Pentoxifylline associated to hypertonic saline solution attenuates inflammatory process and apoptosis after intestinal ischemia/reperfusion in rats

PURPOSE:To evaluate intestinal inflammatory and apoptotic processes after intestinal ischemia/reperfusion injury, modulated by pentoxifylline and hypertonic saline.METHODS:It was allocated into four groups (n=6), 24 male Wistar rats (200 to 250g) and submitted to intestinal ischemia for 40 min and reperfusion for 80 min: IR (did not receive any treatment); HS group (Hypertonic Saline, 4ml/kg-IV); PTX group (Pentoxifylline, 30mg/kg-IV); HS+PTX group (Hypertonic Saline and Pentoxifylline). All animals were heparinized (100U/kg). At the end of reperfusion, ileal fragments were removed and stained on hematoxylin-eosin and histochemical studies for COX-2, Bcl-2 and cleaved caspase-3.RESULTS:The values of sO2 were higher on treated groups at 40 minutes of reperfusion (p=0.0081) and 80 minutes of reperfusion (p=0.0072). Serum lactate values were lower on treated groups after 40 minutes of reperfusion (p=0.0003) and 80 minutes of reperfusion (p=0.0098). Morphologic tissue injuries showed higher grades on IR group versus other groups: HS (p=0.0006), PTX (p=0.0433) and HS+PTX (p=0.0040). The histochemical study showed lesser expression of COX-2 (p=0.0015) and Bcl-2 (p=0.0012) on HS+PTX group. A lower expression of cleaved caspase-3 was demonstrated in PTX (p=0.0090; PTXvsIR).CONCLUSION:The combined use of pentoxifylline and hypertonic saline offers best results on inflammatory and apoptotic inhibitory aspects after intestinal ischemia/reperfusion.São Paulo University Medical SchoolUSP Medical SchoolFederal University of São Paulo Medical SchoolUSP School of MedicineUSP School of Medicine Department of SurgeryUSP Medical School Department of SurgeryUNIFESP, Medical SchoolSciEL

Electronic structure of the Ni-Pd-P and Ni-Pt-P metallic glasses: A pulsed NMR study

A pulsed NMR and magnetic susceptibility study of the electronic structure is reported for the rapidly quenched metallic glass systems: (Ni0.50Pd0.50)100-xPx (where 16≦x≦26.5), (NiyPd1-y)80P20 (where 0.20≦y≦0.80), and (NiyPt1-y)75P25 (where 0.20≦y≦0.68). The 31P Knight shift and nuclear spin-lattice relaxation rate in all three systems depend only on the P concentration, x, and not the Ni concentration, y, nor whether the second transition metal is Pd or Pt. Both the shift and relaxation rate for 31P are attributed solely to the direct contact hyperfine interaction. The 195Pt Knight shift and magnetic susceptibility for (NiyPt1-y)75P25 do depend on both the Ni concentration and temperature, enabling a determination of the contributions to the shift arising from the direct contact hyperfine and core polarization interactions. The results are discussed in terms of a rigid two-band picture with estimates being made for the s- and d-band densities of states and hyperfine coupling constants. There is strong evidence for a transfer of charge from the P metalloid atoms (M) to the d states of the transition-metal atoms (T), which is consistent with the dense random packing model for T100-xMx metallic glasses

Mammalian BTBD12 (SLX4) Protects against Genomic Instability during Mammalian Spermatogenesis

The mammalian ortholog of yeast Slx4, BTBD12, is an ATM substrate that functions as a scaffold for various DNA repair activities. Mutations of human BTBD12 have been reported in a new sub-type of Fanconi anemia patients. Recent studies have implicated the fly and worm orthologs, MUS312 and HIM-18, in the regulation of meiotic crossovers arising from double-strand break (DSB) initiating events and also in genome stability prior to meiosis. Using a Btbd12 mutant mouse, we analyzed the role of BTBD12 in mammalian gametogenesis. BTBD12 localizes to pre-meiotic spermatogonia and to meiotic spermatocytes in wildtype males. Btbd12 mutant mice have less than 15% normal spermatozoa and are subfertile. Loss of BTBD12 during embryogenesis results in impaired primordial germ cell proliferation and increased apoptosis, which reduces the spermatogonial pool in the early postnatal testis. During prophase I, DSBs initiate normally in Btbd12 mutant animals. However, DSB repair is delayed or impeded, resulting in persistent γH2AX and RAD51, and the choice of repair pathway may be altered, resulting in elevated MLH1/MLH3 focus numbers at pachynema. The result is an increase in apoptosis through prophase I and beyond. Unlike yeast Slx4, therefore, BTBD12 appears to function in meiotic prophase I, possibly during the recombination events that lead to the production of crossovers. In line with its expected regulation by ATM kinase, BTBD12 protein is reduced in the testis of Atm−/− males, and Btbd12 mutant mice exhibit increased genomic instability in the form of elevated blood cell micronucleus formation similar to that seen in Atm−/− males. Taken together, these data indicate that BTBD12 functions throughout gametogenesis to maintain genome stability, possibly by co-ordinating repair processes and/or by linking DNA repair events to the cell cycle via ATM

Strategic Decision Behavior and Audit Quality of Big and Small Audit Firms in a Tendering Process

We investigate the strategic decision making of audit firms in a tendering process. In particular, we are interested in how audit firms behave to acquire audit clients and which audit quality is ensured. Our main findings are manifold. First, if two big audit firms are competing, we do not observe that each firm tries to acquire all clients. However, if one big and one small audit firm are competing, we find evidence that the big audit firm generally apply strategies to acquire all available clients. In contrast, the small audit firm uses a clear "Guerilla Strategy" which means that the firm concentrates only on few clients whereas the other clients are almost ignored. Second, small audit firms are better off if more clients do exist in the tendering process. Thus, the legislator should ensure that more audit clients are tendered if the competitiveness of smaller audit firms should be enhanced. Third, in a situation in which the competitive advantage of big audit firms increases over-proportionally, we do not observe that big audit firms are able to decrease the market share of small audit firms markedly or are even able to push small audit firms out of the market. Fourth, we find that the quality level of an audit is higher if the client is acquired by a small audit firm. This implies that increasing the number of smaller audit firms could increase the quality level of the audit market

Multi-task Deep Learning Based CT Imaging Analysis For COVID-19: Classification and Segmentation

ABSTRACTThe fast spreading of the novel coronavirus COVID-19 has aroused worldwide interest and concern, and caused more than one million and a half confirmed cases to date. To combat this spread, medical imaging such as computed tomography (CT) images can be used for diagnostic. An automatic detection tools is necessary for helping screening COVID-19 pneumonia using chest CT imaging. In this work, we propose a multitask deep learning model to jointly identify COVID-19 patient and segment COVID-19 lesion from chest CT images. Our motivation is to leverage useful information contained in multiple related tasks to help improve both segmentation and classification performances. Our architecture is composed by an encoder and two decoders for reconstruction and segmentation, and a multi-layer perceptron for classification. The proposed model is evaluated and compared with other image segmentation and classification techniques using a dataset of 1044 patients including 449 patients with COVID-19, 100 normal ones, 98 with lung cancer and 397 of different kinds of pathology. The obtained results show very encouraging performance of our method with a dice coefficient higher than 0.78 for the segmentation and an area under the ROC curve higher than 93% for the classification.</jats:p