Development of SNP markers for Ayous (<Emphasis Type="Italic">Triplochiton scleroxylon</Emphasis> K. Schum) an economically important tree species from tropical West and Central Africa

182 SNP markers were developed for Ayous (Triplochiton scleroxylon K. Schum) by incorporating information from two next generation sequencing approaches (RADseq Floragenex and AFLPseq IonTorrent PGM) into a single genotyping panel for MassARRAY^® iPLEX?. This set of markers was successfully used to genotype 753 individuals from 43 populations in five Tropical West and Central African Countries. These loci have an expected heterozygosity range of 0.007–0.501 and F _ST from 0 to 0.306.     

国内干细胞移植治疗心血管疾病的临床研究与应用进展

目的:一些研究证实,干细胞移植可以取代坏死心肌细胞、增加有功能的心肌细胞数量,并建立新血管来改善血供、改善心功能。本文旨在总结近年来国内干细胞移植治疗心血管系统疾病方面的情况。资料来源:应用计算机检索Medline、CBM、CNKI数据库2001-01/2006-11期间的相关文献。包括临床研究(不限研究对象年龄、性别)和基础研究,不限体内或体外研究。中文检索词包括“干细胞,移植,临床研究,心肌梗死,心衰”。英文检索词有“stem cell,bonemarrow,mesenchymal,transplantation”。资料选择:共收集到相关文献820篇,阅读全部文章的文题和大部分文章。纳入标准:①与干细胞移植相关。②与治疗心血管系统疾病相关。③与临床研究相关文献。排除标准:综述文献、重复性研究及Meta分析类文章。资料提炼:共得到符合纳入条件的文献225篇,排除595篇。选择其中30篇进行分析,其中英文13篇,中文19篇,其中中文有1篇为手工检索的增刊。资料综合:①国内于2002年陆续开展干细胞移植治疗心血管系统疾病的探索。②国内用于临床治疗的干细胞类型多为骨髓单个核细胞,其他有骨髓间充质干细胞、骨骼肌干细胞和外周血干细胞也见于临床实验的报道。③干细胞输注途径多以冠脉内注射为主,治疗的临床疾病主要为急性、陈旧性心肌梗死与慢性心功能不全等。结论:干细胞移植可以取代坏死心肌细胞、增加有功能的心肌细胞数量,并建立新血管来改善血供、改善心功能,已应用于临床,未出现安全性问题,故认为干细胞移植技术可以作为心血管系统疾病治疗的手段之一。     

Fibrinogen deficiency is compatible with the development of atherosclerosis in mice.

A critical role of the coagulation system in the development of atherosclerosis has been frequently postulated based on a variety of indirect observations, including the expression of procoagulants and fibrinolytic factors within atherosclerotic vessels, the presence of substantial amounts of fibrin(ogen) and fibrin degradation products within intimal lesions, the cellular infiltration and assimilation of mural thrombi into developing plaques, and the identification of high plasma fibrinogen (Fib) levels as an independent risk factor for the development of ischemic heart disease. To directly examine the role of fibrin(ogen) in atherogenesis, Fib-deficient mice were crossed to atherosclerosis-prone apolipoprotein E (apo E)-deficient mice. Both apo E-/- and apo E-/-/Fib-/- mice developed lesions throughout the entire aortic tree, ranging in appearance from simple fatty streaks to complex fibrous plaques. Furthermore, remarkably little difference in lesion size and complexity was observed within the aortae of age- and gender-matched apo E-/- and apo E-/-/Fib-/- mice. These results indicate that the contribution of fibrin(ogen) to intimal mass and local cell adhesion, migration, and proliferation is not strictly required for the development of advanced atherosclerotic disease in mice with a severe defect in lipid metabolism.     

The rat prepubertal uterine myometrium and not the luminal epithelium is predominantly affected by a chronic dietary genistein exposure

Current knowledge about dietary soy isoflavone-induced hormonal effects and potential priming effects for the responsiveness of the organism to other estrogens is insufficient. The present study examined the effects of pre- and postnatal soy isoflavone exposure on estrogen responsiveness by estrogen receptor agonists in the uteri of prepubertal Wistar rats. To this end, offspring were generated from dams already maintained on three dietary groups, (1) a phytoestrogen-free diet, (2) a soy isoflavone-rich diet with 232?ppm daidzein and 240?ppm genistein or (3) a custom-made diet supplemented with 700?ppm genistein (GEN). Then, F1 females continuously exposed to isoflavones from GD1 to PND21 and non-exposed controls were subjected to an immature uterotrophic assay to compare physiological parameters and the response to subcutaneous treatment with 17β-estradiol, GEN or an estrogen receptor subtype (ERα and ERβ)–specific agonist. Uterine wet weight (UWW), luminal epithelial height (LEH) and myometrial thickness (MMT) were determined. In addition, isoflavone plasma levels and mRNA expression profiles of relevant steroid receptors and of molecular markers for proliferation and estrogenicity were assessed for all groups. The influence of dietary isoflavones on the sensitivity to various estrogenic stimuli in these prepubertal animals was minor. Yet, the uterus of immature rats with high chronic GEN exposure alone showed already an increase in UWW, LEH and MMT. The myometrial response to GEN was more pronounced than that of the luminal epithelium, which may be due to a non-uniform distribution of steroid receptors, in particular the progesterone receptor. In conclusion, although the impact of a continuous, prenatally initiated exposure to dietary isoflavones on the uterine physiology of juvenile rats is modest, the possible priming effects of this exposure for beneficial or adverse late-onset consequences in adults should not be neglected.     

Retention of the posterior cruciate ligament versus the posterior stabilized design in total knee arthroplasty: a prospective randomized controlled clinical trial

Background  

Prosthetic design for the use in primary total knee arthroplasty has evolved into designs that preserve the posterior cruciate ligament (PCL) and those in which the ligament is routinely sacrificed (posterior stabilized). In patients with a functional PCL the decision which design is chosen depends largely on the favour and training of the surgeon.     

Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects

CONTEXT: An oral formulation of EP01572, a peptidomimetic growth hormone secretagogue, was studied. An oral delivery system would be preferable in many of the possible therapeutic indications of ghrelin agonists such as EP01572. OBJECTIVES: Our objective was to establish the pharmacological profile and the GH-releasing activity of increasing oral doses of EP01572 in healthy volunteers. In addition, the pharmacokinetics and pharmacological effects of EP01572 were investigated after intraduodenal (ID) administration. SETTING: This study was a single-center escalating dose study with oral and ID applications. SUBJECTS AND METHODS: In the first part, EP01572 was given orally to 36 male subjects; the treatment consisted of one oral dose of either EP01572 or placebo (0.005, 0.05, and 0.5 mg/kg body weight). Six subjects received two additional oral doses of EP01572: 0.125 and 0.25 mg/kg body weight. In the second part, the following treatments were performed in a randomized order: 1) administration of a bolus of saline (placebo) to the small intestine; 2) ID administration of a bolus of EP01572 at 0.2 mg/kg body weight; 3) ID perfusion of a bolus of EP01572 at 0.35 mg/kg body weight; and 4) ID perfusion of a bolus of EP01572 at 0.5 mg/kg body weight. RESULTS: The oral and ID administration of EP01572 induced a rapid and dose-dependent increase in plasma drug concentrations and a potent GH release in healthy male volunteers. CONCLUSIONS: This study showed that EP01572 was active with regard to stimulation of GH release in humans after oral and ID administration.     

Distinct subtypes of urinary bladder epithelial cells with inducible and non-inducible cytochrome P450 1A1

Cultured primary porcine urinary bladder epithelial cells (PUBEC) represent an adequate and easy to handle in vitro system for studies of urothelial toxicity. PUBEC maintain in vivo-like metabolic activities and physiological functions. They express inducible cytochrome P4501A isoenzymes, which are of particular relevance, since they contribute to activation of bladder carcinogens. A possible drawback of PUBEC is their isolation from common domestic pigs that do not represent an inbred strain. In order to further establish PUBEC as a standard in vitro toxicity test system we analysed possible interindividual differences in CYP1A1 inducibility. Interestingly, we observed by flow cytometry that PUBEC obtained from individual pigs consist of two distinct subpopulations with inducible and non-inducible cells. A strong, concentration-dependent CYP1A1 induction was observed in the responsive subpopulation when incubated with benzo[a]pyrene (B[a]P) in a concentration range between 1 and 10 μM. In contrast, no CYP1A1 induction was obtained in the non-responsive subpopulation up to the highest tested concentrations of 100 μM. The fraction of responsive cells showed large interindividual differences ranging from 10 to 65% of the total cell number. For practical purposes it might be reasonable to analyse pools of PUBEC from five pigs which substantially reduce batch to batch variability. In conclusion, we have identified two functionally distinct subpopulations of urinary bladder epithelial cells. It will be interesting to study whether the CYP1A inducible subtype is more susceptible to bladder carcinogens. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Cutaneous larva migrans on the scalp: atypical presentation of a common disease

Cutaneous larva migrans is a pruritic dermatitis due to the inoculation of helminthslarvae in the skin, and it often occurs in children in tropical and subtropicalareas. The authors describe an atypical case of cutaneous larva migrans in a 11year-old child with scalp involvement, an unusual topography for this lesion.