Chromosome Instability on Children with Asthma

Background. Asthma is a complex disease with multiple interactions between genetic and environmental factors. Objective. The aim of our study was to investigate the possible genetic instability in asthmatic patients (AP) with asthma in human cultured peripheral blood lymphocytes. Furthermore, the presence of either cytostaticity or cytotoxicity was demonstrated. Methods. Human peripheral blood lymphocytes were cultured from 18 admitted children to the Pediatric Clinic of the University Hospital of Alexandroupolis (average age 7.2 years), and 9 healthy blood donors were used as control subjects (average age 6.5 years), none of whom was receiving drugs for medical or other reasons. Results. A significant (p < 0.05) increase in spontaneous sister chromatid exchanges (SCEs) frequency in asthmatic patients compared with control subjects was observed. No statistically significant modification in the spontaneous proliferation rate index (PRI) in AP compared with the controls was demonstrated. Finally, MMC induced a statistically significant increase in SCEs frequency both to controls and to AP, with the MMC-induced SCEs rates in AP being statistically (p < 0.01) higher compared to the MMC-induced SCEs in controls. Conclusion. We try to improve a new diagnostic process of possible genetic instability by a combination of genotoxic, cytostatic and cytotoxic effects of asthma on human peripheral lymphocytes.     

Zinc ion dependent B-cell epitope, associated with primary Sjogren's syndrome, resides within the putative zinc finger domain of Ro60kD autoantigen: physical and immunologic properties

The Ro/La ribonucleoprotein (RNP) complex is composed of the proteins Ro60kD, Ro52kD, and La48kD that are in association with one small cytoplasmic RNA (YRNA). Specific protein-RNA and protein-protein interactions are thought to occur through the RNP and zinc-finger secondary structure elements of the Ro60kD protein. The aim of our study was to investigate the antigenic properties of the zinc finger domain of the Ro60KD autoantigen and its contribution to the formation of Ro/La RNP complex. It was found that the peptide VSLVCEKLCNEKLLKKARIHPFHILIA (Zif-1), which corresponds to the natural sequence of the zinc finger domain (301-327), and the peptide C(Acm)NEKLLKKARIC(Acm), analogous to the intermediate loop 310-319 (Zif-3) of the same domain of Ro60KD, are recognized by the majority of anti-Ro/SSA and anti-La/SSB positive sera (82.6% and 77.1%, respectively) in the absence of zinc ions. The same sera failed to react with Zif-1 peptide in the presence of Zn2+. In contrast, the addition of zinc ions was necessary for the binding of Zif-1 to recombinant Ro52KD as shown by direct binding experiments of the recombinant protein with synthetic peptides. Our data suggest the zinc finger domain of Ro60kD contains a B-cell epitope with high specificity for primary Sjogren's syndrome. Furthermore, depending on the presence of zinc ions, the zinc finger domain of the Ro60KD protein can exist in two different conformational states favoring either an interaction with the Ro52KD protein or binding with autoantibodies.     

Common surgical complications in degenerative spinal surgery

The rapid growth of spine degenerative surgery has led to unrelenting efforts to define and prevent possible complications, the incidence of which is probably higher than that reported and varies according to the region of the spine involved (cervical and thoracolumbar) and the severity of the surgery. Several issues are becoming progressively clearer, such as complication rates in primary versus revision spinal surgery, complications in the elderly, the contribution of minimally invasive surgery to the reduction of complication rate. In this paper the most common surgical complications in degenerative spinal surgery are outlined and discussed.     

Secondary intramedullary nailing after distraction osteogenesis: 30 patients followed for 2-12 years

BACKGROUND: There is no consensus about replacement of an external fixator by reamed intramedullary nailing in fracture cases. PATIENTS AND METHODS: We evaluated the outcome in 30 patients (33 segments) of secondary intramedullary nailing during the consolidation phase after callus distraction using an external device. The main reasons for nailing were docking site nonunion (17 patients), angular deformity or fracture of the lengthened area (8 patients) or intolerance of the external device (5 patients), in 11 patients combined with a delayed distracted callus maturation. The average follow-up time was 4 (2-12) years. RESULTS: Intramedullary infection after nailing occurred in 1 case, and slight loss in callus length in 5 cases. Failure of union at the docking site with nail breakage occurred in 1 case. In the other patients, consolidation in the lengthened callus area and also union at the docking site were achieved on average 6 months after nailing. INTERPRETATION: We believe that intramedullary nailing during the consolidation phase after bone lengthening or bone transport is a treatment option for delayed callus maturation or docking site nonunion, reducing prolonged use of the external fixator.     

Endothelin‐1 Acutely Reduces the Permeability of Visceral Sheep Peritoneum In Vitro Through Both Endothelin‐A and Endothelin‐B Receptors

Mesothelium is an important part of the peritoneal barrier for water and ion transport, essential for effective peritoneal dialysis (PD). Peritoneal fibrosis has been associated with PD treatment failure. Endothelin‐1 (ET‐1) is a potent vasoactive peptide, involved in pathologic fibrotic processes. Its action is mediated mainly by endothelin type A (ET_A) and type B (ET_B) receptors. The aim of this study was to investigate, by Ussing chamber experiments, the effect of ET‐1 on the transmesothelial electrical resistance (R_TM) of the isolated visceral sheep peritoneum. Intact sheets of visceral peritoneum were obtained from 40 adult sheep and mounted in Ussing‐type chambers. ET‐1 (10^?7 M), BQ‐123 (ET_A receptor antagonist; 10^?6 M), BQ‐788 (ET_B receptor antagonist; 10^?6 M), and their combinations were added on the apical and the basolateral side of the peritoneum. R_TM was measured before and serially after addition of the substances, and changes were registered as percentage (ΔR_TM %). R_TM increased within 1 min after addition of ET‐1 apically (ΔR_TM 65.03 ± 15.87%; P < 0.05) or basolaterally (ΔR_TM 85.5 ± 20.86%; P < 0.05). BQ‐123 and BQ‐788 and their combination significantly reduced (P < 0.05) the effect of ET‐1 to a similar degree in all cases. These results clearly indicate that ET‐1 reduces ionic permeability of the visceral sheep peritoneum in vitro. Additionally, it is obvious that this inhibitory effect is mediated through both ET_A and ET_B receptors.     

Renal involvement in paroxysmal nocturnal hemoglobinuria: an update on clinical features,pathophysiology and treatment

Objectives: The present review summarizes the available knowledge regarding acute and chronic kidney dysfunction in patients with paroxysmal nocturnal hemoglobinuria (PNH) focusing on its clinical features, pathophysiology and treatment.

Methods: A thorough PubMed search was performed using as main keywords: ‘paroxysmal nocturnal hemoglobinuria’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘eculizumab’.

Results: PNH’s etiopathogenesis is based on acquired mutations that lead to the reduction or absence of CD55 and CD59 complement regulators, which are responsible for some of the disease’s major clinical features, like intravascular hemolysis, cytopenias and thrombosis. PNH is often underdiagnosed, mainly due to its occasional mild manifestations and to its ability to mimic other severe clinical conditions. Various mechanisms have been proposed for the kidney damage attributed to the release of cell-free heme and free iron, including inflammatory response, oxidative stress, nitric oxide depletion, renal ischemia, membrane damage and apoptosis. Eculizumab, a terminal complement inhibitor, provides a safe and effective treatment option, especially when it is initiated early in the presence of kidney damage.

Discussion: Kidney injury is a poorly investigated clinical feature of PNH that affects a significant portion of patients. Increased awareness is needed by physicians to recognize the early signs and symptoms of acute and chronic renal insufficiency, so as to initiate the necessary therapy. It is also important to re-evaluation of PNH-specific treatments during the course of the disease.

Conclusion: Understanding the difficult but at the same time impressive mechanisms behind PNH remains a challenge for treating physicians.