Effect of etoposide (VP16-213) on lipid peroxidation and antioxidant status in a high-dose radiochemotherapy regimen

Summary A total of 13 patients receiving bone marrow transplants (BMT) for treatment of different haematological diseases were investigated. Conditioning therapy preceding BMT consisted of fractionated total-body irradiation (12 Gy) and high-dose chemotherapy with cyclophosphamide (2±60 mg/kg). Patients stratified to be at high risk for relapse (6/13) were additionally treated with etoposide (30 mg/kg). Plasma concentrations of absolute and lipid-standardized antioxidants (-tocopherol and -carotene) decreased following conditioning therapy, presumably as the result of an enhanced breakdown of these antioxidants. Etoposide treatment did not amplify the loss of essential anti-oxidants but significantly increased lipid hydroperoxide concentrations in serum. We suggest that the abnormal generation of lipid hydroperoxides is the result of free radical formation.     

Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer

Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.     

Hemocompatibility of medical connectors with biopassive or bioactive surface coatings

Although medical connectors compose very small parts of the extracorporeal circulation (ECC) system they represent a critical localization where early thromboembolic processes can manifest. In the present study we modified an in vitro closed-loop model with fresh human whole blood for the preclinical evaluation of the hemocompatibility of three types of medical connectors: non-coated (control); with silicone-, and heparin-coating. Each single loop consists of five polycarbonate connectors joined together by five pieces of silicone tubes. Thrombin-antithrombin-III, beta-thromboglobulin (beta-TG), PMN-Elastase, terminal complement complex, CD 11b expression, and surface-absorbed fibrinogen were measured. After 1 and 2 h recirculation, platelet loss, release of beta-TG, and adsorption of fibrinogen were significantly higher (p<0.05) within the non-coated connectors compared to the silicone- and heparin-coated groups. Following this experiment, the connectors were filled again with fresh heparinized whole blood from the same donor to evaluate the influence of prior blood contact. Here, the activation of platelets and coagulation was dependent on the duration of the blood preincubation period. Probably, the coated surfaces possess a reduced, or selective adsorption of plasma proteins, which in turn leads to a faster creation of a blood-friendly secondary superficial membrane, and prevents a further denaturation and hence activation of the adsorbed proteins.     

Rezidivierende Meningitis bei familiärem Mangel der achten Komponente des Komplementsystems

Summary An 18-year-old man suffered from recurrent bacterial meningitis. Investigation of the complement system revealed deficiency of the 8th complement component (C8) in the patient and his sister. Genetic defects of the terminal complement components C5 to C8 predispose toNeisseria infections, probably due to a lack in bacteriolytic activity. It is to be noted that 1 year ago the patient had been hospitalized for a culture-proved pneumococcal meningitis.

     

Neuroendocrine cell markers for pancreatic islets and tumors.

The authors review the application of a variety of neuroendocrine cell markers to identify pancreatic islet cells and tumors. In the past, several empiric histochemical techniques had been used to demonstrate neuroendocrine cells, particularly the Grimelius argyrophilic stain. The development of immunohistochemistry made it possible to demonstrate specific cell products such as regulatory peptides, thus allowing the classification of pancreatic neuroendocrine tumors with a view to clinical symptoms. However, it is not always possible to visualize regulatory peptides in these tumors. It is therefore important to use broad-spectrum neuroendocrine cell markers to identify the neuroendocrine nature. These markers are proteins localized in the secretory granules (core- or membrane-related), in the cytosol, or in the cellular membrane. The markers most commonly used in routine histopathology are the secretory granule proteins chromogranin A and synaptophysin and the cytosolic enzyme neuronspecific enolase. Other new markers (e.g., synaptic vesicle protein 2) are of general diagnostic value. Region-specific antibodies to chromogranin A can be valuable in differentiating between benign and malignant neuroendocrine tumors. Some markers may be related to the functioning characteristics of pancreatic neuroendocrine tumors, such as prohormone convertases. In addition, markers giving further complementary information have been identified, such as five somatostatin receptor subtypes, the expression of which varies markedly in pancreatic neuroendocrine tumors. Antibodies against all somatostatin receptor subtypes are now commercially available, and immunohistochemical investigation of its expression should be routinely applied when considering treatment with somatostatin analogs.     

Changes in blood lactate and respiratory gas exchange measures in sports with discontinuous load profiles

This study compares two different sport events (orienteering = OTC; tennis = TEC) with discontinuous load profiles and different activity/recovery patterns by means of blood lactate (LA), heart rate (HR), and respiratory gas exchange measures (RGME) determined via a portable respiratory system. During the TEC, 20 tennis-ranked male subjects [age: 26.0 (3.7) years; height: 181.0 (5.7) cm; weight: 73.2 (6.8) kg; maximal oxygen consumption (V˙O₂max): 57.3 (5.1) ml·kg⁻¹·min⁻¹] played ten matches of 50 min. During the OTC, 11 male members of the Austrian National Team [age: 23.5 (3.9) years; height: 183.6 (6.8) cm; weight: 72.4 (3.9) kg; V˙O₂max: 67.9 (3.8) ml·kg⁻¹·min⁻¹] performed a simulated OTC (six sections; average length: 10.090 m). In both studies data from the maximal treadmill tests (TT) were used as reference values for the comparison of energy expenditure of OTC and TEC. During TEC, the average V˙O₂ was considerably lower [29.1 (5.6) ml^·kg^−1·min⁻¹] or 51.1 (10.9)% of VO₂max and 64.8.0 (13.3)% of V˙O₂ determined at the individual anaerobic threshold (IAT) on the TT. The short high-intensity periods (activity/recovery = 1/6) did not result in higher LA levels [average LA of games: 2.07 (0.9) mmol·l⁻¹]. The highest average V˙O₂ value for a whole game was 47.8 ml·kg^−1·min⁻¹ and may provide a reference for energy demands required to sustain high-intensity periods of tennis predominately via aerobic mechanism of energy delivery. During OTC, we found an average V˙O₂ of 56.4 (4.5) ml·kg⁻¹·min⁻¹ or 83.0 (3.8)% of V˙O₂max and 94.6 (5.2)% of V˙O₂ at IAT. In contrast to TEC, LA were relatively high [5.16 (1.5) mmol·l⁻¹) although the average V˙O₂ was significantly lower than V˙O₂ at IAT. Our data suggest that portable RGEM provides valuable information concerning the energy expenditure in sports that cannot be interpreted from LA or HR measures alone. Portable RGEM systems provide valuable assessment of under- or over-estimation of requirements of sports and assist in the optimization and interpretation of training in athletes. Electronic Publication     

Blends of alkyloxy-substituted liquid-crystalline aromatic polyesters and copolyesters with poly(ethylene terephthalate)

Blends containing poly(ethylene terephthalate) (PET) and a series of alkyloxy laterally substituted liquid-crystalline copolyesters (HTO5-X series 1 ) in various ratios were prepared in the melt at 260°C by mechanical mixing. The visual and light microscopical appearance of the blends in the solid state and in the melt was found to be homogeneous for those blends which contained an aliphatic-rich HT05-X copolyester. The homogeneous appearance can be explained by a colloidal dispersion of the liquid-crystalline polymer (LCP) in PET. Obvious phase separation in the melt occurs slowly after long periods of time. Phase separation is forced by annealing at about 270°C, where a change of viscosity is observed, and by shearing the sample. Characterization of theblends by DSC experiments shows that the thermal behaviour of all blends is dominated by the phase transitions of PET and that the LC-low-phase of the HTO5-X copolyesters with a high degree of alkyloxy substitution is suppressed. The WAXS diffraction patterns of all blends contained an amorphous halo. For blends with low HTO5-X concentration, inner reflexions from the nematic sanidic phase, as exhibited by the HTO5-X copolyester, could be observed. For blends with higher HTO5-X copolyester concentration, characteristic reflexions from HTO5-X copolyester crystals could be observed. The number of X-ray reflexions of the crystalline LCP in the blend is reduced compared to that of the pure LCP.