New administration model of trans-chalcone biodegradable polymers for the treatment of experimental leishmaniasis

The present study was designed to investigate a new administration model and the antileishmanial activity of a semi-synthetic chalcone, benzylideneacetophenone (trans-chalcone). The antileishmanial activity of this product was first tested in vitro against promastigotes of L. braziliensis, L. tropica, L. infantum and L. amazonensis. An in vivo experiment was carried out using subcutaneous administration of trans-chalcone and implants of synthetic biodegradable polymers, polylactic acid (PLA) and polylactic/glycolic acid (PLGA). This compound showed potent inhibitory effects on the growth of all Leishmania strains examinated. Subcutaneous administration of trans-chalcone at a single dose of 4 mg/kg of body weight reduced lesion development in mice infected with L. amazonensis. A similar inhibition of the lesion growth in mice treated with trans-chalcone and pentamidine was observed. PLA and PGLA implants of trans-chalcone at 4 mg/kg were administered to mice infected with L. amazonensis. PLGA implants induced a highest reduction in the lesion size (31.25%) than PLA implants (10.75%). Treatment in vitro with trans-chalcone at IC50, completely inhibited the pathogenicity of this parasite in vivo. The development of this model provides a new practical technique for delivering drugs and can be useful for experimental leishmaniasis treatment.     

Mechanical properties and in vitro degradation of bioresorbable knitted stents

- The aim of this study was to characterize the mechanical properties and in vitro degradation of bioresorbable knitted stents. Each stent was knitted using a single self-reinforced fibre made out of either PLLA or 96L/4D PLA or 80L/20G PLGA. The mechanical and physical properties of the fibres and stents were measured before and after gamma sterilization, as well as during in vitro degradation. The mechanical properties of the knitted stents made out of bioresorbable fibres were similar to those of commercially available metallic stents. The knitting geometry (loop height) had a marked effect on the mechanical properties of the stents. The rate of in vitro degradation in mechanical and physical properties for the PLLA and 96L/4D PLA stents was similar and significantly lower than that of the 80L/20G PLGA stents. The 80L/20G PLGA stents lost about 35% of their initial weight at 11 weeks. At this time, they had lost all their compression resistance strength. These data can be used as a guideline in planning further studies in vivo.     

Pyogenic liver abscess due to hypervirulent Klebsiella pneumoniae in a 14-year-old boy

A 14-year-old otherwise healthy boy presented with right-sided back pain following high fever. Abdominal computed tomography scan showed a large liver abscess. Klebsiella pneumoniae (KP) was rapidly identified from peripheral blood using the melting temperature mapping (Tm) method, which enables identification of pathogenic microorganisms within four hours after patient sample collection. He was diagnosed with pyogenic liver abscess (PLA) caused by KP on the day of admission. The KP was the hypervirulent (hv) clinical variant (string test positive, serotype K1, sequence type 23, rmpA and magA positive). After intravenous antibiotic therapy and drainage of the abscess, his condition resolved. The highlights of this case report are a healthy child with hypervirulent Klebsiella pneumoniae liver abscess in Japan and the new Tm mapping method for rapid and accurate identification of the pathogenic microorganism.     

Inhibition of AURKA Reduces Proliferation and Survival of Gastrointestinal Cancer Cells With Activated KRAS by Preventing Activation of RPS6KB1

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ⅡA型磷脂酶A2 mRNA在结、直肠癌组织中的表达水平及其意义

目的探讨ⅡA型磷脂酶A2（PLA2GⅡA）mRNA的表达水平与结、直肠癌的关系,为评估PLA2GⅡA对结、直肠癌的临床诊断、病程监测和预后预测的价值和意义提供实验依据。方法应用RT-PCR方法检测33例结、直肠癌患者的结、直肠癌配对组织（癌组织、癌旁组织和肿瘤远端切缘组织）中PLA2GⅡA mRNA的表达水平。用SPSS13.0统计学软件分析3组组织中的PLA2GⅡA mRNA水平的差异及结、直肠癌组织中PLA2GⅡA mRNA表达水平与临床病理因素的相关性。结果①PLA2GⅡA mRNA在结、直肠癌组织的表达水平明显高于癌旁及远端切缘组织,其表达阳性率分别为癌组织组90.91%,癌旁组66.67%,肿瘤远端切缘组51.52%（P〈0.05）。②女性组、早期组和无转移组患者结、直肠癌组织的PLA2GⅡA mRNA表达水平比男性组、晚期组和有转移组高（P〈0.05）。结论 PLA2GⅡA基因可能参与了结、直肠肿瘤的发生和发展过程。     

Cytosolic phospholipase A2 and F2 isoprostanes are involved in semen quality and human infertility—A study on leucocytospermia,varicocele and idiopathic infertility

Phospholipase A₂ (PLA₂) is involved in eicosanoid release, and F₂-isoprostanes (F₂-IsoPs), as free radical-generated eicosanoids released by PLA₂, are indicators of oxidative stress in different human conditions. This study investigated the interplay between cytosolic PLA₂ (cPLA₂), F₂-IsoPs and sperm features in male infertility, when the involvement of oxidative stress has been reported. Semen evaluation was performed following WHO guidelines, sperm ultrastructure was detected by transmission electron microscopy indicating a fertility index, and the percentages of sperm immaturity, apoptosis and necrosis. In sperm cells and seminal plasma, cPLA₂ levels were determined by immunological method, whereas F₂-IsoPs by mass spectrometry. Sperm concentration, morphology, vitality and fertility index values were significantly lower in infertile groups compared with fertile men. An increase in sperm apoptosis and necrosis (p < .01), apoptosis (p < .01) and immaturity (p < .001) was detected in leucocytospermia, idiopathic infertility and varicocele, respectively. Seminal cPLA₂ showed the highest value in varicocele group (p < .05), whereas seminal F₂-IsoPs increased in varicocele (p < .001) and leucocytospermia (p < .05) groups. In the whole population, F₂-IsoP and cPLA₂ levels were positively correlated (p < .05). On the contrary, F₂-IsoPs and cPLA₂ were not significantly different when investigated in sperm cells. Our data indicate that fatty acid oxidation/metabolism plays a role in different male reproductive pathological conditions.     

基因重组人骨形成蛋白-2和聚乳酸复合异位诱导成骨的实验研究

目的：观察基因重组人骨形成蛋白－2（recombinant human Bone Morphofenetic protein-2,rhBMP-2)和聚乳酸（Polylactic acid,PLA)复合形成的活性涂层种植体的异位诱导成骨活性。方法：将rhBMP-2与聚乳酸复合，构建活性涂层种植体，植入兔肌内，于1，4，8周后进行X线、大体观察及组织学观察，检测异位成骨活性。结果：rh-BMP-2/PLA活性复合涂层种植体具有骨诱导能力，PLA为rhBMP-2的良好控释载体。结论：rhBMP-2/PLA涂层具有良好的生物相容性和骨诱导活性，是一种理想的种植体涂层形成。     

PLA/PGA组织膜应用于牙槽嵴黏骨膜扩张初探

目的：了解可降解性材料PLA／PGA组织膜应用于牙槽嵴黏骨膜扩张的生物学性能。方法：40只新西兰大耳白兔建立萎缩性牙槽嵴模型和卵巢切除后模型，按照扩张类型随机分成4组，对PLA／PGA组织膜扩张牙槽嵴黏骨膜后，对各观察时段内PLA／PGA组织膜的生物学性能进行定量和定性观察。结果：PLA／PGA组织膜的降解于4周时开始，24周降解基本完成；12周时组织膜使用组新骨生成率为28％，非使用组为7％；24周时使用组骨改建基本完成，非使用组新骨生成率为13％；48周时使用组骨改建完全，非使用组新骨生成率为39％。结论：PLA／PGA组织膜良好的生物学性能对于促进牙槽嵴增高具有较好的应用前景。     

Tissue engineered extracellular matrices (ECMs) in urology: Evolution and future directions

Autologous gastrointestinal tissue has remained the gold-standard reconstructive biomaterial in urology for >100 years. Mucus-secreting epithelium is associated with lifelong metabolic and neuromechanical complications when implanted into the urinary tract. Therefore, the availability of biocompatible tissue-engineered biomaterials such as extracellular matrix (ECM) scaffolds may provide an attractive alternative for urologists. ECMs are decellularised, biodegradable membranes that have shown promise for repairing defective urinary tract segments in vitro and in vivo by inducing a host-derived tissue remodelling response after implantation. In urology, porcine small intestinal submucosa (SIS) and porcine urinary bladder matrix (UBM) are commonly selected as ECMs for tissue regeneration. Both ECMs support ingrowth of native tissue and differentiation of multi-layered urothelial and smooth muscle cells layers while providing mechanical support in vivo. In their native acellular state, ECM scaffolds can repair small urinary tract defects. Larger urinary tract segments can be repaired when ECMs are manipulated by seeding them with various cell types prior to in vivo implantation. In the present review, we evaluate and summarise the clinical potential of tissue engineered ECMs in reconstructive urology with emphasis on their long-term outcomes in urological clinical trials.