Anti-arrhythmia effect of prolecophen in patients with extrasystole in comparison with other anti-arrhythmia drugs

Oral prolecohen (LEK, Yugoslavia) was given in a single dose of 300 mg to 15 patients with extrasystole of various genesis. The drug produced an antiarrhythmic effect in 50% of patients with ventricular extrasystole, but in those with supraventricular extrasystole. Prolecophenum showed a good tolerance. In 20% of the patients the adverse reactions appeared as mild headache, dizziness, dry mouth, malaise in the epigastric region. There is also evidence for efficacy of other antiarrhythmic agents used in this group of patients.     

Slam Haplotype 2 Promotes NKT But Suppresses Vγ4+ T-Cell Activation in Coxsackievirus B3 Infection Leading to Increased Liver Damage But Reduced Myocarditis

There are two major haplotypes of signal lymphocytic activation molecule (Slam) in inbred mouse strains, with the Slam haplotype 1 expressed in C57Bl/6 mice and the Slam haplotype 2 expressed in most other commonly used inbred strains, including 129 mice. Because signaling through Slam family receptors can affect innate immunity [natural killer T cell (NKT) and γ-δ T-cell receptor], and innate immunity can determine susceptibility to coxsackievirus B3 (CVB3) infection, the present study evaluated the response of C57Bl/6 and congenic B6.129c1 mice (expressing the 129-derived Slam locus) to CVB3. CVB3-infected C57Bl/6 male mice developed increased myocarditis but reduced hepatic injury compared with infected B6.129c1 mice. C57Bl/6 mice also had increased γδ⁺ and CD8⁺interferon-γ⁺ cells but decreased numbers of NKT (T-cell receptor β chain + mCD1d tetramer⁺) and CD4⁺FoxP3⁺ cells compared with B6.129c1 mice. C57Bl/6 mice were infected with CVB3 and treated with either α-galactosylceramide, an NKT cell-specific ligand, or vehicle (dimethyl sulfoxide/PBS). Mice treated with α-galactosylceramide showed significantly reduced myocarditis. Liver injuries, as determined by alanine aminotransferase levels in plasma, were increased significantly, confirming that NKT cells are protective for myocarditis but pathogenic in the liver.Myocarditis is an inflammation of the cardiac muscle that follows microbial infections.¹ Among viruses, enteroviruses including coxsackie B viruses are common etiologic agents.^2,3 Although infectious agents act as a trigger for myocarditis, there is considerable debate as to the actual mechanism(s) of myocardial injury. Viruses directly cause cellular dysfunction either through induced cell death, shut down of cell RNA and protein synthesis, or viral protease cleavage of contractile proteins.^4,5 In addition, cytokines such as IL-1β, IL-6, and tumor necrosis factor α, which are elicited from resident cells in the heart subsequent to infection, can suppress contractility, leading to cardiac dysfunction.⁶ Finally, host immune responses to infection may kill myocytes, leading to cardiac stress. Host response can be directed specifically toward virally infected cardiocytes or infection can trigger autoimmunity to cardiac antigens (autoimmunity), which destroys both infected and uninfected myocytes.⁷Host innate immune responses occur rapidly, subsequent to viral infections, and usually have broad specificity, unlike the classic adaptive immune response, which requires a week or more for development of a measurable response in the naive individual but is highly specific to the inducing pathogen. The innate immune response both helps to control microbe load before generation of the adaptive immune response and has a major impact on the phenotype and intensity of the adaptive response. Two types of T cells representing innate immunity are natural killer T cells (NKT) and T cells expressing the γ-δ T-cell receptor (γδ⁺). A study by Wu et al⁸ showed that in vivo administration of α-galactosylceramide, a ligand that specifically activates NKT cells, protects mice from coxsackievirus B3 (CVB3)-induced myocarditis. Prior studies have shown that signaling through Slam family receptors has a major impact on NKT cell development,^9–11 and that different Slam haplotypes can have distinct effects on NKT cell response and function.^9,12 There are two major Slam haplotypes, Slam haplotype 1 and Slam haplotype 2, that distinguish commonly used inbred mouse strains.^13,14 Slam haplotype 1 is present in C57Bl/6, and Slam haplotype 2 is present in most other commonly used mouse strains including 129S1/SvImJ and BALB/c mice. The congenic B6.129c1 mouse expresses the genetic region of chromosome 1 containing the 129-derived Slam haplotype 2 locus on the C57Bl/6 background and was used previously to show Slam haplotype control of liver NKT cell numbers and NKT cell cytokine production.¹² In addition, Slam haplotypes previously were shown to regulate macrophage tumor necrosis factor production in response to lipopolysaccharide.¹² Although less well studied, Slam family–receptor signaling also has been shown to affect γδ⁺ T-cell development. Studies using human peripheral blood mononuclear cells stimulated in vitro with antibody to CD3 and either IL-2, anti-CD150 (SLAM), or IL-15 showed that all three stimulation protocols resulted in γδ⁺ T-cell survival. However, co-culture with anti-CD3 and anti-CD150 resulted in selective proliferation of CD8⁺CD56⁺γδ⁺ T cells expressing the Vδ1 chain, and cells co-cultured with anti-CD3 and IL-15 resulted in preferential generation of CD8⁻CD56⁻γδ⁺ cells expressing the Vδ2 chain.¹⁵ Therefore, SLAM signaling can impact the generation of a subpopulation of the total γδ⁺ cell population in humans. Prior studies from the Huber laboratory have shown that a subpopulation of γδ⁺ cells is crucial to myocarditis susceptibility subsequent to CVB3 infection¹⁶ and that the relevant γδ⁺ cell expresses both CD8 and the Vγ4 chain.^16,17 This raised the question of whether Slam haplotypes modulated selected γδ⁺ cell subsets in the mouse, as it does in humans, and whether the Slam haplotype specifically could affect activation of the CD8⁺Vγ4⁺ T cell, which is known to be pathogenic in CVB3-induced myocarditis.CVB3 infection of mice results in multiple organ infection, including pancreas, liver, and heart with accompanying tissue injury in all tissues. There are well-established differences in disease susceptibility between BALB/c and C57Bl/6 mice, strains expressing the two distinct Slam haplotypes. C57Bl/6 mice are highly susceptible to type 2 autoimmune hepatitis and develop extensive hepatic inflammation, whereas BALB/c mice are resistant to this disease and show no inflammation.¹⁸ In contrast, BALB/c mice are more susceptible to myocarditis^19–22 compared with the more resistant C57Bl/6 strain. However, there are many genetic differences between BALB/c and C57Bl/6 mice, which may influence disease development or development and activation of specific innate effectors such as NKT and γδ T cells. The goal of the current study was to determine whether Slam haplotype affected NKT and Vγ4⁺ T-cell responses subsequent to CVB3 infection using C57Bl/6 congenic mice in which the Slam locus alone differed between the mouse strains, and whether haplotype-dependent NKT/Vγ4⁺ cell response had a distinct effect in different organs infected with the virus in the absence of the many other genetic differences between BALB/c and C57Bl/6 mice.     

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).

     

Imaging techniques for muscle injury in sports medicine and clinical relevance

Magnetic resonance imaging (MRI) and ultrasound are the imaging modalities of choice to assess muscle injuries in athletes. Most authors consider MRI as the reference standard for evaluation of muscle injuries, since it superiorly depicts the extent of injuries independently of its temporal evolution, and due to the fact that MRI seems to be more sensitive for the detection of minimal injuries. Furthermore, MRI may potentially allow sports medicine physicians to more accurately estimate recovery times of athletes sustaining muscle injuries in the lower limbs, as well as the risk of re-injury. However, based on data available, the specific utility of imaging (including MRI) regarding its prognostic value remains limited and controversial. Although high-quality imaging is systematically performed in professional athletes and data extracted from it may potentially help to plan and guide management of muscle injuries, clinical (and functional) assessment is still the most valuable tool to guide return to competition decisions.     

Laparoscopy assisted transjejunal endoscopic retrograde cholangiography for treatment of intrahepatic duct stones in a post Roux-en-Y patient

We report a case of a 17-year-old female patient, who was operated on for choledocal cyst with Roux-en Y hepatojejunostomy. She was admitted to hospital with recurrent attacks of acute ascending cholangitis due to left intrahepatic duct stones. After a failed attempt at conventional endoscopic retrograde cholangiopancreatography through the anatomical route, she was treated successfully with laparoscopy assisted transjejunal endoscopic retrograde cholangiography.Endoscopic access to the biliary system can be difficult in patients with surgically altered anatomy of the upper gastrointestinal tract (GIT), such as Roux-en-Y reconstruction, because of the changed anatomy. However, endoscopic retrograde cholangiopancreatography (ERCP) is challenging in cases such as our patient;1,2 this is due to the distance needed to be traversed and looping. Our objective in presenting this particular case is to describe and highlight a laparoscopy assisted transjejunal ERCP to permit successful treatment and removal of intrahepatic duct stones in a post Roux-en-Y patient, and to minimize surgical inetervention to reduce unnecessary risks to the patient.     

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.