Herbal medicines in Brazil: pharmacokinetic profile and potential herb-drug interactions

A plethora of active compounds found in herbal medicines can serve as substrate for enzymes involved in the metabolism of xenobiotics. When a medicinal plant is co-administered with a conventional drug and little or no information is known about the pharmacokinetics of the plant metabolites, there is an increased risk of potential herb-drug interactions. Moreover, genetic polymorphisms in a population may act to predispose individuals to adverse reactions. The use of herbal medicines is rapidly increasing in many countries, particularly Brazil where the vast biodiversity is a potential source of new and more affordable treatments for numerous conditions. Accordingly, the Brazilian Unified Public Health System (SUS) produced a list of 71 plant species of interest, which could be made available to the population in the near future. Physicians at SUS prescribe a number of essential drugs and should herbal medicines be added to this system the chance of herb-drug interactions further increases. A review of the effects of these medicinal plants on Phase 1 and Phase 2 metabolic mechanisms and the transporter P-glycoprotein was conducted. The results have shown that approximately half of these medicinal plants lack any pharmacokinetic data. Moreover, most of the studies carried out are in vitro. Only a few reports on herb-drug interactions with essential drugs prescribed by SUS were found, suggesting that very little attention is being given to the safety of herbal medicines. Here we have taken this information to discuss the potential interactions between herbal medicines and essential drugs prescribed to Brazilian patients whilst taking into account the most common polymorphisms present in the Brazilian population. A number of theoretical interactions are pinpointed but more pharmacokinetic studies and pharmacovigilance data are needed to ascertain their clinical significance

Friends or Foes? Cytotoxicity, HPTLC and NMR Analyses of Some Important Naturally Occurring Hydroxyanthraquinones

Hydroxyanthraquinones from plants have been used as both medicinal active ingredients and adulterants in slimming food supplements. Although sensible doses of certain natural hydroxyanthraquinones for laxative effects are generally safe in the short term, chronic intake has been related to tumorigenic, carcinogenic, and genotoxic effects. However, an increasing number of researchers are reporting the antiproliferative properties of the same ingredients in cancer cells, pointing towards a potential nutraceutical value for cancer prevention. Previous studies have evaluated anthraquinones’ anti-proliferative activity against various tumour cell lines and bioavailability in Caco-2 cells. However, there are scarce data about both their cytotoxicity in the later cell line and long-term stability. Therefore, this study will check the purity of several ‘aged’ samples using mutually complementary analytical techniques such as HPTLC and NMR assays as well as evaluate the anti-proliferative activity of the purest of these samples using the Caco-2 cell line. The chromatographic and spectroscopic analyses confirmed the long-term stability of those compounds, and their cytotoxic activity resulted in chrysazin (15 µg/mL) > catenarin (27.29 µg/mL) > rhein (49.55 µg/mL) > helminthosporin (52.91 µg/mL) > aloe-emodin (55.34 µg/mL). Our succinct review of the cytotoxicity of these compounds afforded two results: that this is the first clear report for catenarin being active in colon cancer cells and that this class of compounds needs to be better studied to clearly evaluate their benefit/risk profile in regard to both new chemo preventative nutraceuticals and anticancer therapies

Spectroscopic characterization of mitochondrial G-quadruplexes

Guanine quadruplexes (G4s) are highly polymorphic four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of the first G4 structures within mitochondrial DNA has led to a small revolution in the field. In particular, the G-rich conserved sequence block II (CSB II) can form different types of G4s that are thought to play a crucial role in replication. In this study, we decipher the most relevant G4 structures that can be formed within CSB II: RNA G4 at the RNA transcript, DNA G4 within the non-transcribed strand and DNA:RNA hybrid between the RNA transcript and the non-transcribed strand. We show that the more abundant, but unexplored, G6AG7 (37%) and G6AG8 (35%) sequences in CSB II yield more stable G4s than the less profuse G5AG7 sequence. Moreover, the existence of a guanine located 1 bp upstream promotes G4 formation. In all cases, parallel G4s are formed, but their topology changes from a less ordered to a highly ordered G4 when adding small amounts of potassium or sodium cations. Circular dichroism was used due to discriminate different conformations and topologies of nucleic acids and was complemented with gel electrophoresis and fluorescence spectroscopy studiesThis research was funded by the Gobierno de España—Ministerio de Economía y Competitividad, grant number CTQ2014-59020-R, the Xunta de Galicia, grant numbers ED431B 2019/18, ED431G 2019/03 Centro singular de investigación de Galicia accreditation 2019–2022, and Ph.D. fellowship to S.I. and the European Union (European Regional Development Fund—ERDF)S

Preservice sciencie teacher education : Inquiry into professional practical problems

We present a proposal for preservice science teacher education entitled “Aprendiendo a Enseñar Ciencias en Primaria -Learning to Teach Primary Science- (APENCIP Workbook)" (Rivero et al., 2012). We take as referents for this workbook: inquiry-based science education; teacher education by inquiry into professional practical problems; the interaction with innovative teaching practices through audiovisuals. In the first part, the students prepare a plan to teach some specific content. The discussion and analysis of their proposals will serve as an initial contrast between the different teams, and an introduction to the professional problems they will have to address during the course (the intention being to clearly relate these problems with elements of the curriculum). In the second part, each curricular element and the problems it raises will be worked on sequentially. We shall begin by analysing the first version, and then compare and contrast it with various documents. The process culminates with work on a script for reflection aimed at setting out each team's position relative to the curricular element being analysed, and the team members' responses to the problems addressed. After analysing all the curricular elements selected, a second version of the teaching plan will be elaborated. In the third part, how inquiry-based science education is actually put into practice in the classroom will be visualized from video material and analysed, and a third version of the plan will be elaborated. The final activity is to compare the three versions, and to evaluate the entire process. Our intention is to investigate the prospective teachers' progression of knowledge in this process, and the possible influence that the course, especially the use of videos, may have had on that progression. Cur

Patient and Public Involvement in Sexual and Reproductive Health: Time to Properly Integrate Citizen’s Input into Science

Evidence-based sexual and reproductive health is a global endeavor without borders. Inter-sectorial collaboration is essential for identifying and addressing gaps in evidence. Health research funders and regulators are promoting patient and public involvement in research, but there is a lack of quality tools for involving patients. Partnerships with patients are necessary to produce and promote robust, relevant and timely research. Without the active participation of women as stakeholders, not just as research subjects, the societal benefits of research cannot be realized. Creating and developing platforms and opportunities for public involvement in sexual and reproductive health research should be a key international objective. Cooperation between healthcare professionals, academic institutions and the community is essential to promote quality research and significant developments in women’s health. This cooperation will be improved when involvement of citizens in the research process becomes standard.Spanish Governmen

Towards Ratiometric Sensing of Amyloid Fibrils In Vitro

This is the peer-reviewed version of the following article: Chemistry - A European Journal 2015, 21, 3425–3434, DOI: 10.1002/chem.201406110. The final form has been published at https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201406110. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe aggregation of amyloid‐β peptide and its accumulation in the human brain has an important role in the etiology of Alzheimer’s disease. Thioflavin T has been widely used as a fluorescent marker for these amyloid aggregates. Nevertheless, its complex photophysical behavior, with strong wavelength dependencies of all its fluorescence properties, requires searching for new fluorescent probes. The use of 2‐(2′‐hydroxyphenyl)imidazo[4,5‐b]pyridine (HPIP), which shows two emission bands and a rich excited‐state behavior due to the existence of excited‐state intramolecular processes of proton transfer and charge transfer, is proposed. These properties result in a high sensitivity of HPIP fluorescence to its microenvironment and cause a large differential fluorescence enhancement of the two bands upon binding to aggregates of the amyloid‐β peptide. Based on this behavior, a very sensitive ratiometric method is established for the detection and quantification of amyloid fibrils, which can be combined with the monitoring of fluorescence anisotropy. The binding selectivity of HPIP is discussed on the basis of the apparent binding equilibrium constants of this probe to amyloid‐β (1–42) fibrils and to the nonfibrillar protein bovine serum albumin. Finally, an exhaustive comparison between HPIP and thioflavin T is presented to discuss the sensitivity and specificity of these probes to amyloid aggregates and the significant advantages of the HPIP dye for quantitative determinationsXunta de Galicia European Regional Development Fund Ministerio de Ciencia e Innovación Xunta de Galicia. Grant Numbers: CTQ2010‐21369, CTQ2010‐17835, GPC2013/052, R2014/051 RS MacDonald Charitable TrustS

The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro

<p>Abstract</p> <p>Background</p> <p>Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.</p> <p>Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods.</p> <p>Methods</p> <p>By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10^-5M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control.</p> <p>Results</p> <p>After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels.</p> <p>Conclusion</p> <p>Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.</p

Histiocytoid Sweet Syndrome associated with anorectal lymphogranuloma venereum in a patient with HIV infection

Sweet Syndrome belongs to a group of diseases known as neutrophilic dermatoses. An uncommon variant named Histiocytoid Sweet Syndrome (HSS) can be associated with a variety of conditions, including cancer, infections, drug toxicity and others. Here we present an instance of HSS in an HIV-positive patient in an infectious disease settin

Chemical abundances of late-type pre-main sequence stars in the σ\sigma-Orionis cluster

The young $\sigma$-Orionis cluster is an important location for understanding the formation and evolution of stars, brown dwarfs, and planetary-mass objects. Its metallicity, although being a fundamental parameter, has not been well determined yet. We present the first determination of the metallicity of nine young late-type stars in $\sigma$-Orionis. Using the optical and near-infrared broadband photometry available in the literature we derive the effective temperatures for these nine cluster stars, which lie in the interval 4300--6500 K (1--3 \Msuno). These parameters are employed to compute a grid of synthetic spectra based on the code MOOG and Kurucz model atmospheres. We employ a $\chi^2$-minimization procedure to derive the stellar surface gravity and atmospheric abundances of Al, Ca, Si, Fe, Ni and Li, using multi-object optical spectroscopy taken with WYFFOS+AF2 at at the William Herschel Telescope ($\lambda/\delta\lambda\sim7500$). The average metallicity of the $\sigma$-Orionis cluster is [Fe/H] $= -0.02\pm0.09\pm0.13$ (random and systematic errors). The abundances of the other elements, except lithium, seem to be consistent with solar values. Lithium abundances are in agreement with the "cosmic" $^7$Li abundance, except for two stars which show a $\log \epsilon(\mathrm{Li})$ in the range 3.6--3.7 (although almost consistent within the error bars). There are also other two stars with $\log \epsilon(\mathrm{Li})\sim 2.75$. We derived an average radial velocity of the $\sigma$-Orionis cluster of $28\pm4$km/s. The $\sigma$-Orionis metallicity is roughly solar.Comment: Accepted for publication in Astronomy and Astrophysic