scholarly journals GENOTOXIC AND CARCINOGENIC STUDIES OF NORGESTREL IN DROSOPHILA MELANOGASTER

2018 ◽  
Vol 11 (10) ◽  
pp. 372
Author(s):  
Abou-eisha A ◽  
Adel E El-din
Keyword(s):  
Somatic Mutation ◽  
Cellular Proliferation ◽  
Research Work ◽  
The Body ◽  
The Other ◽  
Direct Stimulation ◽  
Carcinogenic Activity ◽  
Genetic Examination ◽  
First Time

Objective: The aim of this study was to investigate, for the first time, the possible in vivo genotoxic and carcinogenic activity associated with exposure to norgestrel (NGT) drug through employing the very recently established and adjusted genotoxic and tumorigenic methods in Drosophila melanogaster.Methods: Two in vivo genotoxic test systems were used; one detects the somatic mutation and recombination effects (somatic mutation and recombination test [SMART] wing-spot test) and the other detects the primary DNA damage (the comet test) in the body cells of D. melanogaster. On the other hand, the warts (wts)-based SMART assay is a vital genetic examination in Drosophila used to identify and characterize cancer potential of compounds.Results: Four experimental doses of NGT were used (ranging from 0.24 μM to 16 μM). NGT was found to be non-genotoxic at all tested concentrations even at the highest dose level 16 μM and failed to increase the frequency of tumors in the somatic cells of D. melanogaster.Conclusion: Our results strengthen the hypothesis that steroidal drugs might act through a non-genotoxic carcinogen mechanism where the carcinogenic properties occur by direct stimulation of cellular proliferation through a steroid receptor-mediated mechanism. In addition, the results obtained in this research work may contribute to highlighting the importance of NGT as a potent neuroprotective antioxidant drug.

scholarly journals Electro-Quasistatic Animal Body Communication for Untethered Rodent Biopotential Recording

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shreeya Sriram ◽  
Shitij Avlani ◽  
Matthew P. Ward ◽  
Shreyas Sen
Keyword(s):  
Lower Energy ◽  
Sensor Node ◽  
State Of The Art ◽  
The Body ◽  
Animal Body ◽  
Current State ◽  
Communication Modalities ◽  
First Time ◽  
Biopotential Recording

AbstractContinuous multi-channel monitoring of biopotential signals is vital in understanding the body as a whole, facilitating accurate models and predictions in neural research. The current state of the art in wireless technologies for untethered biopotential recordings rely on radiative electromagnetic (EM) fields. In such transmissions, only a small fraction of this energy is received since the EM fields are widely radiated resulting in lossy inefficient systems. Using the body as a communication medium (similar to a ’wire’) allows for the containment of the energy within the body, yielding order(s) of magnitude lower energy than radiative EM communication. In this work, we introduce Animal Body Communication (ABC), which utilizes the concept of using the body as a medium into the domain of untethered animal biopotential recording. This work, for the first time, develops the theory and models for animal body communication circuitry and channel loss. Using this theoretical model, a sub-inch$$^3$$ 3 [1″ × 1″ × 0.4″], custom-designed sensor node is built using off the shelf components which is capable of sensing and transmitting biopotential signals, through the body of the rat at significantly lower powers compared to traditional wireless transmissions. In-vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation $$>99\%$$ > 99 % when compared to traditional wireless communication modalities, with a 50$$\times$$ × reduction in power consumption.

scholarly journals Cyclam-Based Chelators Bearing Phosphonated Pyridine Pendants for 64Cu-PET Imaging : Synthesis, Physico-Chemical Studies, Radiolabeling and Bioimaging.

2020 ◽  
Author(s):  
Richard Knighton ◽  
Thibault Troadec ◽  
Valerie Mazan ◽  
Patricia La Saëc ◽  
Séverine Marionneau-Lambot ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Copper Complexes ◽  
The Body ◽  
Renal Elimination ◽  
X Ray Diffraction ◽  
Physico Chemical ◽  
Chemical Studies ◽  
First Time ◽  
Excellent Stability

Herein we present the preparation of two novel cyclam-based macrocycles (te1pyp and cb-te1pyp), bearing phosphonate-appended pyridine side-arms for the coordination of copper(II) ions in the context of 64Cu PET imaging. The two ligands have been prepared through conventional protection-alkylation sequences on cyclam, and their coordination properties have been thoroughly investigated. The corresponding copper complexes have been fully characterized in the solid-state (X-Ray diffraction analysis) and in solution (EPR and UV-Vis spectroscopies). Potentiometric studies, combined with spectrometry, have also allowed us to determine their thermodynamic stability constants, confirming their high affinity for copper(II) cations. The kinetic inertness of the complexes has also been verified by acid-assisted dissociation experiments, enabling their use in 64Cu-PET imaging in mice for the first time. Indeed, the two ligands could be quantitatively radiolabeled under mild conditions, and the resulting 64Cu complexes have demonstrated excellent stability in serum. PET imaging demon-strated a set of features emerging from the combination of picolinates and phosphonate units: high stability in vivo, fast clear-ance from the body via renal elimination, and most interestingly, very low fixation in the liver. The latter is in contrast with what was observed for monopicolinate cyclam (te1pa), that had a non-negligible accumulation in the liver, owing probably to its different charge and lipophillicity. These results thus pave the way for the use of such phosphonated pyridine chelators for in vivo 64Cu-PET imaging.

scholarly journals Cyclam-Based Chelators Bearing Phosphonated Pyridine Pendants for 64Cu-PET Imaging : Synthesis, Physico-Chemical Studies, Radiolabeling and Bioimaging.

2020 ◽  
Author(s):  
Richard Knighton ◽  
Thibault Troadec ◽  
Valerie Mazan ◽  
Patricia La Saëc ◽  
Séverine Marionneau-Lambot ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Copper Complexes ◽  
The Body ◽  
Renal Elimination ◽  
X Ray Diffraction ◽  
Physico Chemical ◽  
Chemical Studies ◽  
First Time ◽  
Excellent Stability

Herein we present the preparation of two novel cyclam-based macrocycles (te1pyp and cb-te1pyp), bearing phosphonate-appended pyridine side-arms for the coordination of copper(II) ions in the context of 64Cu PET imaging. The two ligands have been prepared through conventional protection-alkylation sequences on cyclam, and their coordination properties have been thoroughly investigated. The corresponding copper complexes have been fully characterized in the solid-state (X-Ray diffraction analysis) and in solution (EPR and UV-Vis spectroscopies). Potentiometric studies, combined with spectrometry, have also allowed us to determine their thermodynamic stability constants, confirming their high affinity for copper(II) cations. The kinetic inertness of the complexes has also been verified by acid-assisted dissociation experiments, enabling their use in 64Cu-PET imaging in mice for the first time. Indeed, the two ligands could be quantitatively radiolabeled under mild conditions, and the resulting 64Cu complexes have demonstrated excellent stability in serum. PET imaging demon-strated a set of features emerging from the combination of picolinates and phosphonate units: high stability in vivo, fast clear-ance from the body via renal elimination, and most interestingly, very low fixation in the liver. The latter is in contrast with what was observed for monopicolinate cyclam (te1pa), that had a non-negligible accumulation in the liver, owing probably to its different charge and lipophillicity. These results thus pave the way for the use of such phosphonated pyridine chelators for in vivo 64Cu-PET imaging.

Effective Induction of Apoptosis by Mistletoe Plant Extracts in an Acute Lymphoblastic Leukemia Model.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1880-1880
Author(s):  
Georg Seifert ◽  
Patrick Jesse ◽  
Aram Prokop ◽  
Tobias Reindl ◽  
Stephan Lobitz ◽  
...  
Keyword(s):  
Cell Death ◽  
Body Weight ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
The Body ◽  
Induction Of Apoptosis ◽  
First Time ◽  
Over Time

Abstract Mistletoe (Viscum album) is one of the most used alternative cancer therapies applied as monotherapy or in combination with conventional therapies. Anti-tumor effects of mistletoe (MT) extracts were related to cytostatic and immunomodulatory effects observed in vitro. Aqueous MT extracts contain the three mistletoe lectins I, II and III as one predominant group of biologically active agents. The MT lectins inhibit protein biosynthesis by inactivating the 60S ribosomal subunit. Mistletoe lectin-I (ML-I) is one important apoptosis inducing compound. It is a heterodimer that consists of a cytotoxic A-chain (ribosome inactivating protein, RIP type 1) linked by a carbohydrate binding B-chain for cellular lectin uptake. However, although MT is widely used, there is a lack of scientific preclinical and clinical data. Here, we describe for the first time efficacy and mechanism of MT extracts against lymphoblastic leukemia in vitro and in vivo. For this purpose, we first investigated both the cytotoxic effect and mechanism of action of two standardized aqueous MT extracts (MT obtained from fir trees (MT-A); MT obtained from pine trees (MT-P)) and isolated ML-I, in three human acute lymphoblastic leukemia (ALL) cell lines (NALM-6, sup-B-15 and REH). MT-A, MT-P and ML-I clearly inhibited cell proliferation as determined by LDH reslease assays at very low concentrations (ML-I LD50 from 0,05 ng/ml to 10 ng/ml depending on the host tree) with MT-P being the most cytotoxic extract. The mechanism of cell death was determined by DNA-fragmentation assays. These indicated dose dependent induction of apoptosis as the main mechanism of cell death. Finally, we evaluated the efficacy of MT-A and MT-P in an in vivo SCID-model of pre-B ALL (NALM-6). For this purpose, mice (n=8/group) were injected i.v. with 1 × 106NALM6 cells and treated by intraperitoneal injections four times per week for 3 weeks (day 1–4; 7–11; 14–18) at varying doses (1, 5 and 50 mg/Kg (plant weight/body weight)). Mice (n=8) treated with PBS and cyclophosphamide (100 mg/kg, once on day 1) were used as negative and positive controls, respectively. Toxicity, peripheral blood counts, bodyweight and survival was determined over time. Interestingly, both MT extracts in all tested concentrations significantly improved survival (up to 55,4 days) in contrast to controls (34,6 days). Furthermore, no hematologic side effects were observed from this treatment as indicated by completely stable blood counts. Also the body weight of treated animals remained stable over time indicating a complete absence of systemic toxicity in the selected dose range. In summary, we demonstrate for the first time efficacy and mechanism of MT extracts against ALL in vitro and in vivo and hereby provide an important base line for the design of clinical trials with these compounds.

scholarly journals DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jayesh Antony ◽  
Minakshi Saikia ◽  
Vinod. V ◽  
Lekshmi. R. Nath ◽  
Mohana Rao Katiki ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Chemotherapeutic Agent ◽  
Drug Formulation ◽  
The Other ◽  
Skin Disorders ◽  
Master Regulator ◽  
Anticancer Properties ◽  
Wrightia Tinctoria ◽  
First Time

Abstract Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential. Herein, for the first time, we report the significant anticancer properties of a semi-purified fraction, DW-F5, from the dichloromethane extract of W. tinctoria leaves against malignant melanoma. DW-F5 exhibited anti-melanoma activities, preventing metastasis and angiogenesis in NOD-SCID mice, while being non-toxic in vivo. The major pathways in melanoma signaling mediated through BRAF, WNT/β-catenin and Akt-NF-κB converging in MITF-M, the master regulator of melanomagenesis, were inhibited by DW-F5, leading to complete abolition of MITF-M. Purification of DW-F5 led to the isolation of two cytotoxic components, one being tryptanthrin and the other being an unidentified aliphatic fraction. The overall study predicts Wrightia tinctoria as a candidate plant to be further explored for anticancer properties and DW-F5 as a forthcoming drug formulation to be evaluated as a chemotherapeutic agent against malignant melanoma.

scholarly journals Effects of long-term in vivo micro-CT imaging on hallmarks of osteopenia and frailty in aging mice

2020 ◽  
Author(s):  
Ariane C. Scheuren ◽  
Gisela A. Kuhn ◽  
Ralph Müller
Keyword(s):  
Body Weight ◽  
Aging Process ◽  
Frailty Index ◽  
Ct Imaging ◽  
Morphometric Parameters ◽  
The Body ◽  
The Other ◽  
Micro Ct

AbstractIn vivo micro-CT has already been used to monitor microstructural changes of bone in mice of different ages and in models of age-related diseases such as osteoporosis. However, as aging is accompanied by frailty and subsequent increased sensitivity to external stimuli such as handling and anesthesia, the extent to which longitudinal imaging can be applied in aging studies remains unclear. Consequently, the potential of monitoring individual mice during the entire aging process – from healthy to frail status – has not yet been exploited. In this study, we assessed the effects of long-term in vivo micro-CT imaging - consisting of 11 imaging sessions over 20 weeks - on hallmarks of aging both on a local (i.e., static and dynamic bone morphometry) and systemic (i.e., frailty index (FI) and body weight) level at various stages of the aging process. Furthermore, using a premature aging model (PolgA(D257A/D257A)), we assessed whether these effects differ between genotypes.The 6th caudal vertebrae of 4 groups of mice (PolgA(D257A/D257A) and PolgA(+/+)) were monitored by in vivo micro-CT every 2 weeks. One group was subjected to 11 scans between weeks 20 and 40 of age, whereas the other groups were subjected to 5 scans between weeks 26-34, 32-40 and 40-46, respectively. The long-term monitoring approach showed small but significant changes in the static bone morphometric parameters compared to the other groups. However, no interaction effect between groups and genotype was found, suggesting that PolgA mutation does not render bone more or less susceptible to long-term micro-CT imaging. The differences between groups observed in the static morphometric parameters were less pronounced in the dynamic morphometric parameters. Moreover, the body weight and FI were not affected by more frequent imaging sessions. Finally, we observed that longitudinal designs including baseline measurements at young adult age are more powerful at detecting effects of in vivo micro-CT imaging on hallmarks of aging than cross-sectional comparisons between multiple groups of aged mice subjected to fewer imaging sessions.

Removal Pathway of Bioactive Glass Resorption Products from the Body

1999 ◽  
Vol 599 ◽  
Author(s):  
W. Lai ◽  
P. Ducheyne ◽  
J. Garino ◽  
C. M. Flaitz
Keyword(s):  
Bioactive Glass ◽  
Excretion Rate ◽  
Atomic Absorption Spectrophotometry ◽  
The Body ◽  
The Other ◽  
Soluble Form ◽  
Control Group ◽  
Flame Atomic Absorption ◽  
Physiological Capacity

AbstractWe traced and quantified the silicon released from bioactive glass (BG) granules in vivo (45S5, 300–355 μm). 1500 mg of BG granules were implanted in the paraspinal muscle of 7 four kg rabbits. Blood samples and 24-hour urine samples were obtained over a 24 week period. Local muscle tissue as well as the following organs were harvested for chemical and histological analyses: brain, heart, kidney, liver, lung, lymph nodes, spleen, and thymus. Flame atomic absorption spectrophotometry was used to measure the concentration of elemental silicon in all the samples after digestion. Tissues and fluids from a sham group of 7 rabbits (underwent surgical procedure but received no implants) were obtained in a similar manner.The urinary silicon of the implanted group was significantly higher than in the control group. From the data, the calculated average excretion rate was approximately 2.4 mg/day, and as such, 100 percent of the implanted silicon was excreted in 19 weeks. No elevated concentrations of silicon were found at the implant site or in the other organs after 24 weeks. Histological appearance of all major organs was normal for all animals in the study.The concentrations of silicon measured in the urine were well below saturation and since no significant increase in silicon was found in the kidney or in the other organs, the increased silicon excretion rate was within the physiological capacity of rabbits. Therefore, it can be concluded that the resorbed silica gel is harmlessly excreted in soluble form through the urine.

EVALUATIVE CHARACTERISTICS IN RESEARCH ADVISORS’ REVIEWS IN THE FRAMEWORK OF ACADEMIC DISCOURSE

2020 ◽  
pp. 42-53
Author(s):  
А.А. Водяницкая
Keyword(s):  
Positive Characteristic ◽  
Research Work ◽  
Personal Characteristics ◽  
Academic Discourse ◽  
The Body ◽  
Structural Elements ◽  
Problem Statement ◽  
Structural Element ◽  
Research Papers ◽  
First Time

Постановка задачи. Работа посвящена изучению оценочных характеристик отзыва научного руководителя, функционирующего в рамках академического дискурса. Впервые выявляются оценочные стратегии и тактики научного руководителя, вербализованные в отзыве при характеризации научно-исследовательской работы магистранта и бакалавра. Результаты. Как показало исследование, посредством оценочных значений, которые выстраивают отзыв о работе выпускника над выпускной квалификационной работой, научные руководители положительно характеризуют исследовательские навыки студентов. Отрицательные оценочные значения не вербализуются, но имплицируются в рекомендациях уделять внимание в дальнейшей работе, например, более планомерной организации исследования. Наиболее универсальной и распространённой характеристикой работы студента является формулировка академический дискурс сформирован , которая включает в себя все положительные оценочные значения, релевантные для научно-исследовательской деятельности в рамках академического дискурса. Во всех структурных элементах отзыва научные руководители прибегают к использованию оценочных значений. В наименьшей степени оценочные значения представлены в разделе Умение работать с научной, методической, справочной литературой и электронными информационными ресурсами. Выводы. Отзыв научного руководителя как жанр академического дискурса представляет собой амальгаму оценочных средств, с помощью которых научный руководитель эксплицирует, а в некоторых случаях и имплицирует своё отношение к проделанной студентом работе. В качестве объекта оценки служат те аспекты научно-исследовательской деятельности, которые выделены как структурные элементы отзыва, а также дополнительные объекты, которые научный руководитель считает необходимым выделить. В ходе исследования были выделены оценочные стратегии импликации, интенсификации, рекомендации и констатации. Problem Statement. The paper focuses on evaluative characteristics of research advisors’ reviews functioning in the framework of academic discourse. Evaluative strategies and tactics have been revealed for the first time as a part of a research advisor’s review. Results. The research has shown that research advisors characterize positively various aspects of graduate students’ research papers and the way they organized their research work. Negative evaluations are not verbalized, but teachers implicitly mention that their students should organize their work more thoroughly in the future. The fact that academic discourse has been acquired by the student to the full extent serves as a positive characteristic of their work, and, therefore, includes all the evaluations relevant for doing a research and for research results. In all the structural elements of the reviews research advisors use a variety of evaluative means. The latter are represented to a lesser extent in the structural element concerning the Ability of a student to retrieve information and to use a variety of information resources. Conclusion. Research advisor’s review as a genre of academic discourse is an amalgam of evaluative means which enable the research advisor to explicitly verbalize his attitude towards a student research work. Evaluative means characterize those aspects of research work which are specified in the body of the review as structural elements. Moreover, teachers specifies work ethic, ethical behavior, personal characteristics that are crucial for the research work. The research has revealed evaluative strategies of intensification, recommendation, stating and implication.

Co-Transplantation of MSC Improves the Engraftment of HSC after Auto-iBMT in Non-Human Primates.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2321-2321
Author(s):  
Shigeo Masuda ◽  
Yoko Obara ◽  
Naohide Ageyama ◽  
Hiroaki Shibata ◽  
Tamako Ikeda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Osteoblastic Differentiation ◽  
The Body ◽  
The Other ◽  
Hematopoietic Stem ◽  
Cynomolgus Monkeys ◽  
Colony Pcr ◽  
Marrow Cavity

Abstract [Background] Mesenchymal stem cells (MSC) have been shown to play critical roles in various in vivo phenomena including osteoblastic differentiation. It has been suggested that, in the bone marrow, hematopoietic stem cells (HSC) reside in osteoblastic niche, which consists of osteoblasts derived from MSC. In mice, previous studies have demonstrated that co-transplantation of MSC improves the engraftment of HSC, especially after transplantation of the cells into the bone marrow cavity directly, namely intra-bone marrow transplantation (iBMT). However, neither the efficacy nor the dynamics such as migration and homing of HSC after iBMT with MSC have been determined in large animals. Here, using non-human primates, we have investigated the effects of co-transplantation of MSC on the engraftment of HSC after autologus iBMT. [Methods] Auto-iBMT of cynomolgus monkeys was performed, using bone marrow stromal cells (as MSC) and CD34-positive cells (as HSC). The latter were divided into two equal aliquots, each of which was genetically marked with a different retroviral vector, G1Na or LNL6. Conditioning of iBMT, TBI or administration of busulfan, was followed by hemi-iBMT; that is, the bone marrow of one side (right or left) of the body was transplanted with one HSC aliquot together with MSC, whereas the other side of the identical body was transplanted with the other HSC aliquot alone. Engraftment of each HSC aliquot was evaluated by colony PCR of bone marrow, as well as by PCR of the genomic DNA obtained from peripheral blood or bone marrow of humerus, femur, and ilium. Both PCR could distinguish the dual markings derived from the two HSC aliquots. [Results] In the first monkey transplanted, we found that the engraftment derived from the co-transplantation aliquot was 4.4-times higher than that derived from the HSC alone aliquot as assessed by colony PCR (48% versus 11%) using the bone marrow samples obtained from the ilium at day 46 post-iBMT. In the second monkey, when the peripheral WBC recovered to 2500–3000/μl after day 28 post-iBMT, 2% of the cells were positive with the retroviral marking derived from the co-transplantation aliquot, although none of them were positive with that derived from the HSC alone aliquot. In addition, colony PCR of the humerus and femur of both sides at day 39 post-iBMT revealed that the engraftment derived from the co-transplantation aliquot was 6.0-times higher than that derived from the HSC alone aliquot. Notably, colony-forming units (CFU) derived from the cotransplantation aliquot were detected in the bone marrow of the opposite side, suggesting that HSC injected into the bone marrow might migrate and achieve homing in the distant bone marrow. [Conclusion] Taken together, these results indicate that, in auto-iBMT of cynomolgus monkeys, co-transplantation of MSC improves the engraftment of HSC, the efficacy of which might be attributable to additional osteoblastic niche, presumably created from co-transplanted MSC.

11 The Role of National Parliaments in the Making of European Law

1998 ◽  
Vol 1 ◽  
pp. 217-231
Author(s):  
Timothy Pratt
Keyword(s):  
European Union ◽  
Maastricht Treaty ◽  
The Body ◽  
The Other ◽  
European Law ◽  
The European Union ◽  
National Parliaments ◽  
Treaty Of Amsterdam ◽  
First Time

While the Community Treaties provided the institutional framework for the European Community, much of what now makes up the constitution of the European Union was not provided for in those Treaties, but evolved within that framework. This is certainly true of the role of national parliaments. There is nothing about the role of national parliaments in any of the Treaties concluded prior to the Maastricht Treaty, and even then the references appear not in the body of the Treaty, but only in two Declarations annexed to it, one on the role of national parliaments in the European Union and the other on the Conference of the Parliaments. While the former states that it is important to encourage greater involvement of national parliaments in the activities of the European Union, it gives no indication of what that involvement should be. The Treaty of Amsterdam goes a step further. It includes a protocol on the role of national parliaments. This is important in that, for the first time, it gives substantive treaty recognition to their involvement in European Union activities. But, while it is markedly more supportive than the Maastricht Declarations, it does not confer any specific powers on national parliaments, nor does it attempt to define their functions.

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