在inside-out膜片上caffeine对猪冠状动脉平滑肌细胞钙激活钾通道的调节作用及ryanodine的影响

目的:利用膜片钳技术,研究咖啡因对钙激活钾通道(calcium-activated potassium channel,KCa)的作用机制,及咖啡因存在时兰尼定(ryanodine)对KCa的影响以阐明冠状动脉平滑肌的调控机制。方法:采用急性酶分离方法,应用膜片钳单通道电流记录技术记录猪冠状动脉平滑肌钿胞上KCa电流活动。电流信号经放大、滤波及A/D、D/A转换后输入微机进行采样和储存。应用PCLAMP9.0软件系统进行数据采集及分析。结果:在内面向外式(inside-out)膜片下,咖啡因(0.1、0.5、1.0、5.0mmol/L)可浓度依赖性地增加通道开放概率,而对电流幅值无明显影响,开放概率增加是通过明显缩短平均关闭时间实现的(n=8,P0.01);洗去药物后通道活性可以恢复到对照水平;5.0mmol/L咖啡因对KCa激活作用最大(P0.01)。在细胞贴附式(cell-attached)膜片上,咖啡因激活KCa后,ryanodine(10-40μmol/L)浓度依赖性地抑制通道开放概率,开放时间缩短,关闭时间延长,对电流幅度无明显影响。结论:在inside-out膜片下,咖啡因能够直接激活猪冠状动脉平滑肌细胞KCa通道。在cell-atta-ched构型上,ryanodine可通过胞内一定的信号通路浓度依赖性间接抑制咖啡因对KCa激活。     

Cell-attached膜片上,咖啡因对猪冠状动脉平滑肌细胞KCa的调节作用

目的:研究咖啡因对猪冠状动脉平滑肌细胞KCa通道的调控机理,以期揭示胞内钙库RyR激活后,局部钙离子浓度升高和KCa的关系。方法:采用急性酶分离方法,应用膜片钳单通道电流记录技术记录大脑皮层神经元猪冠状动脉平滑肌细胞上KCa通道电流活动。电流信号经放大、滤波及A/D、D/A转换后输入微机进行采样和储存。实验数据应用CLAMP9.0软件系统进行数据采集及分析。结果:在cell-attached膜片上咖啡因对KCa通道有明显的作用,咖啡(0.1-5.0 mM)可以增加通道的开放概率(NPo),呈现出浓度依赖性,开放时间延长,关闭时间也随之缩短,而对电流幅值无明显影响,开放概率的增加是通过明显缩短平均关闭时间实现的(n=8,P<0.05);洗去药物后通道活性可以一定程度的恢复到对照水平,再加入一定浓度咖啡因(如1.0mM)可再次激活KCa,激活程度与洗脱前较接近。结论:在细胞贴附式构型上咖啡因浓度依赖性地激活KCa,有饱和性。可能是通过影响胞内信号转导过程而调控KCa活性。     

钙激活钾通道参与重症失血性休克大鼠肠系膜细动脉平滑肌细胞膜的超极化

目的血压降低、血管反应性低下是导致创伤、脓毒性等休克病人死亡的重要原因之一.我室曾提出了致血管反应性降低的细胞膜超极化理论,并报道了ATP敏感钾通道在血管反应性低下中的作用认为随着休克的发展,组织细胞缺血、缺氧加重,ATP耗竭,细胞内乳酸堆积,从而激活了ATP敏感钾通道,使细胞膜超极化,血管舒张.除ATP敏感钾通道外,在微动脉平滑肌细胞中还有两种钾通道,即内向整流钾通道(Kir)和钙激活钾通道(KCa). 其中钙激活钾通道(KCa)在血管平滑肌细胞上尤其丰富,而且在血管平滑肌细胞的肌源性调节中起着重要的作用.本文目的在于进一步阐明钙激活钾通道在休克大鼠肠系膜细动脉平滑肌细胞膜超极化中的作用,从而为临床治疗提供理论基础.     

羟基红花黄色素A通过激活Kv通道舒张大鼠冠状动脉

目的:研究羟基红花黄色素A (hydroxysafflor yellow A,HSYA)对离体大鼠冠状动脉(rat coronary artery,RCA)的舒张作用,并探讨该作用与电压门控性钾通道(Kv通道)的关系。方法:采用DMT离体血管环技术明确HSYA对RCA的肌源性作用及血管内皮对该作用的影响;采用全细胞膜片钳技术观察HSYA对RCA平滑肌细胞Kv电流的影响;采用Western blot技术探讨HSYA对RCA平滑肌细胞Kv1.2和Kv1.5通道蛋白表达的影响。结果:10μmol/L和30μmol/L HSYA能够舒张60 mmol/L KCl或0.1 mmol/L U46619预收缩的RCA(P<0.05),但其对预收缩的内皮完整组和去内皮组RCA舒张作用的差异无统计学显著性(P>0.05);HSYA(3μmol/L、10μmol/L和30μmol/L)可使RCA平滑肌细胞Kv电流显著增加(P<0.05);10μmol/L和30μmol/L HSYA能够增加RCA平滑肌细胞Kv1.2和Kv1.5通道蛋白的表达。结论:HSYA可舒张预收缩的RCA,该作用与血管内皮无关,其可能的机制与增强Kv通道功能和蛋白表达有关。     

UTP对猪冠状动脉平滑肌细胞BK_(Ca)通道作用机制的研究

目的:利用膜片钳技术,研究UTP对急性酶分离的猪冠状动脉平滑肌细胞上BKCa通道的作用,探讨生理条件下UTP调节BKCa通道的机制。方法:应用Cell-attached技术记录急性酶分离的猪冠状动脉平滑肌细胞上BKCa电流。用pCLAMP9.0软件系统进行数据采集及分析。结果:在Cell-attached膜片上,80μM UTP可明显激活BKCa通道(P0.05,n=21)。PLC抑制剂U73122可抑制UTP对BKCa的激活作用(P0.05,n=5)。PKC激动剂PMA(10nM),可使BKCa通道开放概率明显降低(P0.05,n=9)。UTP(80μM)预处理细胞之后,IP3抑制剂2APB(80μM),可使BKCa通道开放受抑(P0.05,n=6)。结论:在Cell-attached膜片上,UTP能激活猪冠脉平滑肌细胞BKCa通道。PLC信使转导通路中的IP3介导的胞内Ca2+释放是UTP激活BKCa通道的重要途径。     

中电导钙激活钾通道在细胞迁移中的作用及研究进展

细胞迁移参与个体发育、伤口愈合、免疫反应、癌症发展等多种生理或病理过程。钙激活钾（Calcium-activated potassium,KCa）通道作为钾通道家族中的重要成员,具有维持膜电位、胞内钙稳态和信号传递等作用。KCa通道参与多种细胞迁移过程,在细胞迁移中的调控机制具有重要临床价值。KCa通道依其单通道电导大小,分为大电导（BKCa）、中电导（IKCa）和小电导（SKCa）三类通道亚型。在细胞迁移相关研究中IKCa通道的报道较多,本文重点综述IKCa通道在细胞迁移中的作用及相关研究进展。     

葛根素对脂多糖诱导N9小胶质细胞激活的抑制作用

目的:探索葛根素对脂多糖(LPS)诱导N9小胶质细胞激活的抑制作用,为其在神经退行性疾病的防治方面提供依据。方法:用MTT法检测脂多糖和葛根素对小胶质细胞的细胞毒性作用;用流式细胞术(FCM)检测葛根素对LPS诱导N9细胞内活性氧(ROS)产生的抑制作用;分别用Griess法和FCM检测细胞培养液和细胞内一氧化氮(NO)含量;用HE染色法观察LPS激活N9细胞,及葛根素恢复细胞静息状态下细胞的形态;以FCM检测细胞凋亡和细胞周期。结果:葛根素(100~200μmol/L)能使LPS激活的N9细胞,从阿米巴样的活化形状明显恢复至静息态的圆形;LPS激活的N9细胞能产生大量的NO到培养液中,葛根素(50~200μmol/L)能使NO的产生减少,其中,高浓度组(200μmol/L)与LPS模型组相比,NO从23.45±0.19μmol/L降至12.43±0.11μmol/L(P0.01)。胞内ROS检测表明:葛根素(200μmol/L)同样明显降低ROS的产生。葛根素对激活的N9细胞胞内ROS的产生具有抑制作用,高浓度组(200μmol/L)能使其恢复至对照组水平;此外,葛根素能显著抑制LPS诱导的细胞凋亡,并恢复LPS对N9细胞G0/G1期的阻滞作用。结论:葛根素具有抑制小胶质细胞激活的作用。     

淋巴细胞膜钾通道及其功能

离子通道在淋巴细胞活化过程中发挥重要作用.钾通道是淋巴细胞膜上的一类重要离子通道,分为2类电压门控钾通道(Kv)和钙激活的钾通道(KCa).Kv有3个亚型n,n'和l型.KCa可分为2类小电导KCa和中电导KCa°Kv是维持细胞静息膜电位的主要承担者.Kv和KCa对Ca2+信号具有重要的调节作用,从而分别在细胞活化的启动和维持阶段发挥主要作用.Kv通过和蛋白激酶的偶联参与了胞内激活信号转导过程.另外,Kv和氯通道共同作用调节细胞容积.对钾通道的深入研究将有助于新型免疫调节剂的研制.     

虎杖甙对大鼠细动脉平滑肌细胞ATP敏感钾通道的影响

目的 :探讨中药虎杖提取物 -虎杖甙扩张休克动物细动脉、改善微循环灌流的作用机制。方法 :应用膜片钳技术的细胞贴附式观察虎杖甙对大鼠肠系膜细动脉平滑肌细胞 ATP敏感钾通道 ( KATP)的影响。结果 :细胞外液加入 0 .2 m mol/L虎杖甙后 ,通道电流幅度无明显改变 ,说明虎杖甙不影响 KATP通道电导 ;但加入虎杖甙后KATP通道动力学发生了明显变化 ,通道开放时间短成分 τ0 1 和长成分τ0 2 增大 ,通道开放时间 Tom延长 ,通道开放概率 Po提高 ,提示KATP通道激活。结论 :虎杖甙具有激活 KATP通道的作用 ,它可能通过使细动脉平滑肌超极化而扩张细动脉 ,从而改善休克动物微循环。     

血管平滑肌钙激活钾通道的调控

钙激活钾通道(KCa)是血管平滑肌上最主要的外向电流通道,它在动作电位的复极和节律性漫波活动中起着重要作用。激活KCa可致超极化而舒张血管,阻断KCa可致去极化而收缩血管。许多药物、神经递质、激素或体内活性物质通过对KCa的激活或阻断,调节着血管张力。KCa开放剂往往通过提高开放概率(PO)而激活KCa。PO的提高可通过以下途径实现:(1)通道开放数目增加;(2)单纯的概率提高;(3)增加通道的电压敏感性和、或钙离子敏感性,表现为PO-V曲线,PO-[Ca2+]曲线左移。KCa开放剂根据激活机制分为两大类:(1)直接激活KCa的药物,如NO、Cromakali…     

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.     

Studien zur humoralen Regulation des erythropoetischen Proliferationsspeichers beim Menschen

Zusammenfassung Die Beeinflussung der Erythroblasten-Proliferation durch das Mikromilieu wurde in vitro mittels Auswertung durch Differential- und Mitosezählungen und Signifikanzberechnung vieler Versuchsreihen auch unter verschiedenen pathologischen Bedingungen getestet.Sowohl die Mitosehäufigkeit wie die Ausreifung waren positiv mit dem Erythropoetingehalt des Medium korreliert. Der Effekt wurde durch Folsäure, Ätiocholanolon und cAMP verstärkt. Cobalt stimulierte ebenso wie Testosteron und Methenolon in vitro unabhängig von der Erythropoetinkonzentration im Medium die Erythroblastenproliferation. Ein vermindertes Eisenangebot störte die endgültige Ausreifung der Erythroblasten zu Retikulozyten und bewirkte dadurch eine Ineffektivität der Erythorpoese. Anhaltspunkte für ein Erythrozyten-Chalon oder einen Erythropoetinhemmkörper ließen sich aus unserem Versuchsansatz nicht gewinnen, weil er die Transformation der pluripotenten in die erythropoetin-sensible Stammzelle nicht einschließt. Als Nebenbefund ergab sich eine Stimulation des granulozytopoetischen Proliferationsspeichers durch Serumzusatz zum Medium von Patienten nach akutem Blutverlust und bei Polycythämia vera.Unterstützt durch die Deutsche Forschungsgemeinschaft     

HLA study in Amerindian Bolivia La Paz Aymaras

Aymara people has been a relatively homogeneous group since Spanish Conquest by 1,532 CE, even if previously represented a group of various cultural defined populations who gave rise to them. They were and are established in Andean Altiplano around Titikaka Lake (Bolivia, Peru), Argentina and Chile neighborhood, speak Aymara language and have been maintained after Europeans arrival at a lower social status than Quechua (Inca) speaking people. However, both Aymara and Quechua populations acknowledge Titikaka Lake as center of their origins; both languages are also related. Specific high frequencies of HLA-A*02, -A*24 and -A*68, HLA-B*35, -B*39 and -B*48, HLA-DRB1*08:02, -DRB1*09:01, and -DRB1*14:02, and HLA-DQB1*04:02, -DQB1*03:02 and -DQB1*03:01 alleles are found in Aymaras and HLA class II haplotypes common to Andean Amerindians (DRB1*08:02-DQB1*04:02 and DRB1*04:03-DQB1*03:02), like Quechua, Aymara, Uros, Lamas and Mapuche are also found in Easter and other Pacific Islands. Giant human head stone statues at Tiwanaku (Titikaka Lake, Bolivia) are also found at Easter Island. Thus, it is possible a gene and cultural flow between Andean Amerindians and Easter and other Pacific Islands, as it was demonstrated by Thor Heyerdahl in his Kon-Tiki expedition which reached Pacific Islands sailing from El Callao Harbour (Lima, Peru).     

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.     

Lipid composition of metacestodes of Taenia taeniaeformis and lipid changes during growth

A lipid analysis was performed on developing metacestodes of Taenia taeniaeformis removed from the livers of rats at times varying from 3 to 35 weeks post infection. Lipid accounted for 7–21% of the dry weight of the parasites. The highest proportions were found at the earlier stages. The distribution was as follows; neutral lipid 27–45%; glycolipid 5–11%; and phospholipid 50–61%. The major neutral lipid was cholesterol, and minor neutral lipids were sterol esters, triglycerides, diglycerides and monoglycerides. Hydrocarbons were present throughout development, but in the highest amounts at the earlier stages. Five different glycolipids were found, all of which were identified as glycosphingolipids. An increase in the proportion of more complex glycolipids was noted as parasites grew older. Ten different phospholipids were identified, with the major components being phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Other phospholipids were: lysophosphatides, phosphatidylinositol, phosphatidic acid, diphosphatidylglycerol, sphingomyelin, and an unknown phospholipid component. Changes in the relative amounts of the two major phospholipids were found when the early and late stages were compared. Two lipids found throughout development were identified as glycosylated dolichol phosphates, and they comprised between 1 and 3% of the total phospholipid fraction. Nineteen fatty acids were detected, and the fatty acid distribution for each lipid class at each stage was determined. Seven major fatty acids were common to each. These were: hexadecanoic, octadecanoic, oleic, linoleic, arachidonic, docosanoic, and docosahexaenoic.     

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.     

Simple Serological Assays for Detecting Rice Tungro Viruses

An attempt was made to produce sensitive and specific polyclonal antisera against the viruses causing rice tungro disease, and to assess their potential for use in simple diagnostic tests. Using a multiple, sequential injection procedure, seven batches of polyclonal antisera against rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV) were produced. These were characterized for their sensitivity and specificity using ring-interface precipitin test and double antibody sandwich (DAS) ELISA. Thirty-one weeks after the first immunization, antiserum batch B6b for RTBV showed the highest ring interface titer (DEP = 1:1920). For RTSV, batches S3, S4b and S5b all had similar titres (DEP = 1:640). In DAS-ELISA, however, significant differences among purified antisera (IgG) batches were observed only at IgG dilution of 10^-3. At that dilution, IgGB4b showed the greatest sensitivity, while IgGS3 showed greatest sensitivity for RTSV. When all IgG batches were tested against 11 tungro field isolates (dual RTBV-RTSV infections) at sample dilution of 1:10, IgGB4b and IgGB6b for RTBV and IgGS3 and IgGS6b for RTSV performed equally well. However, after cross adsorption with healthy plant extracts in a specially prepared healthy plant-Sepharose affinity column, only IgGB6b could be used specifically to detect RTBV in a simple tissue-print assay.     

Is it worthy to take full-course immunotherapy for allergic rhinitis? About efficacy biomarker of allergen immunotherapy

Nowadays, people pay more attention to biomarkers that can predict clinical efficacy of immunotherapy for allergic rhinitis. As the only recognized aetiological treatment, the efficacy of allergen immunotherapy (AIT) has been proved by many studies. However, treatment success depends on compliance and persistence greatly, which can be impaired by the lengthy duration of AIT and socioeconomic status of patients. Besides, ineffectiveness is another factor that accounts for non-adherence. If the clinical efficacy can be predicted in the early stage of immunotherapy, it can help patients choose appropriate treatment plans, increase patient compliance and optimize the allocation of medical resources. This paper mainly focuses on five candidate biomarkers, the sIgE/tIgE ratio before treatment, serum inhibitory activity for IgE, decreased basophil activation, upregulation of Tregs and tolerogenic DCs, reviews the time when potential biomarkers can predict or monitor the efficacy of AIT, discusses the reason why these indicators could serve as efficacy biomarkers and interactions among potential biomarkers.     

Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen

Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, results are reported from a loss‐ and gain‐of‐function survey, using pharmacological modulators of several neurotransmitter pathways to examine possible roles for these pathways in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations, including craniofacial defects, hyperpigmentation, muscle mispatterning and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular‐genetic investigation, and highlight the necessity for in‐depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy.     

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.