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1.
Int J Mol Sci ; 24(13)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37446050

RESUMEN

The rapid rise in research and development following the discovery of photodynamic therapy to establish novel photosensitizers and overcome the limitations of the technology soon after its clinical translation has given rise to a few significant milestones. These include several novel generations of photosensitizers, the widening of the scope of applications, leveraging of the offerings of nanotechnology for greater efficacy, selectivity for the disease over host tissue and cells, the advent of combination therapies with other similarly minimally invasive therapeutic technologies, the use of stimulus-responsive delivery and disease targeting, and greater penetration depth of the activation energy. Brought together, all these milestones have contributed to the significant enhancement of what is still arguably a novel technology. Yet the major applications of photodynamic therapy still remain firmly located in neoplasms, from where most of the new innovations appear to launch to other areas, such as microbial, fungal, viral, acne, wet age-related macular degeneration, atherosclerosis, psoriasis, environmental sanitization, pest control, and dermatology. Three main value propositions of combinations of photodynamic therapy include the synergistic and additive enhancement of efficacy, the relatively low emergence of resistance and its rapid development as a targeted and high-precision therapy. Combinations with established methods such as chemotherapy and radiotherapy and demonstrated applications in mop-up surgery promise to enhance these top three clinical tools. From published in vitro and preclinical studies, clinical trials and applications, and postclinical case studies, seven combinations with photodynamic therapy have become prominent research interests because they are potentially easily applied, showing enhanced efficacy, and are rapidly translating to the clinic. These include combinations with chemotherapy, photothermal therapy, magnetic hyperthermia, cold plasma therapy, sonodynamic therapy, immunotherapy, and radiotherapy. Photochemical internalization is a critical mechanism for some combinations.


Asunto(s)
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Neoplasias/tratamiento farmacológico , Terapia Combinada , Tecnología
2.
Int J Nanomedicine ; 17: 5315-5325, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36411766

RESUMEN

Background: Photodynamic therapy (PDT) is a non-invasive treatment modality that destroys abnormally growing cells or microorganisms. Porphyrins are used as photosensitizers in PDT; however, their clinical application has been limited by their poor water solubility, resulting in aggregation and low quantum yields of reactive oxygen species (ROS). Methods: To overcome these limitations and improve PDT efficacy, we herein report the conjugation of ZnCuInS/ZnS (ZCIS/ZnS) quantum dots (QDs) to 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP). The optimal conditions for QDs porphyrin conjugation formation were systematically evaluated. Discussion: This study further assessed the PDT efficacy and antibacterial potency of the synthesized ZCIS/ZnS-mTHPP conjugates. The PDT efficacy of the QDs, mTHPP, and conjugate was evaluated against the murine metastatic melanoma (B16 F10 Nex2) cell line. This was performed with and without LED irradiation. Results: The conjugate exhibited the highest reduction in cell viability following LED irradiation (72%) compared to the bare QDs (19%) and mTHPP (1%). Antimicrobial studies conducted on E. coli showed that the conjugation exhibits a higher antibacterial effect than the bare QDs, even without light. Conclusion: The results suggest that conjugate is a promising class of materials for anti-cancer and antimicrobial PDT.


Asunto(s)
Fotoquimioterapia , Porfirinas , Puntos Cuánticos , Ratones , Animales , Escherichia coli , Porfirinas/farmacología , Antibacterianos/farmacología , Zinc
3.
Int J Mol Sci ; 23(9)2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35563029

RESUMEN

Nanozymes are synthetic nanoparticulate materials that mimic the biological activities of enzymes by virtue of their surface chemistry. Enzymes catalyze biological reactions with a very high degree of specificity. Examples include the horseradish peroxidase, lactate, glucose, and cholesterol oxidases. For this reason, many industrial uses of enzymes outside their natural environments have been developed. Similar to enzymes, many industrial applications of nanozymes have been developed and used. Unlike the enzymes, however, nanozymes are cost-effectively prepared, purified, stored, and reproducibly and repeatedly used for long periods of time. The detection and identification of pathogens is among some of the reported applications of nanozymes. Three of the methodologic milestones in the evolution of pathogen detection and identification include the incubation and growth, immunoassays and the polymerase chain reaction (PCR) strategies. Although advances in the history of pathogen detection and identification have given rise to novel methods and devices, these are still short of the response speed, accuracy and cost required for point-of-care use. Debuting recently, nanozymology offers significant improvements in the six methodological indicators that are proposed as being key in this review, including simplicity, sensitivity, speed of response, cost, reliability, and durability of the immunoassays and PCR strategies. This review will focus on the applications of nanozymes in the detection and identification of pathogens in samples obtained from foods, natural, and clinical sources. It will highlight the impact of nanozymes in the enzyme-linked immunosorbent and PCR strategies by discussing the mechanistic improvements and the role of the design and architecture of the nanozyme nanoconjugates. Because of their contribution to world health burden, the three most important pathogens that will be considered include viruses, bacteria and fungi. Although not quite seen as pathogens, the review will also consider the detection of cancer cells and helminth parasites. The review leaves very little doubt that nanozymology has introduced remarkable advances in enzyme-linked immunosorbent assays and PCR strategies for detecting these five classes of pathogens. However, a gap still exists in the application of nanozymes to detect and identify fungal pathogens directly, although indirect strategies in which nanozymes are used have been reported. From a mechanistic point of view, the nanozyme technology transfer to laboratory research methods in PCR and enzyme-linked immunosorbent assay studies, and the point-of-care devices such as electronic biosensors and lateral flow detection strips, that is currently taking place, is most likely to give rise to no small revolution in each of the six methodological indicators for pathogen detection and identification. While the evidence of widespread research reports, clinical trials and point-of-care device patents support this view, the gaps that still exist point to a need for more basic research studies to be conducted on the applications of nanozymology in pathogen detection and identification. The multidisciplinary nature of the research on the application of nanozymes in the detection and identification of pathogens requires chemists and physicists for the design, fabrication, and characterization of nanozymes; microbiologists for the design, testing and analysis of the methodologies, and clinicians or clinical researchers for the evaluation of the methodologies and devices in the clinic. Many reports have also implicated required skills in mathematical modelling, and electronic engineering. While the review will conclude with a synopsis of the impact of nanozymology on the detection and identification of viruses, bacteria, fungi, cancer cells, and helminths, it will also point out opportunities that exist in basic research as well as opportunities for innovation aimed at novel laboratory methodologies and devices. In this regard there is no doubt that there are numerous unexplored research areas in the application of nanozymes for the detection of pathogens. For example, most research on the applications of nanozymes for the detection and identification of fungi is so far limited only to the detection of mycotoxins and other chemical compounds associated with fungal infection. Therefore, there is scope for exploration of the application of nanozymes in the direct detection of fungi in foods, especially in the agricultural production thereof. Many fungal species found in seeds severely compromise their use by inactivating the germination thereof. Fungi also produce mycotoxins that can severely compromise the health of humans if consumed.


Asunto(s)
Micotoxinas , Nanoestructuras , Bacterias , Catálisis , Humanos , Inmunoensayo , Nanoestructuras/química , Reproducibilidad de los Resultados
4.
Int J Mol Sci ; 23(6)2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35328629

RESUMEN

Antimicrobial photodynamic therapy and allied photodynamic antimicrobial chemotherapy have shown remarkable activity against bacterial pathogens in both planktonic and biofilm forms. There has been little or no resistance development against antimicrobial photodynamic therapy. Furthermore, recent developments in therapies that involve antimicrobial photodynamic therapy in combination with photothermal hyperthermia therapy, magnetic hyperthermia therapy, antibiotic chemotherapy and cold atmospheric pressure plasma therapy have shown additive and synergistic enhancement of its efficacy. This paper reviews applications of antimicrobial photodynamic therapy and non-invasive combination therapies often used with it, including sonodynamic therapy and nanozyme enhanced photodynamic therapy. The antimicrobial and antibiofilm mechanisms are discussed. This review proposes that these technologies have a great potential to overcome the bacterial resistance associated with bacterial biofilm formation.


Asunto(s)
Antiinfecciosos , Fotoquimioterapia , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Bacterias , Biopelículas , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico
5.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-34832919

RESUMEN

The excellent photothermal properties of gold nanorods (Au-NRs) make them one of the most researched plasmonic photothermal nanomaterials. However, their biological applications have been hampered greatly due to surfactant-induced cytotoxicity. We herein report a simple synthesis of highly biocompatible gelatin stabilized Au-NRs (gelatin@Au-NRs) to address this issue. The optical and structural properties of the as-synthesized gelatin@Au-NRs were investigated by Zetasizer, Ultraviolet-Visible-Near Infrared (UV-Vis-NIR) spectroscopy, high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared spectroscopy (FTIR). The as-synthesized gelatin@Au-NRs were highly crystalline and rod-like in shape with an average length and diameter of 66.2 ± 2.3 nm and 10 ± 1.6 nm, respectively. The as-synthesized gelatin@Au-NRs showed high stability in common biological media (phosphate buffer saline and Dulbecco's Modified Eagle's Medium) compared to CTAB capped Au-NRs. Similarly, the gelatin@Au-NRs showed an improved heat production and outstanding cell viability against two different cancer cell lines; KM-Luc/GFP (mouse fibroblast histiocytoma cell line) and FM3A-Luc (breast carcinoma cell line) compared to CTAB capped Au-NRs and PEG@Au-NRs. An in vitro photothermal therapy study against KM-Luc/GFP showed that gelatin@Au-NRs effectively destroys the cancer cells.

6.
Infect Genet Evol ; 96: 105132, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34775079

RESUMEN

The emergence and worldwide distribution of carbapenem-resistant Acinetobacter baumannii strains has become a major public health threat. The objective of this study was to investigate the clonal relatedness of A. baumannii isolates collected from clinical and extra-hospital environments in Mthatha, South Africa. Forty carbapenem-resistant isolates comprising of clinical (20) and extra-hospital (20) were identified and tested for antimicrobial susceptibility. Detection of carbapenemase encoding genes was performed by Real-time PCR. The clonal relationship of clinical isolates relative to extra-hospital isolates was determined via multilocus sequence typing (MLST). All isolates (clinical and extra-hospital) were resistant to most common antibiotics including carbapenems (imipenem; MIC ≥32 µg/mL and meropenem; MIC ≥32 µg/mL) with the only exception being amikacin (with 3 isolates susceptible), tigecycline (14 isolates susceptible) and colistin (all isolates susceptible). The bla OXA-23-like and the intrinsic bla OXA-51 -like genes were detected in all the isolates tested. The bla OXA-58-like and bla IMP-type genes were detected in 2 clinical isolates whilst the bla OXA-24-like, bla VIM-type, bla NDM-1, bla SIM, and bla AmpC were not detected. The bla OXA-24-like, bla OXA-58-like, bla IMP-type, bla VIM-type, bla NDM-1, bla SIM, and bla AmpC were negative in the extra-hospital isolates. Co-occurrence of bla OXA-23 -like, bla OXA-58-like and bla IMP-type was observed in 2 clinical isolates. The MLST performed on 33 isolates identified 5 existing sequence types (ST) (ST1, ST2, ST25, ST85 and ST215) in clinical isolates and 2 existing STs (ST1 and ST2) in extra-hospital isolates. The most dominant ST was ST2 accounting for 68.8% of the clinical isolates and 82.4% of the extra-hospital isolates. The study demonstrated high prevalence and potential clonal spread of globally-disseminated clonal complex 2 carrying bla OXA-23-like within our local settings. However, ST25 might be an emerging lineage carrying the bla OXA-23-like . Continuous monitoring is important in limiting the spread of these strains in other healthcare settings and the community.


Asunto(s)
Acinetobacter baumannii/clasificación , Antibacterianos/farmacología , Carbapenémicos/farmacología , Tipificación de Secuencias Multilocus , Acinetobacter baumannii/efectos de los fármacos , Hospitales , Humanos , Filogenia , Sudáfrica
7.
Pharmaceutics ; 13(9)2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34575435

RESUMEN

Photothermal therapy has been established recently as a non-invasive treatment protocol for cancer metastatic lymph nodes. Although this treatment approach shows efficient tumour ablation towards lymph node metastasis, the monitoring and reporting of treatment progress using the lymphatic delivery channel still need to be explored. Herein, we investigated the anti-tumour effect of pegylated gold nanorods with a high aspect ratio (PAuNRs) delivered via the lymphatic route in a mouse model. In this study, breast carcinoma (FM3A-Luc) cells were inoculated in the subiliac lymph node (SiLN) to induce metastasis in the proper axillary lymph node (PALN). The treatment was initiated by injecting the PAuNRs into the accessory axillary lymph node (AALN) after tumour metastasis was confirmed in the PALN followed by external NIR laser irradiation under a temperature-controlled cooling system. The anti-tumour impact of the treatment was evaluated using an in vivo bioluminescence imaging system (IVIS). The results showed a time-dependent reduction in tumour activity with significant treatment response. Tumour growth was inhibited in all mice treated with PAuNRs under laser irradiation; results were statistically significant (** p < 0.01) even after treatment was concluded on day 3. We believe that this non-invasive technique would provide more information on the dynamics of tumour therapy using the lymphatically administered route in preclinical studies.

8.
Int J Microbiol ; 2020: 7380740, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32612659

RESUMEN

INTRODUCTION: Carbapenem-resistant Acinetobacter baumannii has been responsible for an increasing number of hospital-acquired infections globally. The study investigated the prevalence of carbapenemase-encoding genes in clinical multidrug-resistant A. baumannii strains. MATERIALS AND METHODS: A total of 100 nonduplicate multidrug-resistant A. baumannii strains were cultured from clinical samples obtained from healthcare facilities in the O. R. Tambo district. The strains were confirmed by detecting the intrinsic bla OXA-51-like gene. Antimicrobial susceptibility testing was performed by VITEK® 2 and autoSCAN-4 systems. The MIC of imipenem and meropenem was rechecked by E-test. Colistin MIC was confirmed by the broth microdilution method. Real-time PCR was performed to investigate the presence of carbapenemase-encoding genes. RESULTS: Most strains showed high resistance rates (>80%) to the antibiotics tested. Resistance to amikacin, tetracycline, and tigecycline were 50%, 64%, and 48%, respectively. All strains were fully susceptible to colistin. The bla OXA-51-like was detected in all strains whilst bla OXA-23-like, bla OXA-58-like, bla OXA-24-like, bla IMP-1, bla VIM, and bla NDM-1 were found in 70%, 8%, 5%, 4%, 3%, and 2% of strains, respectively. None of the tested strains harboured the genes bla SIM and bla AmpC. The coexistence of bla OXA-23-like, and bla IMP-1 or bla OXA-58-like was detected in 1% and 2% strains, respectively. A distinct feature of our findings was the coharbouring of the genes bla OXA-23-like, bla OXA-58-like, and bla IMP-1 in 2% strains, and this is the first report in the Eastern Cape Province, South Africa. The intI1 was carried in 80% of tested strains whilst ISAba1/bla OXA-51-like and ISAba1/bla OXA-23-like were detected in 15% and 40% of the strains, respectively. The detection of bla OXA-23-like, ISAba1/bla OXA-51-like, ISAba1/bla OXA-23-like, and bla OXA-23-like, bla OXA-58-like, and bla IMP-1 carbapenemases in strains had a significant effect on both imipenem and meropenem MICs. CONCLUSIONS: Results showed a high level of oxacillinases producing A. baumannii circulating in our study setting, highlighting the need for local molecular surveillance to inform appropriate management and prevention strategies.

9.
Photodiagnosis Photodyn Ther ; 30: 101752, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32289462

RESUMEN

BACKGROUND: Acinetobacter baumannii is a challenging pathogen due to the rapid development of antimicrobial resistance and biofilm formation. The objective of this study was to evaluate the effect of antimicrobial photodynamic inactivation against biofilms of multidrug-resistant A. baumannii isolated from clinical, abattoir and aquatic sources. METHODS: The isolates were tested for susceptibility to imipenem, meropenem, tigecycline and colistin using autoSCAN-4 automated system and rechecked by the E-test. Methylene blue, Protoporphyrin IX, and a halogen lamp were used in the in vitro assay against biofilms of the isolates. The antimicrobial photodynamic inactivation was assessed by counting colony-forming units (CFU). RESULTS: The isolates from abattoir and aquatic sources were resistant to carbapenems (>64 µg/mL) but susceptible to tigecycline (2 µg/mL) and colistin (Abattoir, 0.35 µg/mL and Aquatic, 0.24 µg/mL), whereas the clinical isolate was susceptible to only colistin (0.5 µg/mL) using the E-test. The log survival percentages of the control group at a concentration of 20 µM were 5 × 10-6 % for Protoporphyrin IX and 2 × 10-6 % for Methylene blue. Therefore, Methylene blue showed higher bacterial reduction of 7.0 log10 colony forming units than 6.0 log10 for Protoporphyrin IX. No significant difference was observed with respect to the origin of isolates and the minimum inhibitory concentrations. CONCLUSION: The results indicate that antimicrobial photodynamic inactivation could be an alternative strategy for the control of infections caused by multi-drug resistant A. baumannii by significantly reducing biofilm growth at a sub-lethal concentrations.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Fotoquimioterapia , Infecciones por Acinetobacter/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Biopelículas , Farmacorresistencia Bacteriana Múltiple , Humanos , Azul de Metileno/farmacología , Azul de Metileno/uso terapéutico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Protoporfirinas
10.
Sci Rep ; 10(1): 4936, 2020 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-32188925

RESUMEN

The toxicity of heavy metals present in binary semiconductor nanoparticles also known as quantum dots (QDs) has hindered their wide applications hence the advent of non-toxic ternary quantum dots. These new group of quantum dots have been shown to possess some therapeutic action against cancer cell lines but not significant enough to be referred to as an ideal therapeutic agent. In this report, we address this problem by conjugating red emitting CuInS/ZnS QDs to a 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin -photosensitizer for improved bioactivities. The glutathione capped CuInS/ZnS QDs were synthesized in an aqueous medium using a kitchen pressure cooker at different Cu: In ratios (1:4 and 1:8) and at varied temperatures (95 °C, 190 °C and 235 °C). Optical properties show that the as-synthesized CuInS/ZnS QDs become red-shifted compared to the core (CuInS) after passivation with emission in the red region while the cytotoxicity study revealed excellent cell viability against normal kidney fibroblasts (BHK21). The highly fluorescent, water-soluble QDs were conjugated to 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) via esterification reactions at room temperature. The resultant water-soluble conjugate was then used for the cytotoxicity, fluorescent imaging and gene expression study against human monocytic leukemia cells (THP-1). Our result showed that the conjugate possessed high cytotoxicity against THP-1 cells with enhanced localized cell uptake compared to the bare QDs. In addition, the gene expression study revealed that the conjugate induced inflammation compared to the QDs as NFKB gene was over-expressed upon cell inflammation while the singlet oxygen (1O2) study showed the conjugate possessed large amount of 1O2, three times than the bare porphyrin. Thus, the as-synthesized conjugate looks promising as a therapeutic agent for cancer therapy.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Nanopartículas del Metal , Porfirinas , Puntos Cuánticos/efectos adversos , Sulfuros , Compuestos de Zinc , Línea Celular Tumoral , Humanos , Leucemia Mieloide/genética , Leucemia Mieloide/metabolismo , Nanopartículas del Metal/química , Microscopía Confocal , Análisis Espectral , Sulfuros/química , Nanomedicina Teranóstica , Compuestos de Zinc/química
11.
Braz. j. infect. dis ; 23(6): 371-380, Nov.-Dec. 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1089307

RESUMEN

ABSTRACT Introduction: The presence of Acinetobacter baumannii outside hospitals remains unclear. This study aimed to determine the prevalence of multidrug-resistance (MDR) A. baumannii in the extra-hospital environment in Mthatha, South Africa and to investigate the frequency of carbapenemase-encoding genes. Material and Methods: From August 2016 to July 2017 a total of 598 abattoir samples and 689 aquatic samples were collected and analyzed presumptively by cultural methods for the presence of A. baumannii using CHROMagar™ Acinetobacter medium. Species identification was performed by autoSCAN-4 (Dade Behring Inc., IL) and confirmed by the detection of their intrinsic blaOXA-51 gene. Confirmed MDR A. baumannii isolates were screened for the presence of carbapenemase-encoding genes, ISAba1 insertion sequence and integrase intI1. Results: In total, 248 (19.3%) Acinetobacter species were isolated. Acinetobacter. baumannii was detected in 183 (73.8%) of which 85 (46.4%) and 98 (53.6%) were recovered from abattoir and aquatic respectively. MDR A. baumannii was detected in 56.5% (48/85) abattoir isolates and 53.1% (52/98) aquatic isolates. Isolates showed high resistance to antimicrobials most frequently used to treat Acinetobacter infections such as piperacillin/tazobactam; abattoir (98% of isolates resistant), aquatic (94% of isolates resistant), ceftazidime (84%, 83%), ciprofloxacin (71%, 70%), amikacin (41%, 42%), imipenem (75%, 73%), and meropenem (74%, 71%). All the isolates were susceptible to tigecycline and colistin. All the isolates carried blaOXA-51-like. The blaOXA-23 was detected in 32 (66.7%) abattoir isolates and 11 (21.2%) aquatic isolates. The blaOXA-58-like was positive in 7 (14.6%) and 4 (7.7%) abattoir and aquatic isolates, respectively. Both groups of isolates lacked blaOXA-24-like, blaIMP-type, blaVIM-type, blaNDM-1, blaSIM, blaAmpC, ISAba1 and inI1. Isolates showed high level of Multiple Antibiotic Resistance Index (MARI) ranging from 0.20-0.52. Conclusion: Extra-hospital sources such as abattoir and aquatic environments may be a vehicle of spread of MDR A. baumannii strains in the community and hospital settings.


Asunto(s)
Humanos , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/genética , Acinetobacter baumannii/aislamiento & purificación , Antibacterianos/uso terapéutico , Sudáfrica/epidemiología , Infecciones por Acinetobacter/transmisión , Infecciones por Acinetobacter/epidemiología , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Prevalencia , Estudios Transversales , Estudios Prospectivos , Acinetobacter baumannii/genética
12.
Braz J Infect Dis ; 23(6): 371-380, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31706742

RESUMEN

INTRODUCTION: The presence of Acinetobacter baumannii outside hospitals remains unclear. This study aimed to determine the prevalence of multidrug-resistance (MDR) A. baumannii in the extra-hospital environment in Mthatha, South Africa and to investigate the frequency of carbapenemase-encoding genes. MATERIAL AND METHODS: From August 2016 to July 2017 a total of 598 abattoir samples and 689 aquatic samples were collected and analyzed presumptively by cultural methods for the presence of A. baumannii using CHROMagar™ Acinetobacter medium. Species identification was performed by autoSCAN-4 (Dade Behring Inc., IL) and confirmed by the detection of their intrinsic blaOXA-51 gene. Confirmed MDR A. baumannii isolates were screened for the presence of carbapenemase-encoding genes, ISAba1 insertion sequence and integrase intI1. RESULTS: In total, 248 (19.3%) Acinetobacter species were isolated. Acinetobacter. baumannii was detected in 183 (73.8%) of which 85 (46.4%) and 98 (53.6%) were recovered from abattoir and aquatic respectively. MDR A. baumannii was detected in 56.5% (48/85) abattoir isolates and 53.1% (52/98) aquatic isolates. Isolates showed high resistance to antimicrobials most frequently used to treat Acinetobacter infections such as piperacillin/tazobactam; abattoir (98% of isolates resistant), aquatic (94% of isolates resistant), ceftazidime (84%, 83%), ciprofloxacin (71%, 70%), amikacin (41%, 42%), imipenem (75%, 73%), and meropenem (74%, 71%). All the isolates were susceptible to tigecycline and colistin. All the isolates carried blaOXA-51-like. The blaOXA-23 was detected in 32 (66.7%) abattoir isolates and 11 (21.2%) aquatic isolates. The blaOXA-58-like was positive in 7 (14.6%) and 4 (7.7%) abattoir and aquatic isolates, respectively. Both groups of isolates lacked blaOXA-24-like, blaIMP-type, blaVIM-type, blaNDM-1,blaSIM, blaAmpC, ISAba1 and inI1. Isolates showed high level of Multiple Antibiotic Resistance Index (MARI) ranging from 0.20-0.52. CONCLUSION: Extra-hospital sources such as abattoir and aquatic environments may be a vehicle of spread of MDR A. baumannii strains in the community and hospital settings.


Asunto(s)
Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/aislamiento & purificación , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/transmisión , Acinetobacter baumannii/genética , Estudios Transversales , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Prevalencia , Estudios Prospectivos , Sudáfrica/epidemiología
13.
Int J Nanomedicine ; 14: 7065-7078, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31507320

RESUMEN

BACKGROUND:  Metal-free, water-soluble and highly stable meso-tetra-(4-sulfonatophenyl) porphyrin (TPPS4) has been studied for their singlet oxygen quantum yield. However, TPPS4 suffers from inherent shortcomings. To address these, TPPS4 was conjugated to ternary copper indium sulphide/ zinc sulphide (CuInS2/ZnS) quantum dots (QDs). PURPOSE:  We herein report for the first time the synthesis of TPPS4-CuInS/ZnS QDs conjugate as an improved photosensitizer. METHODS:  Water-soluble TPPS4 was synthesized from tetraphenylporphyrin (TPPH2) after silica-gel purification. The CuInS/ZnS QDs were synthesized by hydrothermal method at a Cu:In ratio of 1:4. The porphyrin-QDs conjugate was formed via the daggling sulfonyl bond of the porphyrin and amine bond of the QDs. The effect of pH on the optical properties of TPPS4 was evaluated. The effect of Zn:Cu + In ratio on the ZnS shell passivation was examined to reduce structural defects on the as-synthesized QDs. RESULTS: Various spectroscopic techniques were used to confirm the successful conversion of the organic TPPH2 to water-soluble TPPS4. The singlet oxygen generation evaluation shows an improved singlet oxygen quantum yield from 0.19 for the porphyrin (TPPS4) alone to 0.69 after conjugation (CuInS/ZnS-TPPS4) with an increase in the reaction rate constant (k (s-1)).


Asunto(s)
Cobre/química , Indio/química , Porfirinas/síntesis química , Porfirinas/farmacología , Puntos Cuánticos/química , Sulfuros/síntesis química , Compuestos de Zinc/síntesis química , Concentración de Iones de Hidrógeno , Fenómenos Ópticos , Fármacos Fotosensibilizantes , Porfirinas/química , Puntos Cuánticos/ultraestructura , Oxígeno Singlete/química , Espectroscopía Infrarroja por Transformada de Fourier , Sulfuros/química , Temperatura , Compuestos de Zinc/química
14.
Molecules ; 24(13)2019 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-31277423

RESUMEN

Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current 'greener' methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.


Asunto(s)
Antibacterianos/farmacología , Fotoquimioterapia , Porfirinas/farmacología , Animales , Antibacterianos/efectos adversos , Antibacterianos/química , Bacterias/efectos de los fármacos , Humanos , Luz , Fotoquimioterapia/efectos adversos , Porfirinas/efectos adversos , Porfirinas/química
15.
Bioinorg Chem Appl ; 2019: 7147128, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31182957

RESUMEN

Cancer and bacterial diseases have been the most incidental diseases to date. According to the World Health Report 2018, at least every family is affected by cancer around the world. In 2012, 14.1 million people were affected by cancer, and that figure is bound to increase to 21.6 million in 2030. Medicine therefore sorts out ways of treatment using conventional methods which have been proven to have many side effects. Researchers developed photothermal and photodynamic methods to treat both cancer and bacterial diseases. These methods pose fewer effects on the biological systems but still no perfect method has been synthesized. The review serves to explore porphyrin and gold nanorods to be used in the treatment of cancer and bacterial diseases: porphyrins as photosensitizers and gold nanorods as delivery agents. In addition, the review delves into ways of incorporating photothermal and photodynamic therapy aimed at producing a less toxic, more efficacious, and specific compound for the treatment.

16.
Biophys Rev ; 10(1): 49-67, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29294258

RESUMEN

Specially designed functionalized nanomaterials such as superparamagnetic iron oxide, gold, quantum dots and up- and down-conversion lanthanide series nanoparticles have consistently and completely revolutionized the biomedical environment over the past few years due to their specially inferring properties, such as specific drug delivery, plasmonic effect, optical and imaging properties, therapeutic thermal energy productionand excellent irresistible cellular penetration. These properties have been used to improve many existing disease treatment modalities and have led to the development of better therapeutic approaches for the advancement of the treatment of critical human diseases, such as cancers and related malaise. In photodynamic therapy, for example, where the delivery of therapeutic agents should ideally avoid toxicity on nearby healthy cells, superparamagnetic iron oxide nanoparticles have been shown to be capable of making photodynamic therapy (PDT) prodrugs and their associative targeting moieties tumor-specific via their unique response to an external magnetic fields. In this review, the nanomaterials commonly employed for the enhancement of photodynamic therapy are discussed. The review further describes the various methods of synthesis and characterization of these nanomaterials and highlights challenges for improving the efficacy of PDT in the future.

17.
J Expo Sci Environ Epidemiol ; 28(1): 55-63, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-27924816

RESUMEN

Fifty-seven samples of soils commonly ingested in South Africa, Swaziland, Democratic Republic of Congo (DRC), and Togo were analyzed for the concentrations of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), nickel (Ni), and zinc (Zn) and their bioaccessibility in the human gastrointestinal tract. Bioaccessibility values were used to calculate daily intake, and hazard quotient of each trace element, and chronic hazard index (CHI) of each sample. Carcinogenic risk associated with As and Ni exposure were also calculated. Mean pseudo-total concentrations of trace elements in all samples were 7.2, 83.3, 77.1, 15.4, 28.6, 24.9, 56.1, 2.8, and 26.5 mg/kg for As, Cr, Mn, Co, Ni, Cu, Zn, Cd, and Pb, respectively. Percent bioaccessibility of Pb (13-49%) and Zn (38-56%) were highest among trace elements studied. Average daily intake values were lower than their respective reference doses for ell elements except for Pb in selected samples. Samples from DRC presented the highest health risks associated with trace element exposure with most of the samples having CHI values between 0.5 and 1.0. Some samples had higher than unacceptable values of carcinogenic risk associated with As and Ni exposure. Results indicate low trace element exposure risk from ingesting most of the soil samples.


Asunto(s)
Exposición a Riesgos Ambientales/análisis , Metales Pesados/análisis , Suelo , Oligoelementos/análisis , Adolescente , Adulto , Análisis de Varianza , Pruebas de Carcinogenicidad , Niño , Preescolar , República Democrática del Congo/epidemiología , Ingestión de Alimentos , Monitoreo del Ambiente/métodos , Esuatini/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pica/epidemiología , Medición de Riesgo , Sudáfrica/epidemiología , Togo/epidemiología , Adulto Joven
18.
Sci Rep ; 7: 45459, 2017 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-28368042

RESUMEN

Systemic delivery of an anti-cancer agent often leads to only a small fraction of the administered dose accumulating in target sites. Delivering anti-cancer agents through the lymphatic network can achieve more efficient drug delivery for the treatment of lymph node metastasis. We show for the first time that polymeric gold nanorods (PAuNRs) can be delivered efficiently from an accessory axillary lymph node to a tumor-containing proper axillary lymph node, enabling effective treatment of lymph node metastasis. In a mouse model of metastasis, lymphatic spread of tumor was inhibited by lymphatic-delivered PAuNRs and near-infrared laser irradiation, with the skin temperature controlled by cooling. Unlike intravenous injection, lymphatic injection delivered PAuNRs at a high concentration within a short period. The results show that lymphatic administration has the potential to deliver anti-cancer agents to metastatic lymph nodes for inhibition of tumor growth and could be developed into a new therapeutic method.


Asunto(s)
Antineoplásicos/farmacología , Rayos Infrarrojos , Ganglios Linfáticos/efectos de los fármacos , Neoplasias/terapia , Animales , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Oro/química , Liposomas/química , Liposomas/metabolismo , Ganglios Linfáticos/patología , Ganglios Linfáticos/efectos de la radiación , Metástasis Linfática , Ratones , Nanotubos/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Fototerapia , Distribución Tisular
19.
Asian Pac J Trop Med ; 9(5): 426-31, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27261849

RESUMEN

OBJECTIVE: To evaluate the essential oil composition and the anti-inflammatory activity of Cymbopogon validus (C. validus) leaves and flowers. METHODS: A total of 300 g of fresh or dry (leaves and flowers) of C. validus were cut into small pieces and subjected to hydro-distillation method for approximately 5 h using the Clevenger apparatus. The extracted essential oils were then used for testing the anti-inflammatory activity. The anti-inflammatory activity was evaluated by using egg albumin-induced paw edema. RESULTS: The extracted oils had the following yields 2.2% for fresh leaves, 2.0% for dry leaves and 2.4% v/w for dry flowers. GC-MS results revealed that the oils contained artemisia ketone (37.5%), linalool (3.2%-29.6%), northujane (4.4%-16.8%), verbenone (13.5%), naphthalene (1.7%-9.6%), δ-cadinene (0.5%-8.1%), hedycaryol (5.4%-7.6%) and α-eudesmol (6.5%-6.7%) as the major constituents. C. validus essential oils showed significant (P < 0.05) anti-inflammatory effects from the first 30 min after albumin injection compared to aspirin which had a later onset of effect. CONCLUSIONS: The findings of this study show that the essential oil extracted from C. validus fresh or dry leaves and flowers have anti-inflammatory properties; that might be associated with the major components and the minor components found in the essential oils.

20.
Molecules ; 21(6)2016 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-27314316

RESUMEN

We herein report for the first time the synthesis and analgesic properties of silver nanoparticles (Ag-NPs) using buchu plant extract. The as-synthesised Ag-NPs at different temperatures were characterised by UV-Vis spectroscopy, Fourier transform infra-red spectroscopy (FTIR) and transmission transform microscopy (TEM) to confirm the formation of silver nanoparticles. Phytochemical screening of the ethanolic extract revealed the presence of glycosides, proteins, tannins, alkaloids, flavonoids and saponins. The absorption spectra showed that the synthesis is temperature and time dependent. The TEM analysis showed that the as-synthesised Ag-NPs are polydispersed and spherical in shape with average particle diameter of 19.95 ± 7.76 nm while the FTIR results confirmed the reduction and capping of the as-synthesised Ag-NPs by the phytochemicals present in the ethanolic extract. The analgesic study indicated that the combined effect of the plant extract and Ag-NPs is more effective in pain management than both the aspirin drug and the extract alone.


Asunto(s)
Analgésicos/química , Nanopartículas del Metal/química , Extractos Vegetales/administración & dosificación , Alcaloides/química , Analgésicos/administración & dosificación , Animales , Flavonoides/química , Glicósidos/química , Nanopartículas del Metal/administración & dosificación , Ratones , Extractos Vegetales/química , Proteínas/química , Rutaceae/química , Saponinas/química , Plata/química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Taninos/química
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