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Objectives. –Studies performed to assess the diagnostic value of tests for hymenoptera allergy are usually designed to validate the test whereas very few have evaluated these tests in routine diagnostic situations. In fact, the diagnostic value of such tests, especially skin prick-tests and basophil histamine release, has rarely been studied systematically in patients referred by their physician to an allergist for confirmation of the diagnosis and recommendations for immunotherapy. The aim of the present study was to assess the diagnostic value of skin prick-tests, specific IgE assay and basophil histamine release in patients referred to an allergy unit for suspected hymenoptera venom allergy. Patients and methods. – Diagnostic tests were done prospectively in 25 consecutive patients with allergic reactions to hymenoptera venom defined by clinical history and positive intradermal skin tests, including patients with a localized or a more extensive skin reaction associated with malaise and/or respiratory symptoms, and in 21 control subjects. The hymenoptera studied included yellow jacket (YJ) and honeybee (HB). The sensitivity, specificity, concordance and predictive values of the tests were calculated.Results. – The observed sensitivity, specificity, and positive and negatives predictive values of skin prick-tests with 100 μg/mL HB venom (in percent) 33.3; 100; 100; and 85.7, respectively, and with 100 μg/mL YJ venom 30; 100; 100 and 85, respectively. For skin prick-tests with 300 μg/mL HB venom the values were 75; 100; 100 and 94, respectively and for skin prick-tests with 300 μg/mL YJ venom 57; 100; 100 and 90.3, respectively. For specific IgE assays, the values for HB were 100; 95.2; 84 and 100, respectively and for YJ 100; 76.2; 51.2, and 100, respectively. For basophil histamine release the values for HB were 89; 100; 100 and 97.3 for YJ they were 94; 89, 6 and 98.4, respectively. Conclusions. – Skin prick-tests with venom concentrations under 300 μg/mL are not sensitive enough for an accurate diagnosis of hymenoptera allergy. Basophil histamine release appears to be a good complementary test but it needs better standardization. [Copyright &y& Elsevier]

Discusses a study which examined the effect of interferon (IFN)-α 2a on alveolar echinococcosis lesions and the production of interleukin (IL)-10, IL-4, IL-5 and IFN-γ by peripheral blood mononuclear cells from a patient who received IFN-α 2a treatment for concomitant chronic hepatitis due to hepatitis C virus.

In Algeria, cystic echinococcosis (CE) is a serious economic and public health problem. The common sheep/dog cycle is usually considered as the major source of human contamination. But to date the main strain of Echinococcus granulosus involved in the human contamination and the role of other hosts are still unknown. This paper reports an original work performed in northern Algeria combining field observations and molecular analysis. In a first step, examination of 6237 carcasses in slaughterhouses showed high infection and fertility rates in cattle and dromedaries. Then, in a second step, we used a molecular biology approach to identify the E. granulosus strain(s) involved. Forty-six samples from various origins were collected. They were analysed using comparison of PCR-amplified DNA sequences with one genomic (BG 1/3) and two mitochondrial (COI and NDI) targets. Results show the presence of a “sheep” strain of E. granulosus in North Algeria circulating between cattle and ovines and infectious to humans, whereas in South Algeria, a “camel” strain and a “sheep” strain were found to circulate in camels and in sheep, respectively. This study also reports an ambiguous genotype which resembled the “sheep” strain genotype (Gl) on the basis of the partial COI gene sequence, whereas on the basis of the partial NDI gene sequence, it was similar either to the “sheep” strain (Gl) or to the “camel” strain (G6). Besides its basic interest, our study confirms the role of other hosts (mainly cattle) in leading to transmission to humans and suggests that control measures should not only target sheep. [Copyright &y& Elsevier]

Background & Aims: Hepatic alveolar echinococcosis (AE), caused by the larval growth of Echinococcus multilocularis, is one of the most lethal helminthic diseases with no satisfactory treatment. Advances in the understanding of the host's immune response (Th2 responses associated with a progressive form of AE), have driven the research towards immune stimulation as an alternative possibility to treat patients. We previously reported clinical stabilization associated with a shift from a Th2 to a Th1 cytokine profile in an AE patient treated with interferon (IFN)alpha., Methods: The effects of recombinant IFN alpha-2a were analyzed in the susceptible C57BL/6J E. multilocularis infected mice. Parasitic burden, macrophage functions, and specific T-cell responses were studied 15, 45, and 90 days postinfection., Results: After 90 days postinfection, 75% of infected IFN alpha-2a-treated mice had no hepatic lesions and half were fully protected. IFN alpha-2a treatment markedly decreased the abnormally elevated production of IL-10 in both spleen cell cultures and peritoneal macrophage cultures from infected mice and restored phagocytosis and oxidative metabolism of macrophages. It also inhibited IL-6 and IL-13 antigen-induced secretions in spleen cell cultures., Conclusions: Through its immunoregulatory properties, IFN alpha-2a may be effective in a helminthic liver infection and is a promising candidate for clinical application in AE.

Th2 responses, especially IL-10 secretion by circulating mononuclear cells are associated with the progressive form of AE and Th1 responses with resistance. The HLA B8, DR3, DQ2 haplotype is associated with the severity of AE in humans through immune-mediated mechanisms including an elevated production of Interleukin-10 (IL-10). Granulomatous infiltration of mononuclear cells around the parasitic vesicles is a hallmark of this disease; however, cytokine production by granuloma cells has never been studied. Tissue samples were taken in the periparasitic area and in the central area of the periparasitic granulomatous lesions from a patient with a progressive AE at surgery. Six pieces for each zone were incubated in culture medium with antibiotics and IL-2, together with irradiated autologous peripheral blood mononuclear cells as feeder cells. After four days the dead feeder cells were removed by density gradient centrifugation. Lymphocytes were stimulated with Echinococcus multilocularis vesicular fluid antigen (Emf) or PHA to study IL-10, IFN-, and IL-4 production in the supernatant. Emf-stimulated mononuclear cells from the central part of the lesions secreted more IL-10 and less IFN-gamma than cells from the periphery of the granuloma. At the basal level, IL-10 secretion by the locally infiltrating cells was also high and this confirms at the local granuloma level our previous results obtained from cultures of circulating mononuclear cells. The present study confirms that IL-10 secretion is a key feature of the immune response against E. multilocularis in humans. The location of the cells which produce the highest amount of IL-10, those in contact with parasitic structures, suggests that the parasite itself is able to modulate the immune response of the host so that the infiltrating cells cannot participate in the effector phase of the cellular immune response. The nature of the parasitic structures involved and the mechanisms which lead to an imbalanced cytokine production remain to be elucidated.

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis, is a zoonotic helminthic disease that can mimic malignancy. In the 1970s, foci of the disease were found in central China. The aim of the present study was to estimate the prevalence of AE in humans in 2 districts of south Gansu Province, China, by use of ultrasound and Echinococcus serology. After answering an epidemiological questionnaire, 2,482 volunteers from 28 villages underwent ultrasound. Serology via enzyme-linked immunosorbent assay for antibody activity was performed on whole blood collected on filter paper in all subjects; on serum from subjects with an abnormal ultrasound image; and on randomly chosen subjects that either had no lesions or had atypical lesions. At least one (25.3%) abnormal ultrasound image was observed in 630 of the subjects screened. A typical lesion of progressive AE was found in 84 subjects (3.4%). Serologies were positive in 77 (96%) of 80 of patients who had lesions typical of progressive AE. Ultrasound is useful for screening for AE in endemic regions.

In the present study, we assayed the antioxidant properties of Ginkgo biloba (Gb) extract on rats submitted to 21 d of chronic hypoxia. Doses of 25 and 50 mg/kg were examined. Oxygenated free radical production measured by the chemiluminescence technique was significantly decreased in treated rats compared to control rats placed in similar experimental conditions, and this effect was more significant at the 50 mg/kg dose. On the other hand, no antioxidant enzyme activities of the drug were observed towards red blood cells. These results suggest that ginkgo biloba extract has a free radical scavenging action. These antioxidant properties could explain the beneficial hematological properties of Gb extract.

The aim of this study was to analyse the effects of auditory stress on peritoneal and alveolar macrophages in C57 BL/6J mice of advanced age, and to compare the results to those obtained in old mice submitted to a sham stress, and to those observed in young mice submitted to the same auditory stress. We used a chemiluminescence assay to measure the production of free oxygen radicals (FOR) by macrophages. Eight 22 month-old mice were exposed to a sound stress of 110 dB for three consecutive nights; nine were submitted to a sham stress. The results were compared to those obtained in young (8 week-old) mice, 21 submitted to noise stress, and 17 controls. The corticosterone level was not increased after stress in any group. FOR production in old mice was significantly higher than that in young mice. Stress did not induce significant changes in FOR production by alveolar cells in young mice; however, the FOR production by alveolar cells was significantly higher in the stressed group than in the control group of old mice. These results show that noise stress is associated with modifications of macrophage functions that are influenced by cell localization, the behaviour of alveolar and peritoneal macrophages of old mice being clearly different in our experimental model., (Copyright 2000 John Wiley & Sons, Ltd.)

The influence of Vinburnine on red blood cell metabolism and hemoglobin oxygen affinity was investigated in normobaric rats (FiO2: 10%). Two periods of hypoxic exposure were performed (10-21 d). In each experimental series, rats were divided into two groups: Treated rats received a daily intraperitoneal injection of drug (4 mg/kg). Control rats in the same conditions of hypoxia received an isotonic saline solution. For a 10 d exposure period, Vinburnine does not affect red blood cell metabolism nor hemoglobin oxygen affinity. At 21 d period exposure, 2, 3 diphosphoglycerate (2, 3 DPG) and ATP amounts increase in treated rats. The rate of increase was 10% (p<0.05) and 28% (p<0.01), respectively. Red blood cell metabolism effect of Vinburnine was not accompanied by a modification in affinity hemoglobin oxygen (Hb-O2); no statistically significant difference was observed between treated rats and control rats concerning p50 (partial pressure oxygen at half hemoglobin saturation). Results suggest that Vinburnine has a metabolic effect corresponding to a glycolysis anaerobic stimulation, which can improve oxygen delivery to tissues and could explain the favorable hemoreological action of Vinburnine observed in a previous investigation.

The aim of the study was to investigate the systemic and, for the first time, the intestinal humoral events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. Thirty-one mice were divided into three groups; W-2, W-8 and control group. Each mouse of the W-2 and W-8 groups was orally infected with 1,500 E. multilocularis eggs, two weeks and eight weeks before sacrifice respectively. Control group mice received phosphate buffer saline. Measurement of anti-E. multilocularis and non-specific IgG, IgA and IgM, and of a transudation marker, albumin, were performed in serum and intestinal washings by a time-resolved immunofluorometric assay. These results were complemented by microscopic examination of the intestinal mucosa. This infection model is well-suited to the study of mucosal immunity during alveolar echinococcosis. It showed a major specific intestinal response in the early stage of the disease whereas the systemic response predominated later in the disease. Histopathological studies and calculation of the relative coefficient of excretion of Ig also confirmed that the presence of the parasite, even during a short period, was responsible for a local immunological and inflammatory response and for a change in mucosal permeability. Mucosal immunity could thus play a role in tolerance induction against E. multilocularis that could be a prerequisite for the subsequent development of the larvae in the liver, and for the occurrence of the parasitic disease, alveolar echinococcosis.

The aim of this study was to analyze the effects of stress on natural immunity in old mice, and the potential of an immunomodulating drug to correct stress-induced immune abnormalities. We analyzed both the alveolar (ALM) and peritoneal macrophage (PerM) oxidative responses and cytokine productions of TNF-alpha and IL-1alpha, in old mice after exposure to 3 days of noise stress, with and without treatment with RU 41740, an immunomodulating compound. Production of Free Oxygen Radicals (FOR) by ALM and PerM macrophages was evaluated using a luminol-dependent chemiluminescence method at the basal state and after stimulation. Serum corticosterone was also measured. Three groups of 22-24 month-old C57BL/6 mice were studied. Seven mice were treated with RU 41740 (10 mg kg(-1)) every day for 5 days and then exposed to sound stress (110 dB, 1000 Hz, for 3 nights). Ten mice were treated with saline, then submitted to a sham stress. Eight animals received neither treatment nor stress. There was no difference in corticosterone level between the three groups and between these groups and a control group nonstressed, noncannulated. After stimulation by fMetLeuPhe, production of FOR by ALM and PerM significantly increased after stress and returned to normal values after RU 41740 treatment (p < 0.001). The cytokine levels (TNF-alpha and IL-1alpha) decreased after stress and returned to normal levels after RU 41740 treatment. This study shows that, in aged mice, auditory stress is associated with modifications of macrophage functions which are different, depending on their localization and on the function under study. It confirms the immunomodulatory capacities of RU 41740 that was shown to counteract these effects of stress in elderly animals.

The secretion of IL-10 by peripheral blood mononuclear cells (PBMC) and the expression of IL-10 mRNA in fractionated CD4+ and CD8+ lymphocyte subsets and non-B-non-T cells, with and without stimulation by the mitogen phytohemagglutinin-C (PHA-C) and specific Echinococcus multilocularis (E. multilocularis) antigens, were assessed in 7 patients with alveolar echinococcosis (AE) and 6 healthy subjects. Results of studies on IL-10 were compared to those on IFN-gamma, IL-4 and IL-5 in the same patients and control subjects. IL-10 production was significantly higher in patient PBMC-culture supernatants than in the control group supernatants, both at the basal level and after mitogen or specific E. multilocularis antigen stimulation. Both CD4+ and CD8+ lymphocyte populations and non-B-non-T cells of AE patients and controls expressed IL-10 mRNA. Semi-quantification of IL-10 mRNA revealed a significantly higher transcript level in unstimulated-CD8+ T cells from AE patients in comparison with CD8+ T cells of healthy donors. PBMC from patients produced very low levels of IL-4 but the production of IFN-gamma was not significantly depressed compared to the controls. PBMC, isolated from 4 AE patients and 4 control subjects stimulated with specific E. multilocularis antigens, secreted IL-5; IL-5 mRNA was only detected in the CD4+ lymphocyte subset. The secretion of IL-5 and the expression of IL-5 mRNA in healthy subjects could be due to the presence of non-specific mitogenic parasitic factors. This non-specific mitogenic activity of the parasite, besides inducing a high secretion of IL-10 in patients with evolutive AE, may contribute to the lack of host control of parasite growth and to the persistence of granulomatous lesions, due to the inhibition of an efficient Th1 immune response.

A series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octanes and a series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octane 2-spiro derivatives were synthesized from L-(-)-R-cysteine ethyl ester in two steps. The synthetic route involved condensation of the amino acid with an appropriate aldehyde or ketone, then a further condensation of the resultant ethyl thiazolidine-4-carboxylate with an isocyanate or an isothiocyanate. The proliferative response to human lymphocyte mitogen (phytohemagglutinin) was used as a primary screening assay for most of the thiadiazabicyclic compounds in comparison with levamisole. Furthermore, the most active compounds were tested for ability to release soluble receptors (sRIL-2) after mitogenic stimulation of T cells and for ability to activate macrophage oxidative metabolism measured by chemiluminescence. Most compounds were active in all three tests and some showed dose-dependent activity.

In a search for potential immunomodulating agents novel pyrrolo[1,2-c]pyrimidines were synthesized and their structures elucidated by spectroscopic means. Unfortunately, most of them were cytotoxic and devoid of effects on T lymphocyte lymphoblastic transformation. Furthermore, they were inactive in the locomotor activity test in mice.