Expression of CD35 (CR1) and CD11b (CR3) on circulating neutrophils and eosinophils from allergic asthmatic children

Complement receptors on neutrophils and eosinophils play a role in activation and adhesion. During asthmatic reactions these receptors have been found elevated on circulating granulocytes. In the present study we compared the expression of CD35 (complement receptor type 1) and CD11b (complement receptor type 3) on neutrophils and eosinophils from asthmatic and non-asthmatic children. This was done in whole blood samples using depolarized light scattering for the discrimination of neutrophils and eosinophils. The non-stimulated expression as well as the upregulated expression of receptors by the chemotactic peptide N-formylmethionyl-leucyl-phenyl-alanine (fMLP) were studied. The results showed that without prior stimulation only the expression of CD35 on neutrophils was significantly elevated in children with asthma (P<0.05). After up-regulation with fMLP, the CD11b expression on neutrophils (P<0.005, fMLP: 0.002 microM) and eosinophils (P<0.05, fMLP: 0.02 microM) was significantly higher in asthmatic children than in the controls. These results indicate that the inducible expression of CD11b on neutrophils and eosinophils from allergic asthmatic children is primed in vivo.     

Isoquinoline Derivatives Isolated from the Fruit of Annona muricata as 5-HTergic 5-HT1A Receptor Agonists in Rats: Unexploited Antidepressive (Lead) Products

The fruit and the leaves of Annona muricata (Annonaceae) are used in traditional medicine for their tranquillizing and sedative properties. Extracts of the plant have been shown to inhibit binding of [³H]rauwolscine to 5-HTergic 5-HT_1A receptors in calf hippocampus, and three alkaloids, annonaine ( 1 ), nornuciferine ( 2 ) and asimilobine ( 3 ), isolated from the fruit have been shown to have IC50 values of 3 μm , 9 μm and 5 μm , respectively, although in ligand-binding studies it was not possible to determine whether interaction of these ligands with the receptor was agonistic or antagonistic. This paper presents the results of functional assays of the alkaloids. The inhibition of cAMP accumulation was tested in NIH-3T3 cells stably transfected with the 5-HT_1A receptor from man. None of the alkaloids showed antagonistic properties towards the 5-HT_1A receptors because in the antagonistic tests no influence on the forskolin-stimulated increase of cAMP level was detected. Full agonistic properties were measured for all three compounds; the inhibition constants (K_i) for 1, 2 and 3 were < 10 μm . Inhibition of the binding of the radioligand to the 5-HT_1A receptor was observed in every ligand-binding assay performed with the alkaloids; the K_i values for 1, 2 and 3 were in the μm range. These results imply that the fruit of Annona muricata possesses anti-depressive effects, possibly induced by compounds 1, 2 and 3 , and that in the past potent leads for the development of anti-depressive therapeutics have not been used.     

Effect of metoprolol on death and cardiac events during a 2-year period after coronary artery bypass grafting

PURPOSE: To evaluate the effect of long-term treatment with metoprololafter coronary bypass grafting on death and cardiac events. METHODS: Patients in western Sweden on whom coronary artery bypass graftingwas performed between June 1988 and June 1991 were evaluatedfor inclusion during the first 3 weeks after surgery. Majorexclusion criteria were age >75 years, concomitant valvesurgery, traditional contraindications to beta-blockers andunwillingness to participate. Patients were randomized in adouble-blind fashion to 100 mg of metoprolollplacebo daily for2 weeks and thereafter 200 mg daily for 2 years. RESULTS: Of 2365 patients who were operated on, 967 were randomized toeither metoprolol (n=480) or placebo (n=487). Primary end points(death, non-fatal myocardial infarction, unstable angina pectoris,need for coronary artery bypass grafting or percutaneous transluminalangioplasty), were reached by 42 patients in the metoprololgroup (8·8%) as compared with 39 in the placebo group(8·0%) (P=0·73). Of all the patients randomizedto metoprolol, 34% withdrew from blind treatment prematurelycompared with 44% for placebo (P<0·01) CONCLUSION: Prophylactic treatment with metoprolol over a 2-year periodafter coronary artery bypass grafting did not reduce death orthe development of cardiac events. However, the 95% confidencelimits ranged from the possibility of a 30% reduction in eventsto a 68% increase in events if patients were treated with metoprololas compared with placebo.     

Granular cell tumours of the lower respiratory tract

Granular cell tumours rarely involve the lower respiratory tract. We report eight cases surgically resected at our institution. There were four females and four males, aged between 18 to 56 years (mean 40). One tumour associated with a peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1). These tumours were tracheal (1) or bronchial (6) and one case was located in the lung parenchyma. Four cases were multicentric with associated lesions located in a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours, with the largest diameter ranging from 0.5–4.5 cm, were histologically invasive. The tumours were positive for S-100 protein, neuron specific enolase, KP1 (CD68) and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study demonstrates that, in spite of marked anatomical and clinical polymorphism, the rare granular cell tumours of the lower respiratory tract have a constant histological appearance. Our observations confirm that large tumours (> 8–10 mm) usually extend beyond the tracheo-bronchial cartilages and, therefore, only surgical treatment may avoid recurrence.     

Effect of exercise on plasma atrial natriuretic factor and cardiac function in men and women

In order to provide an integrated view of the physiology of atrial natriuretic factor (ANF) during exercise, we studied changes of its plasma concentrations in 13 normal subjects (seven males, six females) during three graded exercise levels and two periods of recovery (5 and 30 min), concomitantly with an assessment of cardiac function and ventricular volumes by multigated radionuclide angiography. Mean ANF levels (+/- SEM) increased in all patients at the second (P less than 0.002) and third (P less than 0.002) exercise levels, and after 5-min recovery (P less than 0.01): in males from 16 +/- 7 to 30 +/- 11 pg ml-1 at the third level, in females from 27 +/- 12 to 61 +/- 33 pg ml-1. Normal values were observed after 30-min recovery. Even if mean ANF levels were all higher in females, this difference did not reach statistical significance (P = 0.06). Significant decreases of ventricular volumes, as well as increases of ejection fraction and rate pressure product, were noted during exercise and were similar in both sexes. The kinetics of plasma ANF concentrations, compared with the increase of rate pressure product, was characterized by a latency and a remanence in recovery. This remanence, also present in the changes of ventricular volumes, supports the hypothesis that other factor(s) like catecholamines might still exert their influence after the exercise stops.     

A Comparison of the Physicochemical and Biological Properties of Mirtazapine and Mianserin

Although the chemical structures of the antidepressants mirtazapine and mianserin are closely related there are considerable differences in their biological properties. To find an explanation of this, various physicochemical properties of mirtazapine and mianserin were measured or calculated. Isosteric replacement of CH in mianserin by N in mirtazapine has profound effects on physicochemical properties. The charge distributions as indicated by NMR and calculated by semi-empirical quantum mechanics differ, not only for the changed aromatic A-ring (as expected), but also in other regions of the molecule. The N5 atom in particular, which is conjugated to the changed aromatic ring, is less negatively charged in mirtazapine than in mianserin. Consequently the oxidation potential of mirtazapine is significantly higher than that of mianserin. Another result of this difference in charge distribution is that the (calculated) dipole-moment vectors of the compounds are oriented roughly perpendicular to each other. The dipole moment of mirtazapine is, moreover, three times larger than that of mianserin; mirtazapine is, therefore, more polar than mianserin and this is reflected in a lower retention index. Finally, the basicity of mirtazapine, expressed as the pK_a value, is slightly but significantly lower than that of mianserin. The observed differences between the physicochemical properties of mirtazapine and mianserin result in different interactions of these two antidepressants with macromolecules, such as receptors, transporters and metabolizing enzymes; this might explain the differences observed in pharmacological activity and metabolic and kinetic behaviour, that is, the reduced affinity for the α₁-adrenoceptor and negligible noradrenaline reuptake of mirtazapine compared with mianserin.     

Acute respiratory distress during Caesarean section under spinal anaesthesia A probable case of anaphylactoid reaction to Syntocinon

A case of life-threatening respiratory distress during a Caesarean section under spinal anaesthesia is reported. Possible causes of the event including anaphylactoid reactions and the methods of their diagnosis are discussed. The most likely cause of the episode was felt to be an anaphylactoid reaction to Syntocinon.     

Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial cells (iEC)

Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of them have a CD28^? phenotype, the phenotype of effector cytotoxic T cells. We asked whether the predominance of CD8⁺ CD28^? T cells in the gut may result from peripheral blood T cells preferentially migrating to the iIEL compartment and adhering to iEC. Compared with CD4 cells, adhesion of resting CD8⁺ T cells to iEC cell lines was significantly higher. Adhesion could be blocked with a MoAb to gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No significant difference in the level of adhesion was observed between CD8⁺ CD28⁺ and CD8⁺ CD28^? T cells. Thus CD8 cells may preferentially migrate to the iIEL compartment, but loss of CD28 expression could occur in situ after migration. Consistent with this hypothesis, the CD8⁺ CD28^? cells became enriched after co-culturing T cells with iEC cell lines and primary iEC. Induction of the CD8⁺ CD28^? phenotype in cord blood and adult T cells was observed in co-cultures with iEC and also with mitogens and superantigens. In the latter case, CD28 down-modulation was seen specifically in the Vβ subset targeted by the superantigen, indicating that loss of CD28 expression is a direct result of T cell receptor (TCR)-mediated stimulation. The combined results suggest that CD8⁺ CD28^? T cells are antigen experienced T cells, and that they may have a survival advantage in the presence of gut epithelial cells in vitro. This may contribute to the predominance of CD8⁺ CD28^? T cells in the iIEL compartment.     

Immunomodulation by hydatid cyst fluid toxin (Echinococcus granulosus)

Since the experimental infection by hydatid cysts ( Echinococcus granulosus ) in mice causes immunomodulation of the host, the effects of hydatid fluid (HF) and fractions of HF were compared in vitro and in vivo . Fractions of HF were obtained using ammonium sulphate precipitation, chloroform/methanol extraction and thin-layer chromatography (TLC). HF proved to be toxic to murine peritoneal macrophages in vitro , and when macrophages were incubated with the different fractions of HF, most toxicity was found in a single TLC-purified fraction with an adjuvant-like effect on the production of specific antibodies against bovine albumin and human red blood cells in mice. Treatment of mice with the toxin caused a drop in the percentage of peripheral blood lymphocytes. Flow-cytometric analysis showed that T-cells from toxin-treated mice had lower membrane-CD3, CD4 and CD8 density, and had higher percentages of CD8⁺ splenocytes and CD4⁺ thymocytes expressing CD25. The toxin caused a down-regulation of CD4 and CD8 expression on thymocytes in vitro , that was dependent on the presence of macrophages. The results may attribute to these toxins a role in the host-parasite relationship of hydatidosis.