Eltrombopag for the treatment of immune thrombocytopenia: The aegean region of Turkey experience

Objective: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. Materials and Methods: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. Results: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. Conclusion: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events. © 2015 Turkish Society of Hematology. All rights reserved

Digital and experimental rock analysis of proppant injection into naturally fractured coal

Proppant-laden fluid injection has been applied to many low permeability reservoirs, such as coal seams, to enhance permeability and thus production. While there are several laboratory-scale experimental studies on proppant placement in hydraulic fractures, the possible infiltration of proppant into natural fractures and its effect on overall permeability has received little attention. We study proppant injection into a naturally fractured coal sample by a combination of experimental and digital rock technologies. The sample was imaged using a helical X-ray computed tomography (micro-CT) scanner in as-received condition. Then, proppants of different size ranges were gradually injected into the sample, using a purpose-built X-ray transparent core flooding system, and the permeability was measured at different effective stresses. Subsequently, the propped sample was re-imaged and registered to the as-received image to map the internal changes. The experimental results indicated almost no permeability change of the sample after proppant injection. While proppant collection in the outlet proved passage of the proppant through the sample, observation of the sample indicated that some of the proppants were accumulated on the inlet face of the core and created a filter leading to no permeability increment. Micro-CT images confirmed that proppants were effectively placed in the sample and kept the fractures open. Numerical computation of permeability, using the digital coal sample in which accumulated proppants at the coal surface were excluded, indicated a significant increase in the sample permeability. Such an increase resulted from the opening of the fractures, particularly in the outlet region. This demonstrated the significance of proppant size selection for coal seam hydraulic fracturing. While proppants were successfully placed in the fractures, the experiment measured the permeability of the system, including proppants accumulated on the inlet, and could not effectively map the internal changes. This, therefore, needs to be considered when an experimental program for proppant injection is executed. To accurately monitor the internal changes, application of digital rock technology is recommended for such experiments

Microbiologically influenced corrosion of cable bolts in underground coal mines: The effect of Acidithiobacillus ferrooxidans

Reports on corrosion failure of cable bolts, used in mining and civil industries, have been increasing in the past two decades. The previous studies found that pitting corrosion on the surface of a cable bolt can initiate premature failure of the bolt. In this study, the role of Acidithiobacillus ferrooxidans (A. ferrooxidans) bacterium in the occurrence of pitting corrosion in cable bolts was studied. Stressed coupons, made from the wires of cable bolts, were immersed in testing bottles containing groundwater collected from an underground coal mine and a mixture of A. ferrooxidans and geomaterials. It was observed that A. ferrooxidans caused pitting corrosion on the surface of cable bolts in the near-neutral environment. The presence of geomaterials slightly affected the pH of the environment; however, it did not have any significant influence on the corrosion activity of A. ferrooxidans. This study suggests that the common bacterium A. ferrooxidans found in many underground environments can be a threat to cable bolts’ integrity by creating initiation points for other catastrophic failures such as stress corrosion cracking

Microbiologically influenced stress corrosion cracking responsible for catastrophic failure of cable bolts

In the past two decades, reports of the premature failure of cable bolts used in the mining and civil industries have been increasing. Previous studies have established that failure occurs through hydrogen-induced stress corrosion cracking (HISCC), which is a type of environmentally assisted hydrogen cracking. However, to date, the cause of HISCC has been unclear. For the first time, we studied the role of microorganisms in the failure of cable bolts using components present in SCC-affected mines. Stressed coupons were prepared from the cable bolt wires and tested in groundwater with additions of sulphate-reducing bacteria, coal, clay, pyrite and lactate. It was found that hydrogen sulphide (H2S) produced by sulphate- and sulphur-reducing bacteria promoted hydrogen diffusion into the steel and, in the presence of stress, caused HISCC. This suggests that control of H2S production should be a priority for mining and civil industries to avoid premature failure of anchoring systems

The effectiveness of epoxy coating for preventing microbially induced corrosion of rock bolts

In the past two decades, the corrosion failures of rock reinforcement bolts in underground coal mines have been increasingly reported. Preliminary studies have shown that these failures were predominantly related to pitting and stress corrosion cracking. The analyses in affected mines indicated microbially induced corrosion (MIC) as one of the primary corrosion causes. As such, there is an urgent demand from industries to develop methods to mitigate MIC-associated failures of rock bolts in underground coal mines. This study examined epoxy coating to determine its effectiveness in preventing biofilm formation on steel surfaces and, in turn, averting MIC. The corrosion-causing bacteria were isolated and enriched from groundwater samples collected from the affected mine sites. Coated and uncoated rock bolt samples were prepared from the bolts and incubated in media in the absence and presence of the corrosion-causing bacteria. Fluorescence microscopy imaging found no evidence of bacterial biomass growth on the surface of the epoxy-coated steel surfaces after 30 days, while the non-coated surfaces were colonised by biomass. The observations suggest the potential of epoxy coating for bolt MIC prevention. Future studies to assess the applicability of epoxy coating in the underground mine environment are recommended

Effects of quercetin induced cell death on a novel gene "URG4/URGCP" expression in leukemia cells

The present study aimed to investigate anti-proliferative and apoptotic effects of quercetin on human leukemia cells and effects of quercetin-induced cell death on a novel gene Up-regulated gene 4/upregulator of cell proliferation (URG4/URGCP), in leukemia cells. URG4/URGCP expression is determined by using RT-PCR. IC 50 of quercetin was determined as 25 microM in CCRF-CEM, HL-60 and K562 cells. In IC 50 dose group, URG4/URGCP expression was decreased 99% in HL-60 cells, 90% in CCRF-CEM cells, and 52% (24 hour) - 99% (72 hour) in K-562 cells. URG4/URGCP may play important roles in the development of leukemia, and might be a useful molecular marker for predicting the prognosis of leukemia via quercetin treatment. © 2012 Dodurga Y, et al

Herpes simplex virus 1 amplicon vector-mediated siRNA targeting epidermal growth factor receptor inhibits growth of human glioma cells in vivo

In primary glioblastomas and other tumor types, the epidermal growth factor receptor (EGFR) is frequently observed with alterations, such as amplification, structural rearrangements, or overexpression of the gene, suggesting an important role in glial tumorigenesis and progression. In this study, we investigated whether posttranscriptional gene silencing by vector-mediated RNAi to inhibit EGFR expression can reduce the growth of cultured human gli36 glioma cells. To "knock down" EGFR expression, we have created HSV-1-based amplicons that contain the RNA polymerase III-dependent H1 promoter to express double-stranded hairpin RNA directed against EGFR at two different locations (pHSVsiEGFR I and pHSVsiEGFR II). We demonstrate that both pHSVsiEGFR I and pHSVsiEGFR II mediated knock-down of transiently transfected full-length EGFR or endogenous EGFR in a dose-dependent manner. The knock-down of EGFR resulted in the growth inhibition of human glioblastoma (gli36-luc) cells both in culture and in athymic mice in vivo. Cell cycle analysis and annexin V staining revealed that siRNA-mediated suppression of EGFR induced apoptosis. Overall HSV-1 amplicons can mediate efficient and specific posttranscriptional gene silencing. Copyright © The American Society of Gene Therapy

An Effective Barrier Coating Technology Against Premature Bolt Failures in Underground Mines

Significant safety and economic consequences accompany the premature failure of bolts, posing sustainability challenges for mining operations. Previous studies have indicated that hydrogen-induced stress corrosion cracking (HISCC), primarily influenced by microbial activities termed microbiologically influenced stress corrosion cracking (MISCC), stands as a major contributor to the premature failure of bolts in underground mines. Presently, an effective mechanism to mitigate these premature failures is lacking. In this study, multiple commercially available coatings undergo testing to assess their susceptibility and suitability in preventing HISCC and MISCC. Additionally, a purpose-developed coating is examined. The results reveal that the tested commercially available coatings either fail to prevent these types of corrosion or are unsuitable for the intricate conditions within underground mines. The laboratory results show the coating has a significant anti-acidic corrosion and anti-MISCC performance. Conversely, the coating formulated in this study successfully averts both MISCC and HISCC, proving its applicability within the complex geological environments prevalent in mines. This breakthrough offers a promising solution to mitigate premature bolt failures in complex underground geological environments. The developed coating presents a viable way forward for enhancing safety, reducing economic losses, and improving the overall sustainability of mining operations

miRNAs in Newt Lens Regeneration: Specific Control of Proliferation and Evidence for miRNA Networking

Background: Lens regeneration in adult newts occurs via transdifferentiation of the pigment epithelial cells (PECs) of the dorsal iris. The same source of cells from the ventral iris is not able to undergo this process. In an attempt to understand this restriction we have studied in the past expression patterns of miRNAs. Among several miRNAs we have found that mir-148 shows an up-regulation in the ventral iris, while members of the let-7 family showed down-regulation in dorsal iris during dedifferentiation. Methodology/Principal Findings: We have performed gain- and loss-of–function experiments of mir-148 and let-7b in an attempt to delineate their function. We find that up-regulation of mir-148 caused significant decrease in the proliferation rates of ventral PECs only, while up-regulation of let-7b affected proliferation of both dorsal and ventral PECs. Neither miRNA was able to affect lens morphogenesis or induction. To further understand how this effect of miRNA up-regulation is mediated we examined global expression of miRNAs after up-regulation of mir148 and let-7b. Interestingly, we identified a novel level of mirRNA regulation, which might indicate that miRNAs are regulated as a network. Conclusion/Significance: The major conclusion is that different miRNAs can control proliferation in the dorsal or ventral iris possibly by a different mechanism. Of interest is that down-regulation of the let-7 family members has also been documented in other systems undergoing reprogramming, such as in stem cells or oocytes. This might indicate tha