The classification and application of toxic Chinese Materia Medica

Many important drugs in the Chinese materia medica (CMM) are known to be toxic, and it has long been recognized in classical Chinese medical theory that toxicity can arise directly from the components of a single CMM or may be induced by an interaction between combined CMM. Traditional Chinese Medicine presents a unique set of pharmaceutical theories that include particular methods for processing, combining and decocting, and these techniques contribute to reducing toxicity as well as enhancing efficacy. The current classification of toxic CMM drugs, traditional methods for processing toxic CMM and the prohibited use of certain combinations, is based on traditional experience and ancient texts and monographs, but accumulating evidence increasingly supports their use to eliminate or reduce toxicity. Modern methods are now being used to evaluate the safety of CMM; however, a new system for describing the toxicity of Chinese herbal medicines may need to be established to take into account those herbs whose toxicity is delayed or otherwise hidden, and which have not been incorporated into the traditional classification. This review explains the existing classification and justifies it where appropriate, using experimental results often originally published in Chinese and previously not available outside China.

Direct anthelmintic effects of condensed tannins from diverse plant sources against Ascaris suum

Ascaris suum is one of the most prevalent nematode parasites in pigs and causes significant economic losses, and also serves as a good model for A. lumbricoides, the large roundworm of humans that is ubiquitous in developing countries and causes malnutrition, stunted growth and compromises immunity to other pathogens. New treatment options for Ascaris infections are urgently needed, to reduce reliance on the limited number of synthetic anthelmintic drugs. In areas where Ascaris infections are common, ethno-pharmacological practices such as treatment with natural plant extracts are still widely employed. However, scientific validation of these practices and identification of the active compounds are lacking, although observed effects are often ascribed to plant secondary metabolites such as tannins. Here, we extracted, purified and characterised a wide range of condensed tannins from diverse plant sources and investigated anthelmintic effects against A. suum in vitro. We show that condensed tannins can have potent, direct anthelmintic effects against A. suum, as evidenced by reduced migratory ability of newly hatched third-stage larvae and reduced motility and survival of fourth-stage larvae recovered from pigs. Transmission electron microscopy showed that CT caused significant damage to the cuticle and digestive tissues of the larvae. Furthermore, we provide evidence that the strength of the anthelmintic effect is related to the polymer size of the tannin molecule. Moreover, the identity of the monomeric structural units of tannin polymers may also have an influence as gallocatechin and epigallocatechin monomers exerted significant anthelmintic activity whereas catechin and epicatechin monomers did not. Therefore, our results clearly document direct anthelmintic effects of condensed tannins against Ascaris and encourage further in vivo investigation to determine optimal strategies for the use of these plant compounds for the prevention and/or treatment of ascariosis.

Solution calorimetry as a tool for investigating drug interaction with intestinal fluid

Solution calorimetry offers a reproducible technique for measuring the enthalpy of solution (ΔsolH) of a solute dissolving into a solvent. The ΔsolH of two solutes, propranolol HCl and mannitol were determined in simulated intestinal fluid (SIF) solutions designed to model the fed and fasted states within the gut, and in Hanks’ balanced salt solution (HBSS) of varying pH. The bile salt and lipid within the SIF solutions formed mixed micelles. Both solutes exhibited endothermic reactions in all solvents. The ΔsolH for propranolol HCl in the SIF solutions differed from those in the HBSS and was lower in the fed state than the fasted state SIF solution, revealing an interaction between propranolol and the micellar phase in both SIF solutions. In contrast, for mannitol the ΔsolH was constant in all solutions indicating minimal interaction between mannitol and the micellar phases of the SIF solutions. In this study, solution calorimetry proved to be a simple method for measuring the enthalpy associated with the dissolution of model drugs in complex biological media such as SIF solutions. In addition, the derived power–time curves allowed the time taken for the powdered solutes to form solutions to be estimated.

Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe

In addition to their expected effects on lipid profile, lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation. Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols. Although it is known that an additional reduction of low-density lipoprotein cholesterol (LDL-C) levels can be induced by the combination of ezetimibe with statins, it is not known if this can enhance some pleiotropic effects, which may be useful in slowing the atherosclerotic process. This study assessed the effects of simvastatin and ezetimibe, in monotherapy or in combination, on markers of endothelial function and insulin sensitivity. Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were randomly allocated to 2 groups receiving either ezetimibe (10 mg/d) or simvastatin (20 mg/d) for 12 weeks, after which the drugs were combined for both groups for an additional 12-week period. Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy. Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated. As expected, both groups receiving drugs in isolation significantly reduced total cholesterol, LDL-C, apolipoprotein B, and triglyceride levels; and additional reductions were found after the combination period (P <.05). After 12 weeks of monotherapy, plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group. No change in homeostasis model assessment of insulin resistance index, area under the curve of insulin, and adiponectin levels was observed tiller either the monotherapies or the combined therapy. However, simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes. Our findings support claims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia. Alternatively, a deleterious effect of ezetimibe on the endothelial function is suggested, considering the increase in intravascular cellular adhesion molecule I and E-selectin levels. Simvastatin and ezetimibe, in isolation or in combination, do not interfere with insulin sensitivity. (C) 2010 Elsevier Inc. All rights reserved.

Hydrogen peroxide is a novel mediator of inflammatory hyperalgesia, acting via transient receptor potential vanilloid 1-dependent and independent mechanisms

Inflammatory diseases associated with pain are often difficult to treat in the clinic due to insufficient understanding of the nociceptive pathways involved. Recently, there has been considerable interest in the role of reactive oxygen species (ROS) in inflammatory disease, but little is known of the role of hydrogen peroxide (H(2)O(2)) in hyperalgesia. In the present study, intraplantar injection of H(2)O(2)-induced a significant dose- and time-dependent mechanical and thermal hyperalgesia in the mouse hind paw, with increased c-fos activity observed in the dorsal horn of the spinal cord. H(2)O(2) also induced significant nociceptive behavior Such as increased paw licking and decreased body liftings. H(2)O(2) levels were significantly raised in the carrageenan-induced hind paw inflammation model, showing that this ROS is produced endogenously in a model of inflammation. Moreover, superoxide dismutase and catalase significantly reduced carrageenan-induced mechanical and thermal hyperalgesia, providing evidence of a functionally significant endogenous role. Thermal, but not mechanical, hyperalgesia in response to H(2)O(2) (i.pl.) Was longer lasting in TRPV1 wild type mice compared to TRPV1 knockouts. It is unlikely that downstream lipid peroxidation was increased by H(2)O(2). In conclusion, we demonstrate a notable effect of H(2)O(2) in mediating inflammatory hyperalgesia, thus highlighting H(2)O(2) removal as a novel therapeutic target for anti-hyperalgesic drugs in the clinic. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Fragment-based and classical quantitative structure-activity relationships for a series of hydrazides as antituberculosis agents

Worldwide, tuberculosis (TB) is the leading cause of death among curable infectious diseases. Multidrug-resistant Mycobacterium tuberculosis is an emerging problem of great importance to public health, and there is an urgent need for new anti-TB drugs. In the present work, classical 2D quantitative structure-activity relationships (QSAR) and hologram QSAR (HQSAR) studies were performed on a training set of 91 isoniazid derivatives. Significant statistical models (classical QSAR, q(2) = 0.68 and r(2) = 0.72; HQSAR, q(2) = 0.63 and r(2) = 0.86) were obtained, indicating their consistency for untested compounds. The models were then used to evaluate an external test set containing 24 compounds which were not included in the training set, and the predicted values were in good agreement with the experimental results (HQSAR, r(pred)(2) = 0.87; classical QSAR, r(pred)(2) = 0.75).

Folkmusikundervisningen på fiol och gitarr och dess historiska rötter

How folk musicians of today learn to play their instruments is an over-all question in this article. One violin lesson and one guitar lesson have been observed at Framnäs folk high school. Three research questions were formulated. What do the two lessons have in common? What are the differences? How could the folk music education of today be related to the Swedish fiddler movement in the 1920s and other folk music traditions? Theoretically, the interpretation of the results was based on the mimesis theory of Ricoeur. Two teachers and three students participated in the study. The results showed that the lessons were structured in a similar way and dominated by master apprenticeship teaching. The violin teacher showed a more respectful attitude towards the tradition compared to the guitar teacher. Great parts of the manifest ideology of the fiddler movement seems to have become concealed into a latent or frozen ideology in the formal folk music education of today. There seems to be no big differences between learning the music by way of visiting an older fiddler hundred years ago compared to the study of music today at a formal institution.

Manifesta och latenta ideologier om lärande inom svensk spelmansrörelse under 1920-talet

The purpose of this article was to illuminate existing educational ideologies in the Swedish fiddler movement (Spelmansrörelsen) 1923-1927. This period was characterized by the organization and to some extent institutionalization of Swedish folk music. Furthermore, the purpose was to discuss the results in relation to the folk music education of today. The empirical data was taken from the journal Hembygden, which was a magazine for scholars, enthusiasts and practitioners of folk music. Theoretically, the study was based on a concept of ideology developed by Sven-Eric Liedman: in every time there are two basic forms of identifiable ideology, manifest and latent. From the empirical material as a whole (around 900 articles), a selection was made to find articles dealing with aspects of learning among the fiddlers (33 articles). After content analysis the following themes were generated: Fiddlers’ repertoire, Fiddlers’ masters, Rooms for learning, Learning formation. The writers in Hembygden often emphasized the autodidactic aspects of learning and especially the importance of learning by ear. This manifest ideology of authenticity presumed that learning directly from another fiddler by playing together was to prefer to formal schooling. In spite of a tendency towards more ensemble playing, the folk music education of today in Sweden is characterized by a similar retrospective ideology as in the 1920s.

Audiovisuella loopar och kollektiv live-looping

 Loop-teknik i solistiska sammanhang är en idag väletablerad musicerande form dock är möjligheterna att använda tekniken i ensembleform ett mer eller mindre oprövat fält. I projektet “Audiovisuella loopar” som genomförts vid Högskolan Dalarna presenteras ett system för kollektiv livelooping där upp till fyra personer loop-musicerar tillsammans och där loopandet samtidigt kan spelas in och spelas upp som videoklipp. Tekniken har visat sig ha en stark kreativ potential. Med enbart en kort instruktion så startar en kollektiv process där den omedelbara feedbacken ger ett “fl ow” som lockar fram skaparglädjen hos musikanterna. Dessa erfarenheter pekar på spännande möjligheter att använda tekniken i musikundervisning och musikterapi.

Avaliação do impacto de uma intervenção restritiva do emprego de antimicrobianos para o controle de infecção hospitalar em pacientes internados em Unidade de Terapia Intensva

Medidas restritivas de controle de antimicrobianos têm sido propostas para controlar surtos epidêmicos de infecção por germes multirresistentes em hospitais, mas são escassas as publicações a respeito de sua eficácia. Em um estudo quaseexperimental com controles históricos, avaliou-se a efetividade de uma intervenção restritiva ao uso de antimicrobianos para controlar a emergência de germes multirresistentes em uma unidade de cuidados intensivos (UTI) de um hospital geral. Os Serviços de Controle de Infecção e Comissão de Medicamentos restringiu o uso de drogas antimicrobianas em pacientes hospitalizados na UTI a não mais que dois agentes simultaneamente, exceto em casos autorizados por aqueles serviços. A incidência de eventos clínicos e bacteriológicos foi comparada entre o ano que precedeu a intervenção e o ano que a seguiu. No total, 225 pacientes com idade igual ou maior de 15 anos , com infecção, internados na UTI por pelo menos 48 horas, foram estudados no ano precedente a intervenção e 263 no ano seguinte a ela. No ano seguinte à intervenção, um percentual menor de pacientes foi tratado simultaneamente com mais de dois antimicrobianos, mas não houve modificação no número total de antimicrobianos prescritos, na duração e no custo do tratamento. Mortalidade e tempo de internação foram similares nos dois períodos de observação. O número de culturas positivas aumentou depois da intervenção, tanto para germes Gram positivos, quanto para germes Gram negativos, principalmente devido ao aumento do número de isolados do trato respiratório. A maioria dos isolados foi Staphylococcus aureus dentre os Gram positivos e Acinetobacter sp dentre os germes Gram negativos. No ano seguinte à intervenção, a sensibilidade dos microorganismos Gram negativos para carbenicilina, ceftazidima e ceftriaxona aumentou, e para o imipenem diminuiu. A ausência de resposta dessa intervenção sobre desfechos clínicos pode ser em conseqüência da insuficiente aderência ou a sua relativa ineficácia. A melhora da sensibilidade microbiana de alguns germes, semaumento de custos ou a incidência de efeitos adversos, encoraja o uso de protocolos similares de restrição de drogas antimicrobianas para reduzir a taxa de resistência bacteriana na UTI.

Propondo um modelo para acompanhamento do processo Composicional

Silva, Alexandre Reche. Propondo um modelo para acompanhamento do processo Composicional. Ictus - Periódico do PPGMUS/UFBA, v. 11, n. 1, p. 11-28, Salvador, BA, 2010.

Sociabilidades e hedonismos: etnografia entre jovens usuários de substâncias psicoativas sintéticas Fortaleza Ceará

This dissertation shows a comparison between practices related to the body, to identities and to the health of young drug takers of synthetic and manipulated psychoactive substances living in Fortaleza. Through ethnographic accompaniment of parties and two social nets of young people I was able to verify the differences and similarities that make these addicted singular and plural in their notion of ethos and world vision. Notions of being hippie/alternative and being punk are present between these nets. Because their use and circulation are developed in environments usually distinct, it is possible to trace singular aspects between the nets and its actions. In parallel, on the attempt to build a triangulated data, I had information related to youth and drugs in local media and in governmental institutions bound to health mental and city security policies. With this junction of data I present a perspective to questions evolving formal and informal important controls to the conduction of their lives and identities. I present this as a sequel to well developed studies in Brasil about youth in interface to drug use, although still not very explored in the state of Ceará.

Otimização evalidação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD

Tuberculosis is a serious disease, but curable in practically 100% of new cases, since complied the principles of modern chemotherapy. Isoniazid (ISN), Rifampicin (RIF), Pyrazinamide (PYR) and Chloride Ethambutol (ETA) are considered first line drugs in the treatment of tuberculosis, by combining the highest level of efficiency with acceptable degree of toxicity. Concerning USP 33 - NF28 (2010) the chromatography analysis to 3 of 4 drugs (ISN, PYR and RIF) last in average 15 minutes and 10 minutes more to obtain the 4th drug (ETA) using a column and mobile phase mixture different, becoming its industrial application unfavorable. Thus, many studies have being carried out to minimize this problem. An alternative would use the UFLC, which is based with the same principles of HPLC, however it uses stationary phases with particles smaller than 2 μm. Therefore, this study goals to develop and validate new analytical methods to determine simultaneously the drugs by HPLC/DAD and UFLC/DAD. For this, a analytical screening was carried out, which verified that is necessary a gradient of mobile phase system A (acetate buffer:methanol 94:6 v/v) and B (acetate buffer:acetonitrile 55:45 v/v). Furthermore, to the development and optimization of the method in HPLC and UFLC, with achievement of the values of system suitability into the criteria limits required for both techniques, the validations have began. Standard solutions and tablets test solutions were prepared and injected into HPLC and UFLC, containing 0.008 mg/mL ISN, 0.043 mg/mL PYR, 0.030 mg.mL-1 ETA and 0.016 mg/mL RIF. The validation of analytical methods for HPLC and UFLC was carried out with the determination of specificity/selectivity, analytical curve, linearity, precision, limits of detection and quantification, accuracy and robustness. The methods were adequate for determination of 4 drugs separately without interfered with the others. Precise, due to the fact of the methods demonstrated since with the days variation, besides the repeatability, the values were into the level required by the regular agency. Linear (R> 0,99), once the methods were capable to demonstrate results directly proportional to the concentration of the analyte sample, within of specified range. Accurate, once the methods were capable to present values of variation coefficient and recovery percentage into the required limits (98 to 102%). The methods showed LOD and LOQ very low showing the high sensitivity of the methods for the four drugs. The robustness of the methods were evaluate, facing the temperature and flow changes, where they showed robustness just with the preview conditions established of temperature and flow, abrupt changes may influence with the results of methods

The Beatles: ensaio sobre a ética do amor

The thesis intends to discuss the ethics by the way of love. So, it uses as a mention the musical work and the set of attitudes of the group that changed the way of thinking across the 20th Century mass-comm, entering a new way of thinking about the World: The Beatles. Analyzing the lyrics and the writing of the songs was searched the comprehension of he intrinsic love message at the Ethics it expresses. At the musical art of The Beatles political messages had been announced in a time that the World sought a Ethic way beyond the several declared war and the Cold War. Taking the Edgar Morin works as a base, O método 6, Ética (2005), it sought to understand the idea who permeates the human relations: the good, the possible, the necessary. Another works used as a cognitive base were Meus demônios (2003), Cultura de massas no Século XX: neurose (2005), Cultura de massas no Século XX (2006), The Beatles Anthology (2000) and Many years from now (2000). Holding the Ethics idea showed by Morin were established imaginary lines that perpass the behavior of the group known in the entire World understood till nowadays as tolerance, comprehension, peace, love and endurance messengers. The Beatles operate during the sixties a musical reborn, which allowed to the people the discussion and the reflexion about the World and the human being new behavior,endurance but acting with tolerance. Permeating the basic study, we find the Beatles way, the group origin, the fast walk till success, the spiritual choice, who guide their behavior and the end of the band. The music used as a masscomp instrument passes by the condition of a simple way of communicating. It deeply action feeds feelings, allows transcendence and is showed as target of human being transformation. The Ethics in music passes by the ideological barriers and becomes to comprehension with a clear synthony for the man, cause the polyphony and the new musical order establish the messages worldwide

Lévi-Strauss Mitológicas: Mito e música entre o largo e o prestíssimo

This study was elaborated based on our research of the work Mithologiques by the anthropologist Claude Lévi-Strauss (1908-2009), which affirms that languages, indigenous myths and music are related. He proposes that the understanding of myths occurs in a similar manner as with an orchestral score. In the course of his tetralogy we investigated the musical terms used in the analysis and in the division of the chapters, especially in the first volume of his work. Several compositional procedures and forms are named. Composers in pairs are categorized: Sebastian Bach for the code, Ludwig van Beethoven for the message, and Richard Wagner for the myths. In this deduction, we structured in parts: theme and variations, sonata and fugue with the aforementioned composers. Within the greatness of anthropological study, from among over 800 myths, we selected the first five of the indigenous tribe Bororo to discuss within the Theme and Variation segment. In the Sonata part there are two myths with the same theme: The wife of the jaguar which relates to the compositional structure, and four myths about The origin of women. Finally, in the segment related to the Fugue, we collected four myths that address The shortness of life. Honoring the many terms expressed in opposition, contrast, or symmetry under consideration in Levi-Strauss work, we entitled this thesis emphasizing the migration between the tempos Largo and Prestíssimo as these are oppositional presentations in music. Fifteen musical myths accompany the work supported by selected narratives. In light of this we questioned, we questioned: how are incest, murder and other events part of a society that elevates nature as an extension of life itself? And how did Lévi-Strauss think that anthropology harmonized with music? In the preparation of this study, philosophers like Peter Sloterdijk discuss the circular territory of Mythology