Discovery of protein biomarkers for renal diseases

Animal models and human studies have been useful in dissecting the molecular mechanisms of renal disease and finding new disease targets; however, translation of these findings to new clinical therapeutics remains challenging. Difficulties with detecting early disease, measuring drug effectiveness, and the daunting cost of clinical trials hampers the development of new therapeutics for renal diseases. Many existing laboratory tests were discovered because of inspired recognition that a particular protein might prove useful in clinical practice. New unbiased genomic and proteomic techniques identify many constituents present in biologic samples and thus may greatly accelerate biomarker research. This review focuses on the steps needed to develop new biomarkers that are useful in laboratory and clinical investigations, with particular focus on new proteomic screening technologies. New biomarkers will speed the laboratory and clinical development of new treatments for renal diseases through mechanistic insights, diagnoses that are more refined, early detection, and enhanced proof of concept testing.     

Polymerase chain reaction assay for Cydia pomonella granulovirus detection in Cydia pomonella population

The polymerase chain reaction (PCR) assay was successfully used to identify Cydia pomonella granulovirus (CpGV) in larvae of Cydia pomonella L. (codling moth). PCR with the primers CpGV-2A/CpGV-2B and CpGV-3A/CpGV-3B was found suitable for detection of CpGV. The primers Cp-I/Cp-II and Cp-III/Cp-IV were able to identify the transposable element TCp3.2 in C. pomonella larvae. The presence of CpGV in the larvae from orchards,which had been infected with CpGV was tested during 2 years post infection. (p.i.). CpGV was found in as many as 15% of the surviving larvae 1 year p.i. in one location. The virus was not detected in CpGV-infected orchards 2 years p.i. or in natural C. pomonella populations. This result suggests a poor persistence of CpGV in surviving C. pomonella individuals and its slow spread in a natural host population. One the other hand, the presence of a transposable element, transposon TCp3.2 may correlate with virus redistribution in this insect population.     

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Background

Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.

Methods

552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.

Results

The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.

Conclusion

Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy.     

平胃散对湿阻中焦模型大鼠血浆抗利尿激素及红细胞内钠、钾浓度的影响

目的:探索湿阻中焦证的病理机制,并探讨平胃散对湿阻中焦证的作用机理。方法:选用湿阻中焦证大鼠模型,给予平胃散配伍利水药,观测各组大鼠血浆抗利尿激素(ADH)的浓度及红细胞内电解质Na~+、K~+浓度。结果:湿阻造模组大鼠与正常组相比ADH显著升高(P<0.01);细胞内的Na~+增高,K~+显著降低(P<0.05)。给予平胃散后,高、中、低剂量组及加泽泻组大鼠ADH基本恢复正常;细胞内的Na~+下降至接近于正常,K~+尤明显变化;不造模给药组与正常组比较ADH显著升高(P<0.05),Na~+、K~+明显下降(P均<0.01)。结论:(1)血浆ADH浓度升高、细胞内Na~+增多、K~+降低在湿阻中焦证形成中起重要作用。(2)平胃散治疗湿阻中焦证的作用机理与调节ADH和细胞内Na~+、K~+浓度有关,且可能存在双向调节机制。     

Statistical methods for building better biomarkers of chronic kidney disease

The last two decades have witnessed an explosion in research focused on the development and assessment of novel biomarkers for improved prognosis of diseases. As a result, best practice standards guiding biomarker research have undergone extensive development. Currently, there is great interest in the promise of biomarkers to enhance research efforts and clinical practice in the setting of chronic kidney disease, acute kidney injury, and glomerular disease. However, some have questioned whether biomarkers currently add value to the clinical practice of nephrology. The current state of the art pertaining to statistical analyses regarding the use of such measures is critical. In December 2014, the National Institute of Diabetes and Digestive and Kidney Diseases convened a meeting, “Toward Building Better Biomarker Statistical Methodology,” with the goals of summarizing the current best practice recommendations and articulating new directions for methodological research. This report summarizes its conclusions and describes areas that need attention. Suggestions are made regarding metrics that should be commonly reported. We outline the methodological issues related to traditional metrics and considerations in prognostic modeling, including discrimination and case mix, calibration, validation, and cost-benefit analysis. We highlight the approach to improved risk communication and the value of graphical displays. Finally, we address some “new frontiers” in prognostic biomarker research, including the competing risk framework, the use of longitudinal biomarkers, and analyses in distributed research networks.     

Cystic intracranial lesions: magnetic resonance imaging

Thirty-three patients with cystic intracranial lesions were examined with both magnetic resonance (MR) imaging and CT scanning. The abnormalities imaged included 11 arachnoid cysts, 10 cystic tumors, six postoperative cysts, and three colloid cysts. The intensity patterns of the cyst contents as encoded with routine spin-echo imaging sequences enabled subdivision of the cysts into three categories. Arachnoid and postoperative cysts had an intensity pattern identical to cerebrospinal fluid. More proteinaceous cysts, including inflammatory cysts and nonhemorrhagic tumoral cysts, had an intermediate intensity pattern with characteristically low intensity on the short TR sequence (0.5 sec), but had clearly higher intensity than cerebrospinal fluid on the long TR sequences (2 sec). Finally, three cystic tumors with hemorrhagic fluid and three colloid cysts had a distinctly different pattern of high intensity on all four MR sequences through the same section. MR was superior to CT in characterizing intracranial cystic lesions because of its ability to categorize cysts into these three groups on the basis of the intensity pattern of cyst contents, thereby improving diagnostic specificity and patient management.