Comparing CB1 receptor GIRK channel responses to receptor internalization using a kinetic imaging assay.

The type 1 cannabinoid receptor (CB1R) mediates neurotransmitter release and synaptic plasticity in the central nervous system. Endogenous, plant-derived, synthetic cannabinoids bind to CB1R, initiating the inhibitory G-protein (Gi) and the ß-arrestin signaling pathways. Within the Gi signaling pathway, CB1R activates G protein-gated, inwardly-rectifying potassium (GIRK) channels. The ß-arrestin pathway reduces CB1R expression on the cell surface through receptor internalization. Because of their association with analgesia and drug tolerance, GIRK channels and receptor internalization are of interest to the development of pharmaceuticals. This research used immortalized mouse pituitary gland cells transduced with a pH-sensitive, fluorescently-tagged human CB1R (AtT20-SEPCB1) to measure GIRK channel activity and CB1R internalization. Cannabinoid-induced GIRK channel activity is measured by using a fluorescent membrane-potential sensitive dye. We developed a kinetic imaging assay that visualizes and measures CB1R internalization. All cannabinoids stimulated a GIRK channel response with a rank order potency of WIN55,212-2 > (±)CP55,940 > Δ9-THC > AEA. Efficacy was expressed relative to (±)CP55,940 with a rank order efficacy of (±)CP55,940 > WIN55, 212-2 > AEA > Δ9-THC. All cannabinoids stimulated CB1R internalization with a rank order potency of (±)CP55,940 > WIN55, 212-2 > AEA > Δ9-THC. Internalization efficacy was normalized to (±)CP55,940 with a rank order efficacy of WIN55,212-2 > AEA > (±)CP55,940 > Δ9-THC. (±)CP55,940 was significantly more potent and efficacious than AEA and Δ9-THC at stimulating a GIRK channel response; no significant differences between potency and efficacy were observed with CB1R internalization. No significant differences were found when comparing a cannabinoid's GIRK channel and CB1R internalization response. In conclusion, AtT20-SEPCB1 cells can be used to assess cannabinoid-induced CB1R internalization. While cannabinoids display differential Gi signaling when compared to each other, this did not extend to CB1R internalization.

A Multipronged Bioengineering, Spectroscopic and Theoretical Approach in Unravelling the Excited-State Dynamics of the Archetype Mycosporine Amino Acid.

Mycosporine glycine (MyG) was produced by the fermentation of a purposely engineered bacterial strain and isolated from this sustainable source. The ultrafast spectroscopy of MyG was then investigated in its native, zwitterionic form (MyGzwitter), via femtosecond transient electronic absorption spectroscopy. Complementary nonadiabatic (NAD) simulations suggest that, upon photoexcitation to the lowest excited singlet state (S1), MyGzwitter undergoes efficient nonradiative decay to repopulate the electronic ground state (S0). We propose an initial ultrafast ring-twisting mechanism toward an S1/S0 conical intersection, followed by internal conversion to S0 and subsequent vibrational cooling. This study illuminates the workings of the archetype mycosporine, providing photoprotection, in the UV-B range, to organisms such as corals, macroalgae, and cyanobacteria. This study also contributes to our growing understanding of the photoprotection mechanisms of life.

Liquid- liquid (Cyclohexanone: Cyclohexanol) separation using augmented tight nanofiltration membrane: A sustainable approach.

Organic solvent nanofiltration (OSN) is an incipient technology in the field of organic liquid-liquid separation. The incomplete separations and complexity involved in these, forces many organic liquids to be released as effluents and the adverse effects of these on environment is enormous and irreparable. The work prominences on the complete separation of industrially significant cyclohexanone: cyclohexanol (keto-alcohol oil) and heptane: toluene mixtures. The separations of these above-mentioned organic liquid mixtures were carried out using the fabricated Lewis acid modified graphitic carbon nitride (Cu2O@g-C3N4) incorporated polyvinylidene difluoride (PVDF) composite membranes. These fabricated membranes showed a separation factor of 18.16 and flux of 1.62 Lm-2h-1 for cyclohexanone: cyclohexanol mixture and separation of heptane and toluene mixture (with heptane flux of 1.52 Lm-2h-1) showed a separation factor of 9.9. The selectivity and productivity are based on the polarity and size of the organic liquids. The role of Cu2O@g-C3N4 is influencing the pore size distribution, increased divergence from solubility parameters, polarity, solvent uptake and porosity of the composite membranes. The developed composite membranes are thus envisioned to be apt for a wide range of liquid-liquid separations due to its implicit nature.

Effect of venlafaxine on anhedonia and amotivation in patients with major depressive disorder.

OBJECTIVE: Serotonin norepinephrine reuptake inhibitors (SNRIs) have been postulated to afford benefits in alleviating anhedonia and amotivation. This post hoc pooled analysis evaluated the effect of venlafaxine XR, an SNRI, on these symptoms in patients with major depressive disorder (MDD). METHODS: Data was pooled from five short-term randomized, placebo-controlled studies of venlafaxine XR for the treatment of MDD, comprising 1087 (venlafaxine XR, n = 585; placebo, n = 502) adult subjects. The change from baseline score in the MADRS anhedonia factor (based on items 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]) for anhedonia, and in motivational deficits (based on 3 items of HAM-D17: involvement in work and activities, psychomotor retardation, and energy level [ie, general somatic symptoms]) for amotivation, were measured through 8 weeks. Mixed model repeated measures (MMRMs) were used to analyze changes over time and ANCOVA to analyze the change from baseline at week 8 with LOCF employed to handle missing data. RESULTS: At the end of 8 weeks, the change from baseline was significantly greater in patients on venlafaxine XR in both anhedonia (mean, 95% CI: -2.73 [-3.63, -1.82], p < 0.0001) and amotivation scores (mean, 95% CI: -0.78 [-1.04, -0.52], p < 0.0001) than those on placebo. For both measures, the between-group separation from baseline was statistically significant starting from week 2 onwards, and it increased over time. CONCLUSION: This analysis demonstrates that venlafaxine XR is effective in improving symptoms of anhedonia and motivational deficits in patients with MDD.

Conformational and Electronic Variations in 1,2- and 1,5a-Cyclophellitols and their Impact on Retaining α-Glucosidase Inhibition.

Glycoside hydrolases (glycosidases) take part in myriad biological processes and are important therapeutic targets. Competitive and mechanism-based inhibitors are useful tools to dissect their biological role and comprise a good starting point for drug discovery. The natural product, cyclophellitol, a mechanism-based, covalent and irreversible retaining ß-glucosidase inhibitor has inspired the design of diverse α- and ß-glycosidase inhibitor and activity-based probe scaffolds. Here, we sought to deepen our understanding of the structural and functional requirements of cyclophellitol-type compounds for effective human α-glucosidase inhibition. We synthesized a comprehensive set of α-configured 1,2- and 1,5a-cyclophellitol analogues bearing a variety of electrophilic traps. The inhibitory potency of these compounds was assessed towards both lysosomal and ER retaining α-glucosidases. These studies revealed the 1,5a-cyclophellitols to be the most potent retaining α-glucosidase inhibitors, with the nature of the electrophile determining inhibitory mode of action (covalent or non-covalent). DFT calculations support the ability of the 1,5a-cyclophellitols, but not the 1,2-congeners, to adopt conformations that mimic either the Michaelis complex or transition state of α-glucosidases.

Extraction and antioxidant capacity of mycosporine-like amino acids from red algae in Japan.

Mycosporine-like amino acids (MAAs) are the natural UV-absorbing compounds with antioxidant activity found in microalgae and macroalgae. We collected red algae Asparagopsis taxiformis, Meristotheca japonica, and Polysiphonia senticulosa from Nagasaki, where UV radiation is more intense than in Hokkaido, and investigated the effect of UV radiation on MAA content. It was suggested that A. taxiformis and M. japonica contained shinorine and palythine, while UV-absorbing compound in P. senticulosa could not be identified. The amounts of these MAAs were lower compared to those from Hokkaido. Despite an increase in UV radiation in both regions from February to April, MAA contents of red algae from Nagasaki slightly decreased while those from Hokkaido significantly decreased. This difference was suggested the amount of inorganic nitrogen in the ocean. Antioxidant activity of MAAs increased under alkaline conditions. The extract containing MAAs from P. senticulosa showed the highest antioxidant activity among 4 red algae.

Multiplexed quantification of venlafaxine and metabolites in human plasma by liquid chromatography-tandem mass spectrometry.

BACKGROUND: Venlafaxine (VEN) and its O-demethylated metabolite, O-desmethylvenlafaxine (ODV), are commonly prescribed serotonin-norepinephrine reuptake inhibitors, approved for the treatment of depression and anxiety. Both are metabolized to inactive metabolites via cytochrome P450 enzymes. While previous studies have focused on quantifying VEN and ODV, bioanalytical methods for the simultaneous measurement of all metabolites are needed to fully characterize the pharmacology of VEN and ODV. METHODS: K2EDTA plasma was spiked with VEN, ODV, N-desmethylvenlafaxine (NDV), N,O-didesmethylvenlafaxine (NODDV), and N,N-didesmethylvenlafaxine (NNDDV). Drugs and metabolites were extracted via protein precipitation and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The multiplexed assay was validated in accordance with regulatory recommendations, and evaluated in remnant plasma samples from persons prescribed venlafaxine. RESULTS: The analytical measuring range for venlafaxine and all four metabolites was 5-800 ng/mL. Standard curves were generated via weighted quadratic (NNDDV) or linear (VEN, ODV, NDV, NODDV) regression of calibrators. Inter-assay imprecision was between 1.9-9.3% for all levels of all analytes. Minor matrix effects were observed, and both recovery efficiency and process efficiency were >96% for all analytes. All other assay validation assessments met acceptance criteria. Drug concentrations measured from remnant plasma specimens obtained from patients with current venlafaxine prescriptions (37.5-450 mg/day) yielded NDDV, NDV, and NODDV metabolite concentrations in 6/21, 14/21, and 20/21 samples, respectively. The ratio of active to inactive analytes ranged from 0.74 to 14.5, with a median of 6.39. CONCLUSIONS: An efficient and accurate LC-MS/MS method was developed and validated for the quantification of VEN, ODV, and all three inactive metabolites in plasma. The assay met all acceptance criteria, and may be used in future studies of the pharmacokinetics of these drugs.

Unveiling of the antileishmanial activities of Linalool loaded zinc oxide nanocomposite through its potent antioxidant and immunomodulatory effects.

This study aimed to produce linalool loaded zinc oxide nanocomposite (LZNPs) and assess its in vitro and in vivo antileishmanial effects against Leishmania major. LZNPs was produced through the synthesis of an ethanolic solution containing polyvinyl alcohol. The average size of LZNPs was determined to be 105 nm. The findings indicated that LZNPs displayed significant (p < 0.01) antileishmanial effects on promastigotes and amastigotes. Following exposure of promastigotes to LZNPs, there was a notable rise in the percentage of early and late apoptotic cells from 9.0 to 57.2 %. The gene expression levels of iNOS, IFN-γ, and TNF-α in macrophages were upregulated in a dose-dependent approach following exposure to LZNPs. LZNPs alone and in conjunction with glucantime (Glu) resulted in a reduction in the diameter and parasite load of CL lesions in infected mice. Treatment of the CL-infected mice with LZNPs at 25 and 50 mg/kg mainly in combination with Glu-reduced the tissue level of malondialdehyde (MDA), increased both gene and protein expression of the antioxidant enzymes as well as raised the expression level of IFN-γ and IL-12 cytokines, whereas caused a significant reduction in the expression level of IL-4. The present study shows that LZNPs has potent antileishmanial effects and controls CL in a mice model through its antioxidant and immunomodulatory properties. Further investigation, especially in clinical trials, could explore the potential use of this nanocomposite in managing and treating CL.

CYP2D6 Phenotype Influences Pharmacokinetic Parameters of Venlafaxine: Results from a Population Pharmacokinetic Model in Older Adults with Depression.

In this study, we aimed to improve upon a published population pharmacokinetic (PK) model for venlafaxine (VEN) in the treatment of depression in older adults, then investigate whether CYP2D6 metabolizer status affected model-estimated PK parameters of VEN and its active metabolite O-desmethylvenlafaxine. The model included 325 participants from a clinical trial in which older adults with depression were treated with open-label VEN (maximum 300 mg/day) for 12 weeks and plasma levels of VEN and O-desmethylvenlafaxine were assessed at weeks 4 and 12. We fitted a nonlinear mixed-effect PK model using NONMEM to estimate PK parameters for VEN and O-desmethylvenlafaxine adjusted for CYP2D6 metabolizer status and age. At both lower doses (up to 150 mg/day) and higher doses (up to 300 mg/day), CYP2D6 metabolizers impacted PK model-estimated VEN clearance, VEN exposure, and active moiety (VEN + O-desmethylvenlafaxine) exposure. Specifically, compared with CYP2D6 normal metabolizers, (i) CYP2D6 ultra-rapid metabolizers had higher VEN clearance; (ii) CYP2D6 intermediate metabolizers had lower VEN clearance; (iii) CYP2D6 poor metabolizers had lower VEN clearance, higher VEN exposure, and higher active moiety exposure. Overall, our study showed that including a pharmacogenetic factor in a population PK model could increase model fit, and this improved model demonstrated how CYP2D6 metabolizer status affected VEN-related PK parameters, highlighting the importance of genetic factors in personalized medicine.

Insight into the mechanism of action of ORG27569 at the cannabinoid type one receptor utilising a unified mathematical model.

Allosteric modulation of CB1 is therapeutically advantageous compared to orthosteric activation as it potentially offers reduced on-target adverse effects. ORG27569 is an allosteric modulator that increases orthosteric agonist binding to CB1 but decreases functional signalling. ORG27569 is characterised by a delay in disinhibition of agonist-induced cAMP inhibition (lag); however, the mechanism behind this kinetic lag is yet to be identified. We aimed to utilise a mathematical model to predict data and design in vitro experiments to elucidate mechanisms behind the unique signalling profile of ORG27569. The established kinetic ternary complex model includes the existence of a transitional state of CB1 bound to ORG27569 and CP55940 and was used to simulate kinetic cAMP data using NONMEM 7.4 and Matlab R2020b. These data were compared with empirical cAMP BRET data in HEK293 cells stably expressing hCB1. The pharmacometric model suggested that the kinetic lag in cAMP disinhibition by ORG27569 is caused by signal amplification in the cAMP assay and can be reduced by decreasing receptor number. This was confirmed experimentally, as reducing receptor number through agonist-induced internalisation resulted in a decreased kinetic lag by ORG27569. ORG27569 was found to have a similar interaction with CP55940 and the high efficacy agonist WIN55,212-2, and was suggested to have lower affinity for CB1 bound by the partial agonist THC compared to CP55940. Allosteric modulators have unique signalling profiles that are often difficult to interrogate exclusively in vitro. We have used a combined mathematical and in vitro approach to prove that ORG27569 causes a delay in disinhibition of agonist-induced cAMP inhibition due to large receptor reserve in this pathway. We also used the pharmacometric model to investigate the common phenomenon of probe dependence, to propose that ORG27569 binds with higher affinity to CB1 bound by high efficacy orthosteric agonists.

Function of Presynaptic Inhibitory Cannabinoid CB1 Receptors in Spontaneously Hypertensive Rats and Its Modification by Enhanced Endocannabinoid Tone.

We studied whether the function of presynaptic inhibitory cannabinoid CB1 receptors on the sympathetic nerve fibres innervating resistance vessels is increased in spontaneously hypertensive rats (SHR) like in deoxycorticosterone (DOCA)-salt hypertension. An increase in diastolic blood pressure (DBP) was induced by electrical stimulation of the preganglionic sympathetic neurons or by phenylephrine injection in pithed SHR and normotensive Wistar-Kyoto rats (WKY). The electrically (but not the phenylephrine) induced increase in DBP was inhibited by the cannabinoid receptor agonist CP55940, similarly in both groups, and by the endocannabinoid reuptake inhibitor AM404 in SHR only. The effect of CP55940 was abolished/reduced by the CB1 receptor antagonist AM251 (in both groups) and in WKY by endocannabinoid degradation blockade, i.e., the monoacylglycerol lipase (MAGL) inhibitor MJN110 and the dual fatty acid amide hydrolase (FAAH)/MAGL inhibitor JZL195 but not the FAAH inhibitor URB597. MJN110 and JZL195 tended to enhance the effect of CP55940 in SHR. In conclusion, the function of presynaptic inhibitory CB1 receptors depends on the hypertension model. Although no differences occurred between SHR and WKY under basal experimental conditions, the CB1 receptor function was better preserved in SHR when the endocannabinoid tone was increased by the inhibition of MAGL or the endocannabinoid transporter.

Influence of solvents on the bond strength of resin sealer to intraradicular dentin after retreatment

Abstract This study evaluated the removal of filling material with ProTaper Universal Rotary Retreatment system (PTR) combined with solvents and the influence of solvents on the bond strength (PBS) of sealer to intraradicular dentin after canal reobturation. Roots were endodontically treated and distributed to five groups (n = 12). The control group was not retreated. In the four experimental groups, canals were retreated with PTR alone or in combination with xylol, orange oil, and eucalyptol. After filling material removal, two specimens of each group were analysed by SEM and µCT to verify the presence of filling remnants on root canal walls. The other roots were reobturated and sectioned in 1-mm-thick dentin slices that were subjected to the push-out test. Data were analysed by two-way ANOVA and Tukey’s test (α = 0.05). SEM and µCT analysis revealed that all retreatment techniques left filling remnants on canal walls. The control group (3.47 ± 1.21) presented significantly higher (p < 0.05) PBS than the experimental groups. The groups retreated with PTR alone (2.59 ± 0.99) or combined with xylol (2.54 ± 0.77) and orange oil (2.32 ± 0.93) presented similar bond strength (p > 0.05), and differed significantly from the group with eucalyptol (1.89 ± 0.63). The solvents reduced the PBS of the sealer to dentin and no retreatment technique promoted complete removal of filling material.

Dissolution of a mineral trioxide aggregate sealer in endodontic solvents compared to conventional sealers

Abstract The aim of this study is to evaluate the solubility of a Mineral Trioxide Aggregate sealer (MTA-Fillapex) compared with five other sealers, calcium hydroxide (Sealapex), resin (Realseal), zinc oxide-eugenol (Tubli-Seal), and two epoxy resins (AH-26 and AH-Plus), in chloroform and eucalyptoil in static and ultrasonic environments. Samples of each sealer were prepared (n = 180) and then divided into 12 groups that were immersed in solvents for 5 and 10 min in static and ultrasonic environments. The mean weight loss was determined, and the values were compared using Student's t-test, One-way ANOVA, and Tukey's HSD post-hoc test (p < 0.05). In chloroform, MTA-Fillapex, AH-26, and Sealapex displayed moderate solubility with no significant difference in dissolution (p = 0.125); however, their dissolution was significantly lower than that of AH-Plus (p < 0.001), which was almost fully dissolved after 10 minutes. Realseal was significantly less soluble than all sealers (p < 0.001). In eucalyptoil, MTA-Fillapex showed low solubility, as all of the sealers did, but Tubli-Seal was significantly more soluble than other sealers (p < 0.001). Using ultrasonic activation resulted in a significantly higher dissolution rate in chloroform for all sealers except MTA-Fillapex after 10 min (p = 0.226). In eucalyptoil, ultrasonic activation significantly increased the dissolution rate of all sealers except MTA-Fillapex after 5 and 10 min, Sealapex at 10 min, and AH-Plus at 5 min (p > 0.05). In conclusion, MTA-Fillapex was not sufficiently dissolved in either solvent. Ultrasonic activation had limited effectiveness on MTA-Fillapex dissolution, whereas it significantly increased the efficiency of solvents in dissolving a number of endodontic sealers.

Hydroxylation of 1,8-cineole by Mucor ramannianus and Aspergillus niger

The monoterpenoid 1,8-cineole is obtained from the leaves of Eucalyptus globulus and it has important biological activities. It is a cheap natural substrate because it is a by-product of the Eucalyptus cultivation for wood and pulp production. In this study, it was evaluated the potential of three filamentous fungi in the biotransformation of 1,8-cineole. The study was divided in two steps: first, reactions were carried out with 1,8-cineole at 1 g/L for 24 h; afterwards, reactions were carried out with substrate at 5 g/L for 5 days. The substrate was hydroxylated into 2-exo-hydroxy-1,8-cineole and 3-exo-hydroxy-1,8-cineole by fungi Mucor ramannianus and Aspergillus niger with high stereoselectivity. Trichoderma harzianum was also tested but no transformation was detected. M. ramannianus led to higher than 99% of conversion within 24 h with a starting high substrate concentration (1 g/L). When substrate was added at 5 g/L, only M. ramannianus was able to catalyze the reaction, but the conversion level was 21.7% after 5 days. Both products have defined stereochemistry and could be used as chiral synthons. Furthermore, biological activity has been described for 3-exo-hydroxy-1,8-cineol. To the best of our knowledge, this is the first report on the use of M. ramannianus in this reaction.

Análise das propriedades químicas, biológicas e antimicrobianas de solventes endodônticos / Analysis of chemical, biological and antimicrobial properties of endodontic solvents

O objetivo deste estudo foi avaliar as propriedades químicas, biológicas e antimicrobianas dos solventes endodônticos, Citrol, Eucaliptol, d-Limoneno, Xilol e Endosolv E. Dentre os testes químicos, foram avaliados a microdureza dentinária, onde utilizamos blocos de dentina bovina que foram expostos aos solventes por 2 períodos, 5 e 15 min e submetidos ao teste de microdureza. Outro teste químico foi a capacidade de dissolução dos materiais obturadores pelo teste de imersão nos solventes em 3 períodos, 2, 5 e 15 min. Para essa avaliação foram, confeccionados corpos de prova dos cimentos, AH Plus, Acroseal, Sealer 26, Endofill, MTA Fillapex e RealSeal SE e dos cones de guta-percha estandardizado Dentsply (DP), ProTaper e Resilon. Um terceiro teste, foi realizado para avaliar a capacidade de desobturação dos canais radiculares e o efeito da agitação ultrassônica dos solventes endodônticos após a desobturação. Sessenta incisivos centrais superiores foram divididos em 6 grupos sendo um para cada solvente (n=10) mais um grupo controle (solução fisiológica). Todos dentes foram instrumentados e obturados pela mesma técnica e escaneados no Micro-CT. Os dentes foram então desobturados utilizando ProTaper Retratamento/ProTaper Universal como técnica para todos grupos, associada a um dos solventes e foram escaneados novamente para a avaliação do volume de material remanescente após a desobturação. Cada um dos dentes foi desobturado e preenchido com o mesmo solvente utilizado na desobturação. Cada solvente foi agitado pelo ultrassom por 1 min e novamente foram escaneados e avaliados os volumes restantes dos materiais nos canais radiculares. Na avaliação biológica, utilizamos o teste de citotoxicidade com células de camundongo NIH-3T3 pelo ensaio MTT. As culturas celulares foram plaqueadas e submetidas aos solventes diluídos nas concentrações de 0.5 a 2.5%, e avaliados quanto à viabilidade celular. Por fim o último teste foi o antimicrobiano, avaliado pelo teste de...

The aim of this study was to evaluate the chemical, biological and antimicrobial properties of the Endodontic solvents, Citrol, Eucalyptol, d-Limonene, Xylene and Endosolv E. First chemical properties analysis were evaluated by dentin microhardness, where we used bovine dentin blocks that were exposed to the solvents in 2 periods, 5 and 15 min and subjected to the microhardness test. Second test was to evaluate the ability of endodontic solvents to dissolve root-filling materials by immersion test in, 2, 5 and 15 minutes. Specimens of sealers, AH Plus, Acroseal, Sealer 26, Endofill, MTA Fillapex an RealSeal SE and guttapercha Dentsply (DP), ProTaper and Resilon points were prepared and evaluated in the three periods. Next test was conducted to evaluate the ability of solvents to desobturate root canals filled and analyse the effect of the ultrasonic passive agitation of solvents after canal unfill procedure. Sixty maxillary central incisors were prepared and obturated by same technique and randomly divided into 6 groups, one for each solvent (n=10) and a control group (saline solution). Teeth were scanned in Microcomputed Tomography (Micro-CT), unfilled with ProTaper Retratament/Protaper Universal with one of the solvents and scanned again. The residual root-fillings volumes were analysed and all teeth root canal were filled with the same solvent used in unfilling process and were passive-ultrasonically agitated (PUl) for 1 min. All teeth were scanned again in Micro-CT and data were analysed. Biological properties assessments were evaluated by cytotoxicity test with NIH-3T3 mouse cells by MTT assay. Cell cultures were subjected to diluted solvents at concentrations of 0.5 to 2.5%, and cell viability were analysed. Last evaluation in our study was the antimicrobial test. A total of 60 bovine dentin specimens infected intraorally were exposed for 5 min in direct contact to one of the solvents evaluated. After that, the dentin blocks with biofilms were...

Análise das propriedades químicas, biológicas e antimicrobianas de solventes endodônticos / Analysis of chemical, biological and antimicrobial properties of endodontic solvents

O objetivo deste estudo foi avaliar as propriedades químicas, biológicas e antimicrobianas dos solventes endodônticos, Citrol, Eucaliptol, d-Limoneno, Xilol e Endosolv E. Dentre os testes químicos, foram avaliados a microdureza dentinária, onde utilizamos blocos de dentina bovina que foram expostos aos solventes por 2 períodos, 5 e 15 min e submetidos ao teste de microdureza. Outro teste químico foi a capacidade de dissolução dos materiais obturadores pelo teste de imersão nos solventes em 3 períodos, 2, 5 e 15 min. Para essa avaliação foram, confeccionados corpos de prova dos cimentos, AH Plus, Acroseal, Sealer 26, Endofill, MTA Fillapex e RealSeal SE e dos cones de guta-percha estandardizado Dentsply (DP), ProTaper e Resilon. Um terceiro teste, foi realizado para avaliar a capacidade de desobturação dos canais radiculares e o efeito da agitação ultrassônica dos solventes endodônticos após a desobturação. Sessenta incisivos centrais superiores foram divididos em 6 grupos sendo um para cada solvente (n=10) mais um grupo controle (solução fisiológica). Todos dentes foram instrumentados e obturados pela mesma técnica e escaneados no Micro-CT. Os dentes foram então desobturados utilizando ProTaper Retratamento/ProTaper Universal como técnica para todos grupos, associada a um dos solventes e foram escaneados novamente para a avaliação do volume de material remanescente após a desobturação. Cada um dos dentes foi desobturado e preenchido com o mesmo solvente utilizado na desobturação. Cada solvente foi agitado pelo ultrassom por 1 min e novamente foram escaneados e avaliados os volumes restantes dos materiais nos canais radiculares. Na avaliação biológica, utilizamos o teste de citotoxicidade com células de camundongo NIH-3T3 pelo ensaio MTT. As culturas celulares foram plaqueadas e submetidas aos solventes diluídos nas concentrações de 0.5 a 2.5%, e avaliados quanto à viabilidade celular. Por fim o último teste foi o antimicrobiano, avaliado pelo teste de...

The aim of this study was to evaluate the chemical, biological and antimicrobial properties of the Endodontic solvents, Citrol, Eucalyptol, d-Limonene, Xylene and Endosolv E. First chemical properties analysis were evaluated by dentin microhardness, where we used bovine dentin blocks that were exposed to the solvents in 2 periods, 5 and 15 min and subjected to the microhardness test. Second test was to evaluate the ability of endodontic solvents to dissolve root-filling materials by immersion test in, 2, 5 and 15 minutes. Specimens of sealers, AH Plus, Acroseal, Sealer 26, Endofill, MTA Fillapex an RealSeal SE and guttapercha Dentsply (DP), ProTaper and Resilon points were prepared and evaluated in the three periods. Next test was conducted to evaluate the ability of solvents to desobturate root canals filled and analyse the effect of the ultrasonic passive agitation of solvents after canal unfill procedure. Sixty maxillary central incisors were prepared and obturated by same technique and randomly divided into 6 groups, one for each solvent (n=10) and a control group (saline solution). Teeth were scanned in Microcomputed Tomography (Micro-CT), unfilled with ProTaper Retratament/Protaper Universal with one of the solvents and scanned again. The residual root-fillings volumes were analysed and all teeth root canal were filled with the same solvent used in unfilling process and were passive-ultrasonically agitated (PUl) for 1 min. All teeth were scanned again in Micro-CT and data were analysed. Biological properties assessments were evaluated by cytotoxicity test with NIH-3T3 mouse cells by MTT assay. Cell cultures were subjected to diluted solvents at concentrations of 0.5 to 2.5%, and cell viability were analysed. Last evaluation in our study was the antimicrobial test. A total of 60 bovine dentin specimens infected intraorally were exposed for 5 min in direct contact to one of the solvents evaluated. After that, the dentin blocks with biofilms were...

Chemical composition and antibacterial activities of seven Eucalyptus species essential oils leaves

BACKGROUND: In this paper, we have studied the essential oils chemical composition of the leaves of seven Eucalyptus species developed in Tunisia. Eucalyptus leaves were picked from trees growing in different arboretums in Tunisia. Choucha and Mrifeg arboretums located in Sedjnene, region of Bizerte (Choucha: E. maideni, E. astrengens et E. cinerea; Mrifeg : E. leucoxylon), Korbous arboretums located in the region of Nabeul, North East Tunisia with sub-humid bioclimate, (E. lehmani), Souiniet-Ain Drahem arboretum located in region of Jendouba (E. sideroxylon, E. bicostata). Essential oils were individually tested against a large panel of microorganisms includingStaphylococcus aureus (ATCC 6539), Escherichia coli (ATCC 25922), Enterococcus faecalis (ATCC29212), Listeria ivanovii (RBL 30), Bacillus cereus (ATCC11778). RESULTS: The yield of essential oils ranged from 1.2% to 3% (w/w) for the different Eucalyptus species. All essential oils contain α-pinene, 1,8-cineol and pinocarveol-trans for all Eucalyptus species studied. The 1,8-cineol was the major compound in all species (49.07 to 83.59%). Diameter of inhibition zone of essential oils of Eucalyptus species varied from 10 to 29 mm. The largest zone of inhibition was obtained for Bacillus cereus (E. astrengens) and the lowest for Staphylococcus aureus (E. cinerea). The essential oils from E. maideni, E. astrengens, E. cinerea (arboretum of Bizerte), E. bicostata(arboretum of Aindraham) showed the highest antibacterial activity against Listeria ivanovii and Bacillus cereus. CONCLUSION: The major constituents of Eucalyptus leaves essential oils are 1,8-cineol (49.07 to 83.59%) and α-pinene (1.27 to 26.35%). The essential oils from E. maideni, E. astrengens, E. cinerea, E. bicostatashowed the highest antibacterial activity against Listeria ivanovii and Bacillus cereus, they may have potential applications in food and pharmaceutical products.

Women survivors of intimate partner violence: the difficult transition to independence / Mujeres supervivientes de la violencia ejercida por sus parejas: la difícil transición hacia la autonomía / Mulheres sobreviventes de violência exercida por parceiros íntimos – a difícil transição para a autonomia

Objective To understand the trajectories that women go through from entering into to leaving relationships involving intimate partner violence (IPV), and identify the stages of the transition process. Method We utilized a constructivist paradigm based on grounded theory. We ensured that the ethical guidelines of the World Health Organization for research on domestic violence were followed. The analysis focused on narratives of 28 women survivors of IPV, obtained from in-depth interviews. Results The results showed that the trajectories experienced by women were marked by gender issues, (self) silencing, hope and suffering, which continued after the end of the IPV. Conclusion The transition process consists of four stages: entry - falls in love and becomes trapped; maintenance - silences own self, consents and remains in the relationship; decides to leave - faces the problems and struggles to be rescued; (re) balance - (re) finds herself with a new life. This (long) process was developed by wanting (and being able to have) self-determination. .

Objetivo Conhecer as trajetórias que as mulheres percorrem desde a entrada até à saída de relações de violência exercida por parceiros íntimos (VPI), e identificar as fases do processo de transição. Método Utilizou-se um paradigma construtivista com recurso à grounded theory. Salvaguardaram-se as orientações éticas da OMS em matéria de investigação sobre violência doméstica. A análise centrou-se em narrativas de 28 mulheres sobreviventes de VPI, obtidas em entrevistas em profundidade. Resultados Referem que as trajetórias percorridas pelas mulheres foram atravessadas por questões de género, (auto)silenciamento, esperança e sofrimento, o que ultrapassou o fim da VPI. Conclusión O processo de transição é constituído por quatro fases: entrada - enamora-se e fica aprisionada; manutenção - auto-silencia-se, consente e permanece na relação; decisão de saída - enfrenta o problema e luta pelo resgate; (re)equilíbrio - (re)encontra-se com uma nova vida. Este (longo) processo foi atravessado por querer (e poder) autodeterminar-se. .

Objetivo Conhecer as trajetórias que as mulheres percorrem desde a entrada até à saída de relações de violência exercida por parceiros íntimos (VPI), e identificar as fases do processo de transição. Método Utilizou-se um paradigma construtivista com recurso à grounded theory. Salvaguardaram-se as orientações éticas da OMS em matéria de investigação sobre violência doméstica. A análise centrou-se em narrativas de 28 mulheres sobreviventes de VPI, obtidas em entrevistas em profundidade. Resultados Referem que as trajetórias percorridas pelas mulheres foram atravessadas por questões de género, (auto)silenciamento, esperança e sofrimento, o que ultrapassou o fim da VPI. Conclusão O processo de transição é constituído por quatro fases: entrada - enamora-se e fica aprisionada; manutenção - auto-silencia-se, consente e permanece na relação; decisão de saída - enfrenta o problema e luta pelo resgate; (re)equilíbrio - (re)encontra-se com uma nova vida. Este (longo) processo foi atravessado por querer (e poder) autodeterminar-se. .