Proteomic profiling of serum samples from chikungunya-infected patients provides insights into host response

Background

Chikungunya is a highly debilitating febrile illness caused by Chikungunya virus, a single-stranded RNA virus, which is transmitted by Aedes aegypti or Aedes albopictus mosquito species. The pathogenesis and host responses in individuals infected with the chikungunya virus are not well understood at the molecular level. We carried out proteomic profiling of serum samples from chikungunya patients in order to identify molecules associated with the host response to infection by this virus.

Results

Proteomic profiling of serum obtained from the infected individuals resulted in identification of 569 proteins. Of these, 63 proteins were found to be differentially expressed (≥ 2-fold) in patient as compared to control sera. These differentially expressed proteins were involved in various processes such as lipid metabolism, immune response, transport, signal transduction and apoptosis.

Conclusions

This is the first report providing a global proteomic profile of serum samples from individuals infected with the chikungunya virus. Our data provide an insight into the proteins that are involved as host response factors during an infection. These proteins include clusterin, apolipoproteins and S100A family of proteins.     

Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss

Our recent animal and human studies revealed that chronic hyponatremia is a previously unrecognized cause of osteoporosis that is associated with increased osteoclast numbers in a rat model of the human disease of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We used cellular and molecular approaches to demonstrate that sustained low extracellular sodium ion concentrations ([Na(+)]) directly stimulate osteoclastogenesis and resorptive activity and to explore the mechanisms underlying this effect. Assays on murine preosteoclastic RAW 264.7 cells and on primary bone marrow monocytes both indicated that lowering the medium [Na(+)] dose-dependently increased osteoclast formation and resorptive activity. Low [Na(+)], rather than low osmolality, triggered these effects. Chronic reduction of [Na(+)] dose-dependently decreased intracellular calcium without depleting endoplasmic reticulum calcium stores. Moreover, we found that reduction of [Na(+)] dose-dependently decreased cellular uptake of radiolabeled ascorbic acid, and reduction of ascorbic acid in the culture medium mimicked the osteoclastogenic effect of low [Na(+)]. We also detected downstream effects of reduced ascorbic acid uptake, namely evidence of hyponatremia-induced oxidative stress. This was manifested by increased intracellular free oxygen radical accumulation and proportional changes in protein expression and phosphorylation, as indicated by Western blot analysis from cellular extracts and by increased serum 8-hydroxy-2'-deoxyguanosine levels in vivo in rats. Our results therefore reveal novel sodium signaling mechanisms in osteoclasts that may serve to mobilize sodium from bone stores during prolonged hyponatremia, thereby leading to a resorptive osteoporosis in patients with SIADH.     

低钠血症与老年股骨转子间骨折的相关性研究

目的:探讨低钠血症与老年股骨转子间骨折的相关性。方法:于2011年2月至2017年8月在承德医学院附属医院的住院患者中选取单侧新鲜闭合性股骨转子间骨折患者340例(其中老年患者(年龄≥60岁)282例)及同期住院的非骨折老年患者162例为研究对象,将其中444例老年患者进行分组,根据有无发生骨折分为骨折组和非骨折组。记录患者入院后首次抽血生化检验结果中钠离子值,比较两组患者的一般情况和低钠血症发生情况。在340例股骨转子间骨折患者中比较不同年龄段间骨折发生率、低钠血症发生率,分析低钠血症与老年股骨转子间骨折的相关性。结果:骨折组患者与非骨折组患者性别、年龄段、合并慢性疾病方面进行比较差异无统计学意义(P0.05)。骨折组患者低钠血症发生率明显高于非骨折组,差异有统计学意义(P0.05)。在年龄≥60岁患者中,骨折发生率与低钠血症发生率呈显著正相关(P0.05)。结论:低钠血症与老年股骨转子间骨折的发生相关,纠正低钠血症有助于预防老年股骨转子间骨折的发生。     

La urea en el manejo del síndrome de secreción inadecuada de la ADH: una revisión sistemática de la literatura

Urea has been recently proposed for the management of hyponatremia linked to the syndrome of inappropriate secretion of ADH (SIADH). The objective of the study was to review the levels of evidence for treatment of hyponatremia associated with SIADH with urea. We performed a: systematic review of experimental trials and grading according to SIGN. No clinical trials were found. The 6 studies analysed had methodological limitations and were prone to biases. In conclusion, there is no evidence to support the efficacy of urea for the treatment of hyponatremia following SIADH.