Oral probiotic treatment of Lactobacillus rhamnosus Lcr35® prevents visceral hypersensitivity to a colonic inflammation and an acute psychological stress.

AIMS: This study evaluated the efficacy of a repeated oral treatment with two active pharmaceutical ingredients (Lcr Lenio® and Lcr Restituo® ) derivated from the probiotic bacterial strain Lactobacillus rhamnosus Lcr35® in two animal models mimicking different features of irritable bowel syndrome (IBS). IBS is characterized by visceral pain associated with alteration of bowel transit. IBS patients present visceral hypersensitivity with peripheral and central origins. METHODS AND RESULTS: The injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the proximal colon as well as an acute partial restraint stress (PRS) produces colonic hypersensitivity measured in conscious rats by a decrease in pain threshold in response to distal colonic distension. Visceral hypersensitivity was produced by injection of TNBS 7 days before colonic distension or by acute PRS on testing day. Treatments were performed once a day during eight consecutive days. CONCLUSIONS: This study indicates that an 8-day probiotic treatment (Lcr Lenio and Lcr Restituo) produces an antihypersensitivity activity in both TNBS and PRS visceral pain models. As this probiotic strain attenuates peripherally and centrally induced visceral hypersensitivity in rats, it may be active in treatment of IBS symptoms. An immunomodulatory effect of the probiotics was highlighted in the TNBS model on the IL-23 secretion, suggesting a mechanism of action involving a regulation of the local IL-23/Th17 immune activation. SIGNIFICANCE AND IMPACT OF THE STUDY: Two formulas of Lcr35® probiotic strain show very encouraging results for the treatment of IBS patients. Further studies are needed to better understand the role and mechanisms of probiotics on the pathogenesis of IBS.

Binding Potency of Heparin Immobilized on Activated Charcoal for DNA Antibodies.

In vitro experiments showed that heparin adsorbed on activated charcoal can bind antibodies raised against native and single-stranded DNA in a diluted sera pool with a high level of these DNA. Thus, heparin used as anticoagulant during hemosorption procedure can demonstrate supplementary therapeutic activity resulting from its interaction with various agents involved in acute and chronic inflammatory reactions such as DNA- and RNA-binding substances, proinflammatory cytokines, complement components, growth factors, etc. Research and development of heparin-containing carbonic adsorbents for the therapy of numerous inflammatory and autoimmune diseases seems to be a promising avenue in hematology.

Airborne pollen levels and drug consumption for seasonal allergic rhinoconjunctivitis: a 10-year study in France.

BACKGROUND: Few time-series studies, and none lasting longer than 4 years, have investigated the etiology of treated seasonal allergic rhinoconjunctivitis (SAR) on the basis of anti-allergic medication prescriptions. The aim of this article was to study the short-term relationship between pollen exposure and drug-treated SAR over 10 years in an urban area in central France. METHODS: A SAR case was defined as the association between an oral antihistamine and a local anti-allergic drug on the same prescription. The relationship between daily changes in pollen concentrations and daily changes in the number of treated SAR cases was analysed using generalized additive models, taking into account confounding factors such as air pollution, weather and days of the week. RESULTS: Between 2003 and 2012, the total yearly number of treated SAR cases rose from 7265 to 11 315. The relative risk of treated SAR associated with an interquartile increase in pollen concentration increased significantly for Fraxinus, Betula, Carpinus, Platanus, Poaceae and Urticaceae for the whole pollen season, and for Urticaceae in the first semester. CONCLUSIONS: The prevalence of treated SAR cases rose by about 55% in 10 years. The study not only confirmed the highly allergenic role of Fraxinus, Betula and Poaceae pollens but also showed a relatively unknown association between treated SAR and Carpinus and Platanus pollens, despite their pollen counts being <1% of overall pollen concentration. It also showed robust correlations with Urticaceae pollens, especially during the first semester, suggesting a potential allergenic role of Parietaria pollination in this non-Mediterranean area.

Eosinophilic activity and bronchial hyperresponsiveness within an asthmatic paediatric population.

BACKGROUND: Our study aims to assess the importance of serum eosinophil cationic protein (ECP) levels as a non-invasive marker of bronchial hyperresponsiveness (BHR) in children with asthma, and may predict objectively the asthmatic severity and sensitivities. METHODS: This study, which was carried out on 75 asthmatic patients from a paediatric population (average age: nine years old, sex-ratio M/F: 1.64), is based on both interrogation conducted by the clinician and biological explorations, essentially serological testing of ECP and eosinophilia determination, as well as the measurement of serological IgE amounts. RESULTS: The analysis of the questionnaires and the biological results allowed us to evaluate the clinico-biological relations within this population. ECP, more than eosinophilia, proves to be a relevant marker of asthma severity (p<0.05) and sensitivities within this given population (r=0.65). CONCLUSION: We were able to show that the evaluation of the serological levels of ECP seems to be a good biological marker of asthma.

Roles of capsule and lipopolysaccharide O antigen in interactions of human monocyte-derived dendritic cells and Klebsiella pneumoniae.

In humans, Klebsiella pneumoniae is a saprophytic bacterium of the nasopharyngeal and intestinal mucosae that is also frequently responsible for severe nosocomial infections. Two major factors of virulence, capsular polysaccharide (CPS) and lipopolysaccharide (LPS) O antigen, are involved in mucosal colonization and the development of infections. These bacterial surface structures are likely to play major roles in interactions with the mucosal immune system, which are orchestrated by a network of surveillance based on dendritic cells (DCs). To determine the roles of K. pneumoniae CPS and LPS in the DC response, we investigated the response of immature human monocyte-derived DCs to bacterial challenge with a wild-type strain and its isogenic mutants deficient in CPS or LPS O-antigen production. As observed by flow cytometry and confocal laser microscopy, the rate of phagocytosis was inversely proportional to the amount of CPS on the bacterial cell surface, with LPS playing little or no role. The K. pneumoniae wild-type strain induced DC maturation with upregulation of CD83, CD86, and TLR4 and downregulation of CD14 and DC-SIGN. With CPS mutants, we observed a greater decrease in DC-SIGN, suggesting a superior maturation of DCs. In addition, incubation of DCs with CPS mutants, and to a lesser extent with LPS mutants, resulted in significantly higher Th1 cytokine production. Combined, our findings suggest that K. pneumoniae CPS, by hampering bacterial binding and internalization, induces a defective immunological host response, including maturation of DCs and pro-Th1 cytokine production, whereas the LPS O antigen seems to be involved essentially in DC activation.

[Intra-alveolar haemorrhage without renal damage as the initial presenting feature of Goodpasture's syndrome: case report and review of literature]. / Hémorragie intra-alvéolaire isolée révélant un syndrome de Goodpasture sans atteinte rénale : à propos d'une observation et revue de la littérature.

Isolated pulmonary involvement in Goodpasture's syndrome is exceptionally described. We report a 36-year-old woman with pulmonary haemorrhage and review 28 additional cases of the literature. In fact, these patients had often mild urine abnormalities and constant glomerular lesions. Antiglomerular basement membrane antibodies testing should be systematically ordered in patients presenting with alveolar haemorrhage. Goodpasture's syndrome without renal abnormality could be an early stage of the disease with a better prognosis.

[Crozet protocol: does a lipid-rich meal interfere with cryoglobulinemia assay?]. / Protocole Crozet : le dosage des cryoglobulinémies est-il perturbé par un repas riche en lipides ?

Cryoglobulins are serum immunoglobulins that precipitate reversibly at low temperature. It is important to determine their presence, because they can be responsible for severe complications. They can also reveal underlying conditions, in particular hepatitis C and haematological diseases. Laboratory investigations of cryoglobulins are problematic and require adherence to strict preanalytical conditions. We decided to determine wether a patient really needs to be in a fasting state when a blood sample is taken. In practice, this requirement is difficult for us to meet, because of our large patient population (consultations in a teaching Hospital). We therefore devised a protocol, called the Crozet protocol based on the assay of cryoglobulinemia in healthy volunteers, before and after a meal rich in lipids. Ten patients were tested. Cryoglobulinemia assays were performed according to the technique of Hartree. Lipid profiles were measured on Modular P (Roche Diagnostics). Cryoglobulinemia assay does not seem to be unduly affected by a meal rich in lipids, in particular in triglycerides. Hence the patient does not necessarily have to be on an empty stomach at blood sampling. This study allowed us to modify our threshold of significance (from 15 to 30 microg/mL), which confirmed our view of the physiological character of a low cryoglobulinemia level. Studies involving a greater number of healthy subjects are needed to accurately establish a new threshold and to confirm our findings.

Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action?

It is well known that leptin, the ob gene product, is involved in the regulation of food intake and thermogenesis. Recent studies also demonstrate that leptin may be able to modulate functions of cells involved in nonspecific immune response such as phagocytosis and secretion of cytokines by macrophages. This and the prominent implication of polymorphonuclear neutrophils (PMNs) in infectious response suggested a possible role of leptin as a modulator of PMN functions. We detected a leptin receptor on the PMN membrane by immunocytochemistry with an anti-leptin receptor. Using chemiluminescence we then demonstrated that leptin enhances oxidative species production by stimulated PMNs. These results show for the first time that a functional leptin receptor is present on PMNs and that leptin may be able to influence their oxidative capacity.

Specific and nonspecific immune responses to fasting and refeeding differ in healthy young adult and elderly persons.

BACKGROUND: Undernutrition is a main cause of immunodeficiency. Many confounding factors limit the interpretation of immune function in hospitalized elderly patients. OBJECTIVE: We compared the effects of short-term fasting and refeeding on lymphocyte subset distribution and neutrophil function in healthy subjects. DESIGN: Seven young adult (x +/- SE age: 24 +/- 2 y) and 8 elderly (71 +/- 3 y) subjects were fed standardized diets (1.6 x predicted resting energy expenditure; 16% protein) for 7 d. They then fasted for 36 h and were refed for 4 h (42 kJ/kg). Lymphocyte subsets were quantified by using fluorochrome-conjugated monoclonal antibodies. Neutrophil chemotactic migration was evaluated by using a 2-compartment chamber. Neutrophil reactive oxygen species production was measured by using a luminol-amplified chemiluminescence assay and oxidation of 2'7'-dichlorofluorescein diacetate. RESULTS: Baseline total and cytotoxic T lymphocyte subpopulations were lower in elderly than in adult subjects (P < 0.01). Nutritional state had a significant effect (P < 0.05) on total, helper, and cytotoxic T and B lymphocyte counts in all subjects, and the response of lymphocyte subpopulations to nutritional fluctuations was significantly affected by age. The chemotactic index was lowered by fasting in both groups (P < 0.05 compared with basal values). After refeeding, neutrophil migration was restored in adult but not elderly subjects. The superoxide anion production rate increased with fasting and reverted to prefasting values with refeeding in both groups (P < 0.05). Fasting induced a significant decrease in hydrogen peroxide production in stimulated neutrophils that was reversed by refeeding in adult but not elderly subjects. CONCLUSION: The lack of response of lymphocyte subpopulation counts and neutrophil function to nutritional changes may help to explain the proneness of elderly persons to infection.

Increase in complement component C3 is an early response to experimental magnesium deficiency in rats.

The importance of the inflammatory process in the pathology of experimental Mg-deficiency has been reconsidered but the sequence of events leading to inflammatory response remains unclear. In this study, the effect of Mg-deficiency on complement system by measuring total C3 concentration, mRNA abundance for rat pre-pro complement C3 in liver by RT-PCR, complement haemolytic activity and C3 activation by Western Blot was studied. Weaning male Wistar rats were fed either Mg-deficient or control experimental diets for 2 or 8 days. At 8 days, a characteristic inflammatory response of Mg-deficiency including hyperaemia, leukocytosis and enlarged spleen was accompanied by an increase in the total C3 quantity in plasma. Moreover, at 8 days, RT-PCR analysis indicated higher level of mRNA rat pre-pro complement C3 in liver from Mg-deficient rats compared to control rats. Even if the inflammatory syndrome was not observed in rats after 2 days, total plasma C3 was shown to be significantly increased as compared to total plasma C3 level in control rats. Because of the high variability of complement haemolytic activity values in Wistar rats, weaning male Sprague-Dawley rats were used in a second experiment. At 8 days, the inflammatory response of Sprague-Dawley rats was accompanied by an increase in total C3 quantity and by a higher haemolytic activity. The Western Blot technique failed to display distinct bands resulting from C3 cleavage in plasma from Mg-deficient rats. Since, the complement C3 is a positive acute phase reactant, the elevation of C3 indicates that the modification of inflammatory response is an early event of Mg-deficiency. However, complement activation does not appear to be involved in the acute phase of the deficiency.

Atopy parameters in asthmatic infants.

We evaluated various atopy parameters in 44 asthmatic infants aged 1-3 years: nonspecific parameters (total IgE and eosinophilia), and specific parameters relative to 21 allergens (specific IgE and skin tests), together with tests of leukotriene release by blood leukocytes (cellular allergen stimulation test; CAST) in the presence of a mixture of 21 allergens. Thus far 17 infants have displayed no sign of atopy, but 27 met at least one criterion. Eight met nonspecific criteria, and the others single or multiple criteria. Of the 21 allergens, 20 gave rise to at least one sensitization in this population. The specific IgE was more frequently positive than the skin tests. Dissociations between the two types of specific tests were practically systematic. Different phenotypes based on the chosen parameters were individualized, demonstrating heterogeneity in the expression of atopy in these young infants. The polyvalent CAST was positive only when other criteria of atopy were also positive (specific IgE and/or skin tests), and the range of intensity of the responses obtained supports reactivity rather than sensitization.

High magnesium concentration in vitro decreases human leukocyte activation.

In view of experimental data suggesting that pharmacological magnesium (Mg) therapy could be expected to temper hypersensitivity, the aim of the present study was to assess the effect of in vitro high Mg concentration (8 mmol/l vs. 0.8 mmol/l) on human leukocyte activation. The first experiment in nine healthy volunteers was performed on total leukocyte suspension containing 82 +/- 4 per cent of neutrophils. The results demonstrate the inhibitory effect of high Mg concentration as shown by the significant reduction of superoxide anion production following phorbol myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP) activation. Moreover, neutrophils activated with fMLP showed an increased respiratory burst when incubated in low Mg concentration (0.2 mmol/l) as compared to normal Mg concentration (0.8 mmol/l). Similarly, high concentration of Mg resulted in a significant reduction in superoxide anion production by eosinophils in response to PMA in five eosinophilic patients. In patients showing Hymenoptera venom hypersensitivity, high Mg concentration resulted in a significant reduction of sulphidoleukotrienes production by leukocytes in response to venom allergen (six patients) or in response to zymosan activated particules (fourteen patients). Taken together, the results suggests that Mg acts via a non specific mechanism and appears to be non specific to a particular cell type. As Mg counteracts calcium in many physiological and pathological processes, it is reasonable to hypothesise that extracellular Mg can diminish leukocyte activation by its calcium antagonism.

[Chronic urticaria and Hashimoto-Hashimoto's thyroiditis: report of 6 cases]. / Urticaire chronique et thyroïdite de HashimotoHashimoto: à propos de six cas.

PURPOSE: Chronic urticaria is a common skin disorder. The cause is rarely determined. Autoimmune diseases, particularly autoimmune thyroiditis, have been implicated in the occurrence of chronic urticaria. METHODS: We reviewed clinical records of patients with Hashimoto's disease and chronic urticaria. RESULTS: In our department, six patients had presented chronic urticaria associated with Hashimoto's thyroiditis: four patients, of which three treated with L-thyroxine were euthyroid, the other two were hypothyroid. Hashimoto's thyroiditis had been diagnosed for three patients during the investigation of chronic urticaria. Three patients developed chronic urticaria though they were treated with thyroid suppression for Hashimoto's disease. Two of them had a dramatic improvement with opotherapy. One patient who was euthyroid without treatment improved with hormonal therapy. The fourth patient had a partial remission with thyroid hormones and was cured with corticotherapy. CONCLUSION: The mechanism by which thyroid autoimmunity is associated with urticaria is poorly understood. A cross-linking of IgE receptors of mastocytes induced by antithyroid antibodies may be a cause of histamine release. Hormonal therapy may be a potent event for the clinical improvement by the suppression of chronic thyroid stimulation. Assay of thyroid hormone and antithyroid antibodies should be performed in patients with chronic urticaria. Discovery of Hashimoto's thyroiditis with chronic urticaria requires thyroid hormone replacement not only in hypothyroid but also euthyroid patients.

[Multiple complications of monoclonal IgM]. / Multiples complications d'une IgM monoclonale.

A 64 year old woman with monoclonal IgM Kappa cryoglobulinemia had developed neurologic, vascular and bone involvements. If each features were previously reported, their association appears to be rare. The polyneuropathy was consistent with an IgM anti MAG neuropathy rather than a cryoglobulinemic neuropathy. The vascular occlusion is well known in dysglobulinemia. The diffuse osteosclerosis without medullary fibrosis or myeloproliferative disorder was as like as a Schnitzler's syndrome (chronic urticaria, osteosclerosis, monoclonal IgM Kappa gammopathy.

[Ophthalmologic manifestations of systemic vasculitis: report of six cases and review of the literature]. / Manifestations ophtalmologiques des vascularites systémiques: analyse de six observations et revue de la littérature.

PURPOSE: Study of characteristics of ocular involvement in systemic vasculitis. METHODS: We describe six cases of systemic vasculitis with ocular involvement observed between 1992 and 2000. These cases are compared with those reported in the literature. RESULTS: Our patients suffered from Wegener's granulomatosis (four cases), periarteritis nodosa and Churg-Strauss syndrome. Ocular manifestations were conjunctivitis, scleritis, orbital pseudotumor, optic neuritis and extraocular muscle palsy. These manifestations are similar to those reported in the literature. Their treatment requires steroids and immunosuppressive drugs. In one of our cases, intravenous immunoglobulins were effective in controlling an optic neuritis. CONCLUSION: Ocular involvement in systemic vasculitis may concern any orbital structure. It usually occurs during the course of vasculitis but may be one of its first manifestations. It requires an appropriate treatment to prevent ophthalmic complications and especially blindness.

[Cold agglutinins and cryoglobulinemia in a patient with hepatitis C]. / Agglutinines froides et cryoglobulinémie chez un patient avec une hépatite C.

OBJECTIVES: Cold agglutinins and cryoglobulins are uncommon in the same patient as observed in our case. CASE REPORT: A 74-year-old patient suffered repeated episodes of hemolytic anemia for one year and had hepatitis C anti-virus antibodies. Mixed cryoglobulinemia was found at levels which increased during episodes of acute hemolysis in addition to anti-I cold agglutinins. Two-dimensional electrophoresis revealed identical oligoclonal cold agglutinins and cryoglobulins. DISCUSSION: Unlike mixed cryoglobulinemia, cold agglutinins are not known to occur subsequent to hepatitis C infection. The identical immunoglobulins observed in our patient suggest a common origin. Chronic anti-I cold oligoclonal agglutinins are rarely observed and could be an intermediary step towards monoclonal lymphopathy as has been described in prolonged hepatitis C infection.

[Analysis of eosinophilia and ECP levels in blood and nasal secretions of 119 nasal polyposis patients]. / Analyse des taux d'éosinophiles et d'ECP dans le sang et les sécrétions nasales chez 119 patients atteints de polypose naso-sinusienne.

OBJECTIVE: The aim of this prospective study was to determine eosinophilia and ECP (Eosinophilic Cationic Protein) levels in blood and in nasal secretions of patients with nasal polyposis (NP). PATIENTS: 119 patients with NP were prospectively studied. The control group included 25 patients. METHODS: They included: questionnaire about asthma and intolerance to aspirin; nasal endosopic grading; nasal symptoms scoring; allergy testing; measurements of serum and nasal values of eosinophilia expressed as a percentage; measurements of serum and nasal values of ECP expressed in ng/ml; the Spearman correlation test, the T series and Khideux tests were used in the statistical analysis. RESULTS: In NP group, 66 were asthmatic (As) and 53 non asthmatics (NAs), 40 were atopic (ATo), and 79 were non atopic (NAto). Values of nasal eosinophilia and nasal ECP in NP patients were significantly higher (respectively 40.7+/-35.6% and 22.8+/-48.0 ng/ml) than the control group (respectively 3.0+/-14% and 2.1+/-3.6 ng/ml). Nasal and serum eosinophilia values in asthmatic patients (As) (respectively 47+/-36% and 7.6+/-6.3%) were significantly higher (p<0.05) than in non asthmatic patients (NAs) (respectively 32.6+/-33.8% and 4.6+/-3.1%). No difference was found in nasal and serum ECP values between asthmatic and non asthmatic patients. Nasal eosinophilia values were significantly correlated (p=0.02) with nasal scoring in NP patients. No correlation was found between nasal ECP and serum ECP values and clinical scoring. CONCLUSION: Nasal eosinophilia and nasal ECP values are significantly increased in NP. Nasal eosinophilia seems to be a relevant biological marker of clinical severity (association with asthma and a high clinical score) in NP patients. By contrast, nasal ECP cannot be consider as a marker of clinical severity.

Is IgG4-Related Disease a Cause of Xerostomia? A Cohort Study of 60 Patients.

Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated. Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody. Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome. Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD.