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1.
J Biophotonics ; : e202300568, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38651324

RESUMEN

We investigate the efficacy of photodynamic antimicrobial chemotherapy (PACT) and its combination with an antibiotic in the treatment of diabetic foot ulcers (DFUs) in rats using a novel cationic amino acid porphyrin-based photosensitizer. The research findings demonstrate that the combination of novel cationic photosensitizer-mediated PACT and an antibiotic exhibits significant therapeutic efficacy in treating deep ulcers in a rat model of DFUs. Moreover, the PACT + Antibiotic group displays enhanced angiogenesis, improved tissue maturation, and superior wound healing effect. Micro-computed tomography examination showed that the periosteal reaction was most obvious in the PACT + Antibiotic group. The cortical bone volume ratio (BV/TV), the bone mineral density, and trabecular thickness were significantly higher in the PACT + Antibiotic group than in the model group (p < 0.05). The combination of PACT and antibiotic plays a sensitizing therapeutic role, which provides a new idea for the clinical treatment of DFUs.

2.
Front Microbiol ; 13: 876166, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35531297

RESUMEN

Osteomyelitis is deep tissue inflammation caused by bacterial infection. If such an infection persists, it can lead to dissolution and necrosis of the bone tissue. As a result of the extensive use of antibiotics, drug-resistant bacteria are an increasingly common cause of osteomyelitis, limiting the treatment options available to surgeons. Photodynamic antibacterial chemotherapy has attracted increasing attention as a potential alternative treatment. Its advantages are a broad antibacterial spectrum, lack of drug resistance, and lack of toxic side effects. In this study, we explored the impact of the new photosensitizer LD4 in photodynamic antimicrobial chemotherapy (PACT), both alone and in combination with an antibiotic, on osteomyelitis. A rabbit tibial osteomyelitis model was employed and microbiological, histological, and radiological studies were performed. New Zealand white rabbits (n = 36) were randomly divided into a control group, antibiotic group, PACT group and PACT + antibiotic group for treatment. In microbiological analysis, a reduction in bacterial numbers of more than 99.9% was recorded in the PACT group and the PACT + antibiotic group 5 weeks after treatment (p < 0.01). In histological analysis, repair of the damaged bone tissue was observed in the PACT group, and bone repair in the PACT + antibiotic group was even more significant. In radiological analysis, the X-ray Norden score showed that the severity of bone tissue defects or destruction followed the pattern: PACT + antibiotic group < PACT group < antibiotic group < control group.

3.
Front Microbiol ; 12: 622410, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33717010

RESUMEN

Cationic porphyrin conjugate, protoporphyrin IX-methyl ethylenediamine derivative (PPIX-MED) has a potent photosensitive antibacterial effect on clinically isolated bacteria, including methicillin-resistant Staphylococcus aureus, (MRSA), Escherichia coli, and Pseudomonas aeruginosa. This study investigated (i) the PPIX-MED-mediated antimicrobial photodynamic effect on these three species in vitro and (ii) the effect of antimicrobial photodynamic therapy (aPDT) combined with the use of an antibiotic on the healing in vivo of third-degree burns of rats with the wounds infected by these bacterial species. PPIX-MED exerted a potent inhibitory effect on the growth of the three bacterial species by producing reactive oxygen species when photoactivated. PPIX-MED-mediated antimicrobial photodynamic therapy (PPIX-MED-aPDT) had high bacterial photoinactivation ability in vitro, with a minimum inhibitory concentration of 15.6 µM PPIX-MED against each of the three types of bacteria and minimum bactericidal concentrations of 31.25 µM against MRSA and E. coli and 62.5 µM against P. aeruginosa. In rats with third-degree burns infected by a mixture of these bacteria, the bactericidal efficiency of PPIX-MED-aPDT-combined-with-antibiotic treatment was higher than that of antibiotic or aPDT treatment alone. This was confirmed by analysis of viable bacterial counts in wound tissue and blood. Enzyme-linked immunosorbent assay revealed that aPDT-combined-with-antibiotic treatment resulted in an obvious reduction in tumor necrosis factor-alpha and interleukin-6 levels compared with the no-treatment control group and the other treatment groups. Immunohistochemistry revealed that the expression of basic fibroblast growth factor and CD31 (a marker of neovascularization), expressed in burn wound tissue was higher in the aPDT-combined-with-antibiotic treatment group than in the other groups. PPIX-MED-aPDT has a promising bactericidal effect both in vitro and in vivo, and PPIX-MED-aPDT-combined-with-antibiotic treatment enhanced the healing of infected third-degree burns in rats.

4.
PLoS One ; 15(9): e0237851, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32877414

RESUMEN

This study examined the antibacterial effect of protoporphyrin IX-ethylenediamine derivative (PPIX-ED)-mediated photodynamic antimicrobial chemotherapy (PPIX-ED-PACT) against Pseudomonas aeruginosa in vitro and in vivo. PPIX-ED potently inhibited the growth of Pseudomonas aeruginosa by inducing reactive oxygen species production via photoactivation. Atomic force microscopy revealed that PPIX-ED-PACT induced the leakage of bacterial content by degrading the bacterial membrane and wall. As revealed using acridine orange/ethidium bromide staining, PPIX-ED-PACT altered the permeability of the bacterial membrane. In addition, the antibacterial effect of PPIX-ED-PACT was demonstrated in an in vivo model of P. aeruginosa-infected wounds. PPIX-ED (100 µM) decreased the number of P. aeruginosa colony-forming units by 4.2 log10. Moreover, histological analysis illustrated that the wound healing rate was 98% on day 14 after treatment, which was 10% higher than that in the control group. According to the present findings, PPIX-ED-PACT can effectively inhibit the growth of P. aeruginosa in vitro and in vivo.


Asunto(s)
Antibacterianos/uso terapéutico , Fotoquimioterapia , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/fisiología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Animales , Antibacterianos/farmacología , Membrana Celular/efectos de los fármacos , Membrana Celular/efectos de la radiación , Etilenodiaminas/química , Etilenodiaminas/farmacología , Etilenodiaminas/uso terapéutico , Femenino , Luz , Ratones , Ratones Endogámicos BALB C , Viabilidad Microbiana/efectos de los fármacos , Modelos Biológicos , Células 3T3 NIH , Fotoblanqueo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Protoporfirinas/química , Protoporfirinas/farmacología , Protoporfirinas/uso terapéutico , Pseudomonas aeruginosa/efectos de la radiación , Cicatrización de Heridas/efectos de los fármacos
5.
Eur J Med Chem ; 92: 35-48, 2015 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-25544685

RESUMEN

Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective modality for the treatment of infection with the advantage of circumventing multidrug resistance, receives great attention in recent years. The photosensitizer is the crucial element in PACT, and cationic porphyrins have been demonstrated to usually be more efficient than neutral and negatively charged analogues towards bacteria in PACT. In this work, three native basic amino acids, l-lysine, l-histidine and l-arginine, were conjugated with amino porphyrins as cationic auxiliary groups, and 13 target compounds were synthesized. This paper reports their syntheses, structural characterizations, oil-water partition coefficients, singlet oxygen generation yields, photo-stability, as well as their photo inactivation efficacies against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa in vitro. The preliminary structure-activity relationship was discussed. Compound 4i, with porphyrin bearing four lysine moieties, displays the highest photo inactivation efficacy against the tested bacterial strains at 3.91 µM with a low light dose (6 J/cm(2)), and it is stable in serum and lower cytotoxicity to A929 cells. These basic amino acid-porphyrin conjugates are potential photosensitizers for PACT.


Asunto(s)
Aminoácidos/farmacología , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Aminoácidos/química , Antibacterianos/síntesis química , Antibacterianos/química , Línea Celular , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Porfirinas/química , Relación Estructura-Actividad
6.
Lasers Med Sci ; 29(3): 1131-8, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24249355

RESUMEN

The incidence of methicillin-resistant strains of Staphylococcus aureus (MRSA) is increasing globally, making urgent the discovery of novel alternative therapies for infections. Photodynamic antimicrobial chemotherapy (PACT), based on oxidative damage to subcellular structures, has the advantage of circumventing multidrug resistance, and is becoming a potential therapeutic modality for methicillin-resistant bacteria. The key to PACT is photosensitization. This study demonstrates the efficiency of PACT using α-D-galactopyranosyl zinc phthalocyanines (T1-T4) for the photosensitization of MRSA, Escherichia coli, and Pseudomonas aeruginosa. Bacterial suspensions were illuminated with 650-nm light from a semiconductor laser at 0.2 W/cm(2), and the energy density was maintained at 6 J/cm(2) in the presence of different concentrations of photosensitizer. The treatment response was evaluated based on the numbers of bacterial colony-forming units. PACT with these phthalocyanines strongly affected MRSA, but weakly affected E. coli and P. aeruginosa. The efficiency of PACT on MRSA with these four phthalocyanine compounds decreased in the order T1 > T2 > T3 > T4. T1-PACT eliminated >99% of MRSA in a concentration range of 25-50 µM and at an energy density of 6 J/cm(2). Uptake measurements revealed that the PACT effect correlated with the bacterial uptake of the photosensitizer and that 4-30-fold more T1 than T2-T4 was taken up by the MRSA strain, which was confirmed with laser confocal microscopy. These data suggest that T1 is an efficient PACT photosensitizer for MRSA.


Asunto(s)
Antiinfecciosos/farmacología , Galactosa/farmacología , Indoles/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Compuestos Organometálicos/farmacología , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Escherichia coli/efectos de los fármacos , Galactosa/química , Indoles/química , Isoindoles , Pruebas de Sensibilidad Microbiana , Microscopía Confocal , Compuestos Organometálicos/química , Pseudomonas aeruginosa/efectos de los fármacos , Compuestos de Zinc
7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 28(1): 18-20, 2008 Jan.
Artículo en Chino | MEDLINE | ID: mdl-18422110

RESUMEN

Glasses with zero focal-length lens and different shades of red, yellow and blue were studied in terms of absorbance by UV-Vis spectral absorption method. The effect of lens with different shades of the same color on stereoscopic vision was comparatively studied from the medical view. The study has shown that, for yellow and blue lens, there is no difference in the absorbance between the deep-color and light-color lens in UV; at 550 nm, the absorbance of deep-color lens is higher than that of light-color lens. Whereas, for red lens, the absorbance of light-color lens in UV is higher, and at 550 nm, still higher than that of deep-color. Those with light-color glasses of yellow or blue have much better stereoscopic vision than those with deep-color glasses, while the case is inversed as to those wearing red glasses. The conclusion can be drawn that the effect of lens with different shades on stereoscopic vision depends on the absorbance of lens at 550 nm, and the higher the absorbance, the stronger the effect.


Asunto(s)
Percepción de Profundidad , Anteojos , Absorción , Color , Humanos , Espectrofotometría Ultravioleta
8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 22(4): 548-9, 2002 Aug.
Artículo en Chino | MEDLINE | ID: mdl-12938360

RESUMEN

The experiment makes C60 composite material by mixing up C60 and polymethyl methacrylate. Then three minor studies are conducted: (1) Studying the relation of refractivity of the material with the change in temperature. (2) Studying the different change in refractivity with different amount of C60 in the composite material. (3) Studying the change in refractivity of the material radiated with ultraviolet radiation. A comparison is made between the above three cases. The result shows that: under different circumstances, the change in refractivity with the change of temperature differ.


Asunto(s)
Fulerenos/química , Polimetil Metacrilato/química , Fenómenos Químicos , Química Física , Compuestos Orgánicos/química , Propiedades de Superficie , Temperatura , Rayos Ultravioleta
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