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.

Antileishmanial and Cytotoxic Effects of Essential Oil and Methanolic Extract of Myrtus communis L

Plants used for traditional medicine contain a wide range of substances that can be used to treat various diseases such as infectious diseases. The present study was designed to evaluate the antileishmanial effects of the essential oil and methanolic extract of Myrtus communis against Leishmania tropica on an in vitro model. Antileishmanial effects of essential oil and methanolic extract of M. communis on promastigote forms and their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 hr. In addition, their leishmanicidal activity against amastigote forms was determined in a macrophage model, for 72 hr. Findings showed that the main components of essential oil were alpha-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%). Findings demonstrated that M. communis, particularly its essential oil, significantly (P<0.05) inhibited the growth rate of promastigote and amastigote forms of L. tropica based on a dose-dependent response. The IC50 values for essential oil and methanolic extract was 8.4 and 28.9 mug/ml against promastigotes, respectively. These values were 11.6 and 40.8 mug/ml against amastigote forms, respectively. Glucantime as control drug also revealed IC50 values of 88.3 and 44.6 mug/ml for promastigotes and amastigotes of L. tropica, respectively. The in vitro assay demonstrated no significant cytotoxicity in J774 cells. However, essential oil indicated a more cytotoxic effect as compared with the methanolic extract of M. communis. The findings of the present study demonstrated that M. communis might be a natural source for production of a new leishmanicidal agent.

Antileishmanial and Cytotoxic Effects of Essential Oil and Methanolic Extract of Myrtus communis L

Plants used for traditional medicine contain a wide range of substances that can be used to treat various diseases such as infectious diseases. The present study was designed to evaluate the antileishmanial effects of the essential oil and methanolic extract of Myrtus communis against Leishmania tropica on an in vitro model. Antileishmanial effects of essential oil and methanolic extract of M. communis on promastigote forms and their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 hr. In addition, their leishmanicidal activity against amastigote forms was determined in a macrophage model, for 72 hr. Findings showed that the main components of essential oil were alpha-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%). Findings demonstrated that M. communis, particularly its essential oil, significantly (P<0.05) inhibited the growth rate of promastigote and amastigote forms of L. tropica based on a dose-dependent response. The IC50 values for essential oil and methanolic extract was 8.4 and 28.9 mug/ml against promastigotes, respectively. These values were 11.6 and 40.8 mug/ml against amastigote forms, respectively. Glucantime as control drug also revealed IC50 values of 88.3 and 44.6 mug/ml for promastigotes and amastigotes of L. tropica, respectively. The in vitro assay demonstrated no significant cytotoxicity in J774 cells. However, essential oil indicated a more cytotoxic effect as compared with the methanolic extract of M. communis. The findings of the present study demonstrated that M. communis might be a natural source for production of a new leishmanicidal agent.

The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration / 药学学报

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

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. .

Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine / Pneumonite intersticial e miocardiopatia simultâneas induzidas por venlafaxina

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities) and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF) of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case.

A venlafaxina é um inibidor de recaptação de serotonina e noradrenalina utilizado como antidepressivo. A variabilidade individual ou interações entre fitoterápicos e fármacos podem causar toxicidade induzida por drogas. Relatamos o caso de uma paciente de 35 anos diagnosticada com pneumonite intersticial e miocardiopatia dilatada atribuídas à venlafaxina. A paciente procurou atendimento médico devido a dispneia e tosse seca, que começaram três meses após iniciar tratamento com venlafaxina para depressão. Concomitantemente tomava suplementos fitoterápicos contendo Centella asiatica e Fucus vesiculosus. A radiografia e a CT de tórax revelaram doença pulmonar parenquimatosa (micronódulos difusos e opacidades em vidro fosco) e, simultaneamente, foi diagnosticada uma miocardiopatia por ecocardiograma, que revelou uma fração de ejeção ventricular esquerda (FEVE) de 21%. Uma investigação ampla foi realizada, incluindo LBA, estudos de imagem, detecção de doenças autoimunes, cateterismo cardíaco direito e biópsia miocárdica. Após a exclusão de outras etiologias e a aplicação da Escala de Probabilidade de Reações Adversas a Medicamentos de Naranjo, foi assumido o diagnóstico de pneumonite/miocardiopatia síncronas associadas à venlafaxina. Já foi demonstrado que os suplementos fitoterápicos utilizados pela paciente podem inibir a isoenzima do complexo enzimático citocromo P450, responsável pelo metabolismo da venlafaxina. Após a descontinuação da venlafaxina, verificou-se uma rápida melhora clínica com regressão das alterações radiológicas e normalização da FEVE. Este é um importante caso de toxicidade cardiopulmonar induzida por droga. A administração circunstancial de inibidores da isoenzima CYP2D6 e a presença de um fenótipo de metabolização lenta de CYP2D6 podem ter resultado na acumulação tóxica da venlafaxina e na manifestação clínica subsequente. Aqui, é discutida a hipótese de a fosfolipidose macrofágica ser o mecanismo de toxicidade.

Myoclonic seizures in a preterm baby: is this a presentation of venlafaxine withdrawal?

Venlafaxine, a serotonin and norepinephrine reuptake inhibitor, is increasingly used in pregnant women with pre-existing depression who require continued treatment. However, its in uteroeffects on the developing fetus are not clear. Herein, we report the unusual presentation of venlafaxine withdrawal in a female preterm baby of 29 weeks gestation, who presented with myoclonic seizures on her second day of life. The seizures were confirmed using amplitude-integrated electroencephalography, and other possible causes of neonatal seizures were excluded. The baby responded to treatment with phenobarbitone and phenytoin. Magnetic resonance imaging of her brain was unremarkable at corrected gestational age of 39 weeks and 2 days. On follow-up at the corrected age of five months, she was well and developing normally with no further seizures. To the best of our knowledge, this is the first report of seizures in a preterm baby resulting from maternal venlafaxine use.

Essential oils from two Eucalyptus from Tunisia and their insecticidal action on Orgyia trigotephras (Lepidotera, Lymantriidae)

BACKGROUND: Essential oils extracted from aromatic and medicinal plants have many biological properties and are therefore an alternative to the use of synthetic products. The chemical composition of essential oils from two medicinal plants (Eucalyptus globulus and E. lehmannii) was determined and, their insecticidal effects on the third and fourth larval stages of Orgyia trigotephras were assessed. RESULTS: Larvae were collected from Jebel Abderrahmane (North-East of Tunisia), conserved in groups of 50/box (21 × 10 × 10 cm) at a temperature of 25°C. Larvae were tested for larvicidal activities of essential oils. Each oil was diluted in ethanol (96%) to prepare 3 test solutions (S1 = 0.05%, S2 = 0.10% and S3 = 0.50%). Essential oils were used for contact, ingestion and Olfactory actions and compared to reference products (Bacillus thuringiensis and Decis). Olfactory action of essential oils shows that larvae mortality is higher than contact action, lower than ingestion action. MTM and FTM of S3 of E. lehmannii were respectively 1 h 32 min and 1 h 39 min are higher than those of E. globulus (MTM = 51 min and FTM = 1 h 22 min 34 sec). Contact action of E. lehmannii oil shows low insecticidal activity compared to E. globulus. MTM are respectively (1 min 52 sec and 1 min 7 sec), FTM are (2 min 38 sec, 1 min 39 sec), are the shortest recorded for S3, on the third stage of larvae. The fourth stage of larvae, MTM are (2 min 20 sec and 2 min 9 sec), FTM are (3 min 25 sec, 3 min 19 sec). Ingestion action of essential oils is longer than the contact action, since the time of death exceeds 60 minutes for all species. CONCLUSION: Results shows that essential oils have a toxic action on nerves leading to a disruption of vital system of insects. High toxic properties make these plant-derived compounds suitable for incorporation in integrated pest management programs.

Synergistic effect and mechanism of cineole and terpineol on in-vitro transdermal delivery of Huperzine A from microemulsions

The aim of the present study was to investigate the influence and the mechanisms of cineole and terpineol on the in-vitro transdermal delivery of huperzine A from microemulsions, and their potential synergistic effect on the permeation enhancement. The transdermal delivery of huperzine A from microemulsions with different concentrations of cineole and terpineol through the rat abdominal skin was determined by Franz-type diffusion cells. The partition coefficient of huperzine A between the full thickness skin and microemulsion was determined. Attenuated total reflection-Fourier transform infrared spectroscopy [ATR-FTIR] was carried out to analyze the effects of cineole and terpineol on the biophysical properties of the stratum corneum [SC] and the mechanisms of permeation enhancement. These results indicated that cineole and terpineol could synergistically increase the transdermal delivery of huperzine A from microemulsions through increasing the partition and diffusion coefficients of huperzine A. ATR-FTIR studies further validated the synergistic effect and revealed that the enhancing mechanisms were due to increasing the disorderliness and fluidity of SC lipid alkyl chains, disrupting the structure of keratin in SC, and extracting SC lipids. In conclusion, cineole and terpineol, acting synergistically to enhance the transdermal delivery of huperzine A from microemulsions, might provide an alternative permeation enhancer combination for the transdermal delivery of huperzine A

Valibose, an alpha-glucosidase inhibitor, ameliorates the metabolic disorder of glucose and lipids and the nephropathy in streptozotocin-induced diabetic rats / 药学学报

This study is to evaluate the anti-diabetic effects of the alpha-glucosidase inhibitor valibose in a streptozotocin (STZ)-induced type 1 diabetes rat model. Diabetes was induced by a single dose of STZ (58 mg x kg(-1), ip) in SD rats, rats with elevated fasting blood glucose levels (250-450 mg x dL(-1)) were selected and divided into five groups (n = 10 in each). Another ten normal SD rats were chosen as normal group. Valibose mixed with the high sucrose diets (0.4, 1.0 and 2.5 mg 100 g(-1) diets) or acarbose (30 mg x 100 g(-1) diets) was administrated in the diabetic rats for about 5 weeks. In all groups, fasting and postprandial plasma glucose, plasma lipids, glycosylated serum protein, N-acetyl-beta-D-glucosaminidase (NAG), creatinine (Cre), blood urea nitrogen (BUN) and urine sugar levels were determined during the treatment. At the end of the experiment, the morphological alterations in kidney were evaluated by hematoxylin-eosin (HE) staining. After 3-weeks administration, valibose significantly decreased postprandial and fasting blood glucose, urine glucose, and reduced the levels of serum fructosamine. Valibose also decreased plasma triglyceride and cholesterol levels after 4 weeks treatment. These results indicated that valibose ameliorated metabolic disturbance of glucose and lipids in STZ-induced diabetic rats. In addition, valibose markedly reduced level of serum NAG and BUN, and decreased the weight index of kidney. HE staining showed reduced kidney pathological changes after valibose treatment. The findings of the present study indicate that valibose may be a novel alpha-glucosidase inhibitor for the prevention from hyperglycemia in STZ-induced type 1 diabetes rats. And valibose might have a potential role for protecting against diabetic nephropathy during hyperglycemia.

The agonist binding mechanism of human CB2 receptor studied by molecular dynamics simulation, free energy calculation and 3D-QSAR studies / 药学学报

CB2-selective agonists have drawn attention in drug discovery, since CB2 becomes a promising target for the treatment of neuropathic pain without psychoactive or other CNS-related side effects. However, the lack of experimental data of the 3D structures of human cannabinoid receptors hampers the understanding of the binding modes between ligands and CB2 by traditional methods. In the present work, combinational molecular modeling studies including flexible docking, MD simulations and free energy calculations were performed to investigate the interaction modes and mechanism of CB2-unselective agonist CP55940 and CB2-selective agonist GW842166X, separately binding with the homology model of CB2 in a DPPC/TIP3P simulated membrane environment. The binding free energies calculated by MM-PBSA method give an explanation for the activity differences of the studied ligands. Binding free energies decomposition by MM-GBSA method shows that the van der Waals interaction is the dominant driving force during the binding process. Our MD simulations demonstrate that Phe197 could be a critical residue for the binding of CB2-selective agonists. Furthermore, by using the MD simulated binding conformer as a template, the 3D-QSAR studies were performed with the comparative molecular field analysis (CoMFA) approach on a set of GW842166X analogues. A combinational exploration of both CoMFA steric and potential contour maps for CB2 affinities and the MD studied interaction modes sheds light on the structural requirements for CB2 agonists and serves as a basis for the design of novel CB2 agonists.

The influence of storage time on content of volatile oil and cineole of Chimonanthus salicifolius / 中国中药杂志

The vapour distillation was used to extract the volatile oil of Chimonanthus salicifolius with different storage time, determine the content of cineole in volatile oil by GC, to study the influence of storage time on the content of volatile oil and cineole of C. salicifolius. We found that the content of volatile oil in fresh herbs of C. salicifolius was 0.023 0 mL x g(-1), it was decreased to 0.020 0, 0.017 5 mL x g(-1) respectively after storing for 4, 12 months; the GC methodological study of precision, stability and repeatability, RSD < 2%, the average recovery rate was 99.50%, RSD 1.7%; the content of cineole in fresh volatile oil was 54.30%, it was increased to about 62% and remained stably with the time. Therefore, the content of volatile oil and cineole of C. salicifolius can change with the storage time; GC method for the determination of the content of cineole is accurate, reliable, specific and repeatable, it's suitable as a quality control method of C. salicifolius.

Warfarin: pharmacological profile and drug interactions with antidepressants / Varfarina: perfil farmacológico e interações medicamentosas com antidepressivos

Oral anticoagulants are among the drugs with the greatest number of drug interactions. The concomitant use of several medications is a common practice in patients with cardiovascular problems, who often also present with depression; therefore, the probability of an interaction occurring between warfarin and the antidepressants is high, and may result in increased or decreased anticoagulant activity. Since the possible interactions between these two classes of drugs have been poorly explored in literature, with a risk to the patients who use them, we reviewed the pharmacology of warfarin and its possible interactions with antidepressants. Of the antidepressants analyzed, those that showed relevant effects on the interaction with warfarin were, in decreasing order: paroxetine, venlafaxine, fluoxetine, and duloxetine.

Os anticoagulantes orais estão entre as drogas com maior número de interações medicamentosas. O uso concomitante de vários medicamentos é uma prática comum em pacientes com problemas cardiovasculares, os quais frequentemente também apresentam depressão; assim, a probabilidade de ocorrer alguma interação entre a varfarina e os antidepressivos é bem expressiva, podendo resultar em um aumento ou uma diminuição da atividade anticoagulante. Como as possíveis interações entre essas duas classes de medicamentos se mostraram pouco exploradas na literatura, com risco aos pacientes que fazem uso delas, revisamos a farmacologia da varfarina e suas possíveis interações com antidepressivos. Dos antidepressivos analisados, os que apresentaram efeitos relevantes na interação com a varfarina foram, em ordem decrescente: paroxetina, venlafaxina, fluoxetina e duloxetina.

Comparison of monoamine reuptake inhibitors for the immobility time and serotonin levels in the hippocampus and plasma of sub-chronically forced swim stressed rats

The current study was aimed at comparing the behavioral and biochemical [5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels] effects of monoamine reuptake inhibitors [fluoxetine, venlafaxine and imipramine] in sub-chronically forced swim stressed rats. At the given doses of 10, 20 and 30 mg/kg, among aforesaid antidepressants, the imipramine treatment alone caused significant decline in the immobility time of rats [IC[50] - 20 mg/kg]. In the hippocampus of rats, the imipramine treatment caused significant elevation of 5-hydroxytryptamine [5-HT] whereas, the fluoxetine and venlafaxine elicited significant increase in 5-hydroxyindoleacetic acid [5-HIAA] levels. Likewise, in the plasma of rats, the imipramine treatment significantly increased the 5-HIAA levels whereas, the fluoxetine and venlafaxine treatment significantly elevate the 5-HT levels. It can therefore be inferred that the imipramine did not act like other monoamine reuptake inhibitors in biochemical study, which could possibly underlie its ability to be detected in forced swim test [behavioral study]. Moreover, the re-uptake inhibition of 5-HT is not accountable for the antidepressant action exhibited in forced swim test