeruginosa. The antioxidant potential of the synthesized compounds was also investigated according to ferric reducing power, total antioxidant activity and DPPH radical scavenging assays. All tested compounds showed excellent antioxidant activity in comparison with sulfadiazine and sulfisoxazole which were used as parent sulfonamides. Moreover, some of them showed an antioxidant activity comparable with that of ascorbic acid. In general, the compounds designed based on a sulfadiazine skeleton (compounds 4a1-6, 5a1-6) are more active than those obtained from sulfisoxazole (compounds 4b1-6, 5b1-6), and the N-(arylidene)hydrazinoacetyl sulfonamide derivatives 4a1-6, 4b1-6 are more active than their azetidionone analogues 5a1-6, 5b1-6.


Asunto(s)
Antibacterianos/síntesis química , Antioxidantes/síntesis química , Azetidinas/síntesis química , Sulfonamidas/química , Antibacterianos/farmacología , Antioxidantes/farmacología , Azetidinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad
11.
Pharmaceutics ; 15(3)2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36986836

RESUMEN

Wound management represents a continuous challenge for health systems worldwide, considering the growing incidence of wound-related comorbidities, such as diabetes, high blood pressure, obesity, and autoimmune diseases. In this context, hydrogels are considered viable options since they mimic the skin structure and promote autolysis and growth factor synthesis. Unfortunately, hydrogels are associated with several drawbacks, such as low mechanical strength and the potential toxicity of byproducts released after crosslinking reactions. To overcome these aspects, in this study new smart chitosan (CS)-based hydrogels were developed, using oxidized chitosan (oxCS) and hyaluronic acid (oxHA) as nontoxic crosslinkers. Three active product ingredients (APIs) (fusidic acid, allantoin, and coenzyme Q10), with proven biological effects, were considered for inclusion in the 3D polymer matrix. Therefore, six API-CS-oxCS/oxHA hydrogels were obtained. The presence of dynamic imino bonds in the hydrogels' structure, which supports their self-healing and self-adapting properties, was confirmed by spectral methods. The hydrogels were characterized by SEM, swelling degree, pH, and the internal organization of the 3D matrix was studied by rheological behavior. Moreover, the cytotoxicity degree and the antimicrobial effects were also investigated. In conclusion, the developed API-CS-oxCS/oxHA hydrogels have real potential as smart materials in wound management, based on their self-healing and self-adapting properties, as well as on the benefits of APIs.

12.
Polymers (Basel) ; 15(17)2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37688274

RESUMEN

Wound management represents a well-known continuous challenge and concern of the global healthcare systems worldwide. The challenge is on the one hand related to the accurate diagnosis, and on the other hand to establishing an effective treatment plan and choosing appropriate wound care products in order to maximize the healing outcome and minimize the financial cost. The market of wound dressings is a dynamic field which grows and evolves continuously as a result of extensive research on developing versatile formulations with innovative properties. Hydrogels are one of the most attractive wound care products which, in many aspects, are considered ideal for wound treatment and are widely exploited for extension of their advantages in healing process. Smart hydrogels (SHs) offer the opportunities of the modulation physico-chemical properties of hydrogels in response to external stimuli (light, pressure, pH variations, magnetic/electric field, etc.) in order to achieve innovative behavior of their three-dimensional matrix (gel-sol transitions, self-healing and self-adapting abilities, controlled release of drugs). The SHs response to different triggers depends on their composition, cross-linking method, and manufacturing process approach. Both native or functionalized natural and synthetic polymers may be used to develop stimuli-responsive matrices, while the mandatory characteristics of hydrogels (biocompatibility, water permeability, bioadhesion) are preserved. In this review, we briefly present the physiopathology and healing mechanisms of chronic wounds, as well as current therapeutic approaches. The rational of using traditional hydrogels and SHs in wound healing, as well as the current research directions for developing SHs with innovative features, are addressed and discussed along with their limitations and perspectives in industrial-scale manufacturing.

13.
Pharmaceutics ; 15(10)2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37896252

RESUMEN

Generally, NSAIDs are weakly soluble in water and contain both hydrophilic and hydrophobic groups. One of the most widely used NSAIDs is ibuprofen, which has a poor solubility and high permeability profile. By creating dynamic, non-covalent, water-soluble inclusion complexes, cyclodextrins (CDs) can increase the dissolution rate of low aqueous solubility drugs, operating as a drug delivery vehicle, additionally contributing significantly to the chemical stability of pharmaceuticals and to reducing drug-related irritability. In order to improve the pharmacological and pharmacokinetics profile of ibuprofen, new thiazolidin-4-one derivatives of ibuprofen (4b, 4g, 4k, 4m) were complexed with ß-CD, using co-precipitation and freeze-drying. The new ß-CD complexes (ß-CD-4b, ß-CD-4g, ß-CD-4k, ß-CD-4m) were characterized using scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and a phase solubility test. Using the AutoDock-VINA algorithm included in YASARA-structure software, we investigated the binding conformation of ibuprofen derivatives to ß-CD and measured the binding energies. We also performed an in vivo biological evaluation of the ibuprofen derivatives and corresponding ß-CD complexes, using analgesic/anti-inflammatory assays, as well as a release profile. The results support the theory that ß-CD complexes (ß-CD-4b, ß-CD-4g, ß-CD-4k, ß-CD-4m) have a similar effect to ibuprofen derivatives (4b, 4g, 4k, 4m). Moreover, the ß-CD complexes demonstrated a delayed release profile, which provides valuable insights into the drug-delivery area, focused on ibuprofen derivatives.

14.
RSC Adv ; 12(10): 6303-6313, 2022 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-35424561

RESUMEN

The first access to 3,5-disubstituted imidazo[1,2-d][1,2,4]thiadiazole derivatives is reported. The series were generated from 2-mercaptoimidazole, which afforded the key intermediate bearing two functional positions. The SNAr reactivity toward tosyl release at the C-3 position was investigated and a regioselective electrophilic iodination in C-5 position was performed to allow a novel C-C bond using Suzuki-Miyaura reaction. Palladium-catalyzed cross-coupling conditions were optimized. A representative library of various boronic acids was employed to establish the scope and limitations of the method. To complete this methodological study, the influence of the nature of the C-3 imidazo[1,2-d][1,2,4]thiadiazole substitutions on the arylation in C-5 was investigated.

15.
Polymers (Basel) ; 14(15)2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35956710

RESUMEN

This study presents the production, characterization, and application of celandine (Chelidonium majus L.) extracts (aqueous, acidic, alcoholic, and ultrasound) on wool fibers and their characterization. The study aims to obtain an ecologically dyed wool support that possesses biocompatible and antimicrobial activities. The plant extracts were characterized based on pH, total polyphenol content, and berberine content. Ecologically dyed wool supports were characterized based on scanning electron microscopy, levelness index, color measurements, contact angle indirect biocompatibility, and antibacterial analysis. According to the obtained results, celandine extract can be considered a potential candidate for the sustainable dyeing and functionalization of wool fibers.

16.
Pharmaceutics ; 14(10)2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36297600

RESUMEN

The study aim was to develop and validate a high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) method to simultaneously determine glibenclamide (Gli) and silymarin (Sil) released from chitosan (CS) microparticles in aqueous solutions. The CS microparticles were synthesized using an ionic gelation method, and their morphology, swelling degree, encapsulation efficiency and active substance release were investigated. Gli and Sil were loaded in different concentrations, and their identification and quantification were performed using the HPLC-ESI-MS method, which was further validated. The drugs' characteristic m/z was found in the higher intensity of retention time (Rt) (Gli, 8.909 min; Sil A, 5.41 min; and Sil B, 5.66 min). The method selectivity and precision are very good, and the blank solution proved no interference. The linearity of the answer function is very good for Sil A (R2 = 1), Sil B (R2 = 0.9998) and Gli (R2 = 0.9991). For Gli, we obtained a limit of detection (LOD) = 0.038 mg/mL and limit of quantification (LOQ) = 1.275 mg/mL; for Sil A, a LOD = 0.285 mg/mL and LOQ = 0.95 mg/mL; and for Sil B, a LOD = 0.045 mg/mL and LOQ = 0.15 mg/mL. A high-resolution HPLC-ESI-MS method was developed and validated, which allowed the simultaneous determination of Gli and Sil loaded in CS microparticles, in a concentration range of 0.025-1 mg/mL.

17.
Artículo en Inglés | MEDLINE | ID: mdl-33669711

RESUMEN

The aim of this study was to assess the psycho-emotional impact and the adjustment degree of Romanian general practitioners (GPs) in the coronavirus disease 2019 (COVID-19) pandemic context. With a cross-sectional design, the study included 677 GPs to whom a validated questionnaire based on different items targeting three factors was sent: burden of prevention, presence of stress symptoms, and adjustment to pandemic. The burden of prevention and the adjustment effort to the pandemic were felt significantly more by female doctors and by GPs working in associated offices. The case definition quality, the support received, the professional life changes, and the stress symptoms proved to be the main predictors for the adjustment to pandemic. The adjustment measurement questionnaire can be used in further studies to identify the most supportive public health practices in difficult epidemiological contexts.


Asunto(s)
COVID-19/psicología , Médicos Generales/psicología , Actitud del Personal de Salud , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Rumanía/epidemiología
18.
Biomed Pharmacother ; 139: 111678, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33964802

RESUMEN

In this study we present design and synthesis of nineteen new nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold (NO-IND-TZDs) (6a-s), as a new safer and efficient multi-targets strategy for inflammatory diseases. The chemical structure of all synthesized derivatives (intermediaries and finals) was proved by NMR and mass spectroscopic analysis. In order to study the selectivity of NO-IND-TZDs for COX isoenzymes (COX-1 and COX-2) a molecular docking study was performed using AutoDock 4.2.6 software. Based on docking results, COX-2 inhibitors were designed and 6o appears as the most selective derivative which showed an improved selective index compared with indomethacin (IND) and diclofenac (DCF), used as reference drugs. The biological evaluation of 6a-s, using in vitro assays has included the anti-inflammatory and antioxidant effects as well as the nitric oxide (NO) release. Referring to the anti-inflammatory effects, the most active compound was 6i, which was more active than IND and aspirin (ASP) in term of denaturation effect, on bovine serum albumin (BSA), as indirect assay to predict the anti-inflammatory effect. An appreciable anti-inflammatory effect, in reference with IND and ASP, was also showed by 6k, 6c, 6q, 6o, 6j, 6d. The antioxidant assay revealed the compound 6n as the most active, being 100 times more active than IND. The compound 6n showed also the most increase capacity to release NO, which means is safer in terms of gastro-intestinal side effects. The ADME-Tox study revealed also that the NO-IND-TZDs are generally proper for oral administration, having optimal physico-chemical and ADME properties. We can conclude that the compounds 6i and 6n are promising agents and could be included in further investigations to study in more detail their pharmaco-toxicological profile.


Asunto(s)
Indometacina/análogos & derivados , Indometacina/farmacología , Donantes de Óxido Nítrico/farmacología , Tiazolidinas/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/síntesis química , Antioxidantes/farmacología , Aspirina/farmacología , Simulación por Computador , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Diclofenaco/farmacología , Diseño de Fármacos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Humanos , Indometacina/química , Espectroscopía de Resonancia Magnética , Simulación del Acoplamiento Molecular , Donantes de Óxido Nítrico/química , Donantes de Óxido Nítrico/toxicidad , Albúmina Sérica Bovina/química , Relación Estructura-Actividad
19.
Mater Sci Eng C Mater Biol Appl ; 130: 112436, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34702521

RESUMEN

Improving wound healing by developing innovative dressing materials has been an important focus over the past few years in the biomedical field. In this regard, the current study focuses on developing new dressings based on acrylate-endcapped urethane-based polymers (AUPs). The materials have been processed into films and electrospun mats. Exudate uptake capacity, mechanical properties and fiber morphology were evaluated herein. The results showed superior uptake capacity of both films and mats when compared to Aquacel®Ag, Exufiber® and Help®. Addition of a high molar mass poly(ethylene glycol) to the AUP polymers benefits both the film and electrospun dressings in terms of flexibility and elongation. An in vivo study was conducted to assess the wound healing properties of these dressings on an acute wound model induced to rats. A macroscopic evaluation indicated that wound contraction and wound fraction percentages were improved significantly in case of the AUP-materials when compared to both the positive (Aquacel®Ag) and negative (Exufiber® and Help®) controls. A histopathological assay, to underline the changes noticed on a macroscopical level, was also performed. The data obtained proved that the developed dressings are beneficial towards tissue regeneration and accelerated wound healing. These findings offer a practical yet adequate strategy for the fabrication of acrylate-endcapped urethane-based materials for wound healing applications.


Asunto(s)
Hidrogeles , Uretano , Acrilatos , Animales , Vendajes , Hidrogeles/farmacología , Ratas , Cicatrización de Heridas
20.
Macromol Biosci ; 21(11): e2100230, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34491617

RESUMEN

Wound dressings under the form of films constituted of modified alginate (methacrylated alginate - AlgMA) versus a gelatine derivative containing norbornene functionalities (GelNB) are developed and evaluated for their moisturizing effects, followed by further in vivo testing to assay their wound healing potential. The gel fraction results shows that AlgMA and GelNB films displayed a high crosslinking efficiency while the swelling assay reveals a stronger water uptake capacity for AlgMA films compared to GelNB and to commercial dressing AquacelAg, used as positive control. Referring to the in vivo wound healing effect, the GelNB films not only exhibit proper healing properties, yet is higher to the AquacelAg, while the AlgMA films exhibit similar wound healing effect as the positive control. On a microscopic level, the healing phases (from inflammation to proliferation and contraction) are present for both materials, yet at a faster rate for the GelNB films, which is in line with the macroscopic findings. These results provide data which support that GelNB films outperform AlgMA films, but both can be used for wound healing applications.


Asunto(s)
Alginatos/química , Gelatina/química , Hidrogeles/química , Cicatrización de Heridas , Animales , Vendajes , Masculino , Ratas , Ratas Wistar
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