RESUMEN
Aims - to compare the color changes, the surface roughness and morphology of the enamel bleached with two different bleaching solutions (chemical and laser activated), preceded or not with acid etching. Thirty teeth of bovine prepared and haphazardly assigned to 2 groups (n=15) depending on bleaching technique. Each group subdivided to 3 subgroup (n=5) consistent with acid etching by 37% phosphoric acid. Atomic force microscopy and VITA easy shade spectrophotometer were performed twice for all the specimens before and after bleaching. ANOVA, the Paired sample t-test, and the independent sample t-test used for statistical analysis. As for the color changes, the groups that were bleached by the chemical method, the difference among the three subgroups was statistically significant. This also applies to the groups bleached with the laser method. When comparing the results of the chemical bleaching subgroups with the laser bleaching ones, the difference was not significant. Roughness results showed significant differences between certain subgroups and non-significant differences among others. However, the difference was statistically significant between the chemical and laser groups, laser technique resulted in less surface roughness than the chemical one. Acid etching before bleaching produced better colour change in both the chemical and laser assisted bleaching. In chemical bleaching, surface roughness was higher when acid etching was used. This was also true for laser bleaching technique. In general, laser assisted bleaching produced less surface roughness than chemical bleaching.
Asunto(s)
Grabado Ácido Dental , Esmalte Dental , Propiedades de Superficie , Blanqueamiento de Dientes , Esmalte Dental/efectos de los fármacos , Esmalte Dental/química , Bovinos , Animales , Blanqueamiento de Dientes/métodos , Propiedades de Superficie/efectos de los fármacos , Color , Ácidos Fosfóricos/química , Ácidos Fosfóricos/farmacología , Microscopía de Fuerza Atómica , Blanqueadores Dentales/química , Blanqueadores Dentales/farmacología , Espectrofotometría , Rayos LáserRESUMEN
OBJECTIVES: To assess the impact of various organic and inorganic acids on the roughness, demineralization, and collagen secondary structures of human dentin and to compare these effects with those of traditional agents, specifically phosphoric acid (PA) and ethylenediaminetetraacetic acid (EDTA). METHODS: Coronal dentin discs (n = 10) were examined by optical profilometry (roughness) and ATR-FTIR before and after conditioning with 32 % PA, 3 % nitric acid (NA), 20 % citric acid (CA), 20 % phytic acid (IP6) or 17 % EDTA. Spectra data were processed to quantify dentin demineralization (DM%) and percentage area of amide I curve-fitted components of ß-turns, 310-helix, α-helix, random coils, ß-sheets, and collagen maturation index. Statistical analysis was performed by one-way ANOVA or Kruskal-Wallis for DM% and roughness parameters, and paired t-test/Wilcoxon test for amide I components at significance level set at α = 0.05. RESULTS: All treatments resulted in increased roughness parameters, with the most significant changes occurring primarily with PA, while EDTA exhibited the least changes. DM% was NA>PA>IP6>CA>EDTA in a descending order. Regarding amide I components, NA demonstrated a significant reduction in ß-turns, 310-helices, and α-helices and it increased ß-sheets and random coils. PA resulted in reduction in ß-turns and α-helices while it increased ß-sheets. CA and EDTA did not cause significant changes. The collagen maturation index significantly increased only after IP6 treatment. CONCLUSIONS: The effect on dentin roughness parameters, demineralization, and collagen secondary structures varied based on the type of dentin surface treatment. CLINICAL SIGNIFICANCE: Understanding the impact of acids on the intrinsic properties of dentin is clinically essential for gaining insights into how these effects influence adhesion to dentin, the long-term stability of resin-based restorations, and the success of remineralization therapies.
Asunto(s)
Ácido Cítrico , Colágeno , Dentina , Ácido Edético , Ácidos Fosfóricos , Propiedades de Superficie , Desmineralización Dental , Dentina/efectos de los fármacos , Humanos , Ácido Edético/farmacología , Ácido Edético/química , Ácido Cítrico/farmacología , Ácido Cítrico/química , Ácidos Fosfóricos/química , Ácidos Fosfóricos/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Ácido Fítico/farmacología , Ácido Fítico/química , Estructura Secundaria de Proteína , Grabado Ácido Dental , Ensayo de Materiales , Conformación Proteica en Hélice alfaRESUMEN
STATEMENT OF PROBLEM: Phosphoric acid is commonly used in dentistry as an etchant but can result in excessive demineralization of dentin, a major contributor to the instability of dentin-bonded restorations. Nevertheless, research on the development of etchants that can reduce acid damage is sparse. PURPOSE: The purpose of this in vitro study was to investigate the effects of polyvinylpyrrolidone-modified phosphoric acid on the dentin bonding of an etch-and-rinse adhesive. MATERIAL AND METHODS: Protective etchants were prepared by adding polyvinylpyrrolidone to 35% phosphoric acid aqueous solutions: the 3 concentrations were 0.5% (P0.5% group), 1% (P1% group), and 2% (P2% group) w/v. The treatment agent of the control group (C) was 35% phosphoric acid gel. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), microhardness, microtensile bonding strength (µTBS), nanoleakage, and in situ zymography were used to evaluate the appearance of the protective etchant on dentin bonding. The results were analyzed with a 1-way ANOVA test (α=.05). RESULTS: SEM showed no obviously exposed collagen fiber in the P1% and P2% groups. FTIR showed less demineralization of the dentin surface, and microhardness was higher after treatment with the protective etchant (P<.05). The µTBS of P1% (70 ±9.2 MPa) was the highest, and group C (44 ±5.8 MPa) was the lowest in all groups (P<.05). Moreover, there was weaker MMP activity in the P1% and P2% groups (P<.05). CONCLUSIONS: This study demonstrated that the protective etchant effectively reduced demineralization, enhanced bond strength, and reduced nanoleakage and enzyme activity within the hybrid layer.
Asunto(s)
Recubrimiento Dental Adhesivo , Desmineralización Dental , Humanos , Povidona , Ácidos Fosfóricos/química , Ácidos Fosfóricos/farmacología , Microscopía Electrónica de Rastreo , Dentina , Resistencia a la Tracción , Recubrimientos Dentinarios/química , Ensayo de Materiales , Cementos de Resina/químicaRESUMEN
This study evaluates the effect of the deproteinization agents hypochlorous acid and sodium hypochlorite upon the bonding of the two different pit and fissure sealant, self-adhesive flowable composites with the enamel. Thirty-six third molars were randomly divided into six different groups. The groups were formed as follows: Group 1: 37% phosphoric acid + VertiseTM Flow; Group 2: 200 ppm hypochlorous acid + 37% phosphoric acid VertiseTM Flow; Group 3: 5.25% sodium hypochlorite + 37% phosphoric acid + VertiseTM Flow; Group 4: 37% phosphoric acid + Constic; Group 5: 200 ppm hypochlorous acid + 37% phosphoric acid + Constic; Group 6: 5.25% sodium hypochlorite + 37% phosphoric acid + Constic. In each group, samples were obtained that were rectangular prisms in shape (n = 12). Groups to which a deproteinization agent was applied (Groups 2, 3 and 5, 6) showed statistically higher microtensile bonding strength than Group 1, Group 4. There was no statistically significant difference in terms of microtensile bonding strength values between the Groups 3 and the Group 6. The study found that the groups to which deproteinization agents were applied had statistically higher microtensile bonding strength values compared with those groups to which acid and fissure sealants were applied. In this study, it was concluded that the use of fissure-sealing self-adhesive flowable composites after acid application to permanent tooth enamel provides an acceptable bond strength given the limitations of in vitro studies. In line with the results obtained, it was observed that in addition to the removal of the inorganic structure with the application of acid, the removal of the organic structure with the use of deproteinization agent increased the bond strength to the enamel.
Asunto(s)
Recubrimiento Dental Adhesivo , Selladores de Fosas y Fisuras , Humanos , Selladores de Fosas y Fisuras/farmacología , Ácido Hipocloroso/farmacología , Cementos de Resina/química , Cementos de Resina/farmacología , Hipoclorito de Sodio/farmacología , Cementos Dentales/farmacología , Recubrimiento Dental Adhesivo/métodos , Ácidos Fosfóricos/farmacología , Esmalte Dental , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
OBJECTIVE: To analyze the effect of Katana™ Cleaner (KC) in nanomechanical and triboscopic properties of etched dentin. METHODS: Dentin disks from human third molars were prepared. Two main groups of study were established in function of the etching conditioning, phosphoric acid (PA) and Clearfil SE Bond primer (CSEB). Four subgroups were tested within each group: i) untreated dentin (UD), ii) etched dentin (ED) [(PAED/CSEB)], iii) etched dentin contaminated with saliva (PAED+S)/(CSEB+S), and iv) etched and contaminated dentin treated with KC (PAED+S+KC)/(CSEB+S+KC). Nano-DMA testing and imaging, atomic force microscopy (AFM) analysis and nanoroughness (SRa) measurements were obtained. Field emission scanning electron microscopy (FESEM) images were also acquired. RESULTS: Phosphoric acid etched dentin samples and those specimens contaminated with saliva (PAED+S) attained the highest SRa values, that decreased after Katana™ Cleaner application (PAED+S+KC). In the group of dentin treated with CSEB primer, all subgroups performed similar, except in CSEB+S that attained the highest SRa values. The treatment with KC restored the original values of complex modulus of the untreated dentin. KC application produced the lowest and the highest tan delta values on PAED and CSEB groups, respectively. CONCLUSION: Katana™ Cleaner provided equally mature dentin surfaces after any of the etching methods. Tan delta increased when Katana™ Cleaner was applied on the dentin surface previously etched and contaminated with saliva, regardless the kind of etchant, thus facilitating the dissipation of energy for elastic recoil during loading. CLINICAL SIGNIFICANCE: Katana™ Cleaner application after saliva contamination originated similar low roughness levels, regardless the type of etching method. Both complex and storage moduli were similar, after Katana™ Cleaner application, in any case.
Asunto(s)
Recubrimiento Dental Adhesivo , Recubrimientos Dentinarios , Humanos , Recubrimientos Dentinarios/química , Dentina/química , Cementos de Resina/química , Ácidos Fosfóricos/farmacología , Ácidos Fosfóricos/química , Saliva , Propiedades de Superficie , Microscopía Electrónica de Rastreo , Recubrimiento Dental Adhesivo/métodos , Ensayo de MaterialesRESUMEN
STATEMENT OF PROBLEM: Secondary caries is a major factor in the failure of dental restorations. However, studies on the fabrication of acid-resistant and antibacterial dentin to improve dentin bonding are sparse. PURPOSE: The purpose of this in vitro study was to compare the effects of 2 types of fluoride-containing etchants on dentin bonding and explore the feasibility of formulating an altered dentin substrate to improve dentin bonding. MATERIAL AND METHODS: NaF-containing and SnF2-containing etchants were developed by adding sodium fluoride and stannous fluoride to a 35% phosphoric acid aqueous solution. Two groups (N1 and N2) containing NaF, 10 and 30 mg/mL respectively, and 2 groups (S1 and S2) containing SnF2, 18.6 and 55.8 mg/mL respectively, were formulated. The etchant of the control group (C) was 35% phosphoric acid gel. Scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), Fourier transform infrared spectroscopy (FTIR), microhardness, antierosion, and antibacterial tests were performed on the treated dentin. Moreover, the microtensile bond strength (µTBS) of each group was tested, and the fracture mode was determined after testing. Statistical analysis was performed with the 2-way ANOVA test (α=.05). RESULTS: The exposed collagen fiber was observed in group C, and minerals were formed on the dentin in the experimental groups. SEM, FTIR, and the microhardness test indicated more remineralization in the SnF2-containing etchant groups. The µTBS of S1 (77.5 ±10.36 MPa) was the highest in all groups, and group C (38.5 ±9.01 MPa) was the lowest. Moreover, the antierosion and antibacterial properties of the S2 group were the best among all groups (P<.05). CONCLUSIONS: Compared with NaF-containing etchant, SnF2-containing etchant could improve the dentin substrate, increase remineralization, improve bonding strength, and enhance antibacterial ability, especially by increasing resistance to acid erosion.
Asunto(s)
Recubrimiento Dental Adhesivo , Caries Dental , Humanos , Ácidos Fosfóricos/farmacología , Ácidos Fosfóricos/análisis , Ácidos Fosfóricos/química , Microscopía Electrónica de Rastreo , Dentina/química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Resistencia a la Tracción , Ensayo de Materiales , Recubrimientos Dentinarios/farmacología , Recubrimientos Dentinarios/uso terapéutico , Cementos de Resina/químicaRESUMEN
We describe here the design, synthesis, physicochemical properties, and hepatitis B antiviral activity of new 2'-O-alkyl ribonucleotide N3'âP5' phosphoramidate (2'-O-alkyl-NPO) and (thio)-phosphoramidite (2'-O-alkyl-NPS) oligonucleotide analogs. Oligonucleotides with different 2'-O-alkyl modifications such as 2'-O-methyl, -O-ethyl, -O-allyl, and -O-methoxyethyl combined with 3'-amino sugar-phosphate backbone were synthesized and evaluated. These molecules form stable duplexes with complementary DNA and RNA strands. They show an increase in duplex melting temperatures of up to 2.5°C and 4°C per linkage, respectively, compared to unmodified DNA. The results agree with predominantly C3'-endo sugar pucker conformation. Moreover, 2'-O-alkyl phosphoramidites demonstrate higher hydrolytic stability at pH 5.5 than 2'-deoxy NPOs. In addition, the relative lipophilicity of the 2'-O-alkyl-NPO and NPS oligonucleotides is higher than that of their 3'-O- counterparts. The 2'-O-alkyl-NPS oligonucleotides were evaluated as antisense (ASO) compounds in vitro and in vivo using Hepatitis B virus as a model system. Subcutaneous delivery of GalNAc conjugated 2'-O-MOE-NPS gapmers demonstrated higher activity than the 3'-O-containing 2'-O-MOE counterpart. The properties of 2'-O-alkyl-NPS constructs make them attractive candidates as ASO suitable for further evaluation and development.
Asunto(s)
Oligonucleótidos Antisentido , Oligonucleótidos , Oligonucleótidos/farmacología , Oligonucleótidos/química , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/farmacología , Ácidos Fosfóricos/farmacología , Ácidos Fosfóricos/química , Amidas/farmacología , Amidas/químicaRESUMEN
This study evaluated dentin enzymatic degradation based on the total matrix metalloproteinase (MMP) activity of demineralized dentin matrices before and after exposure to phosphoric acid (PA), glycolic acid (GA), and ferulic acid (FA). The release of hydroxyproline (HP), ultimate tensile strength (UTS), and dentin permeability (DP) were also evaluated. Dentin collagen matrices were assessed according to total MMP activity before and after treatment with the tested acids (n=10) for 15 seconds and compared with the control (GM6001 inhibitor). Dentin beams were analyzed for HP release and UTS after the treatments. Dentin discs were tested for DP at a pressure of 5 psi before and after treatment with the acids (n=10). The FA group had a lower percentage of enzymatic inhibition than the PA and GA groups (p<0.0001). No significant difference in UTS was found among the acids (p=0.6824), but HP release was significantly higher in the FA group than in the PA and GA groups (p<0.0001). No significant difference in DP was found for the acids (p=0.0535). GA led to less activation of MMPs and less release of HP, whereas the UTS and DP for GA were like those found for PA. In contrast, FA promoted greater enzymatic activity and greater release of HP, while having similar results to GA and PA regarding mechanical properties.
Asunto(s)
Dentina , Glicoles , Glicoles/metabolismo , Resistencia a la Tracción , Ácidos Fosfóricos/farmacología , PermeabilidadRESUMEN
PURPOSE: To evaluate the effect of application time and viscosity of meta-phosphoric acid (MPA) and ortho-phosphoric acid (OPA) on the push-out resin-dentin bond strength (PBS) and nanoleakage (NL) at the adhesive-root dentin interface. METHODS AND MATERIALS: Ninety-six roots of premolars were endodontically prepared and randomly assigned into groups according to the (i) acid (OPA and MPA), (ii) viscosity (gel and liquid), and (iii) application time (7 and 15 seconds). Fiber posts were cemented to the roots, which were then transversally sectioned into serial slices. The slices (cervical, medium, and apical) were subjected to PBS or NL. Analysis of the dentin etching pattern was performed using scanning electron microscopy (SEM). The PBS (MPa) and NL (%) data were subjected to three-way repeated-measures analysis of variance (ANOVA) and Tukey's test (α=0.05). RESULTS: The cross-product interaction was significant for both PBS and NL (p<0.001). No significant difference in the PBS was observed with the use of OPA compared to MPA (p>0.05). Higher PBS values were observed in the groups etched for 15 seconds compared to 7 seconds, regardless of the acid, viscosity, or root third (p<0.05). Lower NL was observed for MPA etching when compared to OPA etching (p<0.05), and these values were not affected by increasing the application time or acid viscosity (p>0.05). A more pronounced etching pattern was observed with OPA than MPA regardless of the acid viscosity. CONCLUSION: The use of 40% meta-phosphoric acid promoted adequate bond strength without increasing dentin demineralization or void spaces in the hybrid layer.
Asunto(s)
Recubrimiento Dental Adhesivo , Técnica de Perno Muñón , Cavidad Pulpar , Dentina , Recubrimientos Dentinarios/química , Ensayo de Materiales , Ácidos Fosfóricos/farmacología , Cementos de Resina/química , ViscosidadRESUMEN
OBJECTIVES: The humid oral environment adversely affects the interaction between a functionalised primer and dentine collagen after acid-etching. Robust adhesion of marine mussels to their wet substrates instigates the quest for a strategy that improves the longevity of resin-dentine bonds. In the present study, an etching strategy based on the incorporation of biomimetic dopamine methacrylamide (DMA) as a functionalised primer into phosphoric acid etchant was developed. The mechanism and effect of this DMA-containing acid-etching strategy on bond durability were examined. METHODS: Etchants with different concentrations of DMA (1, 3 or 5 mM) were formulated and tested for their demineralisation efficacy. The interaction between DMA and dentine collagen, the effect of DMA on collagen stability and the collagenase inhibition capacity of the DMA-containing etchants were evaluated. The effectiveness of this new etching strategy on resin-dentine bond durability was investigated. RESULTS: All etchants were capable of demineralising dentine and exposing the collagen matrix. The latter strongly integrated with DMA via covalent bond, hydrogen bond and Van der Waals' forces. These interactions significantly improve collagen stability and inhibited collagenase activity. Application of the etchant containing 5 mM DMA achieved the most durable bonding interface. CONCLUSION: Dopamine methacrylamide interacts with dentine collagen in a humid environment and improves collagen stability. The monomer effectively inactivates collagenase activity. Acid-etching with 5 mM DMA-containing phosphoric acid has the potential to prolong the longevity of bonded dental restorations without compromising clinical operation time. CLINICAL SIGNIFICANCE: The use of 5 mM dopamine methacrylamide-containing phosphoric acid for etching dentine does not require an additional clinical step and has potential to improve the adhesive performance of bonded dental restorations.
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Bivalvos , Recubrimiento Dental Adhesivo , Grabado Ácido Dental , Animales , Cementos Dentales/metabolismo , Dentina/metabolismo , Recubrimientos Dentinarios/química , Ensayo de Materiales , Ácidos Fosfóricos/química , Ácidos Fosfóricos/farmacología , Cementos de Resina/química , Propiedades de Superficie , Resistencia a la TracciónRESUMEN
Aryloxy triester phosphoramidate prodrugs of the monophosphate derivatives of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) were synthesized as lipophilic derivatives that can improve cell uptake. Despite the structural similarity of IPP and DMAPP, it was noted that their phosphoramidate prodrugs exhibited distinct stability profiles in aqueous environments, which we show is due to the position of the allyl bond in the backbones of the IPP and DMAPP monophosphates. As the IPP monophosphate aryloxy triester phosphoramidates showed favorable stability, they were subsequently investigated for their ability to activate Vγ9/Vδ2 T cells and they showed promising activation of this subset of T cells. Together, these findings represent the first report of IPP and DMAPP monophosphate prodrugs and the ability of IPP aryloxy triester phosphoramidate prodrugs to activate Vγ9/Vδ2 T cells highlighting their potential as possible immunotherapeutics.
Asunto(s)
Amidas/farmacología , Hemiterpenos/farmacología , Compuestos Organofosforados/farmacología , Ácidos Fosfóricos/farmacología , Linfocitos T/efectos de los fármacos , Amidas/síntesis química , Amidas/química , Voluntarios Sanos , Hemiterpenos/química , Humanos , Compuestos Organofosforados/química , Ácidos Fosfóricos/síntesis química , Ácidos Fosfóricos/químicaRESUMEN
BACKGROUND: Dentin hypersensitivity (DH) is a common dental clinical condition presented with a short and sharp pain in response to physical and chemical stimuli. Currently no treatment regimen demonstrates long-lasting efficacy in treating DH, and unesthetic yellow tooth color is a concern to many patients with DH. AIM: To develop a bi-functional material which can occlude dentinal tubules in-depth and remineralize dentin for long-lasting protection of the dentin-pulp complex from stimuli and bleach the tooth at the same time. METHODS: A mixture containing CaO, H3PO4, polyethylene glycol and H2O2 at a specific ratio was mechanically ground using a planetary ball. The mineralizing complex paste was characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Dentin was exposed to the synthesized paste for 8 h and 24 h in vitro. The mineralizing property was evaluated using SEM and microhardness tests. Red tea-stained tooth slices were exposed to the synthesized paste for 8 h and 24 h in vitro. The bleaching effect was characterized by a spectrophotometer. RESULTS: The complex paste had very a fine texture, was injectable, and had a gel-like property with 2.6 (mass/volume) % H2O2 concentration. The X-ray diffraction pattern showed that the inorganic phase was mainly monetite (CaHPO4). The mineralizing complex paste induced the growth of inorganic crystals on the dentin surface and in-depth occlusion of dentin tubules by up to 80 µm. The regenerated crystals were integrated into the dentin tissue on the dentin surface and the wall of dentinal tubules with a microhardness of up to 126 MPa (versus 137 Mpa for dentin). The paste also bleached the stained dental slices. CONCLUSION: The mineralizing complex paste is a promising innovative material for efficient DH management by remineralizing dentin and in-depth occlusion of dentin tubules, as well as tooth bleaching.
Asunto(s)
Fosfatos de Calcio/farmacología , Ácidos Fosfóricos/farmacología , Blanqueamiento de Dientes , Dentina/efectos de los fármacos , Dentina/ultraestructura , Dureza , Humanos , Peróxido de Hidrógeno/análisis , Remineralización Dental , Difracción de Rayos XRESUMEN
The bone regenerative capacity of synthetic calcium phosphates (CaPs) can be enhanced through the enrichment with selected metal trace ions. However, defining the optimal elemental composition required for bone formation is challenging due to many possible concentrations and combinations of these elements. We hypothesized that the ideal elemental composition exists in the inorganic phase of the bone extracellular matrix (ECM). To study our hypothesis, we first obtained natural hydroxyapatite through the calcination of bovine bone, which was then investigated its reactivity with acidic phosphates to produce CaP cements. Bioceramic scaffolds fabricated using these cements were assessed for their composition, properties, and in vivo regenerative performance and compared with controls. We found that natural hydroxyapatite could react with phosphoric acid to produce CaP cements with biomimetic trace metals. These cements present significantly superior in vivo bone regenerative performance compared with cements prepared using synthetic apatite. In summary, this study opens new avenues for further advancements in the field of CaP bone biomaterials by introducing a simple approach to develop biomimetic CaPs. This work also sheds light on the role of the inorganic phase of bone and its composition in defining the regenerative properties of natural bone xenografts.
Asunto(s)
Biomimética , Regeneración Ósea/efectos de los fármacos , Fosfatos de Calcio/farmacología , Cerámica/farmacología , Metales/farmacología , Oligoelementos/farmacología , Animales , Cementos para Huesos/química , Fosfatos de Calcio/química , Bovinos , Ácido Cítrico/farmacología , Fuerza Compresiva , Cristalografía por Rayos X , Durapatita/química , Durapatita/aislamiento & purificación , Femenino , Ensayo de Materiales , Metales/análisis , Metales/uso terapéutico , Ácidos Fosfóricos/farmacología , Ratas , Ratas Sprague-Dawley , Espectroscopía Infrarroja por Transformada de Fourier , Tibia/diagnóstico por imagen , Tibia/efectos de los fármacos , Tibia/lesiones , Oligoelementos/análisis , Oligoelementos/uso terapéutico , Microtomografía por Rayos XRESUMEN
Phosphoramidates are becoming increasingly recognized as molecular targets for therapeutic development. Their biological functions are significantly influenced by their inherent properties such as reactivity, as well as the P-N backbone which allows for structural diversity. In this study we report the synthesis of novel carbohydrate-based phosphoramidate derivatives via the Staudinger-phosphite reaction; along with an evaluation of their adjuvant activity in combination with popular antibiotics. Our targets involved variation in both the sugar residue as well as the identity of the phosphoramidate. Moderate to excellent yields of these derivatives were obtained. Notable adjuvant activity was observed with the halogenated phosphoramidates. For the fluorinated glucose derivative in particular, a remarkable 32-fold decrease in the MIC of Ampicillin was obtained against Methicillin-resistant S. aureus.
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Amidas/farmacología , Antibacterianos/farmacología , Carbohidratos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ácidos Fosfóricos/farmacología , Amidas/síntesis química , Amidas/química , Antibacterianos/síntesis química , Antibacterianos/química , Conformación de Carbohidratos , Carbohidratos/química , Pruebas de Sensibilidad Microbiana , Ácidos Fosfóricos/síntesis química , Ácidos Fosfóricos/químicaRESUMEN
The effect of thermal, acid and alkali pretreatment methods on biological hydrogen (BHP) and bioethanol production (BP) from grass lawn (GL) waste was investigated, under different process schemes. BHP from the whole pretreatment slurry of GL was performed through mixed microbial cultures in simultaneous saccharification and fermentation (SSF) mode, while BP was carried out through the C5yeast Pichia stipitis, in SSF mode. From these experiments, the best pretreatment conditions were determined and the efficiencies for each process were assessed and compared, when using either the whole pretreatment slurry or the separated fractions (solid and liquid), the separate hydrolysis and fermentation (SHF) or SSF mode, and especially for BP, the use of other yeasts such as Pachysolen tannophilus or Saccharomyces cerevisiae. The experimental results showed that pretreatment with 10 gH2SO4/100 g total solids (TS) was the optimum for both BHP and BP. Separation of solid and liquid pretreated fractions led to the highest BHP (270.1 mL H2/g TS, corresponding to 3.4 MJ/kg TS) and also BP (108.8 mg ethanol/g TS, corresponding to 2.9 MJ/kg TS) yields. The latter was achieved by using P. stipitis for the fermentation of the hydrolysate and S. serevisiae for the solid fraction fermentation, at SSF.
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Biocombustibles/análisis , Etanol/síntesis química , Hidrógeno/metabolismo , Poaceae/química , Residuos , Fermentación , Lignina/química , Ácidos Fosfóricos/farmacología , Ácidos Sulfúricos/farmacología , TemperaturaRESUMEN
Synthetic pathways have been developed to access a series of N-benzylated phosphoramidic acid derivatives as novel, achiral analogues of the established Plasmodium falciparum 1-deoxy-d-xylulose-5-phosphate reductase (PfDXR) enzyme inhibitor, FR900098. Bioassays of the targeted compounds and their synthetic precursors have revealed minimal antimalarial activity but encouraging anti-trypanosomal activity - in one case with an IC50 value of 5.4 µM against Trypanosoma brucei, the parasite responsible for Nagana (African cattle sleeping sickness). The results of relevant in silico modelling and docking studies undertaken in the design and evaluation of these compounds are discussed.
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Amidas/síntesis química , Amidas/farmacología , Antimaláricos/síntesis química , Antimaláricos/farmacología , Ácidos Fosfóricos/síntesis química , Ácidos Fosfóricos/farmacología , Tripanocidas/síntesis química , Tripanocidas/farmacología , Amidas/química , Animales , Antimaláricos/química , Bovinos , Ácidos Fosfóricos/química , Plasmodium falciparum/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
This work aimed to estimate the inactivation kinetic parameters of four potential beer spoilage bacteria (Lactobacillus brevis DSM 6235, Lactobacillus casei ATCC 334, Pediococcus damnosus DSM 20289 and Pediococcus damnosus ATCC 29358) inoculated in brewing yeast submitted to acid washing with purposes of yeast recycle. The experiments were conducted at 4 °C in solutions with pH 1.5, pH 2, and pH 3 adjusted employing 85% phosphoric acid. The acid washing treatment of brewing yeasts in the most common pH used (pH 2.0) demanded almost 50 min for the first decimal reduction (δ) of L. brevis DSM 6235. Sensible strains to acid washing such as P. damnosus DSM 20289 demanded almost 70 min for 4 log reductions to be achieved. On the other hand, pH reduction of the acid washing from 2.0 to 1.5 allowed 4 log reduction of L. brevis DSM 6235) to be obtained in less than 50 min, without ruining brewer's yeast viability. Acid washing in pH 1.5 is a viable method for the inactivation of bacterial contaminants of brewing yeasts. Recycling of brewing yeasts through this approach may contribute to a more sustainable and environmental-friendly industry.
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Cerveza/microbiología , Lactobacillaceae/efectos de los fármacos , Ácidos Fosfóricos/farmacología , Levaduras/crecimiento & desarrollo , Reactores Biológicos/microbiología , Fermentación , Contaminación de Alimentos/prevención & control , Microbiología de Alimentos , Concentración de Iones de Hidrógeno , Cinética , Lactobacillaceae/clasificación , Lactobacillaceae/crecimiento & desarrollo , Lactobacillaceae/metabolismo , Levaduras/metabolismoRESUMEN
A novel Strandberg type polyoxomolybdate based organic-inorganic hybrid solid, [{4,4'-H2bpy}{4,4'-Hbpy}2{H2P2Mo5O23}]·5H2O (1) has been synthesized and structurally characterized by the single crystal X-ray diffraction technique. The structure consists of a discrete type phosphomolybdate cluster, [H2P2Mo5O23]4-, connected with three protonated 4,4'-bipyridine molecules by strong hydrogen bonding interactions. The In vitro anti-tumoral activity of compound (1) was tested against human breast cancer (MCF-7), human lung cancer (A549) and human liver cancer (HepG2) cells. The Strandberg type cluster was used against the MCF-7 and A549 cancer cells for the first time hitherto. It shows considerable inhibitory effect with IC50 values of 33.79 µmol L-1, 25.17 µmol L-1, and 32.11 µmol L-1 against HepG2, A549 and MCF-7 respectively. The anti-tumoral activity of 1 was also found to be comparable with that of a routinely used chemotherapeutic agent, methotrexate (MTX), with an IC50 value of 42.03 µmol L-1 for HepG2, 26.93 µmol L-1 for A549 and 49.79 µmol L-1 for MCF-7. The anti-proliferation activity is mediated by the arrest of the A549 and HepG2 cells in the S phase and MCF-7 in the G2/M phase of the cell cycle as suggested by flow cytometry. Results suggest that apoptosis and necrosis pathways ultimately lead to the death of the cancer cells.
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Antineoplásicos/farmacología , Materiales Biocompatibles/farmacología , Molibdeno/farmacología , Ácidos Fosfóricos/farmacología , Compuestos de Tungsteno/farmacología , Células A549 , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Células MCF-7 , Ratones , Modelos Moleculares , Molibdeno/química , Ácidos Fosfóricos/química , Relación Estructura-Actividad , Compuestos de Tungsteno/síntesis química , Compuestos de Tungsteno/químicaRESUMEN
This study aimed to model the inactivation of Lactobacillus brevis DSM 6235 while retaining the viability of yeasts during washing brewer's yeast with phosphoric acid and chlorine dioxide. The independent variables in the acid washing were pH (1-3) and temperature (1-9 °C), whereas in the washing with chlorine dioxide, concentration (10-90 mg/L) and temperature (5-25 °C) were assessed. The predictive models obtained for the four response variables γLA, γCl (decimal reduction of L. brevis DSM 6235), Vf/V0LA, and Vf/V0Cl (brewer's yeast viability ratio) were found to have R2 > 0.80 and values of Fcalc > Freference. Then, the models were considered predictive and statistically significant (p < 0.10). Our results indicated that phosphoric acid and chlorine dioxide washing resulted in up to 7 and 6.4 (log CFU/mL) decimal reductions of L. brevis DSM 6235, respectively. On the other hand, the viability of the brewer's yeast ranged from 22.3 to 99.4%. L. brevis DSM 6235 inactivation was significantly influenced by parameters pH(Q) and T°C(Q) when phosphoric acid was applied, and by parameters mg/L(L), mg/L(Q), T°C(Q), and mg/L × T°C when ClO2 was applied. The validation of the models resulted in bias (γLA, 0.93/Vf/V0LA, 0.99 - γCl, 1.0/Vf/V0Cl, 0.99) and accuracy values (γLA, 1.12/Vf/V0LA, 1.01 - γCl, 1.08/Vf/V0Cl, 1.03). The results of this study indicate that it might be possible to decontaminate brewer's yeast through acid and chlorine dioxide washing while keeping its viability. This procedure will result in the reduction of costs and the lower generation of brewer's waste.
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Compuestos de Cloro/farmacología , Fermentación , Levilactobacillus brevis/fisiología , Viabilidad Microbiana , Óxidos/farmacología , Ácidos Fosfóricos/farmacología , Saccharomyces cerevisiae/fisiología , Cerveza/microbiología , Concentración de Iones de Hidrógeno , Levilactobacillus brevis/efectos de los fármacos , Saccharomyces cerevisiae/efectos de los fármacos , TemperaturaRESUMEN
The specific targeting of protein-protein interactions by phosphoserine-containing small molecules has been scarce due to the dephosphorylation of phosphoserine and its charged nature at physiological pH, which hinder its uptake into cells. To address these issues, we herein report the synthesis of phosphoserine aryloxy triester phosphoramidates as phosphoserine prodrugs that are enzymatically metabolized to release phosphoserine. This phosphoserine-masking approach was applied to a phosphoserine-containing inhibitor of 14-3-3 dimerization, and the generated prodrugs exhibited improved pharmacological activity. Collectively, this provided a proof of concept that the masking of phosphoserine with biocleavable aryloxy triester phosphoramidate masking groups is a viable intracellular delivery system for phosphoserine-containing molecules. Ultimately, this will facilitate the discovery of phosphoserine-containing small-molecule therapeutics.