Functional status of hip joint after surgical and conservative treatment of acetabular fracture

Both conservative and surgical treatment of acetabular fractures alter biomechanical conditions in the hip joint resulting in various degenerative changes in the acetabulum and the femur head. These changes may progress to secondary coxarthrosis, causing dysfunction of the hip joint. The aim of this paper is to compare the outcomes of both conservative and surgical treatments in different types of acetabular fractures, so that clear indications for either conservative or surgical treatment could be determined. This paper is based on retrospective study of 103 patients with acetabular fracture (21 surgically treated and 82 conservatively treated). In this study the incidence of particular types of acetabulum fractures, the treatment period, the incidence of complications and the functional status of the hip after the treatment were analyzed. In patients with anterior fracture surgical treatment lasted three times less than conservative treatment and resulted in far better functional status of the hip joint compared to conservatively treated patients. However, in patients with transverse fractures the functional status was better and the treatment period shorter after the conservative treatment. We believe that the present treatment indications should be corrected so that in anterior column fracture the surgical method should be preferred, whereas the transverse fracture should be treated conservatively. In other types of acetabular fracture, with the radiographic roof arc angle of 45 degrees or less, the surgical method should be preferred to conservative method.     

Monitoring Cell Death in Regorafenib-Treated Experimental Colon Carcinomas Using Annexin-Based Optical Fluorescence Imaging Validated by Perfusion MRI

Objective

To investigate annexin-based optical fluorescence imaging (OI) for monitoring regorafenib-induced early cell death in experimental colon carcinomas in rats, validated by perfusion MRI and multiparametric immunohistochemistry.

Materials and Methods

Subcutaneous human colon carcinomas (HT-29) in athymic rats (n = 16) were imaged before and after a one-week therapy with regorafenib (n = 8) or placebo (n = 8) using annexin-based OI and perfusion MRI at 3 Tesla. Optical signal-to-noise ratio (SNR) and MRI tumor perfusion parameters (plasma flow PF, mL/100mL/min; plasma volume PV, %) were assessed. On day 7, tumors underwent immunohistochemical analysis for tumor cell apoptosis (TUNEL), proliferation (Ki-67), and microvascular density (CD31).

Results

Apoptosis-targeted OI demonstrated a tumor-specific probe accumulation with a significant increase of tumor SNR under therapy (mean Δ +7.78±2.95, control: -0.80±2.48, p = 0.021). MRI detected a significant reduction of tumor perfusion in the therapy group (mean ΔPF -8.17±2.32 mL/100 mL/min, control -0.11±3.36 mL/100 mL/min, p = 0.036). Immunohistochemistry showed significantly more apoptosis (TUNEL; 11392±1486 vs. 2921±334, p = 0.001), significantly less proliferation (Ki-67; 1754±184 vs. 2883±323, p = 0.012), and significantly lower microvascular density (CD31; 107±10 vs. 182±22, p = 0.006) in the therapy group.

Conclusions

Annexin-based OI allowed for the non-invasive monitoring of regorafenib-induced early cell death in experimental colon carcinomas, validated by perfusion MRI and multiparametric immunohistochemistry.     

Bioclipse: an open source workbench for chemo- and bioinformatics

Background  

There is a need for software applications that provide users with a complete and extensible toolkit for chemo- and bioinformatics accessible from a single workbench. Commercial packages are expensive and closed source, hence they do not allow end users to modify algorithms and add custom functionality. Existing open source projects are more focused on providing a framework for integrating existing, separately installed bioinformatics packages, rather than providing user-friendly interfaces. No open source chemoinformatics workbench has previously been published, and no sucessful attempts have been made to integrate chemo- and bioinformatics into a single framework.     

Generation of active protein phosphatase 2A is coupled to holoenzyme assembly

Protein phosphatase 2A (PP2A) is a prime example of the multisubunit architecture of protein serine/threonine phosphatases. Until substrate-specific PP2A holoenzymes assemble, a constitutively active, but nonspecific, catalytic C subunit would constitute a risk to the cell. While it has been assumed that the severe proliferation impairment of yeast lacking the structural PP2A subunit, TPD3, is due to the unrestricted activity of the C subunit, we recently obtained evidence for the existence of the C subunit in a low-activity conformation that requires the RRD/PTPA proteins for the switch into the active conformation. To study whether and how maturation of the C subunit is coupled with holoenzyme assembly, we analyzed PP2A biogenesis in yeast. Here we show that the generation of the catalytically active C subunit depends on the physical and functional interaction between RRD2 and the structural subunit, TPD3. The phenotype of the tpd3Δ strain is therefore caused by impaired, rather than increased, PP2A activity. TPD3/RRD2-dependent C subunit maturation is under the surveillance of the PP2A methylesterase, PPE1, which upon malfunction of PP2A biogenesis, prevents premature generation of the active C subunit and holoenzyme assembly by counteracting the untimely methylation of the C subunit. We propose a novel model of PP2A biogenesis in which a tightly controlled activation cascade protects cells from untargeted activity of the free catalytic PP2A subunit.     

Die Giltigkeit des Energiemengengesetzes für den negativen Galvanotropismus der Wurzel

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