Keggin‐Type Polyoxometalate ([PMo12O40]3−) in Radical Initiating Systems: Application to Radical and Cationic Photopolymerization Reactions

New photoinitiating systems based on a polyoxometalate (POM) are proposed: phosphomolybdic acid in combination with silane, germane, or iodonium salt can be used to generate silyl, germyl, or phenyl radicals as well as silylium cations. The photochemical mechanisms are studied by steady‐state photolysis and electron spin resonance. The phosphomolybdic acid/silane/iodonium salt system can initiate either the radical photopolymerization of acrylates or the cationic photopolymerization of epoxides. The synthesis of interpenetrated polymer networks can also be carried out. The mechanical properties of the synthesized polymers are affected by the presence of POM in the matrix, as shown by their dynamic mechanical analysis (DMA).

     

Medical therapy of a left-sided native valve endocarditis with neurologic sequela

Infective endocarditis could present with a plethora of signs and symptoms. Among the rarity of its presentation is acute confusion associated with neurological deficits, mimicking stroke especially in the young population. We report a case of a 33-year-old young man with acute right-sided hemiparesis and confusion 2 weeks after tooth extraction. The brain CT and MRI was consistent with new infarction on the left middle and anterior cerebral arteries’ territory. Echocardiography unveiled the existence of posterior mitral valve leaflet vegetation. Blood culture grew Group B beta-haemolytic Streptococcus, sensitive to penicillin. Two weeks of intravenous gentamicin with 6 weeks of intravenous benzylpenicillin were administered. In this case report, we highlight the importance of recognition of infective endocarditis in a young patient presenting with cerebrovascular accident following tooth extraction.A wide variety of organisms have been attributed to infections of native heart valves. Among them are staphylococci, streptococci, and the group of Haemophilus, Aggregatibacter (previously Actinobacillus), Cardiobacterium, Eikenella corrodens, Kingella (HACEK) organisms. Aortic or mitral valves (left-sided) accounts for the vast majority of endocarditis cases in non-intravenous drug users. Right sided infective endocarditis contributes 5-10% of all cases of endocarditis, usually among intravenous drug users.1 Emboli from left-sided valvular vegetation can become dislodged or fragmented into the brain via systemic circulation, resulting in neurological complications. In contrast with the right sided embolus, the right sided infective endocarditis may cause embolic phenomenon due to preexisting congenital heart diseases such as patent foramen ovale, atrial septal defect, or ventricular septal defect. In this case report, we highlight the importance of recognition of infective endocarditis with an embolic stroke in a young confused patient with normal cardiac valve following a simple dental extraction procedure.     

Association between BMI-1 expression, acute graft-versus-host disease, and outcome following allogeneic stem cell transplantation from HLA-identical siblings in chronic myeloid leukemia

Expression of CD7, ELA-2, PR-3, and the polycomb group gene BMI-1 reflects the intrinsic heterogeneity and predicts prognosis of patients with chronic myeloid leukemia (CML) who were not treated with allogeneic stem cell transplantation (allo-SCT). This study investigated whether expression of these genes determined outcome following allo-SCT in a cohort of 84 patients with chronic-phase (CP) CML. We found that patients expressing BMI-1 at a "high" level before allo-SCT had an improved overall survival (P = .005) related to a reduced transplantation-related mortality. In multivariate analysis, when adjusted for the European Group for Blood and Marrow Transplantation (EBMT)-Gratwohl score and other prog-nostic factors, there was an independent association between BMI-1 expression and grades 2 to 4 acute graft-versus-host disease (relative risk [RR] = 2.85; 95% confidence interval [CI], 1.3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions.     

Infantile pyknocytosis,a rare cause of hemolytic anemia in newborns: report of two cases in twin girls and literature overview

Infantile pyknocytosis is a rare cause of neonatal jaundice and hemolytic anemia. We report on two cases in twin girls that were diagnosed on peripheral blood smear reading. Pyknocytosis should be considered in cases of early unexplained severe hemolytic anemia, and systematic peripheral smear review performed. Its management consists of phototherapy and RBC transfusion.     

Inhibitory receptor molecules in chronic hepatitis B and C infections: novel targets for immunotherapy?

Chronic HBV and HCV infections are the leading cause of liver‐related morbidity and mortality. For effective antiviral immunity, virus‐specific T cells are required, but these cells have been shown to be weak or absent in chronic HBV and HCV patients. One of the mechanisms that underlies the impaired T‐cell response is the result of the continuously high viral load that causes HBV‐specific and HCV‐specific T cells to become exhausted, which is characterized by impaired proliferation, cytokine production and cytotoxic activity of T cells as well as high susceptibility to apoptosis. In vitro studies from chronic HBV and HCV patients as well as in vivo studies in animal models demonstrated a reversible state of T‐cell exhaustion, which can be manipulated to reinvigorate the specific antiviral immune responses. In chronic HCV infection, this concept has been explored in clinical trials by administration of specific antibody to block the inhibitory pathways. The manipulation of inhibitory receptors is a promising and potential strategy for immunotherapeutic interventions in chronic HBV and HCV patients to facilitate complete elimination of the viruses or sustained viral control. Copyright © 2013 John Wiley & Sons, Ltd.     

Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors

In continuation of our previous work on the design and synthesis of topoisomerase II (Topo II) inhibitors and DNA intercalators, a new series of quinoxaline derivatives were designed and synthesized. The synthesized compounds were evaluated for their cytotoxic activities against a panel of three cancer cell lines (Hep G‐2, Hep‐2, and Caco‐2). Compounds 18b, 19b, 23, 25b , and 26 showed strong potencies against all tested cell lines with IC₅₀ values ranging from 0.26 ± 0.1 to 2.91 ± 0.1 µM, comparable with those of doxorubicin (IC₅₀ values ranging from 0.65 ± 0.1 to 0.81 ± 0.1 µM). The most active compounds were further evaluated for their Topo II inhibitory activities and DNA intercalating affinities. Compounds 19b and 19c exhibited high activities against Topo II (IC₅₀ = 0.97 ± 0.1 and 1.10 ± 0.1 µM, respectively) and bound the DNA at concentrations of 43.51 ± 2.0 and 49.11 ± 1.8 µM, respectively, whereas compound 28b exhibited a significant affinity to bind the DNA with an IC₅₀ value of 37.06 ± 1.8 µM. Moreover, apoptosis and cell‐cycle tests of the most promising compound 19b were carried out. It was found that 19b can significantly induce apoptosis in Hep G‐2 cells. It has revealed cell‐cycle arrest at the G2/M phase. Moreover, compound 19b downregulated the Bcl‐2 levels, indicating its potential to enhance apoptosis. Furthermore, molecular docking studies were carried out against the DNA–Topo II complex to examine the binding patterns of the synthesized compounds.     

Wilson disease: copper deficiency and iatrogenic neurological complications with zinc therapy

A 17‐year‐old female was diagnosed with Wilson disease and commenced on oral zinc therapy. She re‐presented 6 months later with a fall and had classical signs of subacute combined degeneration of the spinal cord confirmed on nerve conduction studies, as a result of zinc‐induced copper deficiency. After 6 months of copper therapy, she made a complete recovery with no residual neurological deficits. Early detection of zinc‐induced copper deficiency and stringent follow‐up mechanisms are crucial. Early initiation of copper replacement may both limit and completely reverse neurological deficits.     

Cardiac-specific inducible and conditional gene targeting in mice

Mouse genetic engineering has revolutionized our understanding of the molecular and genetic basis of heart development and disease. This technology involves conditional tissue-specific and temporal transgenic and gene targeting approaches, as well as introduction of polymorphisms into the mouse genome. These approaches are increasingly used to elucidate the genetic pathways underlying tissue homeostasis, physiology, and pathophysiology of adult heart. They have also led to the development of clinically relevant models of human cardiac diseases. Here, we review the technologies and their limitations in general and the cardiovascular research community in particular.