Susceptibility of mice to rotavirus infection: effects of age and administration of corticosteroids.

We examined susceptibility to the murine rotavirus, epizootic diarrhea of infant mice virus (EDIM), in normal suckling and weaned mice and in suckling mice treated with glucocorticoids. Normal mice 1 to 40 days old were inoculated by gastrin intubation with high doses of EDIM and subsequently evaluated for rotavirus infection by solid-phase radioimmunoassay, by electron microscopy of intestinal tissue sections or by both. Radioimmunoassay and electron microscopy showed a concordance of 89.5% in the detection of rotavirus infection. After a period of low susceptibility to EDIM infection during the first 3 days after birth (23%), susceptibility was high for the next 11 days (95%), but decreased abruptly as mice approached weaning (41% on days 15 through 17). Mice 34 days or older did not develop EDIM infection after inoculation, but rotavirus antigen was detected in 12% of uninoculated mothers nursing inoculated litters. Administration of cortisone acetate to 8-day-old mice induced partial intestinal maturation prematurely. At 3 to 6 days after cortisone acetate treatment, susceptibility to EDIM infection decreased to 60% compared with 94% in age-matched controls. Our data suggest (i) that susceptibility of mice to EDIM infection is age dependent, decreasing in concert with intestinal maturation, and (ii) that glucocorticoids, which induce premature partial intestinal maturation, modulate susceptibility of mice to EDIM.     

The role of the p33:p33/p92 interaction domain in RNA replication and intracellular localization of p33 and p92 proteins of Cucumber necrosis tombusvirus

Replication of plus-stranded RNA viruses is performed by the viral replicase complex, which, together with the viral RNA, must be targeted to intracellular membranes, where replication takes place in membraneous vesicles/spherules. Tombusviruses code for two overlapping replication proteins, the p33 auxiliary protein and the p92 polymerase. Using replication-competent fluorescent protein-tagged p33 of Cucumber necrosis virus (CNV), we determined that two domains affected p33 targeting to peroxisomal membranes in yeast: an N-proximal hydrophobic trans-membrane sequence and the C-proximal p33:p33/p92 interaction domain. On the contrary, only the deletion of the p33:p33/p92 interaction domain, but not the trans-membrane sequence, altered the intracellular targeting of p92 protein in the presence of wt p33 and DI-72(+) RNA. Moreover, unlike p33, p92 lacking the trans-membrane sequence was still functional in supporting the replication of a replicon RNA in yeast, whereas the p33:p33/p92 interaction domain in both p33 and p92 was essential for replication. In addition, p33 was also shown to facilitate the recruitment of the viral RNA to peroxisomal membranes and that p33 is colocalized with (+) and (-)-stranded viral RNAs. Also, FRET and pull-down analyses confirmed that p33 interacts with other p33 molecules in yeast cells. Based on these data, we propose that p33 facilitates the formation of multimolecular complexes, including p33, p92, viral RNA, and unidentified host factors, which are then targeted to the peroxisomal membranes, the sites of CNV replication.     

Value of adipokines in predicting the severity of acute pancreatitis: Comprehensive review

AIM: To analyze the prognostic value of adipokines in predicting the course, complications and fatal outcome of acute pancreatitis (AP).METHODS: We performed the search of PubMed database and the systemic analysis of the literature for both experimental and human studies on prognostic value of adipokines in AP for period 2002-2012. Only the papers that described the use of adipokines for prediction of severity and/or complications of AP were selected for further analysis. Each article had to contain information about the levels of measured adipokines, diagnosis and verification of AP, to specify presence of pancreatic necrosis, organ dysfunction and/or mortality rates. From the very beginning, study was carried out adhering to the PRISMA checklist and flowchart for systemic reviews. To assess quality of all included human studies, the Quality Assessment of Diagnostic Accuracy Studies tool was used. Because of the high heterogeneity between the studies, it was decided to refrain from the statistical processing or meta-analysis of the available data.RESULTS: Nine human and three experimental studies were included into review. In experimental studies significant differences between leptin concentrations at 24 and 48 h in control, acute edematous and acute necrotizing pancreatitis groups were found (P = 0.027 and P < 0.001). In human studies significant differences between leptin and resitin concentrations in control and acute pancreatitis groups were found. 1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AP. This threshold yielded a sensitivity of 70%, specificity 85%, positive predictive value 64%, negative predictive value88% (area under curve 0.75). Resistin and visfatin concentrations differ significantly between mild and severe acute pancreatitis groups, they correlate with severity of disease, need for interventions and outcome. Both adipokines are good markers for parapancreatic necrosis and the cut-off values of 11.9 ng/mL and 1.8 ng/mL respectively predict the high ranges of radiological scores. However, the review revealed that all nine human studies with adipokines are very different in terms of methodology and objectives, so it is difficult to generalize their results. It seems that concentrations of the leptin and resistin increases significantly in patients with acute pancreatitis compared with controls. Serum levels of adiponectin, visfatin and especially resitin (positive correlation with Acute Physiology and Chronic Health Evaluation II, Ranson and C-reactive protein) are significantly different in mild acute pancreatitis and severe acute pancreatitis patients, so, they can serve as a markers for the disease severity prediction. Resistin and visfatin can also be used for pancreatic and parapancreatic necrosis prediction, interventions needs and possible, outcome.CONCLUSION: High levels of adipokines could allow for prediction of a severe disease course and outcome even in small pancreatic lesions on computed tomography scans.     

Influence of residual blood autotransfused from cardiopulmonary bypass circuit on clinical outcome after cardiac surgery

Autotransfusion of the residual blood from the cardiopulmonary bypass (CPB) circuit is considered to be one of the methods enabling reduction in the need for transfusion, the possible adverse effects of which are well known and documented. The aim of the study was to evaluate the effectiveness of the autologous autotransfusion of centrifuged red blood cells from the residual blood of the CPB circuit in patients following heart surgery. Three groups of patients who underwent heart surgery were examined. The first group (Group 1) consisted of 37 patients who received all of the residual blood in the bypass circuit after CPB (collected into sterile plastic bags) during the early postoperative period. The second group (Group 2) consisted of 45 patients who did not receive the residual blood following CPB. The third group (Group 3) consisted of 42 patients who underwent reinfusion of centrifuged red blood cells from the residual blood remaining in the CPB circuit during the early postoperative period. Hematocrit (Hct) values 12 hours after the operation were found to be higher in Group 3 compared with those of the first and the second groups (by 13.2% and 11.1%, respectively). Blood loss during the first 12 hours after the operation and during the time spent in the intensive care unit did not differ between the groups. The number of transfusions was significantly lower in Group 3 (28.57%) in comparison with that of Groups 1 and 2 (37.83% and 38.10%, respectively). The rate of infective complications in Group 3 was lower in comparison with both Group 1 and Group 2 (9.2% and 18.1%, respectively). The duration of in-hospital stay in Group 3 was 25.8% shorter than Group 1. We conclude that autotransfusion of centrifuged red blood cells processed from the residual blood of the CPB circuit after CPB was effective in increasing Hct values 12 hours postoperatively, reducing the need for donor blood product transfusions, the rate of infective complications and lenght of stay in hospital.     

Porosity of Calcium Silicate Hydrates Synthesized from Natural Rocks

In this work, the suitability of natural raw materials with various modifications of SiO₂—granite sawing waste (quartz) and opoka (a mixture of cristobalite, tridymite, quartz, and an amorphous part)—for the 1.13 nm tobermorite and xonotlite synthesis is examined, and their specific surface area, pore diameter and volume, and the predominant pores are determined. Hydrothermal syntheses were carried out at 200 °C for 12 and 72 h from mixtures with a molar ratio of CaO/SiO₂ = 1.0. X-ray diffraction analysis, simultaneous thermal analysis, and scanning electronic microscopy were used, which showed that in the lime–calcined opoka mixture the formation of crystalline calcium silicate hydrates takes place much faster than in the lime–granite sawing waste mixture. The high reactivity of amorphous SiO₂ results in the rapid formation of 1.13 nm tobermorite and xonotlite (12 h). According to Brunauer, Emmet and Taller (BET) analysis data, this product features a specific surface area of ~68 m²/g, a total pore volume of 245 × 10⁻³ cm³/g, and has dominating 1–2.5 nm and 5–20 nm diameter pores. This porosity of the material should provide good thermal insulation properties of the products made from it as no air convection occurs in the fine pores.     

The Granule Size Mediates the In Vivo Foreign Body Response and the Integration Behavior of Bone Substitutes

The physicochemical properties of synthetically produced bone substitute materials (BSM) have a major impact on biocompatibility. This affects bony tissue integration, osteoconduction, as well as the degradation pattern and the correlated inflammatory tissue responses including macrophages and multinucleated giant cells (MNGCs). Thus, influencing factors such as size, special surface morphologies, porosity, and interconnectivity have been the subject of extensive research. In the present publication, the influence of the granule size of three identically manufactured bone substitute granules based on the technology of hydroxyapatite (HA)-forming calcium phosphate cements were investigated, which includes the inflammatory response in the surrounding tissue and especially the induction of MNGCs (as a parameter of the material degradation). For the in vivo study, granules of three different size ranges (small = 0.355–0.5 mm; medium = 0.5–1 mm; big = 1–2 mm) were implanted in the subcutaneous connective tissue of 45 male BALB/c mice. At 10, 30, and 60 days post implantationem, the materials were explanted and histologically processed. The defect areas were initially examined histopathologically. Furthermore, pro- and anti-inflammatory macrophages were quantified histomorphometrically after their immunohistochemical detection. The number of MNGCs was quantified as well using a histomorphometrical approach. The results showed a granule size-dependent integration behavior. The surrounding granulation tissue has passivated in the groups of the two bigger granules at 60 days post implantationem including a fibrotic encapsulation, while a granulation tissue was still present in the group of the small granules indicating an ongoing cell-based degradation process. The histomorphometrical analysis showed that the number of proinflammatory macrophages was significantly increased in the small granules at 60 days post implantationem. Similarly, a significant increase of MNGCs was detected in this group at 30 and 60 days post implantationem. Based on these data, it can be concluded that the integration and/or degradation behavior of synthetic bone substitutes can be influenced by granule size.     

A population‐based single nucleotide polymorphism array analysis of genomic aberrations in younger adult acute lymphoblastic leukemia patients

Adult acute lymphoblastic leukemia (ALL) is characterized by a high frequency of abnormal karyotypes some of which are related to outcome. Single nucleotide polymorphism (SNP) array analysis provides a highly sensitive platform to detect large and small genomic aberrations. SNP array profiling data in adult ALL are limited and further systematic studies of this patient group are needed. We performed a population‐based SNP array analysis of genomic aberrations and their influence on survival in 66 Lithuanian 18–65 year old ALL patients diagnosed between 2007 and 2013. Most aberrations were detected in chromosome arm 9p, chromosome arm 6q, chromosome arm 13q, and chromosome 17. The recurrently targeted copy number abnormalities involved several leukemia‐related genes—CDKN2A/B, MLL, IKZF1, PAX5, RB1, TP53, and ETV6. We identified several new recurrent aberrations with possible new target genes: SMARCA4 in 19p13.2, RNASEL in 1q25.3, ARHGEF12 in 11q23.3, and LYL1 in 19p13.2. Aberrations in chromosome 13 and the RB1 gene as well as CDKN2A/B gene status were related to the outcome. © 2015 Wiley Periodicals, Inc.