The visual acuity impairment as the only sign of cerebral aneurysms--case report

Cerebral aneurysms are the most common reason of subarachnoid haemorrhage at the age of 50-60. Though the results of such haemorrhage are severe (high morbidity and mortality), it is quite often, the first noticeable sign of the problem. Previous symptoms i. e. headache, ophthalmic disturbances, temporary neurological symptoms are often passed over. The authors present the case of a young woman with cerebral aneurysms, in which the visual acuity impairment was the only symptom of the disease.     

Why human pemphigoid autoantibodies do not trigger disease by the passive transfer into mice?

The recapitulation of disease features in animals by the transfer of patient autoantibodies has been used to demonstrate the autoimmune nature of several diseases. Failure of disease induction by the passive transfer of autoantibodies has been assigned to a limited cross-reactivity of the autoantibodies with the murine tissue. However, the possibility that the passively transferred "inflammatory" patient autoantibodies may not be able to unfold their pathogenic potential due to restricted Fc-dependent effector functions has not yet been systematically explored. In this study we analyze the interaction of patients' autoantibodies with murine complement and granulocytes. Bullous pemphigoid is a blistering disease associated with autoantibodies, which are thought to induce subepidermal blistering by activating complement and granulocytes. The passive transfer of patients autoantibodies failed to induce skin blistering in wild type mice. The cross-reactivity of pemphigoid autoantibodies with murine antigens was analyzed in silico, ex vivo and by the passive transfer of IgG in vivo. Complement-fixing ability of patients' autoantibodies was evaluated by complement-binding test. Granulocyte activation was assessed by reactive oxygen species production assay and the cryosection model. We have found that although pemphigoid autoantibodies bound to murine skin in vitro and in vivo, they showed a lower capacity to fix murine complement and a reduced ability to activate murine granulocytes when compared with human complement and cells, respectively. These results indicate that for disease models using the passive transfer of patient autoantibodies, their interaction with the innate factors of the host should be optimized to match the human situation.     

The effects of orexins on monoaminerg-induced changes in vasopressin level in rat neurohypophyseal cell cultures

The effects of orexin–monoaminergic compound interactions on vasopressin release were studied in 14-day neurohypophyseal cell cultures from adult rats, prepared by an enzymatic dissociation technique. The vasopressin contents of the supernatants were determined by radioimmunoassay. Following administration of either orexin-A or orexin-B in increasing doses, significant changes were not observed in the vasopressin levels of the supernatant media. The vasopressin level substantially increased after epinephrine, norepinephrine, serotonin, histamine, dopamine or K⁺ treatment. Preincubation with either orexin-A or orexin-B reduced the epinephrine-, histamine- or serotonin-induced increases in vasopressin level, but the vasopressin concentrations of the supernatant media remained above the control level. There was no significant difference in decreasing effect between orexin-A and orexin-B. Neither orexin-A nor orexin-B induced changes in vasopressin release following monoaminergic compound treatment. The results indicate that the changes in vasopressin secretion induced by the monoaminergic system can be directly influenced by orexin system. It may be presumed that the orexins can play a physiological role in the regulation of the water metabolism by reducing the effect of increased vasopressin release caused by monoaminergic compounds. The interactions between the monoaminergic and orexin systems regarding vasopressin secretion occur at both the hypothalamic and the neurohypophyseal level.     

The role of the oral flora in the pathogenesis of aspiration pneumonia

The bacterial pneumonia is one of the most frequent complications leading to death among hospitalized patients. The morbidity and mortality of pneumonia is extremely high in the intensive care units and in chronic nursing stations, especially in institutes dealing with old patients. The most common form of lung infection is the aspiration pneumonia. Periodontal diseases play an evident role in the etiology of aspiration pneumonia due to their effect to alter the oral bacterial flora. Authors review the significance of pathogen microorganisms originating from the oral cavity in the development of bacterial pneumonia. The extent of the affected population is discussed and the importance of their oral hygiene and bacterial flora is also specified. The bacterial, enzymatic and molecular pathomechanisms leading to aspiration pneumonia are described, and high risk populations and treatment types are determined. The possibilities of prevention methods for aspiration pneumonia are fully explained and recent directions of actual researches and proposals to minimize the incidence of this disease are summarized.     

Iron sucrose induced morphological and functional changes in the rat kidney

Treatment of anemia in uremic patients requires simultaneous supplementation of erythropoietin and iron. Because of the impaired iron absorption from the gastrointestinal tract in conditions of renal insufficiency, intravenous supplementation is a treatment of choice in such conditions. Iron compounds used for intravenous supplementation induce several systemic side effects, and therefore, we studied the effect of chronic exposure to iron sucrose in rats on renal function. Experiments were performed on male Wistar rats, which were infused intraperitoneally every 4 days, for 28 days with iron sucrose in a dose 1 mg/kg bw or 10 mg/kg bw diluted in 20 mL of the dialysis fluid. Control animals were infused with plain dialysis fluid. Renal function was evaluated at the beginning and at the end of the study. Additionally morphology of the kidneys was evaluated in all animals after 28 days of the study. Chronic exposure of rats to iron sucrose resulted in increased accumulation of PAS-positive material in their glomeruli: + 38% at Fe 1 mg/kg bw P < 0.05 and + 42% at Fe 10 mg/kg/bw P < 0.01 and collagen in the peritubular area: + 40% at Fe 1 mg/kg bw P < 0.005 and + 77% at Fe 10 mg/kg/bw P < 0.001. Only renal clearance of urea was decreased by 53%, P < 0.01 in rats exposed to iron sucrose at a dose of 10 mg/kg bw. Chronic exposure of rats to iron sucrose results in morphologic changes of the kidney; however, mild impairment in renal function was observed only at the highest (10 mg Fe/kg bw) concentration of iron sucrose.     

Effectiveness of cephalosporins in the sputum of patients with nosocomial bronchopneumonia

Nosocomial bronchopneumonia is a frequent complication in patients with chronic intratracheal intubation. Despite targeted antibiotic treatment, production of abundant bronchial secretion containing pathogen bacteria often tends to be chronic, and so mortality drastically increases. This problem led to an investigation of the penetration of five cephalosporin antibiotics into the sputum. Serum and sputum were collected from 24 chronically intubated patients having purulent nosocomial bronchopneumonia treated in an intensive care unit (ICU). Patients received the following doses intravenously every 24 h: five received 70 mg/kg of body weight cefuroxime, four received 110 mg/kg cefamandole, six received 80 mg/kg ceftriaxone, four received 80 mg/kg ceftazidime, and five received 80 mg/kg cefepime. Antibiotic concentrations in the serum and sputum were evaluated by capillary electrophoresis. MICs were determined for bacteria isolated from the purulent bronchial secretions. The mean levels of the cephalosporins in the sputum did not reach the MICs for the bacteria isolated from the same samples. Ceftriaxone was the only one of the investigated five cephalosporins that had a measurable concentration in the sputum (1.4 +/- 1.2 mg/liter). The low concentration of antibiotics in the purulent tracheobronchial secretion can be one of the many reasons for ineffective therapy of nosocomial bronchopneumonia in intubated patients in the ICUs. In the case of intubated or mechanically ventilated patients having chronic bronchopneumonia, determination of drug concentration in the bronchial secretion might be considered when selecting an antibiotic for treatment.     

A study to determine the safety and efficacy of imatinib mesylate in patients with chronic phase of chronic myeloid leukemia after interferon therapy failure. Four year follow-up

Targeted therapy with the use of imatinib mesylate is a recognized option for patients with chronic myeloid leukemia (CML) not eligible for allogeneic hematopoietic cell transplantation. We present results of a multicenter phase II study on the use of imatinib in chronic phase after failure to interferon-alpha (IFN-alpha). Sixty patients (27 female, 33 male), median age 46 (range, 21-64), were included with hematologic relapse (n= 11), hematologic refractoriness (n=4), cytogenetic relapse/ /+65resistance (n=40) or intolerance to IFN-alpha (n=5). The median time from CML diagnosis was 39 months (range, 4-132), the median time of IFN-alpha therapy equaled 23 months (range, 1-78). Imatinib mesylate was administered at a dose of 400 mg/day for 1 year. In patients who achieved major cytogenetic response (MCR) the therapy was continued until progression. Thirty-three (55%) patients achieved MCR after one year of treatment. At 4 years the cumulative incidence of complete cytogenetic response equaled 40% (95% CI, 29-56). Among 27 patients who did not achieve MCR at 12 moths, in 12 cases the study course was discontinued prematurely because of blast crisis (n=9), prolonged neutropenia (n=l), severe transaminases elevation (n=l) or incidental death not related to the study drug or disease (n=l). The probability of OS at 4 years equaled 82% (95% CI, 72-91) and was lower for patients with the disease duration >36 months and those with Sokal index > or =0.8. Among patients who achieved MCR, the probability of progression-free survival was 78% (95% CI, 69-85). Time to progression (cytogenetic, n=6; blast crisis, n=l) varied from 3-36 months. Conclusions: Imatinib mesylate is characterized by good tolerance and allows achieving cytogenetic response in more than half of late chronic phase CML patients with failure of interferon therapy. However, the progression rate is substantial, which raises concern regarding the curative potential of monotherapy with imatinib in this group of patients.     

Evaluation of antinociceptive and antioxidant properties of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one in mice

The aim of this study was to evaluate the influence of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) on nociceptive thresholds in mouse models of persistent pain. Influence of LPP1 on motor coordination and its antioxidant capacity in mouse brain tissue homogenates were also assessed. Pain sensitivity thresholds in animals treated with LPP1 were established using 5 % formalin solution in normoglycemic mice and in streptozotocin (STZ)-treated diabetic mice in the von Frey, hot plate, innocuous, and noxious cold water tests (water at 10 °C and 4 °C, respectively). Motor deficits were assessed in the rotarod test, whereas antioxidant capacities were evaluated using ferric reducing ability of plasma (FRAP) assay, catalase (CAT), and superoxide dismutase (SOD) activities. LPP1was antinociceptive in both phases of the formalin test, in particular, in the late phase (at doses 0.9–30 mg/kg for 66–99 % vs. control normoglycemic mice) and in a statistically significant manner increased nociceptive thresholds in response to mechanical, heat, and noxious cold stimulation in neuropathic mice (at 30 mg/kg for 274, 192, and 316 %, respectively vs. diabetic control). LPP1 did not impair motor coordination of mice in the rotarod revolving at 6 or 18 rpm. In brain tissue homogenates, it demonstrated antioxidant capacity in FRAP assay and increased SOD activity for 63 % (acute administration) and 28 % (chronic administration) vs. control. No influence on CAT activity was observed. LPP1 has significant antinociceptive properties in the formalin model and elevates pain thresholds in neuropathic mice. It has antioxidant capacity and is devoid of negative influence on animals' motor coordination.