RESUMEN
BACKGROUND: Periodontitis is a common oral disease characterized as inflammation on gingival tissue and alveolar bone resorption. Spirulina maxima has been reported to have anti-oxidative and anti-inflammatory effects on gastric ulcers. However, its effects on gingival inflammation and alveolar bone resorption of periodontitis have not been studied. PURPOSE: This study was designed to investigate the effects of S. maxima on the P. gingivalis-induced periodontitis and to elucidate its mechanism. METHODS: The phycocyanin contents in S. maxima were identified by high-performance liquid chromatography. 8-week old SD rats were induced periodontitis by inoculation with P. gingivalis for 14 days. The rats were then orally treated with S. maxima 100, 200, 400 mg/kg, or indomethacin (IND, positive control) 5 mg/kg for an additional 14 days. Inflammatory responses, expressions of collagenases in gingival tissue, osteoclast formation and activation, alveolar bone resorption, osteogenesis-related markers, and BMP2/Smad signaling in alveolar bone were measured. RESULTS: Pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and inflammatory transcription factor NF-κB were decreased in gingival tissue by S. maxima administration. Also, myeloperoxidase (MPO) activity and matrix metalloproteinase (MMPs) expression were decreased by S. maxima administration. Conversely, S. maxima increased IL-4, anti-inflammatory cytokine from Th2 cells. The osteoprotegerin (OPG) / receptor activator of NF-κB ligand (RANKL) expression ratio, which represents osteoclast-osteoblast balance, was increased in S. maxima-treated groups. The alveolar bone loss and the number of TRAP-positive osteoclast cells were also declined in S. maxima-treated groups while the osteoblasts count was increased. Besides, in S. maxima-treated groups, the osteogenesis-related factors were promoted and BMP-2/Smad pathway was up-regulated in a periodontitis condition. CONCLUSION: S. maxima reduces periodontitis induced by P. gingivalis through anti-inflammatory effect and resultant reduction in bone loss, suggesting that S. maxima might be a potential agent for treating periodontitis.
Asunto(s)
Pérdida de Hueso Alveolar/tratamiento farmacológico , Infecciones por Bacteroidaceae/complicaciones , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Porphyromonas gingivalis , Spirulina/química , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/microbiología , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Infecciones por Bacteroidaceae/tratamiento farmacológico , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Periodontitis/metabolismo , Ficocianina/análisis , Ratas Sprague-Dawley , Proteínas Smad/metabolismoRESUMEN
BACKGROUND: The Sri Lankan traditional betel quid (TBQ) which had been extensively used in the country before its colonization is claimed to have antiperiodontopathic effects in the Sri Lankan folklore. However, there is no reported scientific evidence to support the claimed antiperiodontopathic effects mediated by this TBQ. The present study was carried out to investigate the protective effect of the Sri Lankan TBQ in the pathogenesis of periodontitis. METHODS: We investigate the ethyl acetate extract of the Sri Lankan TBQ for its antibacterial effects against the keystone periodontopathic bacterium, P. gingivalis and also its antioxidant potential, which is important to protect the periodontium from oxidative stress. Further, its safety was analyzed using the cytokinesis block micronucleus assay on human peripheral blood lymphocytes (PBLs). RESULTS: Ethyl acetate extract of this TBQ inhibited the growth of P. gingivalis with a minimum bactericidal concentration (MBC) of 125 µg/ml. It was found to be a rich source of polyphenols and displayed considerable DPPH and ABTS radical scavenging activities and a strong ferric reducing antioxidant power. This extract could protect the cultured human gingival fibroblasts from H2O2 induced oxidative stress. In addition, this TBQ extract was not genotoxic to human PBLs even at a concentration of 2.5 mg/ml. Moreover, it exhibited protective effects against bleomycin induced genotoxicity in PBLs. CONCLUSION: Ethyl acetate extract of the Sri Lankan TBQ is a source of natural antibacterial compounds against P. gingivalis. It is also a source of natural antioxidants which can protect human gingival fibroblasts from H2O2 induced oxidative stress. These properties of the TBQ may have contributed to its claimed antiperiodontopathic effects. Besides, it was found to be relatively non-toxic to human cells. Thus this TBQ extract has a huge potential to be developed as a novel adjunctive therapeutic lead against periodontitis.
Asunto(s)
Antibacterianos/farmacología , Infecciones por Bacteroidaceae/tratamiento farmacológico , Periodontitis/tratamiento farmacológico , Piper betle , Extractos Vegetales/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Técnicas In Vitro , Hojas de la Planta , Porphyromonas gingivalis , Sri LankaRESUMEN
Amyloid-ß (Aß) accumulation is one of the main pathological hallmarks of Alzheimer's disease (AD). Porphyromonas gingivalis (P. gingivalis), the pathogen of chronic periodontitis, could cause Aß accumulation and was identified in the brain of AD patients. Salvianolic Acid B (SalB) has been proven to have the neuroprotective effect. Whether SalB could protect against P. gingivalis-induced cognitive impairment is still unknown. In this study, a P. gingivalis-infected mouse model was employed to study the neuroprotective role of SalB. The results showed that SalB (20 and 40 mg/kg) treatment for 4 weeks could shorten the escape latency and improve the percentage of spontaneous alternation in the P. gingivalis-infected mice. SalB inhibited the levels of reactive oxygen species and malondialdehyde, while increased the levels of antioxidative enzymes (superoxide dismutase and glutathione peroxidase). SalB decreased the levels of IL-1ß and IL-6, increased the mRNA levels of bdnf and ngf in the brain of P. gingivalis-infected mice. In addition, SalB obviously decreased the level of Aß. SalB elevated the protein expression of ADAM10, while downregulated BACE1 and PS1. SalB increased the protein expression of LRP1, while decreased RAGE. In conclusion, SalB could improve cognitive impairment by inhibiting neuroinflammation and decreasing Aß level in P. gingivalis-infected mice.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Infecciones por Bacteroidaceae/complicaciones , Benzofuranos/farmacología , Disfunción Cognitiva/tratamiento farmacológico , Administración Oral , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/análisis , Péptidos beta-Amiloides/inmunología , Animales , Infecciones por Bacteroidaceae/tratamiento farmacológico , Infecciones por Bacteroidaceae/inmunología , Infecciones por Bacteroidaceae/microbiología , Técnicas de Observación Conductual , Conducta Animal/efectos de los fármacos , Benzofuranos/uso terapéutico , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/inmunología , Disfunción Cognitiva/patología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Hipocampo/química , Hipocampo/efectos de los fármacos , Hipocampo/inmunología , Hipocampo/patología , Humanos , Masculino , Malondialdehído/análisis , Malondialdehído/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Porphyromonas gingivalis/inmunología , Porphyromonas gingivalis/aislamiento & purificación , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the microorganisms responsible for dental caries. The research question and the keywords were constructed according to the PICO strategy. The article search was done in Embase, Lilacs, Scielo, Medline, Scopus, Cochrane Library, Web of Science, Science Direct, and Pubmed databases. Randomized clinical trials and in vitro studies were selected in the review. The study was conducted according the PRISMA guideline for systematic review. A total of 34 articles were included in the qualitative analysis and four articles were divided into two subgroups to perform the meta-analysis. Few studies have achieved an effective microbial reduction in microorganisms associated with the pathogenesis of dental caries. The results highlight that there is no consensus about the study protocols for PDT against cariogenic microorganisms, although the results showed the PDT could be a good alternative for the treatment of dental caries.
Asunto(s)
Infecciones por Bacteroidaceae/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Caries Dental/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones por Bacteroidaceae/microbiología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Candida/efectos de los fármacos , Candida/crecimiento & desarrollo , Candida/patogenicidad , Candidiasis/microbiología , Curcumina/farmacología , Caries Dental/microbiología , Humanos , Azul de Metileno/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Porphyromonas gingivalis/crecimiento & desarrollo , Porphyromonas gingivalis/patogenicidad , Colorantes de Rosanilina/farmacología , Infecciones Estreptocócicas/microbiología , Streptococcus/efectos de los fármacos , Streptococcus/crecimiento & desarrollo , Streptococcus/patogenicidad , Cloruro de Tolonio/farmacología , Resultado del TratamientoRESUMEN
The in vivo antibacterial activity of NO-releasing hyperbranched polymers was evaluated against Porphyromonas gingivalis, a key oral pathogen associated with periodontitis, using a murine subcutaneous chamber model. Escalating doses of NO-releasing polymers (1.5, 7.5, and 37.5 mg/kg) were administered into a P. gingivalis-infected chamber once a day for 3 days. Chamber fluids were collected on day 4, with microbiological evaluation indicating a dose-dependent bactericidal action. In particular, NO-releasing polymers at 37.5 mg/kg (1170 µg of NO/kg) achieved complete bacterial eradication (>6-log reduction in bacterial viability), demonstrating greater efficacy than amoxicillin (â¼4-log reduction in bacterial viability), a commonly used antibiotic. Time-kill assays further revealed that largest dose (37.5 mg/kg; 1170 µg of NO/kg) resulted in â¼3-log killing of P. gingivalis after only a single dose. Based on these results, the potential clinical utility of NO-releasing hyperbranched polymers appears promising, particularly for oral health applications.
Asunto(s)
Antibacterianos/química , Antibacterianos/uso terapéutico , Infecciones por Bacteroidaceae/tratamiento farmacológico , Óxido Nítrico/química , Óxido Nítrico/uso terapéutico , Periodontitis/tratamiento farmacológico , Polímeros/química , Porphyromonas gingivalis/efectos de los fármacos , Amoxicilina/uso terapéutico , Animales , Infecciones por Bacteroidaceae/microbiología , Modelos Animales de Enfermedad , Compuestos Epoxi/química , Masculino , Ratones , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Periodontitis/microbiología , Poliaminas/química , Resultado del TratamientoRESUMEN
AIM: To evaluate the antibacterial activity of 12 kaurane-type diterpenes against a panel of bacteria that cause endodontic infection. METHODS & MATERIALS: We conducted tests against bacteria in the planktonic or in the sessile mode, cytotoxic assays for the most promising compounds against human normal lung fibroblast cells, and Porphyromonas gingivalis (ATCC 33277) proteomic analysis. RESULTS & CONCLUSION: Kaurenoic acid and its salt exhibited satisfactory antibacterial action against the evaluated bacteria. Proteomic analysis suggested that these compounds might interfere in bacterial metabolism and virulence factor expression. Kaurane-type diterpenes are an important class of natural products and should be considered in the search for new irrigating solutions to treat endodontic infections.
Asunto(s)
Antibacterianos/farmacología , Infecciones por Bacteroidaceae/tratamiento farmacológico , Diterpenos/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Antibacterianos/química , Infecciones por Bacteroidaceae/microbiología , Biopelículas/efectos de los fármacos , Diterpenos/química , Humanos , Viabilidad Microbiana/efectos de los fármacos , Mikania/química , Extractos Vegetales/química , Hojas de la Planta/química , Porphyromonas gingivalis/crecimiento & desarrollo , Porphyromonas gingivalis/aislamiento & purificación , Pulpitis/tratamiento farmacológico , Pulpitis/microbiologíaRESUMEN
Rheumatoid arthritis (RA) is an inflammatory disease that has been linked to several risk factors, including periodontitis. Identification of new anti-inflammatory compounds to treat arthritis is needed. We had previously demonstrated the beneficial effect of Kava-241, a kavain-derived compound, in the management of Porphyromonas gingivalis-induced periodontitis. The present study evaluated systemic and articular effects of Kava-241 in an infective arthritis murine model triggered by P. gingivalis bacterial inoculation and primed with a collagen antibody cocktail (CIA) to induce joint inflammation and tissular destruction. Clinical inflammation score and radiological analyses of the paws were performed continuously, while histological assessment was obtained at sacrifice. Mice exposed to P. gingivalis and a CIA cocktail and treated concomitantly with Kava-241 exhibited a reduced clinical inflammatory score and a decreased number of inflammatory cells and osteoclasts within joint. Kava-241 treatment also decreased significantly tumor necrosis factor alpha (TNF-α) in serum from mice injected with a Toll-like receptor 2 or 4 (TLR-2/4) ligand, P. gingivalis-lipopolysaccharide (LPS). Finally, bone marrow-derived macrophages infected with P. gingivalis and exposed to Kava-241 displayed reduced TLR-2/4, reduced mitogen-activated protein kinase (MAPK)-related signal elements, and reduced LPS-induced TNF-α factor (LITAF), all explaining the observed reduction of TNF-α secretion. Taken together, these results emphasized the novel properties of Kava-241 in the management of inflammatory conditions, especially TNF-α-related diseases such as infective RA.
Asunto(s)
Antiinflamatorios/farmacología , Artritis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Articulaciones/microbiología , Porphyromonas gingivalis , Pironas/farmacología , Animales , Artritis/microbiología , Infecciones por Bacteroidaceae/sangre , Infecciones por Bacteroidaceae/tratamiento farmacológico , Modelos Animales de Enfermedad , Inflamación/sangre , Inflamación/microbiología , Articulaciones/citología , Articulaciones/efectos de los fármacos , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/microbiología , Masculino , Ratones , Osteoclastos/efectos de los fármacos , Receptor Toll-Like 2/sangre , Factor de Necrosis Tumoral alfa/sangreRESUMEN
In obesity, gut microbiota LPS may translocate into the blood stream and then contribute to adipose tissue inflammation and oxidative stress, leading to insulin resistance. A causal link between periodontal infection, obesity and type 2 diabetes has also been suggested. We evaluated the ability of polyphenols from Antirhea borbonica medicinal plant to improve the inflammatory and redox status of 3T3-L1 adipocytes exposed to LPS of Porphyromonas gingivalis periodontopathogen or Escherichia coli enterobacteria. Our results show that LPS enhanced the production of Toll-like receptor-dependent MyD88 and NFκB signaling factors as well as IL-6, MCP-1, PAI-1 and resistin. Plant polyphenols reduced LPS pro-inflammatory action. Concomitantly, polyphenols increased the production of adiponectin and PPARγ, known as key anti-inflammatory and insulin-sensitizing mediators. Moreover, both LPS increased intracellular ROS levels and the expression of genes encoding ROS-producing enzymes including NOX2, NOX4 and iNOS. Plant polyphenols reversed these effects and up-regulated MnSOD and catalase antioxidant enzyme gene expression. Noticeably, preconditioning of cells with caffeic acid, chlorogenic acid or kaempferol identified among A. borbonica major polyphenols, led to similar protective properties. Altogether, these findings demonstrate the anti-inflammatory and antioxidant effects of A. borbonica polyphenols on adipocytes, in response to P. gingivalis or E. coli LPS. It will be of major interest to assess A. borbonica polyphenol benefits against obesity-related metabolic disorders such as insulin resistance in vivo.
Asunto(s)
Adipocitos/efectos de los fármacos , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Escherichia coli/inmunología , Lipopolisacáridos/inmunología , Polifenoles/farmacología , Porphyromonas gingivalis/inmunología , Células 3T3-L1 , Adipocitos/inmunología , Adipocitos/microbiología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Infecciones por Bacteroidaceae/tratamiento farmacológico , Infecciones por Bacteroidaceae/inmunología , Infecciones por Bacteroidaceae/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/microbiología , Ratones , Estrés Oxidativo/efectos de los fármacos , Plantas Medicinales/química , Polifenoles/química , Polifenoles/aislamiento & purificación , Rubiaceae/químicaRESUMEN
Periodontitis is a severe inflammatory response, leading to characteristic periodontal soft tissue destruction and alveolar bone resorption. Baicalin possesses potent anti-inflammatory activity; however, it is still unclear whether baicalin regulates toll-like receptor (TLR) 2/4 expression and downstream signaling during the process of periodontitis. In this study, the cervical area of the maxillary second molars of rats was ligated and inoculated with Porphyromonas gingivalis (P. gingivalis) for 4weeks to induce periodontitis. Some rats with periodontitis were treated intragastrically with baicalin (50, 100 or 200mg/kg/day) or vehicle for 4weeks. Compared with the sham group, the levels of TLR2, TLR4 and MyD88 expression and the p38 MAPK and NF-κB activation were up-regulated in the experimental periodontitis group (EPG), accompanied by marked alveolar bone loss and severe inflammation. Treatment with 100 or 200mg/kg/day baicalin dramatically reduced the alveolar bone loss, the levels of HMGB1, TNF-α, IL-1ß, and MPO expression, and the numbers of inflammatory infiltrates in the gingival tissues. Importantly, treatment with 100 or 200mg/kg/day baicalin mitigated the periodontitis-up-regulated TLR2, TLR4 and MyD88 expression, and the p38 MAPK and NF-κB activation. Hence, the blockage of the TLR2 and TLR4/MyD88/p38 MAPK/NF-κB signaling by baicalin may contribute to its anti-inflammatory effects in rat model of periodontitis. In conclusion, these novel findings indicate that baicalin inhibits the TLR2 and TLR4 expression and the downstream signaling and mitigates inflammatory responses and the alveolar bone loss in rat experimental periodontitis. Therefore, baicalin may be a potential therapeutic agent for treatment of periodontitis.
Asunto(s)
Antiinflamatorios/uso terapéutico , Infecciones por Bacteroidaceae/tratamiento farmacológico , Flavonoides/uso terapéutico , Factor 88 de Diferenciación Mieloide/metabolismo , Periodontitis/tratamiento farmacológico , Porphyromonas gingivalis/fisiología , Scutellaria baicalensis/inmunología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Infecciones por Bacteroidaceae/inmunología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Modelos Animales , Factor 88 de Diferenciación Mieloide/genética , Periodontitis/inmunología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genéticaRESUMEN
Chronic periodontal diseases are characterised by a dysregulated and exaggerated inflammatory/immune response to plaque bacteria. We have demonstrated previously that oral keratinocytes up-regulate key molecular markers of inflammation, including NF-κB and cytokine signalling, when exposed to the periodontal bacteria Porphyromonas gingivalis and Fusobacterium nucleatum in vitro. The purpose of the current study was to investigate whether α-lipoic acid was able to abrogate bacterially-induced pro-inflammatory changes in the H400 oral epithelial cell line. Initial studies indicated that α-lipoic acid supplementation (1-4 mM) significantly reduced cell attachment; lower concentrations (<0.5 mM) enabled >85% cell adhesion at 24 h. While a pro-inflammatory response, demonstrable by NF-κB translocation, gene expression and protein production was evident in H400 cells following exposure to P. gingivalis and F. nucleatum, pre-incubation of cells with 0.5 mM α-lipoic acid modulated this response. α-Lipoic acid pre-treatment significantly decreased levels of bacterially-induced NF-κB activation and IL-8 protein production, and differentially modulated transcript levels for IL-8, IL-1ß, TNF-α and GM-CSF, TLR2, 4, 9, S100A8, S100A9, lysyl oxidase, NF-κB1, HMOX, and SOD2. Overall, the data indicate that α-lipoic acid exerts an anti-inflammatory effect on oral epithelial cells exposed to periodontal bacteria and thus may provide a novel adjunctive treatment for periodontal diseases.
Asunto(s)
Infecciones por Bacteroidaceae/inmunología , Infecciones por Fusobacterium/inmunología , Fusobacterium nucleatum/inmunología , Queratinocitos/inmunología , FN-kappa B/metabolismo , Porphyromonas gingivalis/inmunología , Infecciones por Bacteroidaceae/tratamiento farmacológico , Línea Celular , Infecciones por Fusobacterium/tratamiento farmacológico , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-8/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/microbiología , Boca/inmunología , Boca/patología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Ácido Tióctico/farmacología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Activación Transcripcional/efectos de los fármacos , Activación Transcripcional/inmunologíaRESUMEN
Previous studies have shown anti-inflammatory potential of alkaline extract of the leaves of Sasa senanensis Rehder (SE). The aim of the present study was to clarity the molecular entity of SE, using various fractionation methods. SE inhibited the production of nitric oxide (NO), but not tumour necrosis factor-α by lipopolysaccharide (LPS)-stimulated mouse macrophage-like cells. Lignin carbohydrate complex prepared from SE inhibited the NO production to a comparable extent with SE, whereas chlorophyllin was more active. On successive extraction with organic solvents, nearly 90% of SE components, including chlorophyllin, were recovered from the aqueous layer. Anti-HIV activity of SE was comparable with that of lignin-carbohydrate complex, and much higher than that of chlorophyllin and n-butanol extract fractions. The CYP3A inhibitory activity of SE was significantly lower than that of grapefruit juice and chlorophyllin. Oral administration of SE slightly reduced the number of oral bacteria. When SE was applied to HPLC, nearly 70% of SE components were eluted as a single peak. These data suggest that multiple components of SE may be associated with each other in the native state or after extraction with alkaline solution.
Asunto(s)
Álcalis/administración & dosificación , Antiinflamatorios/administración & dosificación , Macrófagos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Sasa/química , Estomatitis/tratamiento farmacológico , Animales , Infecciones por Bacteroidaceae/tratamiento farmacológico , Infecciones por Bacteroidaceae/inmunología , Infecciones por Bacteroidaceae/microbiología , Línea Celular , Clorofilidas/farmacología , Citrus paradisi/química , Infecciones por VIH/tratamiento farmacológico , Humanos , Lignina/farmacología , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/metabolismo , Masculino , Ratones , Microsomas Hepáticos/efectos de los fármacos , Óxido Nítrico/metabolismo , Porphyromonas gingivalis/efectos de los fármacos , Porphyromonas gingivalis/crecimiento & desarrollo , Ratas , Estomatitis/inmunología , Estomatitis/microbiología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
A novel injectable thermosensitive hydrogel (CS-HTCC/alpha beta-GP) was successfully designed and prepared using chitosan (CS), quaternized chitosan (HTCC) and alpha,beta-glycerophosphate (alpha,beta-GP) without any additional chemical stimulus. The gelation point of CS-HTCC/alpha beta-GP can be set at a temperature close to normal body temperature or other temperature above 25 degrees C. The transition process can be controlled by adjusting the weight ratio of CS to HTCC, or different final concentration of alpha,beta-GP. The optimum formulation is (CS + HTCC) (2% w/v), CS/HTCC (5/1 w/w) and alpha,beta-GP 8.33% or 9.09% (w/v), where the sol-gel transition time was 3 min at 37 degrees C. The drug released over 3 h from the CS-HTCC/alpha,beta-GP thermosensitive hydrogel in artificial saliva pH 6.8. In addition, CS-HTCC/alpha,beta-GP thermosensitive hydrogel exhibited stronger antibacterial activity towards two periodontal pathogens (Porphyromonas gingivalis, P.g and Prevotella intermedia, P.i). CS-HTCC/alpha, beta-GP thermosensitive hydrogel was a considerable candidate as a local drug delivery system for periodontal treatment.
Asunto(s)
Quitosano/química , Quitosano/uso terapéutico , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/uso terapéutico , Antiinfecciosos/administración & dosificación , Antiinfecciosos/química , Antiinfecciosos/uso terapéutico , Infecciones por Bacteroidaceae/tratamiento farmacológico , Quitosano/administración & dosificación , Quitosano/análogos & derivados , Quitosano/síntesis química , Estabilidad de Medicamentos , Glicerofosfatos/administración & dosificación , Glicerofosfatos/química , Glicerofosfatos/uso terapéutico , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/administración & dosificación , Bombas de Infusión Implantables , Inyecciones Intralesiones , Pruebas de Sensibilidad Microbiana , Enfermedades Periodontales/tratamiento farmacológico , Enfermedades Periodontales/etiología , Enfermedades Periodontales/microbiología , Porphyromonas gingivalis/efectos de los fármacos , Prevotella intermedia/efectos de los fármacos , Espectrofotometría Infrarroja , Temperatura , Termodinámica , ViscosidadRESUMEN
Control of dental plaque-related diseases has traditionally relied on non-specific removal of plaque by mechanical means. As our knowledge of oral disease mechanisms increases, future treatment is likely to be more targeted, for example at small groups of organisms, single species or at key virulence factors they produce. The aim of this review is to consider the current status as regards novel treatment approaches. Maintenance of oral hygiene often includes use of chemical agents; however, increasing problems of resistance to synthetic antimicrobials have encouraged the search for alternative natural products. Plants are the source of more than 25% of prescription and over-the-counter preparations, and the potential of natural agents for oral prophylaxis will therefore be considered. Targeted approaches may be directed at the black-pigmented anaerobes associated with periodontitis. Such pigments provide an opportunity for targeted phototherapy with high-intensity monochromatic light. Studies to date have demonstrated selective killing of Porphyromonas gingivalis and Prevotella intermedia in biofilms. Functional inhibition approaches, including the use of protease inhibitors, are also being explored to control periodontitis. Replacement therapy by which a resident pathogen is replaced with a non-pathogenic bacteriocin-producing variant is currently under development with respect to Streptococcus mutans and dental caries.
Asunto(s)
Antibacterianos , Placa Dental/microbiología , Placa Dental/prevención & control , Enfermedades Periodontales/tratamiento farmacológico , Antibacterianos/química , Antibacterianos/farmacología , Infecciones por Bacteroidaceae/tratamiento farmacológico , Infecciones por Bacteroidaceae/microbiología , Humanos , Luz , Myrtaceae/química , Enfermedades Periodontales/microbiología , Enfermedades Periodontales/prevención & control , Aceites de Plantas/uso terapéutico , Porphyromonas gingivalis/efectos de los fármacos , Prevotella/efectos de los fármacos , Probióticos , Inhibidores de Proteasas/uso terapéutico , Resultado del TratamientoRESUMEN
Porphyromonas gingivalis infections cause problems in periodontal diseases and in certain systemic diseases. There is evidence that Lactobacillus spp. can control populations of P. gingivalis, but there are few data on the effects of purified bacteriocins from Lactobacillus paracasei HL32 on P. gingivalis. The objective of this study was to examine the antibacterial activity of a bacteriocin from L. paracasei HL32 and to relate this activity to its composition. A bacteriocin was purified from culture supernatants of Lactobacillus spp. using a dialysis technique followed by gel-permeation chromatography. Composition of the bacteriocin was characterised by ninhydrin tests, ultraviolet spectrophotometry, thin-layer chromatography, sodium-dodecyl sulphate-polyacrylamide gel electrophoresis, electrospray ionisation mass spectrometry and amino acid analysis. The amino acid sequence from the N-terminal of the bacteriocin was determined. Antibacterial activity was examined by the cylinder plate method, microtitre assay and scanning electron microscopy as compared with standard antibiotics. The bacteriocin had a molecular weight of approximately 56kDa, was comprised of 68% carbohydrate and 32% protein, and showed maximum peak absorbance at 214 and 254nm. The bacteriocin was found to be effective against P. gingivalis; it caused swelling and pore formation on the cell envelope at a minimum bactericidal concentration of 0.14mM, and caused death within 2h. Metronidazole killed P. gingivalis but did not affect the envelope, whereas tetracycline affected P. gingivalis with cell deformation. In conclusion, the bacteriocin from L. paracasei HL32 had the ability to kill P. gingivalis, suggesting that it could be a promising alternative chemotherapeutic agent for P. gingivalis infections.
Asunto(s)
Antibacterianos/uso terapéutico , Bacteriocinas/uso terapéutico , Infecciones por Bacteroidaceae/tratamiento farmacológico , Lactobacillus/metabolismo , Periodontitis/tratamiento farmacológico , Porphyromonas gingivalis/efectos de los fármacos , Secuencia de Aminoácidos , Antibacterianos/aislamiento & purificación , Bacteriocinas/genética , Bacteriocinas/aislamiento & purificación , Pared Celular/efectos de los fármacos , Cromatografía en Capa Delgada , Electroforesis en Gel de Poliacrilamida , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Datos de Secuencia Molecular , Peso Molecular , Porphyromonas gingivalis/ultraestructura , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
To compare the frequencies, concentrations, and antimicrobial susceptibilities of vaginal microbes isolated from women with bacterial vaginosis (BV) before and after therapy, 119 nonpregnant women aged 18 to 45 with clinical and Gram stain evidence of BV were randomized to receive intravaginal clindamycin or metronidazole. Vaginal swabs were collected at baseline and 7 to 12 days, 35 to 45 days, and 70 to 90 days following therapy for quantitative vaginal culture. For the 99 women completing all four visits, statistical analyses were performed comparing differences in vaginal microflora between the two treatment arms and between visits in the same treatment group. Antimicrobial susceptibility testing using the agar dilution method was performed for anaerobic gram-negative rods. Although both therapies resulted in decreased colonization by Gardnerella vaginalis and Mycoplasma hominis, only metronidazole treatment resulted in a significant decrease in the frequency and concentration of Prevotella bivia and black-pigmented Prevotella species. Of the 865 anaerobic gram-negative rods evaluated for susceptibility, only 3 (0.3%) were resistant to metronidazole, whereas clindamycin resistance increased significantly for P. bivia and black-pigmented anaerobic gram-negative rods persisting following clindamycin therapy. Clindamycin-resistant subpopulations of P. bivia and black-pigmented Prevotella species emerged 7 to 12 days after therapy even among women colonized initially by clindamycin-susceptible strains. These resistant subpopulations persisted at high frequencies (42 to 50%) 70 to 90 days following therapy. The two topical agents for treatment of BV have differing microbiologic effects on the vaginal microflora. The emergence of clindamycin-resistant anaerobic gram-negative rods following therapy is of concern.
Asunto(s)
Antibacterianos/uso terapéutico , Bacteroidaceae/efectos de los fármacos , Clindamicina/uso terapéutico , Metronidazol/uso terapéutico , Vaginosis Bacteriana/tratamiento farmacológico , Administración Tópica , Adolescente , Adulto , Antibacterianos/farmacología , Infecciones por Bacteroidaceae/tratamiento farmacológico , Infecciones por Bacteroidaceae/microbiología , Clindamicina/farmacología , Farmacorresistencia Bacteriana , Femenino , Humanos , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Resultado del Tratamiento , Vagina/microbiología , Vaginosis Bacteriana/microbiologíaRESUMEN
BACKGROUND: This study assessed the long-term effects of adjunctive antimicrobial therapy on periodontal disease progression and oral colonization. METHODS: Patients with previously untreated chronic periodontitis and subgingival Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis were randomly assigned to subgingival scaling without (control group) or with systemic amoxicillin plus metronidazole and CHX irrigation (test group). Relative attachment levels were determined and subgingival and mucosal plaque samples were taken at baseline, at 10 days (plaque only) and at 3, 6, 9, 12, 18, and 24 months following initial therapy. During maintenance therapy, patients received supragingival debridement only. RESULTS: After 24 months, the 18 test group patients showed at sites with initial probing depths (PD) > or =7 mm a significantly (P <0.05) higher frequency of 2 mm or more attachment gain (37.3% +/- 4.6%) and lower frequency of attachment loss (7.2% +/- 3.1%) compared to the 17 controls (8.2% +/- 3.9% and 19.1% +/- 13.1%, respectively). Compared to controls, the intraoral prevalence of A. actinomycetemcomitans (up to 18 months) and P. gingivalis (up to 3 months) decreased and that of Eikenella corrodens (at 10 days) increased in test patients (P <0.05). In both treatment groups, the detection frequency of Tannerella forsythensis decreased transiently, while an overall increase was recorded for Treponema ssp. CONCLUSIONS: Over the 24-month period, a single course of the administered adjunctive antimicrobial therapy led to a relative risk reduction of 62% for attachment loss at deep sites. However, with the exception of A. actinomycetemcomitans, it failed to induce long-term changes in the prevalence profiles of oral colonization.
Asunto(s)
Infecciones por Actinobacillus/tratamiento farmacológico , Antibacterianos/uso terapéutico , Infecciones por Bacteroidaceae/tratamiento farmacológico , Clorhexidina/análogos & derivados , Periodontitis/tratamiento farmacológico , Aggregatibacter actinomycetemcomitans , Amoxicilina/uso terapéutico , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Clorhexidina/uso terapéutico , Placa Dental/microbiología , Raspado Dental , Femenino , Humanos , Masculino , Metronidazol/uso terapéutico , Persona de Mediana Edad , Periodontitis/microbiología , Porphyromonas gingivalis , Factores de TiempoRESUMEN
We tested the activity of Novispirin G-10, a novel antimicrobial alpha-helical octadecapeptide structurally related to cathelicidins and other innate immunity peptides, against Chlamydia trachomatis serovars L2, D, and E and three organisms associated with bacterial vaginosis (BV). The peptide's activity against C. trachomatis was measured in 48-h shell vial assays with McCoy cell targets. Exposure to 100 micro g/ml of Novispirin G-10 reduced the infectivity of serovars D and E by 99.4-100% and serovar L2 by 91.7-99.1%. At the same concentration of 100 micro g/ml, Novispirin G-10 rapidly killed >99% of Mobiluncus curtisii, Gardnerella vaginalis, and Prevotella bivia, in standard colony-forming unit (CFU) assays. Given its simple structure and relative lack of cytotoxic and hemolytic activity, Novispirin G-10 may be a useful component of microbicide preparations designed to prevent chlamydial infection and/or remediate the abnormal vaginal flora associated with BV.
Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Infecciones por Chlamydia/tratamiento farmacológico , Chlamydia trachomatis/efectos de los fármacos , Péptidos/farmacología , Péptidos/uso terapéutico , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/microbiología , Péptidos Catiónicos Antimicrobianos/síntesis química , Péptidos Catiónicos Antimicrobianos/química , Infecciones por Bacteroidaceae/tratamiento farmacológico , Línea Celular , Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/clasificación , Ensayo de Unidades Formadoras de Colonias , Femenino , Gardnerella vaginalis/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Mobiluncus/efectos de los fármacos , Péptidos/química , Péptidos/orina , Prevotella/efectos de los fármacos , Estructura Secundaria de Proteína , SerotipificaciónRESUMEN
In this study, we evaluated the current effectiveness of 11 beta-lactam antibiotics for treatment of orofacial odontogenic infections by determining the antimicrobial susceptibility of the major pathogens. The antimicrobial susceptibilities of viridans streptococci (n = 47), Peptostreptococcus (n = 67), Porphyromonas (n = 18), Fusobacterium (n = 57), black-pigmented Prevotella (n = 59) and non-pigmented Prevotella (n = 47) isolated from pus specimens of 93 orofacial odontogenic infections to penicillin G, cefmetazole, flomoxef, cefoperazone, cefoperazone/sulbactam, ceftazidime, cefpirome, cefepime, cefoselis, imipenem and faropenem were determined using the agar dilution method. Penicillin G, most cephalosporins, imipenem and faropenem worked well against viridans streptococci, Peptostreptococcus, Porphyromonas and Fusobacterium. Penicillin G and most cephalosporins, including fourth-generation agents, were not effective against beta-lactamase-positive Prevotella, though they were effective against beta-lactamase-negative strains. Cefmetazole, cefoperazone/sulbactam, imipenem and faropenem expressed powerful antimicrobial activity against beta-lactamase-positive Prevotella. In conclusion, penicillins have the potential to be first-line agents in the treatment of orofacial odontogenic infections. Most of the other beta-lactam antibiotics, including fourth-generation cephalosporins, were not found to have greater effectiveness than penicillins. In contrast, cefmetazole, cefoperazone/sulbactam, imipenem and faropenem were found to have greater effectiveness than penicillins.
Asunto(s)
Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Ceftizoxima/análogos & derivados , Lactamas , Enfermedades de la Boca/microbiología , beta-Lactamas , Infecciones por Bacteroidaceae/tratamiento farmacológico , Cefepima , Cefmetazol/uso terapéutico , Cefoperazona/administración & dosificación , Cefoperazona/uso terapéutico , Ceftazidima/uso terapéutico , Ceftizoxima/uso terapéutico , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana , Quimioterapia Combinada/uso terapéutico , Fusobacterium/efectos de los fármacos , Infecciones por Fusobacterium/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Imipenem/uso terapéutico , Pruebas de Sensibilidad Microbiana , Enfermedades de la Boca/tratamiento farmacológico , Penicilina G/uso terapéutico , Penicilinas/uso terapéutico , Peptostreptococcus/efectos de los fármacos , Porphyromonas gingivalis/efectos de los fármacos , Prevotella/efectos de los fármacos , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus/efectos de los fármacos , Sulbactam/administración & dosificación , Sulbactam/uso terapéutico , CefpiromaRESUMEN
Methyl mercaptan is a major component responsible for oral malodor. This compound arises from the bacterial metabolism of methionine. Here we show that the growth of Porphyromonas gingivalis, a periodontal microorganism that produces large amounts of methyl mercaptan, was strongly inhibited by l-trifluoromethionine (TFM), a fluorinated derivative of methionine. In contrast, TFM had no effect on the growth of bacteria which do not produce methyl mercaptan. In addition, the survival rate of P. gingivalis-infected mice was remarkably increased by the co-injection of TFM. These results suggest that TFM is a promising antibacterial agent specific to the malodorous oral bacteria.
Asunto(s)
Infecciones por Bacteroidaceae/tratamiento farmacológico , Liasas de Carbono-Azufre/metabolismo , Metionina/análogos & derivados , Metionina/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Porphyromonas gingivalis/crecimiento & desarrollo , Animales , Infecciones por Bacteroidaceae/microbiología , Infecciones por Bacteroidaceae/patología , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Halitosis/etiología , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/patogenicidad , Compuestos de Sulfhidrilo/metabolismo , Tasa de Supervivencia , Virulencia/efectos de los fármacosRESUMEN
Local delivery systems of antimicrobial agents for treatment of the periodontal diseases received considerable attention during the past decade due to the disadvantages of the systemic administration. An ideal formulation should exhibit ease of delivery, a good retention at the application site, and a controlled release of the drug. The application of bioadhesive gels provides a long stay in the oral cavity, adequate drug penetration, high efficacy and acceptability. In dentistry and oral medicine, various applications of chitosan, which is a bioadhesive polymer have been proposed due to its favorable properties such as biocompatibility and biodegradability. The aim of this study was to determine the antimicrobial activity of chitosan formulations either in gel or film form against a periodontal pathogen, Porphyromonas gingivalis. The viscosity, bioadhesive properties and antimicrobial activity of chitosans at different molecular weight and deacetylation degree were evaluated in the absence or presence of chlorhexidine gluconate (Chx), incorporated into the formulations at 0.1 and 0.2% concentrations. The flow property of the gels were found to be suitable for topical application on the oral mucosa and to syringe into the periodontal pocket. Bioadhesion of the gels and films examined ex-vivo using fresh porcine buccal mucosa showed that both the film and gel formulations exert bioadhesive properties and was not affected by incorporation of Chx. Chitosan is shown to have an antimicrobial activity against P. gingivalis and this was higher with high molecular weight chitosan. The combination of chitosan with Chx showed a higher activity when compared to that of Chx alone, which would provide Chx application at lower concentrations thus avoiding its unwanted side effects. Chitosan films and gels seem to be promising delivery systems for local therapy of periodontal diseases with its bioadhesive property and antimicrobial activity.