The role of reactive oxygen intermediates in the pathogenesis of chronic apical periodontitis.

The level of malondialdehyde, a stable end product of lipid peroxidation induced by reactive oxygen intermediates and the activity of two potent antioxidant enzymes, superoxide dismutase and glutathione peroxidase, was investigated in tissue homogenates of 22 surgical periapical granuloma specimens. Malondialdehyde levels were significantly higher and glutathione peroxidase activity was significantly lower in periapical granuloma samples than in healthy gingival tissue homogenates, which were used as controls. The activity of superoxide dismutase was similar in periapical granuloma and in control samples. Our results indicate an altered balance between the production and the elimination of toxic oxygen metabolites in chronic apical periodontitis. We hypothesize that reactive oxygen intermediates, which are being produced by activated phagocytic cells abundantly present in periapical granulomas, can contribute to periapical tissue injury and bone loss in this disease.

Fibronectin in bronchoalveolar lavage fluid and plasma of dogs with acute inflammation of the lungs.

Bronchoalveolar inflammation, which was generated in dogs by Broncho-Vaxom instilled into the right lower lobe, was characterized first of all by an increased influx of macrophages. In this non-purulent acute-subacute inflammatory reaction, the lavage fibronectin decreased rapidly three hours after the incubation and then a marked gradual elevation was observed, which persisted throughout the whole two-week process, while plasma fibronectin concentrations were not altered significantly. Changes in the levels of lavage fibronectin may be an important sign for the control of the inflammatory reaction activity in the lungs.

Decreased sensitivity of cytostatic drugs in glucocorticoid receptor-free acute myeloid leukaemia cells. Clinical and experimental observations.

Preliminary clinical observations have suggested that low cellular glucocorticoid receptor (GR) levels might have been connected with multidrug resistance in children with acute myeloblastic leukaemia (AML). To test this possibility, we have developed glucocorticoid resistant subclones of two recently established human myeloid leukaemic cell lines. The cause of glucocorticoid resistance was GR negativity in these subclones. GR positive parent cell lines or GR negative subclones were incubated for 1 h in the presence of Adriamycin, Cytosine-arabinosid, Etoposide or Vincristine, respectively. After short-term (1 h) incubation in suspension cultures cells were washed and plated in clonogenic agar cultures. Each anticancer drug was more potent against both GR positive parent cell lines than against the GR negative subclones. The results of this study suggest that the absence of GRs is a useful marker of multidrug resistance in childhood AML.

Erythrocyte damage in newborn babies caused by hyperbilirubinaemia and hypoxia.

Erythrocyte damage of newborn babies suffering from hyperbilirubinaemia and hypoxia was compared with a control group. In the cases of serum bilirubin level higher than physiological icterus lipid peroxidation of erythrocytes decreased probably due to the antioxidant effect of bilirubin. Moreover, an increase in potassium and protein outflow from patients' red blood cells was observed indicating a membrane damage both in hyperbilirubinaemic and hypoxic groups. Superoxide dismutase activity of serum and erythrocytes did not show significant difference in patients compared with healthy newborns. However, the low serum coeruloplasmin level in the hypoxic group and the low serum transferrin level of babies both with hypoxia and hyperbilirubinaemia suggest an insufficient antioxidant defence against free radicals.

Effects of prostaglandin E2 on the newborn respiratory system.

To test the hypothesis that prostaglandin (PG) E2 is a respiratory depressant in the newborn lamb, 12 chronically catheterized, unanesthetized lambs (age 2 to 6 days) were infused with progressively increasing doses of PGE2 (0.1, 0.5, 1.0 and 5.0 ug/kg/min: 30 min for each dose) into the ascending aorta. PGE2 caused significant, progressive decrease in ventilation (due to decreased tidal volume and breathing rate) heart rate, blood pressure and percent of the time spent in low voltage electrocortical activity (LVA). PGE2 also caused respiratory acidosis, hypoxemia and increased frequency and duration of apneic events (greater than 3 sec). During the infusion, there was a dose related increase in plasma concentration of PGE2. At 30 min post-infusion, all measured variables showed recovery, although arterial pH carbon dioxide tension and plasma PGE2 remained significantly different from control values and the percent time in LVA was even higher than during control. Infusion of the vehicle alone (n = 5) caused no significant changes in any of the measured variables. The results, taken in combination with previous fetal studies, indicate that PGE2 has marked inhibitory effects on breathing movements both before and after birth.

[A case of hybrid acute leukemia in a a child]. / Hybrid acut leukaemias gyermek esete.

Hybrid acute leukaemia is characterized by the presence of lymphoid and myeloid markers in a single cell or in different blast cell subpopulations of the same patient. Authors report on a case of a 14-yr-old girl with hybrid acute leukaemia. Immunofluorescent analysis revealed CD 14, CD 10, CD 19 and HLA-DR antigens in the cell suspension isolated from peripheral blood of the patient. Because of the excess of FAB M1 type blast cells, the patient was treated according to IGCI-1984 protocol. Remission was not achieved despite combined cytotoxic treatment and patient died within 4 weeks following admission. The poor outcome of the disease agrees well with literature data. Hybrid acute leukaemia represents a challenge for the clinical science.

Stimulation of the respiratory burst and promotion of bacterial killing in human granulocytes by intravenous immunoglobulin preparations.

We have examined the effect of two i.v. immunoglobulin preparations on the metabolic and functional activities of neutrophil granulocytes from the peripheral blood. Production of superoxide anion (O2-) by granulocytes was measured through superoxide dismutase inhibitable reduction of ferricytochrome C after incubation of cells for various times together with immunoglobulin (concentration ranging from 0.25 to 5.0 mg/ml). The results showed dose-dependent response of O2- production independent of the incubation time. Granulocytes containing ingested Staphylococcus aureus released a significantly (P less than 0.001) larger amount of O2- and killed a higher number (P less than 0.001) of viable bacteria in the presence of 5 mg/ml immunoglobulin than did cells incubated in the absence of extracellular i.v. immunoglobulin. These data raise the possibility that immunoglobulin concentrates for i.v. use may enhance the anti-bacterial activities of phagocytic cells through direct stimulation of the respiratory burst. Inflammatory reactions observed during i.v. immunoglobulin infusion in hypo- or agammaglobulinaemic patients may also be related to phagocytic cell activation.

Serum antioxidant activity in premature babies.

Autooxidation of bovine-brain homogenate proved to be a good model to determine the antioxidant capacity of sera. It was measured in parallel with the level of ceruloplasmin and apotransferrin in sera of 35 healthy children and 20 premature babies (gestational age 28-33 weeks). Antioxidant capacity was very low in premature babies with a nadir on the 4th postnatal day. Lipid-peroxidation of bovine-brain homogenate could be inhibited in vitro by the addition of exogen antioxidant. In this assay MTDQ-DS, Cavinton, DPA-HC1, vitamin E, A, C showed different antioxidant activity.

Cell membrane fluidity in blast cells of children with acute leukaemia.

Plasma membrane fluidity has been investigated by determining steady-state fluorescence polarization (FP) of the apolar stain 1,6-diphenyl-1,3,5,-hexatriene in intact blast cells, separated from peripheral blood and bone marrow of children with various types of acute leukaemia. FP-values of blast cells taken before antileukaemic therapy were compared with FP-values of peripheral blood and bone marrow mononuclear cells separated from patients in complete remission as well as from control patients and from healthy volunteers. Moreover, fluorescence polarization measurements were also performed using blast cells of leukaemic patients on short-term single-drug prednisolone pretreatment. The results have shown that untreated blast cells have significantly lower FP-values than normal mononuclear cells of peripheral blood or bone marrow. No compartment difference has been observed within blast cells, while normal mononuclear cells from peripheral blood have significantly higher FP-values than bone marrow cells. FP-values of cells separated in remission or during prednisolone treatment do not differ from control values.

Neonatal periventricular leukomalacia: diagnosis and monitoring by real-time ultrasound.

Periventricular leukomalacia is a form of hypoxic-ischaemic encephalopathy developing in preterm babies. During the last year among 387 sonographically screened neonates 11 periventricular neonatal leukomalacia cases were found. Analysing their cases authors discuss its sonographic diagnosis and follow up. In the acute stage characteristic triangular shaped area of increased echogenicity appears at the external angle of the lateral ventricles, later regular shaped echo-free areas of cysts appear in that region. The diagnostic and prognostic significance of cranial sonography in periventricular leukomalacia is discussed.

Sonography of meningoencephalitis and ventriculitis in infancy.

On the basis of eleven own cases sonographic features of infant meningoencephalitis and ventriculitis are discussed. The characteristic findings are as follows: abnormal parenchymal echogenicity of brain, changes of the size and wall echogenicity of cerebral ventricles and that of cerebrospinal fluid echogenicity.

Influence of D-penicillamine on metabolic and functional activities of neutrophil granulocytes.

Influence of D-Penicillamine (DPA) on metabolic and functional activities of neutrophil granulocytes was investigated in vitro by measuring superoxide anion production and beta-glucuronidase release as well as by determining phagocytic and intracellular killing activities of cells. Preincubation with DPA in the concentration range of 0.5-5.0 mM resulted in 28-53% increase in superoxide anion production by granulocytes stimulated with 10(-7) M FMLP. DPA in the same concentration range resulted in 145-371% rise in the FMLP-stimulated beta-glucuronidase release. However, uptake and subsequent killing of viable Staphylococcus aureus was not influenced by incubation of granulocytes with various concentrations of DPA (0.5-5.0 mM). From these results we conclude that DPA may influence the superoxide anion production and beta-glucuronidase release in granulocytes without altering the phagocytic and intracellular killing activities of these cells. We suppose that the unchanged antibacterial activity of neutrophil granulocytes is resulted by the two opposite DPA effects: acting extracellularly reduces free radical level while the direct membrane effect results in enhancing metabolic activity in granulocytes.

An in vitro study of the hydroxyl scavenger effect of Cavinton.

The hydroxyl radical scavenging capability of vinpocetine was studied in vitro by aromatic hydroxylation and deoxyribose degradation methods. Hydroxyl radicals were generated by the Fenton reaction. The effect of vinpocetine was compared to other antioxidants, to mannitol, vitamin E and dimethyl sulfoxide. The antioxidant capacity of vinpocetine is near to vitamin E, and higher than that of mannitol.

[Ultrasonic diagnosis of agenesis of the corpus callosum]. / Corpus callosum agenesia ultrahangdiagnosztikája.

Agenesis of the corpus callosum may be diagnosed successfully in vivo when sonograms demonstrate absence of corpus callosum, absence of pericallosal and cingulate sulci, wide interhemispheric fissure, small laterally positioned frontal horns with concave lateral borders. Two cases of corpus callosum agenesis were diagnosed in early infancy by ultrasound. Ultrasonographic anatomy of the corpus callosum and characteristic ultrasound features and neurological findings of agenesis are described.

[Leading etiologic factors in periventricular bleeding and periventricular leukomalacia]. / A periventricularis vérzés és a periventricularis leukomalaçia kialakulásához vezetö oki tényezök.

Prenatal, intrapartum and postnatal factors were investigated in less than 32 gestational age preterm infants known to have periventricular haemorrhage or periventricular leukomalacia. The diagnoses were established on cranial ultrasonography and/or autopsy. Factors associated with periventricular haemorrhage were: postnatal severe hypercapnia, acidosis and hypoxia. In the periventricular leukomalacia group the incidence of antepartum and intrapartum hypoxia and/or ischaemia (antepartum haemorrhage) were significantly higher than in the control group.

Fibronectin in bronchoalveolar lavage fluid and plasma from children with chronic inflammation of lungs.

Fibronectin/albumin ratios in plasma and in bronchoalveolar lavage fluid were evaluated in patients (1-6 years of age) with recurrent obstructive bronchitis and different interstitial lung diseases. These inflammatory reactions were characterized by increased influx of macrophages on the bronchoalveolar surface, but an increase in the proportion of lymphocytes or neutrophils was also detected in the group of patients with lymphocyte-macrophage or neutrophil-macrophage alveolitis. There was no considerable difference in plasma fibronectin concentrations obtained from healthy children and patients with moderate obstructive bronchitis and slight inflammation of the bronchial mucosa observed bronchoscopically. Levels of plasma fibronectin were elevated in patients with serious bronchial inflammation and different alveolitis, but they were within the normal range. A comparison of lavage fibronectin/albumin ratios with plasma fibronectin/albumin ratios with plasma fibronectin/albumin ratios indicated significant local production of fibronectin in subjects with serious bronchial inflammation and interstitial lung disorders. Fibronectin detected on the bronchoalveolar surface seems to be an important factor in mediating cell-to-cell interactions in the repair of the bronchoalveolar structures, and in tracing the activity of the inflammatory reactions not only in patients with interstitial lung diseases, but also in patients with serious chronic bronchial inflammation.

Cytogenetic investigations on children with acute non-lymphocytic leukemia.

Cytogenetic data from 30 children with acute non-lymphocytic leukemia (ANLL) are evaluated in connection with patient's age, morphological type of leukemia and prognosis. In 20 out of 30 patients clonal chromosome aberrations were found. The frequency of chromosome aberrations and the prognostic parameters in the various morphological and age groups proved to be different and no direct relationship could be found in a given group between the frequency of aberrations and the prognosis. A more detailed analysis of data, however, provided some evidence that chromosome aberrations observed at diagnosis had a prognostic value independent of age and the morphological properties of blast cells: the normal karyotype and the pseudodiploidy proved to be of a favorable value but the hyperdiploidy and polyploidy an unfavorable prognostic parameter. Besides the known cytogenetic differences between childhood and adult ANLL, some similarities are also emphasized.

Fibronectin on the bronchoalveolar surface in children with recurrent obstructive bronchitis.

Fibronectin is normally present in the lower respiratory tract. Significantly increased levels of it were detected in the lavage fluid in patients with interstitial lung diseases. Because this molecule appears to mediate a number of components of the inflammatory process, we evaluated the status of fibronectin in plasma and bronchoalveolar lavage in patients with recurrent obstructive bronchitis when signs of severe chronic mucosal inflammation were observed bronchoscopically. There was no considerable difference in plasma concentrations of fibronectin obtained from healthy children and patients. A comparison of lavage fibronectin/albumin ratios with plasma fibronectin/albumin ratios suggested significant local production, especially when the lavage and plasma ratios were measured in the same patients. Phagocytic activity of alveolar macrophages and blood granulocytes from the same patients was enhanced at both concentrations of fibronectin used. This concentrations referred to values quantified in the lavage fluid. The metabolism of fibronectin seems to be an important factor in tracing the inflammation process not only in adults with chronic interstitial lung diseases, but also in children with recurrent obstructive bronchitis.

Effect of experimental airway inflammation on bronchial hyper-responsiveness induced by Broncho-Vaxom in dogs.

We studied correlation between airway hyper-responsiveness induced by local exposure to a macrophage inductor Broncho-Vaxom and the development of airway inflammation in dogs. To detect airway inflammation, bronchoalveolar lavage and biopsy of airway mucosa were performed. The airway responsiveness was registered by capnograph measuring gas-exchange disturbances during obstructive reactions provocated by inhalation of various concentrations of acetylcholine aerosol. Broncho-Vaxom generated a protracted airway inflammation characterized by a slight and reversible increase in the number of neutrophils at 24 h after induction, and by a long-lasting influx of macrophages peaked about at the second week. The number of macrophages turned to initial levels 3 weeks later. Macrophages migrating to the bronchoalveolar surface were activated because peroxidase positivity and bearing C3b receptors of these cells increased gradually during the inflammatory process. Airway responsiveness measured at 3, 6 and 24 h after induction did not differ significantly from baseline values, but hyper-responsiveness was developed at 96 h using 0.5 and 1.0% acetylcholine aerosol (p less than 0.01 and p less than 0.001) during the non-purulent, macrophage-mediated inflammation. This situation modelled by Broncho-Vaxom induction is very similar to those observed in children with recurrent obstructive bronchitis. The results suggest that a macrophage-mediated inflammation caused by antigens, infections or pollutants may generate a long-lasting airway hyper-responsiveness.