罗红霉素分散片的人体生物等效性研究

研究两种罗红霉素分散片的人体生物等效性。采用高效液相色谱(HPLC)电化学检测法测定20名健康男性受试者单剂量口服罗红霉素分散片受试制剂和参比制剂后,体内罗红霉素的血药浓度,用DAS药动学程序处理试验数据,并对试验结果进行统计分析。罗红霉素受试制剂和参比制剂的峰浓度(Cmax)分别是10．16±1．46、10．34±1．66μg·ml-1;达峰时间(tmax)分别是2．33±0．61、2．28±0．62 h;药时曲线下面积(AUC0→Tn)分别为143．32±25．80、138．93±22．49μg·h·ml-1,AUC0→∞分别为158．63±26．86、153．77±24．75μg·h·ml-1;半衰期(t1／2)分别是:9．00±1．58、8．68±1．66 h。按罗红霉素血药浓度计算,相对生物利用度为103．63％±14．04％,经统计分析两制剂药动学参数均无显著性差异,表明受试制剂和参比制剂生物等效。     

环孢素软胶囊人体生物等效性研究

评价两种环孢素软胶囊(受试制剂和参比制剂)在健康中国人体内的生物等效性。建立测定人全血中环孢素A的高效液相色谱-紫外(HPLC-UV)检测法,并进行方法学验证,采用随机双交叉自身对照试验设计,24名男性健康受试者分别口服受试制剂和参比制剂400mg后,测定环孢素A的血药浓度,计算药动学参数,评价两制剂的生物等效性。环孢素软胶囊(受试制剂)和环孢素软胶囊(参比制剂)中环孢素A主要的药动学参数如下:消除半衰期T1/2分别为(10.114±6.329)h和(9.717±4.076)h,达峰浓度Cmax分别为(2 021.235±298.581)ng.ml-1和(1 992.192±286.923)ng.ml-1,达峰时间Tmax分别为(1.729±0.361)h和(1.813±0.323)h;药时曲线下面积AUC0→t分别为(9 824.811±1 633.026)ng.h.ml-1和(10 316.514±1 395.955)ng.h.ml-1。以AUC0→t计算,环孢素软胶囊的相对生物利用度为(97.2±22.1)%。结果表明两制剂在健康中国人体内具有生物等效性。     

丙戊酸镁缓释片体外释药特性及体内相对生物利用度的研究

目的:研制丙戊酸镁缓释片,并评价其体外释药特性及体内生物等效性。方法:以释放度为主要指标筛选片剂处方及制备工艺,并对12名健康男性受试者进行体内生物利用度研究。结果:以优选的处方,工艺制备的片剂,体外释药性能良好,符合Higuchi方程,持续释药达8h以上。且释药性能稳定,不受溶出介质pH值的影响。其体内药代动力学参数为:Cmax,30.0±4.6ug·ml-1;Tmax,11.5±4.8h;T1/2。17.8±4.6h;F,95±8％。结论:丙戊酸镁缓释片与普通片相比具有缓释特性。相对生物利用度为95±8％。     

法莫替丁片剂的健康人体药代动力学及生物利用度研究

本文报道8名成年健康男性受试者单剂的口服两种法莫替丁片剂的药代动力学及相对生物利用度比较。实验结果表明:8名受试者接受单剂(40mg)交叉给药后所得药时曲线符合一室模型。两种片剂的药代动力学参数分别为:AUC:854.29与803.45μg·h/L,T_(1/2)ke:2.61与2.92h,Cmax:129.44与116.22μg/L,Tmax:2.48与2.52h。     

阿酚咖片中阿司匹林的相对生物利用度研究

对阿酚咖片中的阿司匹林进行相对生物利用度研究。采用反相高效液相色谱法测定 2 4名健康志愿受试者单剂量口服阿酚咖片供试制剂与参比制剂后 ,阿酚咖片中阿司匹林体内活性代谢物水杨酸的血药浓度的变化。用 3P97药动学程序处理试验数据 ,并对试验结果进行方差分析和双单侧 t检验。水杨酸的相对生物利用度为 :10 5 .36 %± 14 .15 % ;两种制剂水杨酸的药时曲线下面积 (AUC0→ T)分别为 :10 3.10± 11.92 μg· h/ ml与 98.4 5±13.4 9μg· h/ ml;达峰时间 (tmax)分别为 :1.5± 0 .5 h与 1.5± 0 .5 h;峰浓度 (Cmax)分别是 :19.31± 2 .4 7μg/ ml与18.95± 2 .4 9μg/ ml。两种制剂中的水杨酸 AU C0→∞ 、AUC0→ T、Tmax及 Cmax经双单侧 t检验进行生物等效性评价 ,表明以制剂中阿司匹林活性代谢产物水杨酸为指标 ,两种制剂生物等效 (t1 ≥ t1 - 0 .0 5( 2 2 ) ,t2 ≥ t1 - 0 .0 5( 2 2 ) )     

金雀异黄酮对不同基因型健康受试者咪达唑仑药代动力学的影响

目的 探讨金雀异黄酮在体内对不同细胞色素酶P450(CYP3A)基因型健康受试者咪达唑仑药代动力学的影响.方法 基因分型筛选CY P3A5* 1/CYP3A5*1、CYP3A5* 1/CYP3A5*3及CYP3A5*3/CYP3A5*3基因型健康受试者各6例.临床试验按照两阶段交叉方案进行:第一阶段18例受试者按随机数字表法分为2组,每组9例,受试者给予金雀异黄酮片或安慰剂口服处理14d,第15天所有受试者口服咪达唑仑.经过14d洗脱期后第二阶段交叉重复试验,分别于口服咪达唑仑后0、0.25、0.5、0.75、1、1.5、2、2.5、3、4、6、8、12、24、36 h时间点抽取血样,高效液相色谱-串联质谱法测定咪达唑仑药代动力学参数.结果 经金雀异黄酮处理后,CY P3A5* 1/CYP3A5*1、CYP3A5* 1/CYP3A5*3基因型受试者咪达唑仑0～36h药物浓度-时间曲线下面积(AUC0→36)明显降低[(120.10±40.28)ng·h·ml-1比( 140.65±55.40)ng·h· ml-1,(110.50±38.14)ng·h·ml-1比( 138.56±30.26)ng·h ·ml-1,均P＜0.05 ]; AUCo→∞亦显著降低[(172.49±56.32) ng·h·ml-1比(229.48±82.61)ng·h·ml-1,(185.96±74.21)ng·h·ml- 1比(286.43±35.62)ng·h·ml-1,均P＜0.05];药物消除半衰期(t1/2)显著缩短[(1.54±0.96)h比(4.01±2.68)h,(1.29±0.87)h比(3.59±1.99)h,均P＜0.05],但对CYP3A5*3/CYP3A5*3基因型受试者咪达唑仑的药代动力学没有影响.结论 金雀异黄酮对CYP3A5* 1/C YP3A5*1、CYP3A5* 1/CYP3A5*3基因型健康受试者咪达唑仑的代谢具有显著的影响.     

HPLC法测定盐酸头孢他美酯片在犬体内的药代动力学及其相对生物利用度

本文采用HPLC法测定了四川抗菌素工业研究所研制的盐酸头孢他美酯片在草犬体内的药代动力学参数及其相对生物利用度(参比药为日本杏林制药株式会社生产的盐酸头孢他美酯片)。 10只草种犬采用随机交叉试验法单剂口服500mg的国产盐酸头孢他美酯片和进口盐酸头孢他美酯片后,测定得其药代动力学参数C_(max)、T_(max)、T(1/2α)、AUC分别为6.0±1.6μg/ml、3.0±0.8h、4.23±0.60h、44.84±15.79μg·h/ml和6.1±1.5μg/ml、2.9±0.9h、4.32±0.53、48.13±13.59μg·h/ml。测得国产品与进口品的相对生物利用度F值为94.13±11.50％(95％可信区间为80.90～107.36％)。     

盐酸西替利嗪片的人体药代动力学研究

目的 建立测定盐酸西替利嗪片的人体药代动力学研究.方法 采用高效液相色谱法,测定20名健康男性志愿者口服盐酸西替利嗪片的血浆药物浓度:结果盐酸西替利嗪半衰期为(7.42±1.50)h,达峰时间为(1.06±0.42)h,峰浓度为(0.46±0.10)μg/mL,滞后时间为(1.25±0.47)h.结论 高效液相色谱方法结果准确,灵敏度高,能满足盐酸西替利嗪人体药代动力学研究的需要,可广泛应用于临床.     

法莫替丁颗粒、片剂药代动力学及生物利用度研究

本文报道8名成年男性健康受试者单剂口服法莫替丁颗粒、片剂药代动力学及相对生物利用度比较。8名受试者接受单剂量(40mg)交叉给药(颗粒剂和片剂)后所得药时曲线符合一室模型。其颗粒剂和片剂的平均药代动力学参数分别为:血浆药物峰浓度:110.29±23.59与112.95±23.36μg/L,药物达峰时间:1.66±0.59与1.97±0.53h,消除半衰期:3.53±0.33与3.18±0.53h,药—时曲线下面积:737.11±147.09与721.42+100.94μg/L·h。其相对生物利用度以片剂为100％,颗粒剂的相对生物利用度为102.96±20.05％。     

饮食结构对大鼠体内氨茶碱的药动学影响

目的探讨不同饮食结构对茶碱在大鼠体内的药动学影响。方法 36只大鼠分为对照组(空腹给药)、标准饮食组(给药前给予标准饮食)和高脂饮食组(给药前给予高脂饮食),各组大鼠灌胃给予氨茶碱,采用高效液相色谱法测定各个时间点血中的茶碱浓度,并用DAS2.0软件计算药动学参数。结果对照组、标准饮食组和高脂饮食组的主要动力学参数如下:血药浓度时间-曲线面积为(305.239±68.728)、(239.927±51.837)和(245.264±53.630)μg·h-1·ml-1,平均驻留时间为(6.935±0.904)、(7.239±0.936)和(7.144±0.661)h,半衰期为(5.066±1.098)、(5.480±1.441)和(5.119±1.230)h,达峰时间为(1.167±0.389)、(1.833±0.389)和(1.917±0.289)h,清除率为(0.069±0.017)、(0.086±0.018)和(0.085±0.018)L·h·kg,峰浓度为-1-1(52.485±10.472)、(35.901±7.534)和(33.309±6.255)μg·ml-1。标准饮食和高脂饮食均可使峰浓度减少,高脂饮食可使达峰时间延长。结论饮食可使茶碱在大鼠体内的药动学参数发生改变。     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

HLA genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.