Białaczka włochatokomórkowa oporna na standardową terapię analogiem puryn – opis przypadku i przegląd piśmiennictwa

Hairy cell leukemia (HCL) is a rare, chronic lymphoproliferative disorder. Currently, purine nucleoside analogs (PNA) constitute the first line treatment of HCL. Cladribine could induce long lasting remission in majority of patients with only a single cycle of therapy. In fact the relapsed patients could be treated successfully with cladribine too. Sometimes we observe the resistance to PNA. Rituximab and chemoimmunotherapy (rituximab plus cladribine) are effective in treatment of refractory HCL.We present a case of a 64-year-old man who was treated with rituximab after second progression of HCL. In March 2011, rituximab was given at a dose of 375 mg/m² i.v. once a week for eight weeks, with result of achievement of PR. During the last hospitalization in March 2013 the persistence of PR was confirmed.     

Małopłytkowość – wskazania do zastosowania cytokin płytkotwórczych

The most common cause of isolated thrombocytopenia is primary immune thrombocytopenia (ITP). For patients failing initial corticosteroid-based treatment and with refractory ITP post-splenectomy, thrombopoietin receptor agonists are indicated. Two of this thrombopoiesis-stimulating agents have been approved for use in ITP – eltrombopag, formulated for oral administration, once a day and romiplostim, which is administered weekly as a subcutaneous injection.     

von Willebrand factor antigen as a prognostic marker in posttraumatic acute lung injury

The specific endothelial cell product von Willebrand factor antigen (vWf:Ag) was measured in plasma and lung function tests were carried out and the following lung injury parameters measured: P(a)O2/F(i)O2 ratio, static respiratory compliance and Murray's lung injury score (LIS) in a follow-up study of 36 severely traumatized patients. Injury severity score (ISS) and APACHE II scores were calculated. Patients were classified according to the presence or absence of acute respiratory distress syndrome (ARDS) complications and survival versus death. Data collection was performed on admission to hospital and after 1-3, 5, 7, 10 days of ICU stay. On all of the occasions investigated, plasma vWf:Ag levels in ARDS patients and nonsurvivors were significantly greater than those in patients without ARDS and survivors, respectively. Significant correlations were observed between initial vWf:Ag concentration and ISS, APACHE II, LIS. Our study suggests that increased concentrations of vWf:Ag in plasma are predictive of the development of ARDS and signal poor prognosis in patients following severe trauma.     

Hemoglobin concentration and acetylcholinesterase activity of oligochaetes in relation to lead concentration in spiked sediments from Ignacio Ramirez reservoir

This paper presents toxicity and uptake data of Limnodrilus hoffmeisteri generated by lead in systems using natural sediments from Ignacio Ramírez reservoir. Lead uptake, hemoglobin concentration, and acetylcholinesterase activity were studied in L. hoffmeisteri exposed to spiked sediments. All assays of lead uptake were conducted using whole sediments. Sediment texture was also considered. Acetylcholinesterase activity and hemoglobin concentration decreased after treatment with lead. Acetylcholinesterase activity and hemoglobin concentration tests indicated a response to the concentration of lead. These results suggest the usefulness of a diversity of bioassays to evaluate the toxicity of sediments polluted with heavy metals.     

Topical interleukin-8 antibody attracts leukocytes in a piglet lavage model

Objective Acute respiratory distress syndrome (ARDS) in young infants is linked with a pulmonary inflammatory response part of which are increased interleukin-8 (IL-8) levels and migration of polymorphonuclear leukocytes (PMNL) into lung tissue. A topical application of an antibody against IL-8 might therefore decrease PMNL migration and improve lung function.Design Randomized, controlled, prospective animal study.Setting Research laboratory of a university childrens hospital.Subjects and interventions Anesthetized, mechanically ventilated newborn piglets (n=22) underwent repeated airway lavage to remove surfactant and to induce lung inflammation. Piglets then received either surfactant alone (S, n=8), or a topical antibody against IL-8 admixed to surfactant (S+IL-8, n=8), or an air bolus injection (control, n=6).Measurements and results After 6 h of mechanical ventilation following intervention, oxygenation [S 169±51 (SD) vs S+IL-8 139±61 mmHg] and lung function (compliance: S 1.3±0.4 vs S+IL-8 0.9±0.4 ml/cmH₂O/kg; extra-vascular lung-water: S 27±9 vs S+IL-8 52±28 ml/kg) were worse in the S+IL-8 group because reactive IL-8 production [S 810 (median, range 447–2323] vs S+IL-8 3485 (628–16180) pg/ml; P<0.05) with facilitated migration of PMNL into lung tissue occurred. Moreover, antibody application caused augmented chemotactic potency of IL-8 [linear regression of migrated PMNL and IL-8 levels: S r²=0.30 (P=ns) vs S+IL-8 r²=0.89 (P=0.0002)].Conclusion Topical anti-IL-8 treatment after lung injury increases IL-8 production, PMNL migration, and worsens lung function in our piglet lavage model. This effect is in contrast to current literature using pre-lung injury treatment protocols. Our data do not support anti-IL-8 treatment in young infants with ARDS.Financial support: supported by Hübner-Stiftung im Stifterverband, Essen; and Deutsche Forschungsgemeinschaft, Bonn, grant KR 1863/1-1     

CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B activation

G protein-coupled receptors (GPCRs) play pivotal roles in regulating various cellular functions. Although many GPCRs induce NF-kappaB activation, the molecular mechanism of GPCR-induced NF-kappaB activation remains largely unknown. CARMA3 (CARD and MAGUK domain-containing protein 3) is a scaffold molecule with unknown biological functions. By generating CARMA3 knockout mice using the gene targeting approach, here we show CARMA3 is required for GPCR-induced NF-kappaB activation. Mechanistically, we found that CARMA3 deficiency impairs GPCR-induced IkappaB kinase (IKK) activation, although it does not affect GPCR-induced IKKalpha/beta phosphorylation, indicating that inducible phosphorylation of IKKalpha/beta alone is not sufficient to induce its kinase activity. We also found that CARMA3 is physically associated with NEMO/IKKgamma, and induces polyubiquitination of an unknown protein(s) that associates with NEMO, likely by linking NEMO to TRAF6. Consistently, we found TRAF6 deficiency also abrogates GPCR-induced NF-kappaB activation. Together, our results provide the genetic evidence that CARMA3 is required for GPCR-induced NF-kappaB activation.