Distribution of 125I-labeled [2-8]-leucopyrokinin, active analog of leucopyrokinin in rats

The brain and internal organs distribution of 125I-labeled [2-8]-leucopyrokinin ([2-8]-LPK), a truncated analog of leucopyrokinin (LPK), an insect myotropic peptide injected into the lateral brain ventricle was determined in rats. A high accumulation of this analog in adrenals and in the hypothalamus and hippocampus of the brain was found. A lesser but significant [2-8]-LPK accumulation in other internal organs and parts of the brain was also observed. The results of the present study confirm results of our previous study performed on the distribution of labeled native LPK in rats. A possible significance of obtained results for the brain function was discussed.     

A novel mechanism of action of the fumagillin analog, TNP-470, in the B16F10 murine melanoma cell line

TNP-470, a semisynthetic derivative of fumagillin, is an acknowledged angiogenesis inhibitor, presently undergoing clinical trials. It exerts an anti-proliferative effect directed against endothelial cells. This effect is known to be based on cell cycle inhibition effected by the p53/p21 pathway. We observed short-term toxicity of TNP-470 in the B16F10 murine melanoma cell line in vitro and investigated the mechanism of action. Cell death occurred as soon as 2 h after the addition of TNP-470, without typical apoptotic features. The toxic effect could be modulated and it depended on the type of culture medium or supplementation with anti-oxidants. Addition of N-acetylcysteine protected B16F10 cells from TNP-470-induced death and inhibited an increase in the generation of reactive oxygen species (ROS), which are detected by the 2',7'-dichlorodihydrofluorescein diacetate probe. We conclude that TNP-470 can induce intracellular generation of ROS, which act toxically inside B16F10 cells. One may suggest that this novel activity of TNP-470 might be beneficial in some cases, but it could also be responsible for some undesirable side-effects. The possibility of its modulation gives a prospect for controlling the action of this potential drug and probably its derivatives.     

Thrombolysis and stent implantation in a child with an acute occlusion of the modified Blalock-Taussig shunt--a case report

A case of a 5-year-old boy with complex heart disease and acute occlusion of modified Blalock-Taussig shunt is presented. The patient was treated with balloon angioplasty and local infusion of recombinant tissue plasminogen activator without persistent good effect. He was successful treated with the implantation of two coronary stents into the occluded shunt.     

Recurrent ventricular fibrillation during a febrile illness as the first manifestation of Brugada syndrome--a case report

A case of a 33-year-old male who was admitted to the hospital due to recurrent ventricular fibrillation during a febrile illness is presented. Initially, the patient was diagnosed with acute myocardial infarction and received thrombolytic treatment. Echocardiography and coronary angiography were normal. Right precordial ECG leads recorded one and two intercostal spaces higher than normal as well as ECG obtained following ajmaline administration revealed a typical Brugada pattern.     

Effects of cardiopulmonary bypass on the expression of adhesive molecules in children undergoing cardiac surgery due to congenital heart disorders

BACKGROUND: Infants and small children who undergo cardiac surgery due to congenital heart disorders, are at risk of developing inflammatory complications and multi-organ failure. AIM: To assess the changes in the expression of adhesive molecules on neutrophils and in peripheral blood plasma in children undergoing cardiac surgery with or without the use of cardiopulmonary bypass (CPB). METHODS: In 18 children who underwent surgery with the use of CPB and in 7 children who underwent surgery without CPB, the expression of CD11b, CD11c and CD62L molecules on neutrophils and soluble adhesive molecules - L-selectin and ICAM-1, was assessed before, during and after cardiac surgery. RESULTS: A significant increase in the expression of CD11b on neutrophils at the time of the initiation of CPB was observed. The most pronounced decrease in the expression of CD11c was detected at the end of surgical procedure. There was also a negative correlation between L-selectin concentration measured at the end of CPB and CPB duration as well as between ICAM-1 concentration and duration of hypothermia. CONCLUSIONS: Cardiac surgery influences the expression of adhesive molecules on neutrophils and in blood plasma. These changes are more pronounced in children who undergo CPB, and depend on CPB duration as well as the use of hypothermia.     

Implantable cardioverter-defibrillators in children

BACKGROUND: Implantable cardioverter-defibrillators (ICD) have been increasingly used in adult patients for the prevention of sudden cardiac death (SCD). The usefulness and feasibility of ICD implantation in children have been less well established. AIM: To analyse indications, results and safety of ICD therapy in children. METHODS: ICDs were implanted in seven children, aged from 6 to 17 years. All patients underwent cardiological evaluation which included analysis of medical history, physical examination, chest X-ray, standard ECG, 24-hour Holter ECG monitoring and echocardiography. RESULTS: In five children devices were implanted due to aborted sudden death (ventricular fibrillation) whereas in the remaining two - as a primary prevention of SCD. Three children had hypertrophic cardiomyopathy, one - dilated cardiomyopathy, one - mitral valve prolapse and QT prolongation, one - congenital long QT syndrome and the remaining patient - idiopathic ventricular tachycardia. Single-chamber devices were implanted in six children, and dual-chamber system - in one patient. In all patients endocardial leads were implanted and ICD pocket was formed under the greater pectoral muscle. During follow-up ranging between four months to 5.4 years, four children developed ventricular fibrillation or ventricular tachycardia which were terminated by appropriate ICD discharges. CONCLUSIONS: 1. ICD implantation in children is effective in the prevention of SCD. 2. In our population, the most frequent indications for device implantation were life-threatening ventricular arrhythmias occurring in patients with cardiomyopathy. 3. Cardiac arrest due to ventricular fibrillation may occur in children without a history of aborted SCD. 4. ICD implantation in children is feasible and safe.     

Failure to recruit anti-inflammatory CD103+ dendritic cells and a diminished CD4+ Foxp3+ regulatory T cell pool in mice that display excessive lung inflammation and increased susceptibility to Mycobacterium tuberculosis

Susceptibility to Mycobacterium tuberculosis is characterized by excessive lung inflammation, tissue damage, and failure to control bacterial growth. To increase our understanding of mechanisms that may regulate the host immune response in the lungs, we characterized dendritic cells expressing CD103 (α(E) integrin) (αE-DCs) and CD4(+) Foxp3(+) regulatory T (T(reg)) cells during M. tuberculosis infection. In resistant C57BL/6 and BALB/c mice, the number of lung αE-DCs increased dramatically during M. tuberculosis infection. In contrast, highly susceptible DBA/2 mice failed to recruit αE-DCs even during chronic infection. Even though tumor necrosis factor alpha (TNF-α) is produced by multiple DCs and macrophage subsets and is required for control of bacterial growth, αE-DCs remained TNF-α negative. Instead, αE-DCs contained a high number of transforming growth factor beta-producing cells in infected mice. Further, we show that T(reg) cells in C57BL/6 and DBA/2 mice induce gamma interferon during pulmonary tuberculosis. In contrast to resistant mice, the T(reg) cell population was diminished in the lungs, but not in the draining pulmonary lymph nodes (PLN), of highly susceptible mice during chronic infection. T(reg) cells have been reported to inhibit M. tuberculosis-specific T cell immunity, leading to increased bacterial growth. Still, despite the reduced number of lung T(reg) cells in DBA/2 mice, the bacterial load in the lungs was increased compared to resistant animals. Our results show that αE-DCs and T(reg) cells that may regulate the host immune response are increased in M. tuberculosis-infected lungs of resistant mice but diminished in infected lungs of susceptible mice.     

Facial nerve anastomosis in the mastoid portion using a cable graft. Case report

We describe a case of a 52-year-old woman in whom surgery for two tumours located in the cerebellar hemisphere and in the posterior petrous bone was complicated by interruption of the facial nerve (CN VII). During the same procedure, anastomosis of CN VII, using a cable graft harvested from the great auricular nerve, was performed. Seven months later the first signs of reinnervation of the facial muscles were noticed. Two and a half years after surgery, CN VII function was assessed as grade II/III according to the House-Brackmann scale. The authors emphasize the significance of immediate repair of CN VII in modern skull base surgery but also the importance of a patient's self-training to obtain the best functional outcome of the facial reanimation. Reconstruction using the great auricular nerve has two significant advantages: first, the patient avoids further procedures for nerve repair, and second, the harvested nerve is located in direct proximity to the operation area.     

Familial occurrence of FXTAS caused by premutation in the FMR1 gene

The FMR1 gene premutation has recently been reported to be associated with a neurodegenerative syndrome, characterized by intention tremor, gait ataxia and cognition deficits in persons older than 50 years. We present a 74-year-old man with very severe intention tremor, slight postural tremor and gait ataxia. The molecular analysis revealed that he was a carrier of 91 CGG repeats in the FMR1 gene. His sister (68 years old), with head tremor, was found to be a carrier of 81 CGG repeats, while his younger brother, also with slight head and postural tremor, was a carrier of 98 CGG repeats. Molecular analysis of the proband's asymptomatic daughter revealed an expansion over 120 CGG. Her daughter, with mild intellectual disability, was a carrier of a full mutation. Thus, in the presented family with heterogeneous clinical presentation we found 4 premutations and one full mutation in the FMR1 gene.