ISOGENIC AUTOSOMES TO BE APPLIED IN OPTIMAL SCREENING FOR NOVEL MUTANTS WITH VIABLE PHENOTYPES IN DROSOPHILA MELANOGASTER

Most insertional mutagenesis screens of Drosophila performed to date have not used target chromosomes that have been checked for their suitability for phenotypic screens for viable phenotypes. To address this, we have generated a selection of stocks carrying either isogenized second chromosomes or isogenized third chromosomes, in a genetic background derived from a Canton-S wild-type strain. We have tested these stocks for a range of behavioral and other viable phenotypes. As expected, most lines are statistically indistinguishable from Canton-S in most phenotypes tested. The lines generated are now being used as target chromosomes in mutagenesis screens, and the characterization reported here will facilitate their use in screens of these lines for behavioral and other viable phenotypes.     

Recurrent Dermatitis and Dermal Hypersensitivity Following a Jellyfish Sting: A Case Report and Review of Literature

Jellyfish envenomation often causes an immediate painful vesiculopapular eruption. Less commonly it can cause a type IV allergic hypersensitivity that manifests with delayed or recurrent cutaneous lesions at the primary site or distant from the primary site. These secondary reactivations may be related to high antijellyfish immunoglobulin levels, intracutaneously sequestered antigen, or cross‐reacting venom. Immunomodulators such as pimecrolimus and tacrolimus and topical and intralesional corticosteroid therapy decrease this recurrent dermatitis. We report a case of a 9‐year‐old girl with a recurrent jellyfish dermatitis lasting more than 1 year after the initial envenomation. The dermatitis finally resolved after treatment with tacrolimus and intralesional triamcinolone acetonide therapy.     

骨形态发生蛋白对去势大鼠股骨颈骨形态、骨密度和骨生物力学的影响

目的:观察在去势大鼠股骨颈植入牛骨形成蛋白后其骨形态、骨密度及骨强度的变化。方法:实验于2006-06/12在解放军兰州军区兰州总医院骨科研究所完成。①实验材料:普通级3个月龄wistar雌性大鼠60只。骨形态发生蛋白冻干粉剂(从幼龄牦牛新鲜长骨皮质中提取)。②实验分组:以同一只大鼠左右肢体为对照,右侧为实验侧,左侧为对照侧。③大鼠摘除卵巢制作绝经后骨质疏松模型经双能X射线骨密度仪检测筛选出造模成功的44只大鼠,实验侧距大转子0.5cm处股骨颈植入牛骨形成蛋白冻干粉剂,对照侧植入牛血清白蛋白。④实验评估:术后4周、8周时麻醉下处死大鼠取材,应用苏木精-伊红染色,组织切片后光镜下观察、CT扫描、双能X射线骨密度仪及万能生物力学机观察大鼠股骨颈骨形态学、骨皮质厚度、骨密度及骨强度的变化。结果:纳入造模成功后的44只大鼠均进入结果分析。①股骨颈骨组织形态学观察:4周时实验侧股骨颈局部骨小梁完整、连续性尚好;对照侧股骨颈局部骨小梁稀少、连续性中断,不完整。8周时实验侧股骨颈骨小梁致密,数量增多、完整,连接成网状结构、分布均匀;对照侧股骨颈骨小梁稀疏、变细、间距变大,呈髓腔扩大。②骨皮质厚度、骨密度及生物力学测定:4周时实验侧和对照侧股骨颈皮质厚度无明显差异,骨密度及最大载荷有明显差异(P<0.05);8周实验侧较对照侧骨皮质厚度明显增加、骨密度、最大载荷均增高[皮质厚度:(2.632±0.042),(1.728±0.034)mm,骨密度:(0.210±0.026),(0.182±0.029)g/mm2,最大载荷:(97.2±8.1),(85.6±7.9)N,P均<0.05]。结论:植入牛骨形成蛋白可以提高去势大鼠股骨颈局部骨皮质厚度、骨密度及生物力学强度,这将可能为绝经后骨质疏松性股骨颈骨折的防治提供一种新的途径。     

Components of respiratory resistance monitored in mechanically ventilated patients.

The interrupter technique is commonly adopted to monitor respiratory resistance (Rrs,int) during mechanical ventilation; however, Rrs,int is often interpreted as an index of airway resistance (Raw). This study compared the values of Rrs,int provided by a Siemens 940 Lung Mechanics Monitor with total respiratory impedance (Zrs) parameters in 39 patients with normal spirometric parameters, who were undergoing elective coronary bypass surgery. Zrs was determined at the airway opening with pseudorandom oscillations of 0.2-6 Hz at end inspiration. Raw and tissue resistance (Rti) were derived from the Zrs data by model fitting; Rti and total resistance (Rrs,osc=Raw+Rti) were calculated at the actual respirator frequencies. Lower airway resistance (Rawl) was estimated by measuring tracheal pressure. Although good agreement was obtained between Rrs,osc and Rrs,int, with a ratio of 1.07+/-0.19 (mean+/-SD), they correlated poorly (r2=0.36). Rti and the equipment component of Raw accounted for most of Rrs,osc (39.8+/-11.9 and 43.0+/-6.9%, respectively), whereas only a small portion belonged to Rawl (17.2+/-6.3%). It is concluded that respiratory resistance may become very insensitive to changes in lower airway resistance and therefore, inappropriate for following alterations in airway tone during mechanical ventilation, especially in patients with relatively normal respiratory mechanics, where the tissue and equipment resistances represent the vast majority of the total resistance.     

Menopause modulates homocysteine levels in diabetic and non-diabetic women

High total homocysteine (tHcy) plasma levels may contribute to the increased cardiovascular risk of Type 2 diabetic women. However, to date, data on factors modulating tHcy concentration in this population are scarce. Fasting tHcy, vitamin B12, folate plasma levels, and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype as well as clinical, biochemical, and lifestyle variables were compared in 91 Type 2 diabetic and 91 matched non-diabetic women (40 pre- and 51 post-menopausal, in each group). Fasting tHcy concentration did not differ between diabetic and control women, even after multivariable adjustment. In both groups, tHcy levels increased after menopause, but the differences were weakened after multivariable adjustment. The MTHFR genotype distribution was in accordance with the Hardy-Weinberg equilibrium, with a similar TT frequency in diabetic (22.2 %) and control women (19.8%). Overall, tHcy plasma concentration was higher in TT homozygous compared to other genotypes. We found a menopause-genotype interaction on tHcy levels (p=0.068 for menopause*genotype interaction); overall, the increase of tHcy concentration in TT subjects was limited to pre-menopause (p<0.0001; adjusted p=0.024), and this was confirmed after considering diabetic and control women separately (p=0.001 and p=0.01, respectively). At multivariate analysis, menopause was an independent correlate of tHcy concentration, together with creatinine, folate and MTHFR genotype. Our data show that menopause has a strong influence on tHcy concentration even in Type 2 diabetic women and demonstrate, for the first time, that it may modulate the association between tHcy and the common MTHFR polymorphism both in diabetic and non-diabetic women.     

Comparison of the effects of high doses of rosuvastatin versus atorvastatin on the subpopulations of high-density lipoproteins

Atorvastatin and rosuvastatin are both highly effective in decreasing low-density lipoprotein cholesterol and triglyceride levels. However, rosuvastatin was shown to be more effective in increasing high-density lipoprotein (HDL) cholesterol levels. The purpose of the study is to compare the effects of daily doses of rosuvastatin 40 mg with atorvastatin 80 mg during a 6-week period on HDL subpopulations in 306 hyperlipidemic men and women. We previously showed that increased levels of large alpha-1 and alpha-2 HDLs decrease the risk of coronary heart disease and protect against progression of coronary atherosclerosis (superior to HDL cholesterol). In this study, both statins caused significant increases in large alpha-1 (p <0.001) and alpha-2 (p <0.001 for rosuvastatin, p <0.05 for atorvastatin) and significant (p <0.001) decreases in small pre-beta-1 HDL levels; however, increases in the 2 large HDL particles were significantly higher for rosuvastatin than atorvastatin (alpha-1, 24% vs 12%; alpha-2, 13% vs 4%; p <0.001). Statin-induced increases in alpha-1 and alpha-2 correlated with increases in HDL cholesterol, whereas decreases in pre-beta-1 were associated with decreases in triglycerides. In subjects with low HDL cholesterol (<40 mg/dl for men, <50 mg/dl for women, n = 99), increases in alpha-1 were 32% versus 11%, and in alpha-2, 21% versus 5% for rosuvastatin and atorvastatin, respectively. In conclusion, our data show that both statins, given at their maximal doses, favorably alter the HDL subpopulation profile, but also that rosuvastatin is significantly more effective in this regard than atorvastatin.     

Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

Objective A high degree of inter‐individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the oestrogen receptor α gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT. Subjects Postmenopausal Caucasian women (n = 208) participating in a placebo‐controlled randomized trial of 3·2 years of hormone therapy (HT). Methods Plasma triglyceride (TG), remnant lipoprotein cholesterol (RLP‐C), and high‐density lipoprotein cholesterol (HDL‐C) levels and HDL subpopulations were assessed at baseline and at follow up. Single nucleotide polymorphisms (SNPs) in ESR1 and in the ATP binding cassette A1 (ABCA1), cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC), lipoprotein lipase (LPL), and scavenger receptor class B type I (SRB1) genes were assessed for their association with baseline plasma levels and HT‐related changes in levels of RLP‐C and HDL subpopulations. Results Carriers of the ESR1 PvuII or IVS1‐1505 variants had lower plasma TG concentrations and higher plasma HDL‐C and α‐1 and preα‐1 HDL particle levels at baseline and showed greater increases in HDL‐C, apo A‐I and α‐1 particle levels after HT than wild‐type carriers. Carriers of the N291S and D9N variants in the LPL gene had significantly higher remnant lipoproteins and lower α‐2 HDL particle levels at baseline. The CETP TaqIB SNP was a significant determinant of baseline plasma HDL‐C and HDL subpopulation profile. Conclusions Single nucleotide polymorphisms in ESR1, CETP and LPL had significant effects on baseline plasma levels of TG‐rich and HDL subpopulations. With the exception of ESR1 SNPs, variation in genes involved in lipid metabolism has a very modest effect on lipoprotein response to HT.     

Flow visualization analysis for evaluation of shear and recirculation in a new closed-type, monopivot centrifugal blood pump

Flow visualization has great potential in analyzing flow patterns of centrifugal blood pumps to locate possible hemolysis and thrombus formation sites. This study focused on the said phenomena thought to correlate with areas of high shear velocity and stagnation and analyzed a new closed-type centrifugal blood pump. As a result of analyzing the flow of inlet and front gap of the impeller, flow in the front gap was approximately 30% of the external flow. Visualization in the back gap showed sufficient exchange also. Analysis in the volute area and around the washout holes revealed high shear locations and quantified the highest shear velocity. Maximum shear on the volute wall was found to be 9,000-19,000 s-1 and was located in the 0.2-mm vicinity of the wall. Based on these results, previous hemolysis tests, and small pump size, one concludes that the analyzed closed-type centrifugal pump has a relatively smooth flow suitable for a totally implantable artificial heart.