Glycosaminoglycans increase levels of free and bioactive IGF-I in vitro

BACKGROUND: It is unclear how IGFs become separated from their IGF-binding proteins (IGFBPs) in vivo. However, the IGFBPs possess binding sites for glycosaminoglycans (GAGs) and interaction with GAGs alters IGFBP ligand affinity. Accordingly, GAGs may control IGF bioavailability. To test this hypothesis, we investigated the effect of GAGs on serum levels of free and bioactive IGF-I, total IGF-I, and IGFBPs in vitro. METHODS: Serum was incubated with increasing concentrations of six different GAGs (heparin, tinzaparin (Innohep), dermatan sulfate, heparan sulfate, non-anticoagulant (nac) heparin, and nac low-molecular weight heparin). To investigate for reversibility, heparin was co-incubated with protamine sulfate (PS). Finally, the effect of heparin was studied in serum from pregnant and post partum women, normal subjects and patients with type 1 diabetes. RESULTS: All GAGs increased free IGF-I in a dose-dependent manner (P<0.0001), whereas total IGF-I and IGFBP levels remained unchanged. However, the potency of the GAGs differed significantly (P<0.0001) and did not relate to their anti-coagulating activity. The effect of heparin on free IGF-I was fully reversed by PS. Heparin increased free and bioactive IGF-I in all tested sera (P<0.0001), but the increase was most pronounced in samples from pregnant women (P<0.0001). CONCLUSION: All tested GAGs stimulated the release of free and bioactive IGF-I in several types of serum, most likely by reversible interaction with the IGFBPs. The effect was most pronounced in pregnancy sera, which are characterized by extensive IGFBP-3 proteolysis. Our findings support the view that GAGs localized in the vessel wall and attached to the extracellular matrix control IGF-I tissue accessibility and bioactivity.     

Paratesticular papillary serous cystadenocarcinoma--a case report

A case of paratesticular papillary serous cystadenocarcinoma in a six year old child is presented. The occurrence of these epithelial tumours of the ovarian type, in the paratesticular region is extremely rare and only six cases have been reported so far. They are thought to arise from Mullerian metaplasia of the peritoneal lining of the tunica vaginalis, appendix testis or mullerian remnants between the testis and spermatic cord.     

Anaemia neonatorum

Ohne Zusammenfassung     

Tumor progression in waiting time for radiotherapy in head and neck cancer.

INTRODUCTION: Waiting-time prior to radiotherapy is a well-known problem. This study aims to determine the impact of time on tumor growth in a patient population with squamous-cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: In a consecutive cohort, all patients with both a diagnostic scan and a treatment-planning scan were identified. In total 648 patients were seen, and 414 treated with primary radiotherapy. Ninety-five had two scans and 61 sets were eligible for comparison. Endpoints were change in tumor volume, tumor volume doubling time (TVD) and disease progression measured by TNM-classification and RECIST criteria. RESULTS: Median interval between eligible scans was 28 (5-95) days. Thirty-eight (62%) had measurable increase in tumor volume, median 46% (6-495%). For all patients TVD was median 99 days, but for the half of patients with fastest growing tumors TVD was 30 days (15-41). Tumor volume increase was significantly correlated to time and histological differentiation. Twelve (20%) developed new lymph-node metastasis and 10 (16%) progressed in TNM-classification. Evaluated by RECIST criteria 18 (30%) patients had progressive disease. INTERPRETATION: This study shows a negative impact of waiting time in patients with SCCHN. Within an average time of 4 weeks the majority of the patients developed significant signs of tumor progression. It was not possible to define a threshold for acceptable time intervals in order to avoid volume changes, or to define a subgroup that has no negative impact of delay.     

顶空气相色谱法测定硝酸芬替康唑原料药中有机溶剂残留量

目的：：建立测定硝酸芬替原料药中二氯甲烷、甲醇和乙醇3种有机溶剂残留量的分析方法。方法：采用毛细管气相色谱法,色谱柱：OV-1301毛细管色谱柱(30 m ×0.53 mm,3.0μm),检测器：FID;检测器温度：250℃;进样器温度：200℃;载气：氮气;顶空进样。结果：在上述色谱条件下,二氯甲烷、甲醇和乙醇分别在2.436~21.924μg·ml-1(r=0.9988),12.268~110.412μg·ml-1(r=0.9995),20.052~180.468μg·ml-1(r=0.9969)质量浓度范围内线性关系良好。平均回收率分别为99.30%(RSD=2.36%,n=9),100.21%(RSD=1.07%, n=9),100.15%(RSD=1.27%, n=9)。结论：该检测方法灵敏、准确、可靠,可用于硝酸芬替康唑原料药的质量控制。     

TK-GFP fusion gene virus vectors as tools for studying the features of HSV-TK/ganciclovir cancer gene therapy in vivo

The fusion gene of herpes simplex virus thymidine kinase and green fluorescent protein (TK-GFP) was shown to be a versatile tool for examining the features of thymidine kinase/ganciclovir gene therapy in vitro. In this study, we used viral vectors carrying the fusion gene to characterize the aspects of this gene therapy form in rodent tumor models. Growth of subcutaneous 9L rat tumors transduced ex vivo with TK-GFP gene was prevented when ganciclovir (GCV) treatment was initiated immediately after tumor inoculation. Established tumors (>100 mm(3)), however, were untreatable despite the initial 55% proportion of TK-GFP positive cells. This was due to a rapid clearance of TK-GFP positive cells, but not GFP positive cells. Propidium iodide staining revealed that TK-GFP lentivirus vector was able to induce apoptosis/necrosis in 9L cells, as opposed to the respective GFP vector. Furthermore, when a subcutaneous nude mouse tumor model was used, the percentage of TK-GFP positive cells in vivo was maintained similarly as in cultured cells, suggesting contribution of a fully functional immune response to the disappearance of fusion gene positive cells. In vivo gene transfer studies: adenovirus TK-GFP vector injections resulted in about 25% gene transfer efficiency to 9L tumors and showed that their growth could be significantly reduced even when the tumor volumes were already >120 mm(3). Part of the effect was shown to be due to cytotoxicity of the vector. In summary, our results demonstrate the utility of TK-GFP fusion gene-carrying viral vectors in animal studies and show that readily detectable therapeutic genes can help us to understand the complicated nature of in vivo cancer gene therapy experiments.     

A comprehensive score reflecting memory‐related fMRI activations and deactivations as potential biomarker for neurocognitive aging

Older adults and particularly those at risk for developing dementia typically show a decline in episodic memory performance, which has been associated with altered memory network activity detectable via functional magnetic resonance imaging (fMRI). To quantify the degree of these alterations, a score has been developed as a putative imaging biomarker for successful aging in memory for older adults (Functional Activity Deviations during Encoding, FADE; Düzel et al., Hippocampus, 2011; 21: 803–814). Here, we introduce and validate a more comprehensive version of the FADE score, termed FADE‐SAME (Similarity of Activations during Memory Encoding), which differs from the original FADE score by considering not only activations but also deactivations in fMRI contrasts of stimulus novelty and successful encoding, and by taking into account the variance of young adults'' activations. We computed both scores for novelty and subsequent memory contrasts in a cohort of 217 healthy adults, including 106 young and 111 older participants, as well as a replication cohort of 117 young subjects. We further tested the stability and generalizability of both scores by controlling for different MR scanners and gender, as well as by using different data sets of young adults as reference samples. Both scores showed robust age‐group‐related differences for the subsequent memory contrast, and the FADE‐SAME score additionally exhibited age‐group‐related differences for the novelty contrast. Furthermore, both scores correlate with behavioral measures of cognitive aging, namely memory performance. Taken together, our results suggest that single‐value scores of memory‐related fMRI responses may constitute promising biomarkers for quantifying neurocognitive aging.     

主动免疫联合传统安胎治疗复发性流产的疗效观察

目的：探讨淋巴细胞主动免疫联合传统安胎治疗复发性流产的临床疗效。方法：将封闭抗体缺乏所致的复发性流产患者分为两组,一组采用淋巴细胞主动免疫加黄体酮及HCG传统安胎治疗为研究组,另一组采用传统安胎治疗（黄体酮加HCG）为对照组,观察两组疗效及妊娠结局。结果：研究组妊娠成功率为82．9％,对照组为56．8％。两组比较,有显著性差异（P〈0．05）。结论：淋巴细胞主动免疫联合黄体酮及HCG治疗封闭抗体缺乏所致的复发性流产临床效果显著,是一种安全可靠的好方法。