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Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene
Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishmania drugs based on natural products and their derivatives. β-Ocimene is a monoterpene found naturally in the essential oils of many plant species which presents antileishmanial activity, and which has not yet been evaluated for its potential to inhibit the etiological agent of leishmaniasis. The aim of this work was to evaluate the activity of β-ocimene against Leishmania amazonensis, its cytotoxicity, and potential mechanisms of action. β-Ocimene presented direct activity against the parasite, with excellent growth inhibition of promastigotes (IC50 = 2.78 μM) and axenic amastigotes (EC50 = 1.12 μM) at concentrations non-toxic to RAW 264.7 macrophages (CC50 = 114.5 µM). The effect is related to changes in membrane permeability and resulting abnormalities in the parasitic cell shape. These were, respectively, observed in membrane integrity and atomic force microscopy assays. β-Ocimene was also shown to act indirectly, with greater activity against intra-macrophagic amastigotes (EC50 = 0.89 μM), increasing TNF-α, nitric oxide (NO), and reactive oxygen species (ROS), with lysosomal effects, as well as promoting decreases in IL-10 and IL-6. Against intra-macrophagic amastigote forms the selectivity index was higher than the reference drugs, being 469.52 times more selective than meglumine antimoniate, and 42.88 times more selective than amphotericin B. Our results suggest that β-ocimene possesses promising in vitro antileishmania activity and is a potential candidate for investigation in in vivo assays.
Journal Article
Totally NOTES (T-NOTES) transvaginal cholecystectomy using two endoscopes: preliminary report
Background
Clinical applications of transvaginal Natural Orifice Transluminal Endoscopic Surgery (NOTES) are still limited in the literature, mostly case reports performed by hybrid procedures with laparoscopic assistance. Avoiding complications from incisions is the main goal for natural orifice surgery. This study reports on a technique developed at our institution that uses two endoscopes inserted into the vagina to perform a Totally NOTES (T-NOTES) transvaginal cholecystectomy, and describes preliminary results.
Methods
IRB approval was obtained at the institution for transvaginal NOTES clinical trials, and informed consent was obtained. The technique of T-NOTES transvaginal cholecystectomy was clinically applied in four female patients with symptomatic cholelithiasis, and data were prospectively documented. Transvaginal NOTES access was obtained by direct vaginal incision, and two endoscopes were simultaneously introduced in the abdominal cavity. Dissection was accomplished with available endoscopic instruments. Ligation of cystic duct and artery was performed using endoscopic clips. Vaginal closure was achieved using the direct-vision sutured technique.
Results
The technique was successfully performed in the four patients. Insufflation and spatial orientation was of good quality. Mean operative time was 210 min. There were no complications during the 30-day follow-up. Postoperative course was uneventful, and patients were released from the hospital on the first postoperative day.
Conclusion
Tranvaginal T-NOTES using two endoscopes provides a feasible method for natural orifice cholecystectomy using available technology. Large-series studies are needed to evaluate the results with respect to safety of the approach.
Journal Article
The impact of a brief mindfulness training on interoception: A randomized controlled trial
Interoception is a collection of different representations of signals originating within the body. The way of perceiving these signals seems to be related to both emotion regulation and dysregulation, and its dysfunction is implicated across a variety of affective disorders. There is a growing body of research investigating the relationship between mindfulness meditation practices and interoception showing an increase in interoceptive processes with regular training. In this study, we assessed the effects of a three-day mindfulness training on interoceptive accuracy and sensibility in a young healthy adult sample. Moreover, we also performed a mediation analysis on interoceptive sensibility and anxiety. Healthy participants (n = 40) naive to mindfulness practices were randomized to a brief mindfulness training (MT) (n = 20, females = 10) or to an active control group (n = 20, females = 10). Participants were assessed before and after the 3-days intervention for both groups on measures of interoception and anxiety in a modified intention-to-treat approach. The brief mindfulness training group increased interoceptive sensibility while active control had no effects on this variable. Five out of eight subdomains of interoceptive sensibility were significantly improved after mindfulness training. There was no significant difference in interoceptive accuracy after training. The effect of a brief mindfulness training on interoceptive sensibility mediated changes in the anxiety state. To date, this is the first study showing a plausible mechanism of a brief mindfulness training to explain the anxiolytic effects of meditation practices. Trial registration: RBR-7b8yh8 , March 28 th 2017 http://www.ensaiosclinicos.gov.br/rg/RBR-7b8yh8/ .
Journal Article
العقل البشري وظاهرة التعلم
يعرض هذا الكتاب آخر ما توصل إليه البحث العلمى والإكتشافات العلمية الحديثة فى مجال وظائف العقل البشرى. وفيه يحاول المؤلف استعراض بعض المواد المرجعية فى مجال البحث فى وظائف العقل البشرى. فيتحدث عن الأجزاء الرئيسية التى يتكون منها المخ وكيفية معالجته للمعلومات التى يستقبلها، بالإضافة إلى وظائف الذاكرة وكيفية استرجاع المعلومات فيها وكيفية انتقال أثر المعرفة لدعم عملية التعلم فى الحاضر والمستقبل.
Book
AMTAC-19, a Spiro-Acridine Compound, Induces In Vitro Antitumor Effect via the ROS-ERK/JNK Signaling Pathway
Colorectal cancer remains a significant cause of mortality worldwide. A spiro-acridine derivative, (E)-1′-((4-bromobenzylidene)amino)-5′-oxo-1′,5′-dihydro-10H-spiro[acridine-9,2′-pyrrole]-4′-carbonitrile (AMTAC-19), showed significant cytotoxicity in HCT-116 colorectal carcinoma cells (half maximal inhibitory concentration, IC50 = 10.35 ± 1.66 µM) and antioxidant effects after 48 h of treatment. In this study, Molegro Virtual Docker v.6.0.1 software was used to investigate the interactions between AMTAC-19 and the Extracellular Signal-Regulated Kinase 1 (ERK1), c-Jun N-terminal Kinase 1 (JNK1), and p38 Mitogen-Activated Protein Kinase α (p38α MAPK). In vitro assays were conducted in HCT-116 cells to evaluate the effect of AMTAC-19 on the modulation of these proteins’ activities using flow cytometry. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence or absence of ERK1/2, JNK, and p38 MAPK inhibitors was used to evaluate the involvement of these enzymes in AMTAC-19 cytotoxicity. ROS production was assessed using the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) assay at various incubation times (30 min, 1 h, 6 h, 12 h, and 24 h), and the MTT assay using N-acetyl-L-cysteine (NAC) was performed. In silico results indicated that AMTAC-19 interacts with ERK1, JNK1, and p38α MAPK. Additionally, AMTAC-19 activated ERK1/2 and JNK1 in HCT-116 cells, and its cytotoxicity was significantly reduced in the presence of ERK1/2 and JNK inhibitors. AMTAC-19 also induced a significant increase in ROS production (30 min and 1 h), while NAC pretreatment reduced its cytotoxicity. These findings support AMTAC-19′s in vitro antitumor effect through ROS-dependent activation of ERK and JNK pathways.
Journal Article
John Philip Sousa's America : the patriot's life in images and words
Just who was John Philip Sousa? This intimate portrait brings Sousa to Life--who he was, why he was driven to succeed, his love of country--and explores his life and times through hundreds of photos, cartoons, short stories, news clippings, quotes, sheet music covers, and magazine ads collected in family scrapbooks, the Sousa Archive in the Library of Congress, and the U.S. Marines archives. This book reveals a quintessentially American story: It is the story of being born to poor immigrant parents and through immeasurable hard work, talent, and self-motivated drive succeeding beyond dreams. But it is also a very personal story of a man with a vision: a man who saw great music ultimately as being from the heart and who sought to bring this music--not just his own--to the world [Publisher description]
Book
Spatio-temporal transcriptome of the human brain
Brain development and function depend on the precise regulation of gene expression. However, our understanding of the complexity and dynamics of the transcriptome of the human brain is incomplete. Here we report the generation and analysis of exon-level transcriptome and associated genotyping data, representing males and females of different ethnicities, from multiple brain regions and neocortical areas of developing and adult post-mortem human brains. We found that 86 per cent of the genes analysed were expressed, and that 90 per cent of these were differentially regulated at the whole-transcript or exon level across brain regions and/or time. The majority of these spatio-temporal differences were detected before birth, with subsequent increases in the similarity among regional transcriptomes. The transcriptome is organized into distinct co-expression networks, and shows sex-biased gene expression and exon usage. We also profiled trajectories of genes associated with neurobiological categories and diseases, and identified associations between single nucleotide polymorphisms and gene expression. This study provides a comprehensive data set on the human brain transcriptome and insights into the transcriptional foundations of human neurodevelopment.
Gene expression in the human brain
Gene expression controls and dictates everything from development and plasticity to ongoing neurogenesis in the brain, yet the temporal dynamics of transcription throughout the brain's lifetime have been mostly unknown. Here, two groups present a large gene-expression database from a variety of human brain samples ranging from before birth to over 80 years in age. Colantuoni
et al
. focus on the prefrontal cortex. Although they note significant expression pattern dynamics throughout development, they identify a consistent molecular architecture of transcription across subjects from different races despite the large number of genetic polymorphisms among them. Kang
et al
. produce a more comprehensive time course, exploring expression in 16 different brain areas, determining that the largest spatiotemporal variability occurs before birth, with transcriptomes in brain regions converging as we age.
Journal Article