Pharmacokinetics-based elucidation on disparity in clinical effectiveness between varieties of Zhi Zhu Wan, a traditional Chinese medical formula

AIM: Zhi Zhu Wan (ZZW) is a classical Chinese medical formulation used for the treatment of functional dyspepsia that attributed to Spleen-deficiency Syndrome. ZZW contains Atractylodes Rhizome and Fructus Citrus Immaturus, the later originates from both Citrus aurantium L. (BZZW) and Citrus sinensis Osbeck (RZZW). The present study is designed to elucidate disparities in the clinical efficacy of two ZZW varieties based on the pharmacokinetics of naringenin and hesperetin. MEHTOD: After oral administration of ZZWs, blood sample was collected from healthy volunteers at designed time points. Naringenin and hesperetin were detected in plasma by RP-HPLC, pharmacokinetic parameters were processed using mode-independent methods with WINNONLIN. RESULTS: After oral administration of BZZW, both naringenin and hesperetin were detected in plasma, and demonstrated similar pharmacokinetic parameters. Ka was 0.384+/-0.165 and 0.401+/-0.159, T(1/2(ke))(h) was 5.491+/-3.926 and 5.824+/-3.067, the AUC (mg/Lh) was 34.886+/-22.199 and 39.407+/-19.535 for naringenin and hesperetin, respectively. However, in the case of RZZW, only hesperetin was found in plasma, but the pharmacokinetic properties for hesperetin in RZZW was different from that in BZZW. T(max) for hesperetin in RZZW is about 8.515h, and its C(max) is much larger than that of BZZW. Moreover, it was eliminated slowly as it possessed a much larger AUC value. CONCLUSION: The distinct therapeutic orientations of the Chinese medical formula ZZWs with different Fructus Citrus Immaturus could be elucidated based on the pharmacokinetic parameters of constituents after oral administration.

Invisível, sutil e palpável: Shén神 nas dimensões diagnose e terapêutica da Racionalidade Médica Chinesa

Shén神 é uma categoria chinesa de sentidos múltiplos e abrangentes, presente na filosofia e na medicina. Direcionaria o processo de surgimento de todas as coisas no universo, como uma força configuradora. Na pessoa, atuaria sobre todos os estágios de desenvolvimento corporal e pessoal, do nascimento até a morte, caracterizando-a como pessoa única no universo. Teve seus sentidos reduzidos pela Medicina Chinesa Contemporânea, hegemônica na China e instituída após a Revolução comunista. Costuma ser traduzida como Espírito ou Mente no ocidente e é indissociável do corpo físico. Está presente em todas as dimensões da Racionalidade Médica Chinesa, observando-se na literatura convencional, grande abrangência de sentidos quando tratada pela dimensão cosmológica, porém costuma ser reduzida aos sentidos de mente, segundo definições ocidentais, quando tratada pelas dimensões de ordem prática: diagnose e terapêutica. O desafio desta tese foi elaborar uma síntese entre os sentidos cosmológicos e as dimensões práticas. Para isso, procedeu a uma pesquisa teórico conceitual, a partir de leituras e interpretações ocidentais de textos clássicos chineses, elaboradas por autores com critério filológico apurado. Observou-se que os sentidos de Shén神 se fazem presentes em ressonância recíproca com diversas outras categorias da Doutrina Médica Chinesa, como Qì氣, Xuè血, Jīng精, Qìng情, Emoções, Zàng-Fǔ贓腑, Órgãos e Vísceras, entre outras. Cada uma delas com atribuições específicas, que, porém, se reorganizariam em ressonância com as outras. Assim, ao proceder a diagnose e instituir uma terapêutica direcionada a cada uma dessas categorias, o terapeuta estaria interferindo diretamente sobre Shén神 e vice versa. Shén神 poderia assumir sentidos diversos, numa visão de totalidade. A partir daí, percebeu-se a necessidade de estudar essas categorias em ressonância com Shén神, além da própria diagnose e da terapêutica, à luz das premissas do Pensamento Chinês. Categorias como processo, totalidade, potencial ou eficácia ajudaram a apreender, não só os amplos sentidos de Shén神, e suas ressonâncias, mas também as peculiaridades do ato de diagnosticar e tratar na Racionalidade Médica Chinesa. Foi, então, elaborada uma visão da Diagnose e da Terapêutica capaz de contemplar Shén神 e suas ressonâncias, que se espera poder utilizar nos serviços de saúde, contribuindo para estratégias de promoção da saúde, estreitamento de vínculos terapeuta-paciente e maior eficácia terapêutica na prática da Racionalidade Médica Chinesa.

Shén神: categoria estruturante da racionalidade médica chinesa

A Medicina chinesa divulgada no ocidente tem sido estudada de forma fragmentada entre as suas diferentes formas de expressão desenvolvidas ao longo da história do Pensamento Médico Chinês. Nesse sentido o texto destaca três possíveis vertentes desta expressão, que denomina: Medicina Clássica Chinesa (GÜ DÀI ZHÖNG YÏ), Medicina Tradicional Chinesa (ZHÖNG YÏ) e Medicina Chinesa Contemporânea (DÄNG DÀI ZHÖNG YÏ). A primeira expressa as formulações nas obras clássicas surgidas a partir do período formativo da Medicina Chinesa, na Dinastia HÀN (206 a.C. a 221 d.C.). A segunda como corpo teórico e prático de conhecimento que, se disseminou no Oriente em geral e, posteriormente, no Ocidente como uma continuidade da Medicina Clássica Chinesa (GÜ DÀI ZHÖNG YÏ). A terceira refere-se à corrente hegemônica, hoje, na República Popular da China e mais tarde nos meios ocidentais. O objetivo do trabalho é investigar como tem sido divulgada no Ocidente por diferentes autores representantes de cada uma dessas vertentes a categoria SHÉN , frequentemente traduzida no Ocidente como Mente ou Espírito. Para tal, leva-se em conta a notoriedade acadêmica, a familiaridade com o idioma chinês, os pressupostos adotados, a história pessoal de cada um desses autores, entendidas como determinantes para suas apreensões de sentidos e significados da categoria SHÉN e, consequentemente, para os sentidos que assumem sua divulgação no Ocidente. Entendendo a Medicina Chinesa como uma Racionalidade Médica, conforme definição de Madel Therezinha Luz composta de seis dimensões: cosmologia, doutrina médica, dinâmica vital, morfologia, diagnose e terapêutica, o trabalho investiga do ponto de vista teórico-conceitual, amparado na Filosofia e Antropologia Médicas como a categoria SHÉN relaciona-se a cada uma das dimensões da Racionalidade Médica Chinesa. SHÉN relaciona-se com diversas outras categorias do Pensamento Médico e Filosófico Chinês, não sendo possível conceituá-lo sem mencionar categorias, tais como DÀO, YÏN YÁNG , TIÄN (Céu), RÉN (Homem), DÌ (Terra), MING (Destino), WÜ XÍNG (Cinco Fases), SÄN BÄO (Três Tesouros), GUÏ e LING Manifesta-se de diferentes formas através de sua relação com os ZÁNG FÜ (Órgãos e Vísceras), interferindo no funcionamento orgânico-visceral, nos aspectos de personalidade, nas emoções, entendidas como uma totalidade corpo-mente-espírito no Pensamento Médico chinês. SHÉN está presente em todas as dimensões da Racionalidade Médica Chinesa, diferindo o grau de importância dado por autores representantes de cada uma das três vertentes da Medicina Chinesa. Autores representantes da Medicina Clássica Chinesa (GÜ DÀI ZHÖNG YÏ) E DA Medicina Tradicional Chinesa (ZHÖNG YÏ) tendem a valorizar sua presença em todas as dimensões. Autores representantes da Medicina Chinesa Contemporânea (DÄNG DÀI ZHÖNG YÏ) tendem a valorizar a participação de SHÉN na dimensão Diagnose. Percebe-se, portanto, que SHÉN ao participar de todas as dimensões ganha o importante papel de estruturante da Racionalidade Médica Chinesa, não podendo, portanto, ser negligenciado nos estudos da Medicina Chinesa, sob pena de comprometer a importância da Racionalidade Médica.

Da homeopatia à medicina chinesa: a trajetória dos pontos de Weihe

Esta dissertação de mestrado é um estudo de natureza sócio-histórico que constrói a trajetória do sistema de Pontos de Weihe, um sistema médico minoritário, cuja origem encontra-se na Homeopatia, porém, seu desenvolvimento o levou de encontro a Acupuntura. Esse estudo tem como objetivo inserir seu objeto de análise na discussão de questões pertinentes ao desenvolvimento conceitual da Homeopatia. Sendo um sistema médico complexo, a racionalidade médica homeopática possui seis dimensões, a saber: morfologia (ou anatomia), dinâmica vital (ou fisiologia), doutrina, diagnóstico, terapêutica e cosmologia. Destas, a dimensão da morfologia e o exame físico da dimensão diagnóstica são compartilhados com a biomedicina, enquanto, as demais, baseiam-se no para digma vitalista, ainda que nem todas tenham sido desenvolvidas conceitualmente e encontrem-se apenas implícitas. Tal situação conferiu à Homeopatia a denominação de racionalidade médica híbrida. Este estudo parte do pressuposto que a Homeopatia é um sistema médico ainda em construção e que deve caminhar para o desenvolvimento conceitual de suas dimensões tendo como elemento norteador sua natureza vitalista. Portanto, espera-se que, ao resgatar-se a história do sistema de Pontos de Weihe, crie-se a possibilidade de repensar a morfologia homeopática, de forma que, ela possa expressar o movimento da força vital na saúde e no adoecimento. Espera-se, também, que, ao revelar uma colaboração possível da Medicina Chinesa, racionalidade médica que compartilha com a Homeopatia o paradigma vitalista, abra-se a possibilidade de repensar a base conceitual da dinâmica vital homeopática. Buscar uma sistematização da dinâmica vital, ao mesmo tempo, compatível com o paradigma vitalista e agregadora dos elementos centrais do pensamento homeopático é passo importante no desenvolvimento desta racionalidade, pois, permite que se parta de um mesmo esquema conceitual, e portanto, de uma mesma base paradigmática, em direção a criação de outros sistemas diagnósticos que concorram com o diagnóstico medicamentoso e o confirmem. Utilizou-se, como fontes primárias e secundárias para a construção da trajetória dos Pontos de Weihe, artigos e livros de Weihe e seus discípulos que, sofreram uma tradução livre do idioma original, o alemão, para o português. O substrato conceitual empregado foram as reflexões de George Canguilhem a respeito da história que se desvia dos obstáculos que impedem sua linearidade, comprometendo a compreensão das descobertas científicas como determinadas por suas condições de aparecimento, transfigurando-as no aparecimento puro daquilo que deveria ser.

Transmitting Chinese Medicine: Changing Perceptions of Body, Pathology, and Treatment in Late Imperial China

Historians of Chinese medicine acknowledge the plurality of Chinese medicine along both synchronic and diachronic dimensions. Yet, there remains a tendency to think of tradition as being defined by some unchanging features. The Chinese medical body is a case in point. This is assumed to have been formalised by the late Han dynasty around a system of internal organs, conduits, collaterals, and associated body structures. Although criticism was voiced from time to time, this body and the micro/ macrocosmic cosmological resonances that underpin it are seen to persist until the present day. I challenge this view by attending to attempts by physicians in China and Japan in the period from the mid 16th to the late 18th century to reimagine this body. Working within the domain of cold damage therapeutics and combining philological scholarship, empirical observations, and new hermeneutic strategies these physicians worked their way towards a new territorial understanding of the body and of medicine as warfare that required an intimate familiarity with the body’s topography. In late imperial China this new view of the body and medicine was gradually re-absorbed into the mainstream. In Japan, however, it led to a break with this orthodoxy that in the Republican era became influential in China once more. I argue that attending further to the innovations of this period—commonly portrayed as one of decline—from a transnational perspective may help to go beyond the modern insistence to frame East Asian medicines as traditional.

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.

Huntington's like conditions in China, A review of published Chinese cases

Background: Knowledge about HD in China is lacking in the international literature. We have therefore analyzed the Chinese literature to thoroughly explore the clinical characteristics of Huntington disease in China. Methods: A computer-based online search of China National Knowledge Infrastructure was performed to review case reports concerning HD published between January 1980 and April of 2011, and the clinical characteristics were extracted. Results: A total of 92 studies involving 279 patients (157 males and 122 females) were collected, 82.0% of which were from provinces of North China. Most of the cases (97.8%) had a family history of HD, and paternal inheritance (65.5%) was higher than maternal inheritance (34.5%). Onset age was 35.8 (± 11.8) years, death occurred with 45.6 (± 13.5) years after a course of 11.6 (± 5.6) years. Involuntary movements were the most frequent reported presentation (found in 52.3%, including 64.4% in the entire body, 19.8% in the upper limbs, and 13.7% in the head and face). Psychiatric symptoms at onset were reported in 16.1%, and cognitive impairment in 1.8%. With disease progression, 99.6% of patients had abnormal movements, 67.9% cognitive impairment, and 35.0% suffered psychiatric symptoms. Of the reported patients, only 22 underwent IT15 gene testing with positive results. Conclusion: HD is a well-reported entity in Chinese medical literature, however, only a small number of instances have been proven by molecular diagnosis. Most of the features resemble what is known in other countries. The highly predominant motor presentation, and the higher male prevalence as well as the apparent concentration in Northern China may be due to observational bias. There is therefore a need to prospectively examine cohorts of patients with appropriate comprehensive assessment tools including genetic testing.

Analysis of the constituents in the rat plasma after oral administration of Yin Chen Hao Tang by UPLC/Q-TOF-MS/MS

A UPLC/Q-TOF-MS/MS method for analyzing the constituents in rat plasma after oral administration of Yin Chen Hao Tang (YCHT), a traditional Chinese medical formula, has been established. The UPLC/MS fingerprints of the samples were established first in vitro and in vivo, with 45 compounds in YCHT and 21 compounds in rat plasma after oral administration of YCHT were detected. Of the 45 detected compounds in vitro, 30 were identified, and all of the 21 compounds detected in rat plasma were identified either by comparing the retention time and mass spectrometry data with that of reference compounds or by mass spectrometry analysis and retrieving the reference literatures. Of the identified 21 compounds in rat plasma, 19 were the original form of compounds absorbed from the 45 detected compounds in vitro, 2 were the metabolites of the compounds existed in YCHT. It is concluded that a rapid and validated method has been developed based on UPLC-MS/MS, which shows high sensitivity and resolution that is more suitable for identifying the bioactive constituents in plasma after oral administration of Chinese herbal medicines, and provides helpful chemical information for further pharmacology and active mechanism research on the Chinese medical formula.

Comparative study on the protective effects of Yinchenhao Decoction against liver injury induced by alpha-naphthylisothiocyanate and carbon tetrachloride

OBJECTIVE: To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine. METHODS: The liver injury in the model rat was induced by alpha-naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl(4) ) respectively, and the effects of Yinchenhao Decoction (, YCHD), a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic, on the two liver injury models were evaluated by analyzing the serum level of alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP), malondialchehyche (MDA), total bilirubin (T-BIL), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) as well as the ratio of liver weight to body weight. The experimental data were analyzed by principal component analytical method of pattern recognition. RESULTS: The ratio of liver weight to body weight was significantly elevated in the ANIT and CCl(4) groups when compared with that in the normal control (P<0.01). The contents of ALT and T-BIL were significantly higher in the ANIT group than in the normal control (P<0.05,P<0.01), and the levels of AST, ALT and ALP were significantly elevated in CCl(4) group relative to those in the normal control P<0.01). In the YCHD group, the increase in AST, ALT and ALP levels was significantly reduced (P<0.05, P<0.01), but with no significant increase in serum T-BIL. In the CCl(4) intoxicated group, the MDA content was significantly increased and SOD, GSH-PX activities decreased significantly compared with those in the normal control group, respectively (P<0.01). The increase in MDA induced by CCl(4) was significantly reduced by YCHD P<0.05). CONCLUSION: YCHD showed significant effects on preventing liver injury progression induced by CCl(4), and the closest or most suitable animal model for damp-heat jaundice syndrome may be the one induced by CCl(4).

Findings report on the endemic fluorosis in the lower reaches of Xiaoqing river [小清河下游地区地方性氟中毒调查报告]

Objective: To find out the present prevalent situation of the endemic fluorosis in the lower reaches of Xiao Qing River , and to look for an effective way to altering sources to lower fluoride level. Methods: To determine the water fluoride content in the drinking water sources and investigate the basic condition of the water sources (type of the water sources, the depth of well, etc) in the three towns of this area . Make a sampling survey of the children aged from 8 to 12 about the dent al fluoro sis and determine the urine fluoride, and the skeletal fluorosis among the crowd over 16 y ears of age. Results: The survey shows that the lower reaches of Xiaoqing river belong to the drinking water type of endemic fluorosis caused by drinking deep well water. In this area, 65.71% of the water sources contain high level of fluoride, 57.51% of the children suffer from dental fluorosis, 0.58% of the crowd over 16 years of age suffer from skeletal fluorosis. High water fluoride rate is related with the depth of the well. If the well is over 500 metres deep, the fluoride content rate is clearly low. Conclusions: In this area, there are still some water sources which contain normal level of fluoride. By increasing the depth of the well down to 500 metres, the problem of high fluoride in water might be solved.

Comparison of ocular modulation transfer function determined by a ray-tracing aberrometer and a double-pass system in early cataract patients

BACKGROUND: The evaluation of retinal image quality in cataract eyes has gained importance and the clinical modulation transfer functions (MTF) can obtained by aberrometer and double pass (DP) system. This study aimed to compare MTF derived from a ray tracing aberrometer and a DP system in early cataractous and normal eyes. METHODS: There were 128 subjects with 61 control eyes and 67 eyes with early cataract defined according to the Lens Opacities Classification System III. A laser ray-tracing wavefront aberrometer (iTrace) and a double pass (DP) system (OQAS) assessed ocular MTF for 6.0 mm pupil diameters following dilation. Areas under the MTF (AUMTF) and their correlations were analyzed. Stepwise multiple regression analysis assessed factors affecting the differences between iTrace- and OQAS-derived AUMTF for the early cataract group. RESULTS: For both early cataract and control groups, iTrace-derived MTFs were higher than OQAS-derived MTFs across a range of spatial frequencies (P < 0.01). No significant difference between the two groups occurred for iTrace-derived AUMTF, but the early cataract group had significantly smaller OQAS-derived AUMTF than did the control group (P < 0.01). AUMTF determined from both the techniques demonstrated significant correlations with nuclear opacities, higher-order aberrations (HOAs), visual acuity, and contrast sensitivity functions, while the OQAS-derived AUMTF also demonstrated significant correlations with age and cortical opacity grade. The factors significantly affecting the difference between iTrace and OQAS AUMTF were root-mean-squared HOAs (standardized beta coefficient = -0.63, P < 0.01) and age (standardized beta coefficient = 0.26, P < 0.01). CONCLUSIONS: MTFs determined from a iTrace and a DP system (OQAS) differ significantly in early cataractous and normal subjects. Correlations with visual performance were higher for the DP system. OQAS-derived MTF may be useful as an indicator of visual performance in early cataract eyes.

Estratégias terapêuticas no tratamento da dor crônica: uma genealogia da Clínica da Dor

O objetivo desse trabalho é analisar a singularidade das estratégias terapêuticas introduzidas pelo modelo das Clínicas da Dor, através de um estudo genealógico desse projeto terapêutico e sua contextualização no âmbito da racionalidade científica moderna. Mais especificamente, pretende-se analisar as transformações na racionalidade médica que permitiram, sucessivamente, a apreensão da dor pelo discurso médico, a concepção da dor como uma doença e a construção e a consolidação do modelo terapêutico das Clínicas da Dor. Para tal, inicialmente, analisamos o modelo terapêutico desenvolvido pelo médico anestesista John Bonica, idealizador do modelo das Clínicas da Dor, destacando as ferramentas conceituais que possibilitaram a compreensão da dor crônica como doença e como fenômeno biopsicossocial. Num segundo momento, realizamos uma descrição e análise dos principais eventos que permitiram a consolidação da medicina da dor como uma prática específica e multidisciplinar, dando destaque à inserção deste modelo no contexto do Sistema Único de Saúde Brasileiro. Finalmente, a partir de uma experiência clínico-institucional buscamos refletir sobre os limites e possibilidades da aplicação prática deste modelo, lançando luz sobre os impasses da clínica e tensões oriundas da problematização, do dualismo mente e corpo e das práticas terapêuticas interdisciplinares.