Adenoviral infection inhibits allergic airways inflammation in mice

BACKGROUND: Recent epidemiological studies have suggested that exposure to certain viruses and bacteria influences the development of allergy and allergic diseases, such as asthma. However, there is a paucity of experimental evidence examining the consequences of concurrent exposure to allergen and infectious agents, and the potential mechanisms by which allergic disease might be averted as a result. OBJECTIVE: To model this situation experimentally, we investigated whether a virally induced immune response, elicited by a replication-deficient human type 5 adenovirus (RDA) administered at a site distant from the airways, could inhibit ovalbumin (OVA)-induced airways eosinophilic inflammation. METHODS: C57BL/6 mice were infected intramuscularly with RDA 16h prior to intraperitoneal OVA sensitization. Cellular and cytokine responses in the lung/airways were examined after an OVA aerosol challenge. RESULTS: RDA infection significantly inhibited the inflammatory response in the lung tissue after antigen challenge. In the bronchoalveolar lavage (BAL), total cell number, eosinophils and lymphocytes were decreased by 70, 85 and 65%, respectively, after antigen challenge in RDA-treated, compared with untreated, mice. RDA infection had no effect on IgE synthesis. The levels of IL-5, IL-4 and IFNgamma in the BAL after antigen challenge were significantly lower in RDA-treated mice. In vitro production of cytokines by splenocytes in response to OVA restimulation revealed a shift from IL-4 in sensitized, PBS-treated mice, to IFNgamma in sensitized mice treated with RDA. Flow cytometric analysis revealed that RDA infection increased the proportion of CD8 T cells in the BAL; this change in T-cell subsets was accompanied by an increase in both CD4 and CD8 T cells positive for intracellular IFNgamma. Inhibition of antigen-induced airways inflammation was IFNgamma-dependent but did not require IL-12, as RDA-treatment inhibited airways inflammation in IL-12 but not IFNgamma knock-out mice. CONCLUSION: This study demonstrates that an immune response against a replication-deficient adenovirus during the initial exposure to OVA inhibits the development of airways inflammation after antigen aerosol challenge.     

Buspirone enhances benzodiazepine receptor binding in vivo

The effects of buspirone on benzodiazepine receptors labelled in vivo with [3H]Ro 15-1788 were investigated. While buspirone did not affect the binding of benzodiazepine receptors in vitro, significant dose-related increases were observed in the in vivo labelling of benzodiazepine receptors in mice. However, similar results were also obtained with various neuroleptic agents and apomorphine. Potential mechanisms that may account for these results are discussed, but the data suggest caution in the use of [11C]Ro 15-1788 in positron emission tomography scanning in humans, since labelling by Ro 15-1788 may be affected by factors unrelated to direct changes at the benzodiazepine receptor site.     

Differential effects of catecholamine antagonists on ethanol-induced excitation in mice

Catecholamine antagonists were assessed for their effects on ethanol-induced motor excitation. Motor excitation was measured in male Swiss-Webster mice using an open-field apparatus. Mice were treated with several doses of ethanol and at each dose, mice were pretreated with pimozide, a dopamine D2 antagonist, Schering 23390, a dopamine D1 antagonist, phenoxybenzamine, a noradrenergic alpha-1 antagonist, or yohimbine, a noradrenergic alpha-2 antagonist. Each mouse was subjected to only one dose regimen, and all injections were given IP. Ethanol produced an increase in locomotor activity. The degree to which pimozide attenuated ethanol excitation decreased with increasing ethanol dosage. At the highest dose of ethanol, pimozide increased ethanol excitation. Schering 23390 attenuated ethanol-induced excitation only at doses which affected motor activity per se. Phenoxybenzamine produced a dose-dependent reduction in ethanol excitation. Yohimbine had its greatest effects at the medium dose (4.0 mg/kg). These observations seem to indicate a role for both the dopamine D2 receptor and the noradrenergic alpha-1 receptor in ethanol-induced motor excitation.     

New aspects of endocrine regulation of calcium metabolism

The maintenance of circulating calcium levels within the narrow physiological range requires the action of two hormones, the polypeptide hormone parathyroid hormone and the steroid hormone 1-alpha-25-dihydroxyvitamin D3. These two hormones act on bone, kidney and intestine to regulate calcium homeostasis. Disorders of mineral metabolism are frequently associated with abnormal regulation of the metabolism of parathyroid hormone or 1-alpha-25-dihydroxyvitamin.     

Begleiteter Suizid nach Entlassung aus der psychiatrischen Klinik

Zusammenfassung Der begleitete Suizid ist in den letzten Jahren zu einem h?ufig und kontrovers diskutierten Thema in der internationalen Literatur geworden. Dabei sind Psychiatrie und psychisch Kranke in der Regel ausgespart, vermutlich weil sich hier neben der allgemeinen ethischen Problematik die Frage nach der Urteils- und Gesch?ftsf?higkeit der Kranken aufdr?ngt. Die Autoren berichten über einen 60j?hrigen Mann und eine 87j?hrige Frau, die sich wenige Tage nach der Entlassung aus der psychiatrischen Klinik das Leben genommen haben. Bei ersterem war der Aufnahmeanla? eine psychotische Episode bei manifester Aids-Erkrankung gewesen, bei letzterer die Mitteilung an ihre Angeh?rigen, sie wolle mit Hilfe von „Exit”, der schweizerischen Freitodorganisation, aus dem Leben scheiden, ohne da? eine gravierende psychiatrische Symptomatik bestand. Die ethischen Implikationen und die M?glichkeiten einer pr?ventiven Intervention in solchen F?llen werden er?rtert.      

Pathophysiology and therapy of hypercalciuria in patients who form recurrent stones.

There are two alternative mechanisms that might be responsible for idiopathic hypercalciuria in recurrent stone formers: increased intestinal absorption of calcium with parathyroid suppression and overflow hypercalciuria (primary intestinal hyperabsorption) or renal calcium leak with compensatory hyperparathyroidism and intestinal hyperabsorption (primary renal-tubular hypercalciuria). In this study, urinary excretion of cAMP, the intracellular effector substance synthetised under parathyroid hormone stimulation, was found to be in the normal range. This finding would argue against intestinal hyperabsorption of calcium as the primary cause of hypercalciuria.     

Isolation and partial characterization of an interleukin-1-like factor from rat testis interstitial fluid

Testicular interstitial fluid (ISF) was collected by in vivo perfusion of rat testes and analyzed for the presence of interleukin-1 (IL-1) activity by utilizing a murine thymocyte proliferation assay. IS obtained from nine rats were all positive with dose-response curves of IL-1 activity similar to those produced by rat testicular aqueous extracts, rat macrophage IL-1 and human recombinant IL-1 alpha. Chromato-focusing of pooled ISF revealed a single peak of IL-1 activity with an estimated isoelectric point of 6.1-6.3. HPLC size exclusion chromatography demonstrated two active peaks with apparent molecular ratios Mr of 15,000-18,000 and 5000-7000, respectively. The molecular properties of the 15,000-18,000 Mr component are very similar to those of an IL-1-like factor previously isolated from seminiferous tubules. Our results indicate that the testicular IL-1-like factor is secreted by the seminiferous tubules into the interstitial tissue. Its function in the testicular interstitium is unknown but it might be relevant for the tendency to testicular relapse of childhood lymphocytic leukemia.     

Atherogenesis in experimental uremia

The development of experimental atherosclerosis was studied in subtotally nephrectomized rats which were subjected to preimmunisation with horseradish peroxidase and subsequent feeding with atherogenic diet. Both in shamoperated pair-fed control animals and in uremic animals, the atherogenic diet caused hyperlipemia which was more pronounced in uremic than in control animals (control animals: triglycerides 1.11 ± 0.04 mmol/l; cholesterol 5.82 ± 0.21 mmol/l; uremia: triglycerides 1.33 ± 0.06; cholesterol 10.9 ± 0.31). An increase of cholesterol was seen both in the VLDL and in the LDL fractions. Despite more pronounced hyperlipemia, lipid concentration in the aortic wall was not increased nor were more marked histological abnormalities encountered in the aorta of uremic animals (cholesterol-fed control: cholesterol 95.4 ± 4.4 μg/mg protein; phospholipids 2.42 ± 0.9 μ/ml protein; cholesterol-fed uremia: cholesterol 96.8 ± 4.9; phospholipids 2.52 ± 0.8).

The results suggest that despite hyperlipemia short-term experimental renal insufficiency does not promote atherogenesis.