Microbiota promotes recruitment and pro-inflammatory response of caecal macrophages during E. tenella infection.

BACKGROUND: Eimeria genus belongs to the apicomplexan parasite phylum and is responsible for coccidiosis, an intestinal disease with a major economic impact on poultry production. Eimeria tenella is one of the most virulent species in chickens. In a previous study, we showed a negative impact of caecal microbiota on the physiopathology of this infection. However, the mechanism by which microbiota leads to the physiopathology remained undetermined. Macrophages play a key role in inflammatory processes and their interaction with the microbiota during E. tenella infection have never been investigated. We therefore examined the impact of microbiota on macrophages during E. tenella infection. Macrophages were monitored in caecal tissues by immunofluorescence staining with KUL01 antibody in non-infected and infected germ-free and conventional chickens. Caecal cells were isolated, stained, analyzed and sorted to examine their gene expression using high-throughput qPCR. RESULTS: We demonstrated that microbiota was essential for caecal macrophage recruitment in E. tenella infection. Furthermore, microbiota promoted a pro-inflammatory transcriptomic profile of macrophages characterized by increased gene expression of NOS2, ACOD1, PTGS2, TNFα, IL1ß, IL6, IL8L1, IL8L2 and CCL20 in infected chickens. Administration of caecal microbiota from conventional chickens to germ-free infected chickens partially restored macrophage recruitment and response. CONCLUSIONS: Taken together, these results suggest that the microbiota enhances the physiopathology of this infection through macrophage recruitment and activation. Consequently, strategies involving modulation of the gut microbiota may lead to attenuation of the macrophage-mediated inflammatory response, thereby limiting the negative clinical outcome of the disease.

Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans.

Increased protection from reactive oxygen species (ROS) is believed to increase life span. However, it has not been clearly demonstrated that endogenous ROS production actually limits normal life span. We have identified a mutation in the Caenorhabditis elegans iron sulfur protein (isp-1) of mitochondrial complex III, which results in low oxygen consumption, decreased sensitivity to ROS, and increased life span. Furthermore, combining isp-1(qm150) with a mutation (daf-2) that increases resistance to ROS does not result in any significant further increase in adult life span. These findings indicate that both isp-1 and daf-2 mutations increase life span by lowering oxidative stress and result in the maximum life span increase that can be produced in this way.

[Papillary thyroid microcarcinomas: review of 230 cases]. / Les microcarcinomes papillaires de la glande tyroïde: à propos de 230 cas.

OBJECTIVES: Papillary microcarcinoma (PMC) is one of the most frequent pathological forms of thyroid cancer Here, we describe the circumstances of diagnosis and the clinical and pathological characteristics of this tumour We also analyze the therapeutic management and compare it with the recent published guidelines. METHODS: Between 2000 and 2006, a total of 230 patients with a PMC of the thyroid gland were included in this retrospective study. We have investigated the correlations between some pathological parameters (plurifocality, lymph node invasion...) and several factors (age, gender, tumour size...). RESULTS: The diagnosis of PMC was suspected in the preoperative period in 15% of the patients, and was confirmed intraoperatively by the pathologist in 42% of the cases. Plurifocal or bilateral PMC were discovered in respectively 30 and 17% of the patients. The rate of lymph node invasion in the central neck (level VI) was 26%. An elevated tumor size was correlated with a higher rate of plurifocal or bilateral PMC and of lymph node metastasis (p < 0.05). The indications for postoperative radioiodine therapy were reduced by approxiately 50% in the second part of our study. There were no case of thyroid PMC-related death. CONCLUSIONS: Even for these small tumours, tumour size remains correlated with the tumour aggressiveness. The place of radioiodine therapy in the management of thyroid PMC was progressively reduced because of the good prognosis of this tumour.

Interferon gamma-signature transcript profiling and IL-23 upregulation in response to Helicobacter pylori infection.

Helicobacter pylori infection is the major cause of gastroduodenal pathologies including gastric cancer. The long persistence of bacteria and the type of immune and inflammatory response determine the clinical issue. In this study, the global gene expression profile after 6 and 12 months of H. pylori infection was investigated in the mouse stomach, using the Affymetrix GeneChip Mouse Expression Array A430. Genes related to the inflammatory and immune responses were focused. Levels of selected transcripts were confirmed by reverse transcription polymerase chain reaction. Twenty- five and nineteen percent of the differentially expressed genes observed at 6 and 12 months post-infection respectively, were related to immune response. They are characterized by an interferon (IFN)gamma-dependent expression associated to a T helper 1 (Th1) polarised response. In-depth analysis revealed that an up-regulation of IL-23p19, took place in the stomach of H. pylori infected-mice. Strong IL-23p19 levels were also confirmed in gastric biopsies from H. pylori-infected patients with chronic gastritis, as compared to healthy subjects. Our microarray analysis revealed also, a high decrease of H+K+-ATPase transcripts in the presence of the H. pylori infection. Association of gastric Th1 immune response with hypochlorhydria through the down-regulation of H+K+-ATPase contributes to the genesis of lesions upon the H. pylori infection. Our data highlight that the up-regulation of IL-23 and of many IFNgamma signature transcripts occur early on during the host response to H. pylori, and suggest that this type of immune response may promote the severity of the induced gastric lesions.

Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients.

BACKGROUND: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease. AIM: The goal of the study is to compare the diagnostic values of seven methods for serum Tg measurement for detecting recurrent disease both during L-T4 treatment and after TSH stimulation. METHODS: Thyroid cancer patients who had no evidence of persistent disease after initial treatment (total thyroidectomy and radioiodine ablation) were studied at 3 months on L-T4 treatment (Tg1) and then at 9-12 months after withdrawal or recombinant human TSH stimulation (Tg2). Sera with anti-Tg antibodies or with an abnormal recovery test result were excluded from Tg analysis with the corresponding assay. The results of serum Tg determination were compared to the clinical status of the patient at the end of follow-up. RESULTS: Thirty recurrences were detected among 944 patients. A control 131I total body scan had a low sensitivity, a low specificity, and a low clinical impact. Assuming a common cutoff for all Tg assays at 0.9 ng/ml, sensitivity ranged from 19-40% and 68-76% and specificity ranged from 92-97% and 81-91% for Tg 1 and Tg2, respectively. Using assays with a functional sensitivity at 0.2-0.3 ng/ml, sensitivity was 54-63% and specificity was 89% for Tg1. Using the two methods with a lowest functional sensitivity at 0.02 and 0.11 ng/ml resulted in a higher sensitivity for Tg1 (81% and 78%), but at the expense of a loss of specificity (42% and 63%); finally, for these two methods, using an optimized functional sensitivity according to receiver operating characteristic curves at 0.22 and 0.27 ng/ml resulted in a sensitivity at 65% and specificity at 85-87% for Tg1. CONCLUSION: Using an assay with a lower functional sensitivity may give an earlier indication of the presence of Tg in the serum on L-T4 treatment and may be used to study the trend in serum Tg without performing any TSH stimulation. Serum Tg determination obtained after TSH stimulation still permits a more reliable assessment of cure and patient's reassurance.

Genetics of lifespan in C. elegans: molecular diversity, physiological complexity, mechanistic simplicity.

The nematode Caenorhabditis elegans is used as a model system for the study of aging. Several mutant strains that have an increased lifespan have been isolated and characterized genetically and molecularly. Molecular analysis reveals that diverse types of gene products can affect worm lifespan, including proteins active in signal transduction, transcription and silencing factors, mitochondrial enzymes, and at least one protein that affects telomere length. Genetic analysis, however, suggests that these activities all converge on a few key mechanisms that impinge on lifespan, namely the production, repair and prevention of molecular damage.

Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria.

We show that the phenotype associated with gro-1(e2400) comprises the whole suite of features that characterize the phenotype of the clk mutants in Caenorhabditis elegans, including deregulated developmental, behavioral, and reproductive rates, as well as increased life span and a maternal effect. We cloned gro-1 and found that it encodes a highly conserved cellular enzyme, isopentenylpyrophosphate:tRNA transferase (IPT), which modifies a subset of tRNAs. In yeast, two forms of the enzyme are produced by alternative translation initiation, one of which is mitochondrial. In the gro-1 transcript there are also two possible initiator ATGs, between which there is a sequence predicted to encode a mitochondrial localization signal. A functional GRO-1::GFP fusion protein is localized diffusely throughout the cytoplasm and nucleus. A GRO-1::GFP initiated from the first methionine is localized exclusively to the mitochondria and rescues the mutant phenotype. In contrast, a protein initiated from the second methionine is localized diffusely throughout the cell and does not rescue the mutant phenotype. As oxygen consumption and ATP concentration have been reported to be unaffected in gro-1 mutants, our observations suggest that GRO-1 acts in mitochondria and regulates global physiology by unknown mechanisms.

Impact of attenuation correction by simultaneous emission/transmission tomography on visual assessment of 201Tl myocardial perfusion images.

UNLABELLED: It has been shown in clinical studies that for subjects with a low likelihood of coronary artery disease (CAD), attenuation correction (AC) improves the specificity of defect detection in the inferior wall (right coronary artery [RCA] region). The aim of this study was to investigate the effect of AC on the visual interpretation of the RCA and anteroseptal (corresponding to the left anterior descending artery [LAD]) regions in CAD patients. METHODS: Fifty-six patients with suspected CAD underwent 20Tl stress/4 h-delayed imaging SPECT using a simultaneous 201Tl emission/99mTc transmission imaging protocol. Images were reconstructed using the maximum likelihood-expectation maximum algorithm without and with AC. The stress/4 h-delayed images were interpreted blindly for reversible or fixed defects in the RCA and LAD regions by three experienced physicians. Coronary angiography, electrocardiography and enzyme findings were used to establish diagnoses of ischemia or infarction, and receiver operating characteristic (ROC) analyses were performed. RESULTS: Statistical testing of ROC curve areas showed that defect detection performance improved with AC when compared with performance without AC in the RCA region. This was mainly the result of a systematic increase in specificity of 12% or more (for any observer and any type of defect) for a similar sensitivity (no definite change in sensitivity values). However, defect detection performance significantly decreased in the LAD territory with AC images (P < 0.05) because of a systematic decrease in sensitivity of 20% or more, with no consistent change in specificity. Similar trends were observed when reversible and fixed defects were considered separately. CONCLUSION: AC significantly affects the visual interpretation of 201Tl stress/4 h-delayed SPECT images. This study confirmed the increase in specificity obtained with AC in the RCA territory. However, in the population considered, the studied AC was deleterious for the LAD territory assessment.

Nitrates improve detection of ischemic but viable myocardium by thallium-201 reinjection SPECT.

Thallium-201 reinjection imaging improves myocardial viability detection when compared to standard 3-4-hr redistribution imaging, however, the extent of ischemic but viable myocardium is still underestimated. We tested whether the sensitivity of reinjection imaging could be increased by giving nitrates postexercise to improve blood flow during the redistribution period. Twenty patients with coronary artery disease were included, 11 of them with a recent myocardial infarction. All patients underwent two exercise/4-hr redistribution 201Tl SPECT protocols: one with reinjection alone and the other with nitrates and reinjection. In the latter case, 20 mg of Isosorbide Dinitrate were given to patients immediately after postexercise imaging. Fifteen patients had reversible defects with reinjection alone, three additional patients were defined as ischemic with nitrates/reinjection protocol. Reinjection alone identified 41 reversible segmental defects, all except one were also evaluated as reversible with nitrates/reinjection. However, among the 54 segments showing fixed defects after reinjection only, 14 (26%) presented as reversible with the nitrates/reinjection protocol. The redistribution extent (segments/patient) was 2.05 +/- 0.41 segments with reinjection alone and 2.75 +/- 0.38 (p < 0.01) with nitrates/reinjection. In 15 patients showing reversible defects with both protocols, the redistribution extent was 2.73 +/- 0.41 segments with reinjection alone and 3.20 +/- 0.40 (p < 0.05) with nitrates/reinjection. Thallium-201 SPECT with nitrates and reinjection improves the detection of ischemic but viable myocardium in comparison to SPECT with reinjection alone.

Phase II scintigraphic clinical trial of malignant melanoma and metastases with iodine-123-N-(2-diethylaminoethyl 4-iodobenzamide).

Preclinical studies established [125I]-N-(2-diethylaminoethyl) 4-iodobenzamide (BZA) as a potential radiopharmaceutical in the management of patients with malignant melanoma. External detection of both murine and human melanotic melanomas was possible after intravenous injection of 125I-BZA in tumor-bearing mice. This article reports a Phase II clinical trial evaluating 123I-BZA as an imaging agent of primary melanomas and metastases. A total of 110 patients with a history of melanoma were investigated in two nuclear medicine departments. Subjects were imaged from 20 to 24 hr after the intravenous injection of 3.5 mCi (130 MBq) of 123I-BZA. After injection, no short-term or long-term side effects were noted. Calculated on a lesion-site basis, diagnostic sensitivity was 81%, accuracy was 87% and specificity was 100%. The melanoma nature of previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The scintigraphies were normal in 44 patients in clinical remission after treatment of malignant melanoma and in seven patients with nonmelanoma disease. No false positive results were observed. Iodine-123-BZA scintigraphy appears to be a safe and useful agent for the detection and follow-up of patients with malignant melanoma. BZA also allowed the detection of unsuspected lesions and the evaluation of the results of various therapeutic procedures such as surgery, chemotherapy, immunobiology, biological therapy or radiotherapy.

Analysis of C-myc amplification by the differential polymerase chain-reaction (d-PCR), study in breast-cancer.

c-myc proto-oncogene amplification seems to have a prognostic value in breast cancer. In this study, quantitative analysis of c-myc amplification was carried out by differential polymerase chain reaction technique (d-PCR) using beta-globin as the reference gene. d-PCR assessment showed coampIification products of c-myc and beta-globin depend on variations in reaction factors such as the genomic DNA concentration, the relative concentrations of the various amplimers, the thermostable DNA polymerase concentration and the number of cycles. However, amplification of c-myc can be estimated quantitatively. In addition, results of individual sets of d-PCR can be expressed on a standard reference scale. A clinical study of 309 patients with breast cancer found c-myc amplification, respectively in 19% (45/236) of primary tumour tissues, 21% (4/19) of subsequent second primary cancers, 36% (4/11) of tumours of patients with bilateral lesions, 40% (8/20) of local recurrence tumours and 22% (5/23) of metastatic lesions. Amplification of c-myc was observed more frequently in histological grades 2-3 (p<0.02), in ER negative (p<0.01) and PgR negative tumours (p<0.02), but was not associated with age, tumour size, nodal status, histology, cytosolic cathepsin D or pS2. d-PCR appears amenable to automation and should facilitate large scale, inter laboratory gene amplification studies.

A radiolabelled iodobenzamide for malignant melanoma staging.

123I-N-(di-ethylamino-2-ethyl) 4 iodobenzamide (I-BZA) has been put forward by the Clermont-Ferrand INSERM U71 group (France) as a tracer for malignant melanoma. We report on the clinical results obtained in 56 studies performed on 48 patients. Whole body scans along with spot views were obtained after injection of 185 MBq of I-BZA. The scans were read by three independent observers and correlated to the clinical findings and the other imaging modalities available, taking into account all lesions larger than 1 cm. Patients were classified into two groups on the basis of a post-treatment survey of patients: group I, in complete remission (24 scans); group II: documented metastases (32 scans). In group 1, 21 studies were truly negative. However, three studies showed positive results. Only one turned out to be a false positive (specificity 95%), the other two revealed unknown lesions and modified the patients' management. In group II, 73% of the known metastases were detected with higher sensitivities (> 80%) for eye and orbit, lung and abdomen. One false positive was reported and four new lesions were detected. I-BZA scintigraphy has the same sensitivity as immunoscintigraphy with higher specificity and without the risk of xenoimmunization. It is a useful tool for staging malignant melanoma which can improve patient management.

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.

C-erb-B2 gene amplification and serum level of c-erb-B2 oncoprotein at primary breast cancer diagnosis.

We studied c-erb-B2 gene amplification of DNA of primary breast tumours without distant metastasis from 236 women admitted to our institute during 1992. For 125 of them, we had a serum sample at diagnosis, before any treatment. C-erb-B2 gene amplification (> or = 2 copies) was observed in 26% (62/236) of the cases. There was a correlation with higher histological grades (p < 0.03) and with absence of hormone receptors: ER-(p < 0.0001). PgR-(p < 0.0001), association ER- and PgR-(p < 0.0000). Large tumours T3 and T4 taken together tended to present more c-erb B2 gene amplifications (p < 0.08). There was no correlation with age, histological type or nodal status. At diagnosis, mean concentration of serum c-erb-B2 oncoprotein was 8.5 +/- 18 U/ml with a median of 4 U/ml (4-150). Choosing a cut-off value of 8 U/ml gave a sensitivity of 21% (26/125). Serum levels of c-erb-B2 oncoprotein were correlated with tumour spread: large tumours T3-T4 (p < 0.001), nodal involvement (N+) (p < 0.01), association T3-T4 and N+(p < 0.0005), high levels of CA 15:3 (normal value < 25 IU/ml) (p < 0.05). There was no other correlation, particularly with age, histological type, hormone receptors or c-erb-B2 gene amplification. c-erb-B2 oncoprotein serum levels could be helpful to detect recurrences. Assessment of c-erb-B2 oncoprotein serum concentration, before treatment, as an independent prognostic factor is necessary.

A single photon emission computed tomography study of cerebral regional perfusion changes induced by a learning task in subjects with mild memory impairment.

Fifteen nondemented subjects with memory complaints underwent serial single photon emission computed tomography (SPECT) studies with technetium-99m-d, l-hexamethyl-propylene amine oxime (HMPAO) as tracer. Scans were carried out under a baseline conditions and during the learning phase of the Memory Efficiency Profile (MEP), a combined visual perception and memory task developed by Rey. Results indicate a positive correlation between activation, as indexed by HMPAO uptake, and neuropsychological assessment. Right temporal activation was correlated with MEP immediate recall. The right cerebellum was correlated with both MEP immediate and delayed recall. This study suggests that SPECT can show cortical activation during cognitive performance in subjects with mild memory impairment.

Study of the frequencies of CYP1A1 gene polymorphisms and glutathione S-transferase mu1 gene in primary breast cancers: an update with an additional 114 cases.

We studied the polymorphisms m1 (Msp1 restriction site) and m2 (codon Val substitution) of CYP1A1 gene and the copy number of glutathione S-transferase mu1 (GSTM1) gene on 487 DNA of breast cancer primary tumours from Caucasian group. Tumours of patients aged 55 years and under at diagnosis presented a great proportion of wild m1 (-/-) genotype; 83.6% vs. 69.5% (p < 0.0006), and a higher percentage of copy number of GSTM1 equal or under one copy; 65.2% vs. 53.4% (p < 0.011) for older patients m1 and m2 variants are closely linked (p < 0.0000). Tumour with a low copy number of GSTM1 is correlated with high histological grading (p < 0.01) and high Cathepsin D concentrations (p < 0.02). The combinations of different genotypes showed that association wild m1 (-/-) genotype and copy number of GSTM1 inferior or equal to one copy is correlated with an early onset of breast cancer primary tumour 44% vs. 6.4% for m1 (-/+) or (+/+) genotype and copy number of GSTM1 superior to one (p < 0.0000). The CYP1A1 gene wild form seems to be associated with early cancer development in Caucasian patients.

[Study of mdm2 gene amplification in primary breast tumors]. / Etude de l'amplification du gène mdm2 dans les tumeurs primitives du sein.

mdm2 (mouse double minute) protein seems lead to p53 inactivation and therefore might potentially play a role in carcinogenesis. We have studied mdm2 gene amplification from 239 primary breast cancer tissues. mdm2 gene was amplified in 10% of cases (25/239). mdm2 amplification was associated with c-erbB2 amplification (P < 10(-3)). No other correlation was found. However there was inverse correlation between c-erbB2 gene amplification and hormonal receptors (P < 10(-4)), only from patients without mdm2 gene amplification.

[Glutathione S-transferase mu 1 (GSTM1): susceptibility gene of breast cancer]. / Glutathion S-transférase mu 1 (GSTM1): gène de susceptibilité du cancer du sein.

Glutathione S-transferases mu (GSTM) are dimeric cytosolic isoenzymes. They catalyze glutathione conjugation upon a large variety of electrophiles as carcinogens, trans-stilbene peroxide or benzo(a)pyrene. The gene GSTM1 is localized on chromosome 1p13, it has drawn attention because it is absent approximately in 50% of the white population. GSTM1 null genotype seems linked with susceptibility to cancers as lung, colon and bladder cancers. We have studied GSTM1 genotype from 373 primary breast tumours. The GSTM1 null genotype was found in 50% of the cases (185/373). The incidence study of GSTM1 copy number on clinical and biological variables displayed a significant difference (p < 0.01) of the GSTM1 genotype, showed by the tumour, according to the patient age at diagnosis. The patients younger than 55 years had a percentage more important of primary tumours (65%) with a copy number of GSTM1 gene, inferior or equal at one, compared to the patients older than 55 years (52%). The tumours, whose cathepsin D level was high, presented few copies of GSTM1 gene (p < 0.03). There was no other relationship, particularly, with tumour size, node status, histological type, hormonal receptors, pS2 cytosolic level GSTM1 gene seems protect the mammary gland from cancerogenesis with its detoxification role. This results had not, pointed out in breast cancer, yet.

Stress protein expression cDNA array study supports activation of neutrophils during acute magnesium deficiency in rats.

Recent studies underline the importance of the immunoinflammatory processes in the pathology of acute magnesium (Mg)-deficiency. The aim of this study was to assess the effect of acute experimental Mg-deficiency in the rat on neutrophil activity. Weaning male Wistar rats were fed either a Mg-deficient or a control diet for 8 days. In this experiment, we measured neutrophil respiratory burst by chemiluminescence; then, to examine the molecular events associated with acute Mg-deficiency, we applied cDNA array technology to define the transcription response in neutrophils of Mg-deficient rats in comparison with controls. In Mg-deficient rats, the characteristic inflammatory response was accompanied by a marked increase in the number of neutrophils. Moreover, as shown by chemiluminescence studies, basal neutrophil activity from Mg-deficient rats was significantly elevated when compared to neutrophils from control rats. Moreover, the chemiluminescence of neutrophils from Mg-deficient rats was significantly higher than that of control rats following phorbol myristate acetate or opsonized zymosan activation. Using cDNA array which includes 207 known rat genes of stress proteins, 102 genes were found to be expressed in neutrophils. Among expressed genes, 78 per cent of genes were found to be expressed more than twofold in neutrophils from Mg-deficient rats compared to control rats. Acute Mg-deficiency was characterized by an induction of genes encoding for proteins involved in apoptosis, heat shock proteins, protein belonging to the cytoskeleton, proteins implicated as stress response regulators and effectors and enzyme implicated in thromboxane synthesis. Then, this experimental strategy allowed to identify a series of genes implicated in the immunoinflammatory process of Mg-deficiency.

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.