RESUMEN
It has not yet been proven whether sepsis affects the tissue around the anal canal. To address this issue, we established three-dimensional models for various types of anorectal abscesses and utilize 3D reconstruction of Magnetic Resonance Imaging scans to assess the extent of muscle damage caused by anorectal abscesses. Patients diagnosed with anorectal abscess, selected from January 2019 to January 2022 underwent pre- and post-operative scanning of pelvic floor and perianal tissues. The aforementioned structures were segmented for the reconstruction of a three-dimensional visual model and measurement of volumes for the abscess as well as the internal and external sphincters and levator ani muscle. The study included a total of 42 patients. Three-dimensional visualization models were created for different types of anorectal abscesses, including perianal, intersphincteric, ischiorectal, and supralevator abscesses. No statistically significant differences were observed in the volume of the internal sphincter, external sphincter, and levator ani muscle between pre- and post-operative patients. The 3D model of anorectal abscess, reconstructed from MRI data, offers a precise and direct visualization of the anatomical structures associated with various types of anorectal abscesses. The infection did not result in any damage to the internal and external anal sphincter and levator ani muscle.
Asunto(s)
Absceso , Canal Anal , Imagenología Tridimensional , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Imagenología Tridimensional/métodos , Absceso/diagnóstico por imagen , Absceso/patología , Persona de Mediana Edad , Adulto , Canal Anal/diagnóstico por imagen , Canal Anal/patología , Anciano , Enfermedades del Ano/diagnóstico por imagen , Enfermedades del Ano/patología , Enfermedades del Recto/diagnóstico por imagen , Enfermedades del Recto/patología , Diafragma Pélvico/diagnóstico por imagen , Diafragma Pélvico/patologíaRESUMEN
Self-assembled cationic polymeric nanostructures have been receiving increasing attention for efficient antibacterial agents. In this work, a new type of antibacterial agents is developed by preparing pH-dependent nanostructured assemblies from cationic copolypeptoid poly(N-allylglycine)-b-poly(N-octylglycine) (PNAG-b-PNOG) modified with cysteamine hydrochloride ((PNAG-g-NH2 )-b-PNOG) driven by crystallization and hydrophobicity of the PNOG blocks. Due to the presence of confined domains arising from crystalline PNOG, persistent spheres and fiber-like assemblies are obtained from the same polymer upon a heating-cooling cycle. This allows for direct comparison of antimicrobial efficiency of nanostructured assemblies with various morphologies that are otherwise similar. Both nanostructured assemblies exhibit extremely low toxicity to human red blood cells, irrespective of the presence of the hydrophobic block. Enhanced antimicrobial performance of the fiber-like micelles compared to the spheres, which result in high selectivity of the fibers, is shown. Notably, the fiber-like micelles show great efficacy in inhibition of the Staphylococcus aureus (S. aureus) biofilm formations and eradication of the mature biofilms, superior to vancomycin. The micelles also show potent in vivo antimicrobial efficacy in a S. aureus infection mouse skin model. With a systematic study, it is demonstrated that both micelles kill the bacteria through a membrane disruption mechanism. These results imply great potential of polypeptoid assemblies as promising excellent candidates for antibacterial treatment and open up new possibilities for the preparation of a new generation of nanostructured antimicrobials.
Asunto(s)
Antiinfecciosos , Nanoestructuras , Infecciones Estafilocócicas , Ratones , Animales , Humanos , Staphylococcus aureus , Micelas , Antibacterianos/farmacología , Antibacterianos/química , Nanoestructuras/química , Polímeros/química , Infecciones Estafilocócicas/tratamiento farmacológico , Modelos Animales de Enfermedad , Biopelículas , Pruebas de Sensibilidad MicrobianaRESUMEN
As awareness of environmental protection increases, environmentally friendly coatings have been receiving great interest. Zwitterionic polymers are considered promising candidates due to their biocompatibility and excellent antifouling properties. In this paper, a type of polypeptoid containing zwitterions on the side chain was synthesized via ring-opening polymerization (ROP) and post-modification. This obtained polypeptoid was subsequently grafted onto the surface of polydimethylsiloxane (PDMS) via plasma and UV-induced surface polymerization. Surface morphology and protein adsorption tests of the resulting coating were systematically carried out. The results show that the modified coating has excellent antifouling properties and thus has great potential for environmentally friendly coating applications.
RESUMEN
The preparation of a type of innovative cationic copolypeptoid antimicrobials containing various hydrophobic moieties that resemble both structure and membrane-lytic antibacterial mechanism of natural antimicrobial peptides (AMPs) is reported. By finely tuning the hydrophilic/hydrophobic balance, the polypeptoids exhibit a wide spectrum of antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria with the lowest minimum inhibitory concentration (MIC) at only 2 µg mL-1 , whereas they also show low haemolytic properties. In particular, high selectivity (>128) is achieved from the polymers with butyl moieties. Moreover, the polypeptoids can readily inhibit the formation of biofilms and effectively eradicate the bacteria embedded in the mature biofilms, which is superior to many natural AMPs and vancomycin. Unlike conventional antibiotics, the polypeptoids possess potent activity against drug-resistant bacteria without visible resistance development after repeated usage. Notably, the polypeptoid antimicrobials not only have inherently fast bactericidal properties and excellent stability against incubation with human plasma, but also show excellent in vivo antibacterial effect. The prepared antimicrobials, coated onto magnetic nanospheres show recycling properties and enhanced antibacterial activity as combined with near-infrared (NIR)-induced photothermal antibacterial therapy.
Asunto(s)
Antibacterianos , Biopelículas , Antibacterianos/química , Antibacterianos/farmacología , Bacterias , Bacterias Grampositivas , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Polysaccharide conjugates are important renewable materials. If properly designed, they may for example be able to carry drugs, be proactive (e.g., with amino acid substituents) and can carry a charge. These aspects can be particularly useful for biomedical applications. Herein, we report a simple approach to preparing polysaccharide conjugates. Thiol-Michael additions can be mild, modular, and efficient, making them useful tools for post-modification and the tailoring of polysaccharide architecture. In this study, hydroxypropyl cellulose (HPC) and dextran (Dex) were modified by methacrylation. The resulting polysaccharide, bearing α,ß-unsaturated esters with tunable DS (methacrylate), was reacted with various thiols, including 2-thioethylamine, cysteine, and thiol functional quaternary ammonium salt through thiol-Michael addition, affording functionalized conjugates. This click-like synthetic approach provided several advantages including a fast reaction rate, high conversion, and the use of water as a solvent. Among these polysaccharide conjugates, the ones bearing quaternary ammonium salts exhibited competitive antimicrobial performance, as supported by a minimum inhibitory concentration (MIC) study and tracked by SEM characterization. Overall, this methodology provides a versatile route to polysaccharide conjugates with diverse functionalities, enabling applications such as antimicrobial activity, gene or drug delivery, and biomimicry.
RESUMEN
BACKGROUND AND PURPOSE: Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds' pharmacokinetics. EXPERIMENTAL APPROACH: Rats received single or multiple doses of ShuXueNing injection (prepared from GBE50 for intravenous administration) or GBE50 (a standardized extract of G. biloba leaves for oral administration). Brain delivery of the ginkgo compounds was assessed with microdialysis. Various rat samples were analysed using liquid chromatography/mass spectrometry. KEY RESULTS: Slow terminal elimination features of the flavonols counterbalanced the influence of poor oral bioavailability on their systemic exposure levels, which also resulted in significant accumulation of the compounds in plasma during the subchronic treatment with ShuXueNing injection and GBE50. Unlike the flavonols, the terpene lactones had poor enterohepatic circulation due to their rapid renal excretion and unknown metabolism. The flavonol glycosides occurred as major forms in plasma after dosing with ShuXueNing injection, while the flavonol aglycone conjugates were predominant in plasma after dosing with GBE50. Cerebral exposure was negligible for the flavonols and low for the terpene lactones. CONCLUSION AND IMPLICATIONS: Unlike the significant systemic exposure levels, the levels of cerebral exposure to the flavonols and terpene lactones are low. The elimination kinetic differences between the two classes of ginkgo compounds influence their relative systemic exposure levels. The information gained is relevant to linking ginkgo administration to the medicinal effects.
Asunto(s)
Flavonoles/farmacocinética , Ginkgo biloba/química , Lactonas/farmacocinética , Terpenos/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Encéfalo/metabolismo , Cromatografía Liquida , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacocinética , Flavonoles/administración & dosificación , Flavonoles/aislamiento & purificación , Glicósidos/administración & dosificación , Glicósidos/farmacocinética , Lactonas/administración & dosificación , Lactonas/aislamiento & purificación , Masculino , Espectrometría de Masas , Microdiálisis , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Hojas de la Planta , Ratas , Ratas Sprague-Dawley , Terpenos/administración & dosificación , Terpenos/aislamiento & purificación , Distribución TisularRESUMEN
Panax notoginseng (Sanqi) is a cardiovascular herb containing ginsenosides that are believed to be responsible for the therapeutic effects of Sanqi. The aim of this study was to evaluate rat exposure to ginsenosides after oral administration of Sanqi extract and to identify the key factors affecting their absorption and disposition. Ginsenosides were administered to rats, either in the form of Sanqi extract or as pure chemicals. The ginsenosides Ra(3), Rb(1), Rd, Re, Rg(1), and notoginsenoside R(1) were the major saponins present in the herbal extract. Systemic exposure to ginsenosides Ra(3), Rb(1), and Rd after oral administration of the extract was significantly greater than that to the other compounds. Considerable colonic deglycosylation of the ginsenosides occurred, but the plasma levels of deglycosylated metabolites were low in rats. Poor membrane permeability and active biliary excretion are the two primary factors limiting systemic exposure to most ginsenosides and their deglycosylated metabolites. In contrast with other ginsenosides, biliary excretion of ginsenosides Ra(3) and Rb(1) was passive. Meanwhile, the active biliary excretion of ginsenoside Rd was significantly slower than that of other saponins. Slow biliary excretion, inefficient metabolism, and slow renal excretion resulted in long-circulating and thus relatively high exposure levels for these three ginsenosides. For these reasons, plasma ginsenosides Ra(3), Rb(1), and Rd were identified as pharmacokinetic markers for indicating rat systemic exposure to Sanqi extract. This is a systematic investigation of the absorption and disposition of ginsenosides from an herb, the information gained from which is important for linking Sanqi administration to its medicinal effects.