Resistance of the Burkholderia cepacia complex to fosmidomycin and fosmidomycin derivatives

The Burkholderia cepacia complex (BCC) is a group of 17 closely related opportunistic pathogens that are able to infect the respiratory tract of cystic fibrosis patients. BCC bacteria are intrinsically resistant to many antibiotics and are therefore difficult to eradicate. Fosmidomycin could be a new therapeutic agent to treat BCC infections as it inhibits 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in the non-mevalonate pathway essential in BCC bacteria for isoprenoid synthesis. In this study, the antimicrobial activity of fosmidomycin and eight fosmidomycin derivatives towards 40 BCC strains was investigated. All BCC strains were resistant to fosmidomycin, although addition of glucose-6-phosphate reduced the minimum inhibitory concentration values of FR900098, the fosmidomycin acetyl derivative, from 512 mg/L to 64 mg/L for Burkholderia multivorans and B. cepacia. This enhanced activity was linked to increased expression of the genes involved in glycerol-3-phosphate transport, which appears to be the only route for fosmidomycin import in BCC bacteria. Furthermore, upregulation of a fosmidomycin resistance gene (fsr) encoding an efflux pump was observed during fosmidomycin and FR900098 treatment. These results strongly suggest that the observed resistance in BCC bacteria is due to insufficient uptake accompanied by fosmidomycin and FR900098 efflux.     

FGFR2、VEGFR2在乳腺癌组织中的表达和临床意义

[目的]本研究探讨成纤维细胞生长因子2型受体(FGFR2)和血管内皮细胞生长因子2型受体(VEG-FR2)在乳腺癌组织中的表达及其临床意义。[方法]应用免疫组化SABC法,检测两种蛋白的表达情况。[结果]FGFR2和VEGFR2在乳腺癌组织中的积分光密度(IOD)表达率平均为分别为78.38±16.4和83.42±18.1。FGFR2、VEGFR2蛋白表达与病理分期和淋巴结转移有关,在乳腺增生病、乳腺癌癌旁组织、乳腺癌中的阳性表达率依次递增(P﹤0.05),而与年龄及分化程度无关。[结论]FGFR2和VEGFR2在乳腺癌中高表达;FGFR2及VEGFR2蛋白的表达强度与乳腺癌病理分期均呈正相关;     

Insulin sensitivity and liver glucose production in the rat are influenced by lifetime food restriction

In both humans and rats, food restriction leads to increased insulin sensitivity and predisposition to hypoglycemia. We hypothesized that metabolic responses to hypoglycemic episodes could be altered in food-restricted rats. To test our hypothesis, plasma glucose levels and liver glucose production during insulin-induced hypoglycemia were assessed. Rats either had free access to food (FF group) or were food restricted from birth (FR group). As adults, they were subjected to insulin-induced hypoglycemia after an overnight fast. Plasma glucose was measured before (time 0) the intraperitoneal injection of insulin (1 U/kg) and at regular intervals for 300 minutes. Some FF and FR rats received oral glucose (100 mg/kg) 15 minutes after insulin injection, and the same time intervals were investigated. The FR rats showed a larger decrease and slower recovery of plasma glucose than the FF group, and this was not influenced by oral glucose. Liver glucose production from glycogenolysis and gluconeogenesis (ie, before and during the infusion of l-alanine) was higher and lower, respectively, in the FR rats than in the FF rats, either with or without oral glucose before liver perfusion. Preference for glycogenolysis could be a metabolic adaptation for the maintenance of plasma glucose levels during fasting despite lower food availability in the FR rats. However, long-term FR increased the severity of hypoglycemia and impaired plasma glucose recovery. In addition, hypoglycemia could not be prevented by glucose administration. Therefore, food restriction in individuals with intensive insulin therapy should be more rigorously examined.     

Characteristic phase distribution in the white matter of infants on phase difference enhanced imaging

Background and purpose

The infantile brain is continuously undergoing development. Non-invasive methods to assess the neurological development of infants are important for the early detection of abnormalities. Some microstructures in the brain have been demonstrated via phase difference-enhanced imaging (PADRE), which may reflect myelin-related microstructures. We aimed to assess the white matter (WM) signal distribution in infants using PADRE and compared it with that using T1-weighted images (T1WI) and diffusion tensor imaging (DTI) on magnetic resonance imaging (MRI).

Endothelin, but not angiotensin II, contributes to the hypoxic contractile response of large isolated pulmonary arteries in the rat

The aims of this study were to investigate whether angiotensin II and/or endothelin could contribute to the hypoxic contractile response of isolated rat pulmonary artery. Experiments were performed for 1 h on noradrenaline precontracted arterial rings in hypoxic conditions (95% N2 and 5% CO2). Nicardipine, lisinopril, losartan, phosphoramidon, FR139317 and bosentan were used to block Ca2+ channels, angiotensin I-converting enzyme, AT1 receptors, endothelin-converting enzyme, ETA receptors, and ETA/ETB receptors, respectively. The profile of the hypoxic contractile response was biphasic, displaying, after a short relaxation, a weak and transient contraction (from 2-4 min) and then, before complete relaxation, a slowly developed but sustained contraction (from 14-60 min). Endothelium removal abolished the transient contraction and reduced (-59%) the sustained contraction. Nicardipine did not modify the transient contraction, but concentration-dependently decreased (from -35% to -100%) the sustained contraction (P = 0.024). Lisinopril and losartan did not affect the response (P = 0.418 and P = 0.973, respectively). Bosentan did not modify the transient contraction, but concentration-dependently decreased (from -14% to -71%) the sustained contraction (P = 0.016), whereas phosphoramidon and FR139317 did not affect the response (P = 0.830 and P = 0.806, respectively). CONCLUSIONS: In rat, (i) both phases of the hypoxic contractile response are endothelium-dependent and independent of angiotensin II; (ii) the transient contraction does not depend on endothelin; (iii) the sustained contraction, which involves calcium influx, appears partly dependent on mature endothelin released from storage granules by stimulating ETB receptors.     

功能调节器矫治乳前牙反瞭对恒切颌影响的头影测量研究

目的　通过对反矫治前、后及追踪复查的头影侧位片进行测量分析 ,说明功能调节器 (FR3)矫治乳牙反对上下颌骨及恒胚牙的生长发育具有重要意义。方法　 FR3矫治乳前牙反 17例 ,男 8例 ,女 9例 ,年龄平均 5 .6岁。对矫治前、后及矫治后与追踪的头影侧位片进行测量分析。研究矫治乳牙反对恒牙胚及颌骨的影响 ,并追踪观察其矫治效果。结果　矫治后 Ptm- 6距、Ptm- ANS距、SNA角显著增大 ,上恒切牙胚向前发育 ;下颌后退 ,S- Ar距增大 ,SNB角及面角减小 ,下恒切牙胚位置后移 ;ANB角增大上下颌基骨关系明显改善 ;下面高及后面高增加。追踪研究表明 ,反解除后 ,Ptm- 6距、Ptm- ANS距、U1- NA距继续增大 ,其余观测值改变不明显。结论　说明 FR3不仅对早期反具有矫形作用 ,而且反的解除有利于发挥出潜在的生长发育潜力 ,因此应大力提倡对早期反尽早的针对病因予以矫治。     

改良型FRⅢ型矫治器矫治安氏Ⅲ类错牙合后舌骨位置的对比研究

目的 比较改良型FRⅢ型矫治器矫治儿童安氏Ⅲ类错牙合前后舌骨位置的变化。方法 选取儿童功能性安氏Ⅲ类错牙合患者40例,实验组和对照组各20例,实验组病例采用改良型FRⅢ型矫治器矫治,对照组病例采用传统FRⅢ型矫治器矫治,对两组病例矫治前后的X线头影测量片上的舌骨位置进行对比分析。结果 改良型FRⅢ型矫治器矫治儿童功能性安氏Ⅲ类错牙合后舌骨的位置,与其治疗前比较,H-FH、H-S、H-Ptm、Ar-H-Me增大（P<0.01）,H-MP、H-RGn减小（P<0.01）;与传统FRⅢ型矫治器矫治后的儿童功能性安氏Ⅲ类错牙合患者的舌骨位置比较,HFH HFH、H-S、H-Ptm增大（P<0.05）,Ar-H-Me角度增大（P<0.01）,H-MP、H-RGn减小（P<0.05）。结论 经改良型FRⅢ型矫治器矫治后的儿童安氏Ⅲ类错牙合患者的舌骨位置,与其治疗前相比,位置更靠后、下,下颌骨与舌骨位置发生了顺时针旋转;比传统FRⅢ型矫治器矫治后下颌骨与舌骨位置发生顺时针旋转的角度更大,下颌在发生后下位移的同时,更有效地促进了舌骨位置的后上移位,对儿童功能性安氏Ⅲ类错牙合患者的舌骨位置有显著影响。