[Chronic pelvic pain syndrome and Crohn's disease : a dangerous association]. / Syndrome douloureux pelvien chronique et maladie de Crohn : une synergie dangereuse.

We present the case of a 54 year old male complaining of abdominal pain localised in the right flank and irradiating in other abdominal regions. The pain was previously associated with kidney stones, but persisted months after their total evacuation. Suffering from Crohn's disease, low dose corticosteroids likely caused a particularly invalidating chronic prostatitis, which antibiotic treatment aggravated the symptoms of Crohn's disease, therefore complicating the therapeutic care by causing a vicious circle. Further epidemiological and microbiological studies are needed in order to establish an association between low dose steroid for Crohn's disease and chronic pelvic pain syndrome.

On présente le cas d'un homme de 54 ans se plaignant d'une douleur dans le flanc droit irradiant dans d'autres régions abdominales. La douleur était précédemment associée à la présence de lithiases urinaires, mais persiste des mois après leur évacuation. Souffrant d'une maladie de Crohn, le traitement par faible dose de corticostéroïdes a vraisemblablement causé une prostatite chronique particulièrement invalidante, dont le traitement antibiotique aggrave les symptômes de la maladie de Crohn compliquant ainsi la prise en charge thérapeutique par un cercle vicieux. Des études épidémiologiques et microbiologiques plus approfondies sont nécessaire afin d'établir l'association entre le traitement stéroïde à faible dose pour la maladie de Crohn et le syndrome douloureux pelvien.

Effects of Endocrine Disruptor Compounds, Alone or in Combination, on Human Macrophage-Like THP-1 Cell Response.

The aim of the present study was to evaluate the immunological effects on human macrophages of four endocrine disruptor compounds (EDCs) using the differentiated human THP-1 cell line as a model. We studied first the effects of these EDCs, including Bisphenol A (BPA), di-ethylhexyl-phthalate (DEHP), dibutyl phthalate (DBP) and 4-tert-octylphenol (4-OP), either alone or in combination, on cytokine secretion, and phagocytosis. We then determined whether or not these effects were mediated by estrogen receptors via MAPK pathways. It was found that all four EDCs studied reduced strongly the phagocytosis of the differentiated THP-1 cells and that several of these EDCs disturbed also TNF-α, IL-1 ß and IL-8 cytokine secretions. Furthermore, relative to control treatment, decreased ERK 1/2 phosphorylation was always associated with EDCs treatments-either alone or in certain combinations (at 0.1 µM for each condition). Lastly, as treatments by an estrogen receptor antagonist suppressed the negative effects on ERK 1/2 phosphorylation observed in cells treated either alone with BPA, DEHP, 4-OP or with the combined treatment of BPA and DEHP, we suggested that estrogen receptor-dependent pathway is involved in mediating the effects of EDCs on human immune system. Altogether, these results advocate that EDCs can disturb human immune response at very low concentrations.

Effects of 4-nonylphenol and/or diisononylphthalate on THP-1 cells: impact of endocrine disruptors on human immune system parameters.

The aim of the present work is to investigate the link between two endocrine disruptor compounds (EDCs), which are chemicals that interfere with the hormone system in human and wildlife, and the human immune response through a study of their effects on the THP-1 human cell line which was used as a model for macrophages. We used two EDCs, diisononylphthalate (DiP) and 4-n-nonylphenol (NP) alone or in combination in order to evaluate the effects of these compounds on several parameters of the immune response - cytokine secretion, phagocytosis and the putative implication of the estrogen receptors - by studying the level of MAPK activation. NP and DiP strongly reduced phagocytosis and modify cytokine secretions. Indeed, differentiated THP-1 cell exposures (i) to 5 and 10 microM of combination of NP and DiP induced an IL-8 level in the medium respectively of 28.9 and 45 percent higher than the level obtained for the control (untreated cells), (ii) to combination of NP and DiP at 10 microM induced an increase of IL-1ß level in comparison to the control level, (iii) to combination of NP and DiP induced an increase of TNF-α level whatever the concentration of EDCs tested (between 0 and 10 microM). Lastly, differentiated THP-1 cell exposure to NP, DiP alone or in combination (2 microM for each condition) induced a decrease of ERK1/2 phosphorylation in comparison to ERK1/2 phosphorylation level of the control. Moreover, differentiated THP-1 cell treatments by ICI-182780 (an estrogen receptor antagonist) supressed the EDC effects on ERK1/2 phosphorylation level which indicates an estrogen receptor-dependent pathway. These results suggest that EDCs have the ability to alter the human immune function, maybe by interfering with endocrine balance.

Oxidative stress induction by nanoparticles in THP-1 cells with 4-HNE production: stress biomarker or oxidative stress signalling molecule?

The aim of this study was to investigate whether carbon black (CB) nanoparticles might induce toxicity to monocytic cells in vitro via an oxidative stress mechanism involving formation of the lipid peroxidation product 4-hydroxynonenal (4-HNE) and the subsequent role of 4-HNE in inducing further cytotoxic effects. ROS production in cells by CB nanoparticles was shown by the oxidation of DCFH after a short time exposure. These particles induced the formation of 4-HNE-protein adducts and significant modification of glutathione content corresponding to an increase of oxidized glutathione form (GSSG) and a decrease of total glutathione (GSX) content. These results attest to an oxidative stress induced by the carbon black nanoparticles, although no induction of HO-1 protein expression was detected. Concerning the effects of a direct exposure to 4-HNE, our results showed that 4-HNE is not cytotoxic for concentrations lower than 12.5 microM. By contrast, it provokes a very high cytotoxicity for concentrations above 25 microM. An induction of HO-1 expression was observed from concentrations above 5 microM of 4-HNE. Finally, glutathione content decreased significantly from 5 microM of 4-HNE but no modification was observed under this concentration. The discrepancy between effects of carbon black nanoparticles and 4-HNE on the intracellular markers of oxidative stress suggests that 4-HNE is not directly implied in the signalling of oxidative toxicity of nanoparticles but is an effective biomarker of oxidative effects of nanoparticles.

The (de)construction of a psychiatric diagnosis: PTSD among former guerrilla and paramilitary soldiers in Colombia.

The demobilisation of guerrillas and paramilitaries in Colombia, also known as irregular armed groups, has raised the question among mental health professionals as to whether ex-combatants who have had repeated exposure to stressful events might meet the requirements for posttraumatic stress disorder (PTSD). Upon arrival at a psychiatric clinic in Bogotá, 76 patients were evaluated by a group of mental health professionals with experience in this diagnosis. Contrary to clinicians' expectations, there was a conspicuous lack of PTSD among this population. Subsequently, the clinical team administered the Clinician Administered PTSD Scale with 21 of these patients; PTSD was found in 57% of the men. The authors consider various arguments that might explain this discrepancy. Differences between the clinical presentation of PTSD among the ex-combatants and the classic descriptions contained in the DSM-IV-TR may be explained by organisational characteristics of the irregular armed groups. Further research is necessary which focuses on the mental health of populations in the context of political violence, such as those encountered in Colombia.

Diagnostic accuracy and yield of multidetector CT angiography in the evaluation of spontaneous intraparenchymal cerebral hemorrhage.

BACKGROUND AND PURPOSE: Multidetector CT angiography (MDCTA) is emerging as the favored initial diagnostic examination in the evaluation of patients presenting with spontaneous intraparenchymal hemorrhage (IPH). This study aims to evaluate the diagnostic accuracy and yield of MDCTA for the detection of vascular etiologies in adult patients presenting to the emergency department with IPH. MATERIALS AND METHODS: We conducted a retrospective study of 623 consecutive adult patients presenting to the emergency department with IPH, who were evaluated with MDCTA during a 9-year period. CT angiograms were reviewed by 2 neuroradiologists to determine the IPH site and the presence of a vascular etiology. Patients with associated subarachnoid hemorrhage in the basal cisterns were excluded from the study. Medical records were reviewed for risk factors and correlation with final diagnosis. The diagnostic accuracy of MDCTA compared with conventional angiography, intraoperative evaluation, and pathologic findings was determined, when available. Multiple-variable logistic regression analysis was performed to determine clinical and radiologic factors that predict a higher yield of MDCTA. RESULTS: MDCTA demonstrated a vascular etiology in 91 patients (14.6%), with a sensitivity of 96%, specificity of 99%, and diagnostic accuracy of 98%. We found independent, statistically significant higher yields of MDCTA in patients with the following characteristics: 1) age younger than 46 years (47%); 2) lobar (20%) or infratentorial (16%) IPH, especially lobar IPH with associated intraventricular hemorrhage (25%); 3) female sex (18%); or 4) neither known hypertension nor impaired coagulation at presentation (33%). CONCLUSIONS: MDCTA is an accurate diagnostic examination in the evaluation of adult patients presenting with spontaneous IPH and should be performed in all patients with the aforementioned clinical and radiologic characteristics.

Effect of polycyclic aromatic hydrocarbons and carbon black particles on pro-inflammatory cytokine secretion: impact of PAH coating onto particles.

It has been suggested that the organic fraction of particulate matter in air pollution has a major role in the toxicity of this pollutant, notably via its effects on inflammation. The major organic compounds adsorbed onto these particles are polycyclic aromatic hydrocarbons (PAH), among which benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), and pyrene (Pyr) are quantitatively the most important. Generally, cells or organisms are exposed to organic extracts of the particles rather than the native particles in order to study the effects of these PAH. In this study, B[a]P, B[b]F, and Pyr were tested alone and/or adsorbed onto carbon black (CB) particles differing in size in order to evaluate their impact on cytokine production (with or without LPS stimulation) by THP-1 macrophage-like cells. PAH induced significant secretion of IL-1beta, IL-8, and IL-12 after 24 or 48 hr of treatment, an effect reinforced by LPS stimulation; no effect on IL-10 secretion was noted. Fine CB particles (260 nm diameter) induced secretion of each cytokine. In general, coating the CB with PAH did not modify the effect of the CB alone; the exception was that LPS-induced IL-1beta secretion was reduced. In contrast, ultrafine CB (14 nm diameter: ufCB) caused a decrease in cytokine secretion; this effect was modified by PAH coating. For example, PAH coating on ufCB amplified the inhibitory effect of ufCB against IL-1beta secretion but did not modify IL-8 formation. Moreover, PAH coating on ufCB tended to minimize the effect of LPS stimulation; this included (i) inhibition of the decrease in IL-12 secretion induced by uncoated ufCB and (ii) stimulation of IL-10 production. It was concluded that adsorption of PAH onto these particles could decrease their bioavailability and so their abilities to affect cell cytokine production. The results also showed that when PAH were adsorbed onto the fine particles, any observed increases in cytokine secretion consistently appeared to be due to the particles themselves. In contrast, while ufCB alone almost uniformly led to decreases in cytokine formation by the cells, the added presence of the test PAHs led to variable effects - depending on whether stimulation with LPS took place or not. Thus, while some PAHs likely to be associated with PM are clearly immunomodulants, their ultimate effects in situ will likely depend on the properties of the particles themselves, in particular, their size.

Oxidative stress induction by short time exposure to ozone on THP-1 cells.

Ozone is a major component of air pollution mainly formed by photochemical reactions of nitrogen oxides with volatile organic compounds and/or carbon monoxide. Numerous studies have shown the association between ozone exposure with pulmonary injuries. This pollutant is a strong oxidant exerting its biological action either by direct reaction with target molecules or by generating reactive oxygen species which result in its biological effects and its toxicity. In order to study the effects of an induced oxidative stress by ozone on THP-1 cell, a human macrophage-like cell line, we used an in vitro system which has been previously used to study the rapid responses to ozone exposure. Using this system, THP-1 cells were subjected to short time exposure (30 min) followed by different incubation times ranging from 4 to 24 h. Our results show that ozone exposure provokes an alteration of the cell membrane translating an induction of lipid peroxidation resulting in a 3.2-fold increase of thiobarbituric reactive substances (TBARS), an increase by 35% of heme oxygenase-1 (HO-1) expression, and significant modifications of the redox status evaluated by glutathione measurement and of antioxidant enzyme activities in THP-1 cells. Our in vitro model constitutes a very interesting tool for the measurement of ozone effect on rapid modifications induced by this pollutant as well as intracellular modifications due to an oxidative stress.

Estrogenic effects in crucian carp (Carassius carassius) exposed to treated sewage effluent.

To assess the estrogenicity of a municipal sewage treatment plant, sexually mature crucian carp of both sexes were exposed for 28 days to domestic treated sewage effluent running with a constant flow of water, with tap water and with different concentrations of the sewage effluent (25%, 50% and 100%). Vitellogenin (VTG), gonadosomatic index (GSI), hepatosomatic index (HSI), and histological abnormalities were used to assess the estrogenic potency of the effluent. Results show a significant (P<0.05) increase in VTG levels in all exposed male fish. A significant (P<0.05) reduction in the GSI was only observed in fish exposed to 100% effluent. Morphological changes were detected by histological evaluation, revealing severe effects on the testes. Spermatogenesis was progressively reduced to total inhibition in fish exposed to 100% effluent. One of the most pronounced effects detected was the presence of oocytes in male gonads, observed in 20% of males exposed to 100% sewage effluent.

Modification of membrane markers on THP-1 cells after ozone exposure in the presence or absence of fMLP.

The impacts of ozone and N-formyl-methionyl-leucyl-phenylalanine (fMLP) on the detection of membrane markers on non-differentiated THP-1 cells were evaluated for in vitro exposures. Several markers, specific for monocytes and macrophages, were identified on the THP-1 cells, allowing their use as a model for alveolar macrophages. Ozone exposure modified not only the detection of membrane markers, especially CD13 and CD14, monocyte and macrophage markers, but also the detection of the specific receptor for fMLP, formyl peptide receptor (FPR). Activation by fMLP also reduced the detection of the CD antigens, and a combined exposure to ozone and fMLP amplified this decrease, probably due to an additive effect of these chemicals. Overall, these results suggest important membrane rearrangements for short-term treatments to ozone and/or fMLP.

Ozone-mediated cytotoxicity after short-term exposure and its relation to the production of cellular metabolites (NO, H2O2).

Alveolar macrophages secrete numerous mediators, playing an important role in host defence. Among these mediators, nitric oxide (NO) and hydrogen peroxide (H2O2) are both involved in bactericidal killing and trigger the release of other cellular metabolites. We have analyzed the effect of an atmosphere polluted with ozone (0.03-0.5 ppm v/v) on the monocytic cell line THP-1, as a model for alveolar macrophages, in vitro. NO and H2O2 were chosen to evaluate cell response to ozone. Cell injury was evaluated using lactate dehydrogenase (LDH) liberation into the medium. An exposure to 0.5 ppm ozone proved to be more toxic to the cells, than 0.1 or 0.03 ppm, evidenced by more LDH being liberated and cytotoxicity reaching values up to 64%. For all ozone concentrations, H2O2 production reached a peak value after 10-15 min of exposure, after which the concentration of extracellular H2O2 production diminished rapidly. The highest NO concentrations were measured with 0.5 ppm ozone, reaching a maximum value of 1460 nmol/L per 5 x 10(6) cells, which is 1.55 times higher than for nonexposed cells. Lower concentrations barely induced higher NO concentrations compared to nonexposed cells. The results indicate that ozone effects not only the viability of human monocytes but also the release of antibacterial and defense signaling molecules and suggest that ozone-mediated cytotoxicity may be related to the secretion of NO and H2O2.

Neurotropic, immunological and gastric effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine in stressed mice.

Previous studies realized in the laboratory have indicated that application of experimental stress (such as unavoidable footshock) induced significant behavioral, gastric and immunological alterations in mice. The aim of this study was to evaluate effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine on stress-induced behavioral, immunological and gastric alterations. Locomotor, postural and exploratory activities have been evaluated by two behavioral tests: light/dark box and staircase tests. Immunological studies were investigated to count white blood cells subpopulations (lymphocytes, neutrophils, monocytes and basophils) by coulter counter. The severity of gastric erosions was evaluated by microscopic technique in mice after experimental stress. The results have demonstrated that low doses of G. sempervirens L. and A. belladonna L. had a significant neurotropic and protective effects on behavioral and gastric alterations induced by experimental stress. The immunological protective effects observed were probably induced via their neurotropic effects. The P. histamine showed a significant immunoprotective and gastroprotective effect in mice exposed to experimental stress.

Rapid identification of Ralstonia eutropha strain CH34 using monoclonal antibodies.

Ralstonia eutropha strain CH34 (formerly Alcaligenes eutrophus CH34) is an aerobic Gram-negative and facultative chemolithotrophic bacteria with plasmid-bound resistance to heavy metals. The presence of Ralstonia eutropha strain CH34 is an indication of environmental heavy metals pollution. The major purpose of this work was to produce monoclonal antibodies (MAbs) against the metal transport outer membrane proteins. In this way, bacteria outer membranes, grown with or without iron, were purified. The electrophoretic pattern of the outer membrane revealed that, in iron starvation conditions, at least four proteins were overexpressed. These outer membranes were used to immunize mice to produce MAbs. About 200 hybridomas were tested by enzyme-linked immunoadsorbent assay (ELISA). Most of these hybridomas exhibited cross reactions with Escherichia coli and Klebsiella aerogenes. Two hybridomas, AE5/7 and AE5/9, produced MAbs that detected specifically Ralstonia eutropha strain CH34. Analysis by Western blotting showed that these MAbs recognized a protein with a molecular weight of about 41 kDa. Moreover, the presence of the two megaplasmids was required for the full expression of the 41-kDa protein, as demonstrated by screening of the derivatives strains by ELISA. These MAbs could be used for a specific and rapid detection of Ralstonia eutropha strain CH34, using direct immunological methods.

A new approach to evaluate toxicity of gases on mobile cells in culture.

A novel technique is described that measures the degree of toxicity of short-term exposure to gaseous pollutants or other chemical compounds on cultured cells, in 30 min. This technique, based on the study of the mobility properties of activated macrophages, consists of an image analysis procedure incorporating a specific exposure chamber (EC). The EC, which is developed from commercial culture flasks (50 ml, 25 cm(2) of culture surface), was first used to maintain cells in culture conditions, overnight, prior to the assay. In order to measure toxicity, it was then connected to the gaseous pollutant or chemical source. After exposing the culture medium and cells to the gas stream for 10 min, fMLP, a chemotactic factor, was added and the mobility of the macrophages measured by superimposing sequential analogue images captured by a CCD camera that were digitised and analysed using a software developed for this purpose. For example, the effect of ozone on macrophage-like cell (THP-1) was investigated. After exposure to 0.1 and 0.5 ppm, cells lost, respectively 79% and 90% of their mobility, compared to the control sample.

Safety and immunogenicity of the synthetic malaria vaccine SPf66 in a large field trial.

In the first field trial with synthetic malaria vaccine SPf66 in a large population naturally exposed to malaria, 9957 persons greater than 1 year old and residing on the Colombian Pacific coast received three doses of the vaccine. To evaluate vaccine safety, clinical observations were made 30 min and 48 h after each immunization. There were no adverse reactions in 95.7% of cases. In the 4.3% of cases with adverse reactions, local induration and erythema were the most frequent. In a randomly selected group of vaccinees, anti-SPf66 antibody titers were measured after the third dose: 93% of the vaccinees raised antibodies to SPf66. Among these, 55% had titers greater than 1:1600. These results demonstrate the safety and immunogenicity of the SPf66 vaccine in a large field trial.

Identification of B- and T-cell epitopes within the MTP40 protein of Mycobacterium tuberculosis and their correlation with the disease course.

Synthetic peptides derived from the amino acid sequence of MTP40, a recently characterized Mycobacterium tuberculosis protein, were tested by two different immunological assays in 91 individuals. For the purposes of this study, the population was distributed in four groups: active tuberculosis (TBC) patients with elevated bacillus loads (BK+), active TBC patients with low bacillus loads (BK-), healthy individuals living in the same household with tuberculous patients (HH), and normal individuals, who had presumably never been in contact with the bacilli (control). We found that T cells of individuals belonging to the HH group showed the highest and most frequent recognition of these peptides in a T-cell proliferation assay, while their antibodies showed the lowest recognition of these peptides when tested by enzyme-linked immunosorbent assay. In contrast, TBC patients revealed an inverse pattern of immune response. Interestingly, one of these peptides (P7) was recognized by T cells of 64% of the HH individuals and by 4.5% of normal donors. Another peptide (P4) was recognized by 55% of sera from BK+ patients and by 5.5% of normal donors. The results presented here indicate the existence of T- and B-cell epitopes within the MTP40 protein. Given the particular recognition pattern of this protein, added to the fact that it appears to be a species-specific antigen of M. tuberculosis, a detailed study of the immune response to it may be useful in the design of more accurate diagnostic tests and an improved vaccine against human TBC.