The Comparison of Selected Methods of Cast Iron Spheroidization in Industrial Conditions

Production of spheroidal graphite cast iron is today quite mastered technology. There are many methods achieving the nodular graphite morphology. Each of these methods have specific characteristics and requirements to technical support, properties and the type of applied modifier. Selection of the spheroidization method is dependent on foundry disposition, production character, economic balance, quality requirements, etc. In case of centrifugally casting the core, which fills body and neck of the roll, is created by ductile iron. Considering the sophisticated production of centrifugally cast rolls for hot rolling mills it is necessary to ensure a high reproducibility and reliability of ductile cast iron production quality in the bulk range of 9-18 t per tapping. These conditions are in the Roll Foundry in Vítkovicke Slevarny, spol. s r.o. provided and verified mastered overpour method and the newly injection of cored wire in the melt

Human lysosomal acid lipase inhibitor lalistat impairs <em>Mycobacterium tuberculosis</em> growth by targeting bacterial hydrolases.

Lalistat inhibits growth of Mycobacterium tuberculosis in bacterial culture as well as in infected macrophages. Target identification by quantitative proteomics revealed a cluster of 20 hydrolytic proteins including members of the lipase family. Lipases are essential for M. tuberculosis fatty acid production and energy storage thus representing promising antibiotic targets

Targeting the endoplasmic reticulummitochondria interface sensitizes leukemia cells to cytostatics.

Combination chemotherapy has proven to be a favorable strategy to treat acute leukemia. However, the introduction of novel compounds remains challenging and is hindered by a lack of understanding of their mechanistic interactions with established drugs. In the present study, we demonstrate a highly increased response of various acute leukemia cell lines, drug-resistant cells and patient-derived xenograft cells by combining the recently introduced protein disulfide isomerase inhibitor PS89 with cytostatics. In leukemic cells, a pro-teomics-based target fishing approach revealed that PS89 affects a whole network of endoplasmic reticulum homeostasis proteins. We elucidate that the strong induction of apoptosis in combination with cytostatics is orchestrated by the PS89 target B-cell receptor-associated protein 31, which transduces apoptosis signals at the endoplasmic reticulum-mitochondria interface. Activation of caspase-8 and cleavage of B-cell receptor-associated protein 31 stimulate a pro-apoptotic crosstalk including release of calcium from the endoplasmic reticulum and an increase in the levels of reactive oxygen species resulting in amplification of mitochondrial apoptosis. The findings of this study promote PS89 as a novel chemosensitizing agent for the treatment of acute leukemia and uncovers that targeting the endoplasmic reticulum-mitochondrial network of cell death is a promising approach in combination therapy

TSPO PET with [18F]GE-180 sensitively detects focal neuroinflammation in patients with relapsing–remitting multiple sclerosis

Purpose Expression of the translocator protein (TSPO) is upregulated in activated macrophages/microglia and is considered to be a marker of neuroinflammation. We investigated the novel TSPO ligand [F-18]GE-180 in patients with relapsing-remitting multiple sclerosis (RRMS) to determine the feasibility of [F-18]GE-180 PET imaging in RRMS patients and to assess its ability to detect active inflammatory lesions in comparison with the current gold standard, contrast-enhanced magnetic resonance imaging (MRI). Methods Nineteen RRMS patients were prospectively included in this study. All patients underwent TSPO genotyping and were classified as high-affinity, medium-affinity or low-affinity binders (HAB/MAB/LAB). PET scans were performed after administration of 189 +/- 12 MBq [F-18]GE-180, and 60-90 min summation images were used for visual analysis and assessment of standardized uptake values (SUV). The frontal nonaffected cortex served as a pseudoreference region (PRR) for evaluation of SUV ratios (SUVR). PET data were correlated with MRI signal abnormalities, i.e. T2 hyperintensity or contrast enhancement (CE). When available, previous MRI data were used to follow the temporal evolution of individual lesions. Resuts Focal lesions were identified as hot spots by visual inspection. Such lesions were detected in 17 of the 19 patients and overall 89 [F-18]GE-180-positive lesions were found. TSPO genotyping revealed 11 patients with HAB status, 5 with MAB status and 3 with LAB status. There were no associations between underlying binding status (HAB, MAB and LAB) and the signal intensity in either lesions (SUVR 1.87 +/- 0.43, 1.95 +/- 0.48 and 1.86 +/- 0.80, respectively; p = 0.280) or the PRR (SUV 0.36 +/- 0.03, 0.40 +/- 0.06 and 0.37 +/- 0.03, respectively; p = 0.990). Of the 89 [F-18]GE-180-positive lesions, 70 showed CE on MRI, while the remainder presented as T2 lesions without CE. SUVR were significantly higher in lesions with CE than in those without (2.00 +/- 0.53 vs. 1.60 +/- 0.15; p = 0.001). Notably, of 19 [F-18]GE-180-positive lesions without CE, 8 previously showed CE, indicating that [F-18]GE-180 imaging may be able to detect lesional activity that is sustained beyond the blood-brain barrier breakdown. Conclusion [F-18]GE-180 PET can detect areas of focal macrophage/microglia activation in patients with RRMS in lesions with and without CE on MRI. Therefore, [F-18]GE-180 PET imaging is a sensitive and quantitative approach to the detection of active MS lesions. It may provide information beyond contrast-enhanced MRI and is readily applicable to all patients. [F-18]GE-180 PET imaging is therefore a promising new tool for the assessment of focal inflammatory activity in MS

TSPO PET for glioma imaging using the novel ligand 18F-GE-180: first results in patients with glioblastoma

Objective The 18-kDa mitochondrial translocator protein (TSPO) was reported to be upregulated in gliomas. F-18-GE-180 is a novel 3rd generation TSPO receptor ligand with improved target-to-background contrast compared to previous tracers. In this pilot study, we compared PET imaging with F-18-GE-180 and MRI of patients with untreated and recurrent pretreated glioblastoma. Methods Eleven patients with histologically confirmed IDH wildtype gliomas (10 glioblastomas, 1 anaplastic astrocytoma) underwent F-18-GE-180 PET at initial diagnosis or recurrence. The PET parameters mean background uptake (SUVBG), maximal tumour-to-background ratio (TBRmax) and PET volume using different thresholds (SUVBG x 1.6, 1.8 and 2.0) were evaluated in the 60-80 min p.i. summation images. The different PET volumes were compared to the contrast-enhancing tumour volume on MRI. Results All gliomas were positive on F-18-GE-180 PET and were depicted with extraordinarily high tumour-to-background contrast (median SUVBG 0.47 (0.37-0.93), TBRmax 6.61 (3.88-9.07)). F-18-GE-180 uptake could be found even in areas without contrast enhancement on MRI, leading to significantly larger PET volumes than MRI-based volumes (median 90.5, 74.5, and 63.8 mL vs. 31.0 mL; p = 0.003, 0.004, 0.013). In percentage difference, the PET volumes were on average 179%, 135%, and 90% larger than the respective MRI volumes. The median spatial volumetric correlation (Sorensen-Dice coefficient) of PET volumes and MRI volumes prior to radiotherapy was 0.48, 0.54, and 0.58. Conclusion F-18-GE-180 PET provides a remarkably high tumour-to-background contrast in untreated and pretreated glioblastoma and shows tracer uptake even beyond contrast enhancement on MRI. To what extent F-18-GE-180 uptake reflects the tumour extent of human gliomas and inflammatory cells remains to be evaluated in future prospective studies with guided stereotactic biopsies and correlation of histopathological results

Comparison of 18F-GE-180 and dynamic 18F-FET PET in high grade glioma: a double-tracer pilot study

BackgroundPET represents a valuable tool for glioma imaging. In addition to amino acid tracers such as F-18-FET, PET targeting the 18-kDa mitochondrial translocator-protein (TSPO) is of high interest for high-grade glioma (HGG) imaging due to its upregulation in HGG cells. F-18-GE-180, a novel TSPO ligand, has shown a high target-to-background contrast in HGG. Therefore, we intra-individually compared its uptake characteristics to dynamic F-18-FET PET and contrast-enhanced MRI in patients with HGG.MethodsTwenty HGG patients (nine IDH-wildtype, 11 IDH-mutant) at initial diagnosis (n=8) or recurrence (n=12) were consecutively included and underwent F-18-GE-180 PET, dynamic F-18-FET PET, and MRI. The maximal tumour-to-background ratios (TBRmax) and biological tumour volumes (BTV) were evaluated in F-18-GE-180 and F-18-FET PET. Dynamic F-18-FET PET analysis included the evaluation of minimal time-to-peak (TTPmin). In MRI, the volume of contrast-enhancement was delineated (VOLCE). Volumes were spatially correlated using the SOrensen-Dice coefficient.ResultsThe median TBRmax tended to be higher in F-18-GE-180 PET compared to F-18-FET PET [4.58 (2.33-8.95) vs 3.89 (1.56-7.15); p=0.062] in the overall group. In subgroup analyses, IDH-wildtype gliomas showed a significantly higher median TBRmax in F-18-GE-180 PET compared to F-18-FET PET [5.45 (2.56-8.95) vs 4.06 (1.56-4.48); p=0.008]; by contrast, no significant difference was observed in IDH-mutant gliomas [3.97 (2.33-6.81) vs 3.79 (2.01-7.15) p=1.000]. Only 5/20 cases showed higher TBRmax in F-18-FET PET compared to F-18-GE-180 PET, all of them being IDH-mutant gliomas. No parameter in F-18-GE-180 PET correlated with TTPmin (p>0.05 each). There was a tendency towards higher median BTVGE-180 [32.1 (0.4-236.0) ml] compared to BTVFET [19.3 (0.7-150.2) ml; p=0.062] with a moderate spatial overlap [median SOrensen-Dice coefficient 0.55 (0.07-0.85)]. In MRI, median VOLCE [9.7 (0.1-72.5) ml] was significantly smaller than both BTVFET and BTVGE180 (p<0.001 each), leading to a poor spatial correlation with BTVGE-180 [0.29 (0.01-0.48)] and BTVFET [0.38 (0.01-0.68)].ConclusionPET with F-18-GE-180 and F-18-FET provides differing imaging information in HGG dependent on the IDH-mutational status, with diverging spatial overlap and vast exceedance of contrast-enhancement in MRI. Combined PET imaging might reveal new insights regarding non-invasive characterization of tumour heterogeneity and might influence patients' management