Gut: An underestimated target organ for Aluminum.

Since World War II, several factors such as an impressive industrial growth, an enhanced environmental bioavailability and intensified food consumption have contributed to a significant amplification of human exposure to aluminum. Aluminum is particularly present in food, beverages, some drugs and airbone dust. In our food, aluminum is superimposed via additives and cooking utensils. Therefore, the tolerable intake of aluminum is exceeded for a significant part of the world population, especially in children who are more vulnerable to toxic effects of pollutants than adults. Faced with this oral aluminum influx, intestinal tract is an essential barrier, especially as 38% of ingested aluminum accumulates at the intestinal mucosa. Although still poorly documented to date, the impact of oral exposure to aluminum in conditions relevant to real human exposure appears to be deleterious for gut homeostasis. Aluminum ingestion affects the regulation of the permeability, the microflora and the immune function of intestine. Nowadays, several arguments are consistent with an involvement of aluminum as an environmental risk factor for inflammatory bowel diseases.

Toxicological consequences of experimental exposure to aluminum in human intestinal epithelial cells.

Aluminum (Al), a non-essential element, is ubiquitous in industrialized societies. Whereas adult intake is estimated between 3 and 12 mg/day according to dietary aluminum studies conducted in many countries, it is not known if aluminum may have a toxic effect on intestinal epithelium. The aim of this work was to evaluate the cytotoxicity and RNA expression patterns induced in HT-29 cells by aluminum. Both classical toxicological methods and a global transcriptomic approach were used. Cytotoxicity determined by MTT assay showed a time and dose dependent decrease of cell viability in aluminum treated cells compared to control cells. Cell cycle analysis by flow cytometry revealed that aluminum induced accumulation of cells in phase G0/G1, associated with a decrease in the proportion of cells in S and G2/M phases. Aluminum led to apoptosis as evidenced by nuclear morphology changes and mitochondrial membrane perturbations, and induced reactive oxygen species generation. Transcriptomic pattern argued in favor of pro-tumorigenic and pro-inflammatory effects of aluminum in intestinal epithelial cells. These results highlight several pathways by which aluminum has a disturbing impact on intestinal epithelial cells, supporting that the effects of aluminum on intestine warrants further investigation.

Open-angle glaucoma and paraoptic cyst: first description of a series of 11 patients.

We report 11 patients who were referred to our institution for severe open-angle glaucoma who had a paraoptic cyst on MR imaging. All cysts were extraoptic and retrolaminar; most were deforming the adjacent optic nerve. Cysts had a high signal on T2 and FLAIR sequences, and a variable signal on T1 and variable echogenicity, suggesting different proteinaceous content. Arterial vascularization of the optic nerve was normal. Cyst volumes were inversely correlated with the severity of glaucoma on the same eye (P < .01-.05, Spearman correlation coefficient). We hypothesized that such cysts may reflect a valve mechanism, which would allow preservation of the translamina cribrosa pressure and thus could preserve visual function. The rarity of this association, together with the frequent mass effect of the cyst on the optic nerve, stresses the necessity of long-term follow-up in these patients.

Optic neuritis revealing Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease is a rare systemic disease with uncommon neurological involvement. We report the case of a 30-year-old Asian woman who presented a rapidly progressive loss of vision. Magnetic resonance imaging (MRI) of the optic nerve revealed an inflammation of the left optic nerve with chiasmatic involvement, without any encephalic or medullar lesion. Thoracic computed tomography scan showed bilateral axillary lymphadenopathy. Analysis of a biopsy of the axillary lymph node showed typical histological findings of Kikuchi-Fujimoto disease. There was no clinical or biological sign of associated systemic lupus erythematosus. The patient spontaneously recovered normal visual acuity in 4 weeks, with resolution of MRI abnormalities. No optic neuritis relapse or neurological event occurred in a 3-year follow-up. To our knowledge this is the first case of optic neuritis associated with Kikuchi-Fujimoto disease.

Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice.

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10(-/-)) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor.

[Intraorbital pressure measured before, during, and after surgical decompression in Graves' orbitopathy]. / Mesure de la pression intraorbitaire avant, pendant et après décompression orbitaire osseuse dans l'orbitopathie dysthyroïdienne.

PURPOSE: In Graves' orbitopathy, the volumetric increase of the oculomotor muscles and orbital fat leads to exophthalmia and a rise in orbital pressure. This rise in pressure may be implicated in the appearance of a compressive optic neuropathy. To investigate this increase in pressure and its variations accompanying surgical decompression, systematic measurements were taken before, during, and after every case of orbital decompression in Graves' disease. RESULTS: The intraorbital pressure before the surgical procedure was 14.05 mmHg ± 9.19 for a normal value estimated in the literature at 4 mmHg ± 1.5 (statistically significant difference, P<0.0001). In the group presenting a compressive optic neuropathy (NO), the preoperative pressure was 26.8 mmHg ± 7.85 versus 9.8 mmHg ± 4.2 in the group without NO: the pressure was significantly higher in the group with NO (P<0.001). After orbital decompression (one to three walls depending on the severity of the exophthalmia), the pressure was measured at 4.3 mmHg ± 2.53 for the entire series: 6.4 mmHg ± 2.07 in the group with NO versus 3.6 mmHg ± 2.32 in the group without NO (significant difference, P<0.05). The total decrease in pressure induced by the surgery was 9.75 mmHg ± 7.55 and was significantly greater for the group with NO: reduction of 20.4 mmHg versus 6.2 mmHg for the group without NO (P<0.001). The reduction in pressure was greater after collapse of the first wall (floor) than after collapse of following walls for all groups (P<0.001). The maximum pressure observed during the intervention (caused by the instruments) was measured at 78.3 mmHg ± 23.47 without pupillary changes. DISCUSSION: This study shows that the intraorbital pressure is increased in Graves' orbitopathy and more in serious forms with compressive optic neuropathy. Orbital decompression, as its name indicates, provides decompression and a return to a near-normal orbital pressure situation. Compressive optic neuropathy does not result only from the direct compression of the oculomotor muscles on the optic nerve, but also from an overall rise in the pressure level within the orbital cavity. CONCLUSION: Intraorbital pressure is increased in Graves' orbitopathy, participating in the appearance of compressive optic neuropathy. Orbital decompression provides a significant reduction in intraorbital pressure.

[Clinical polymorphism of myasthenia gravis beginning with isolated ocular symptoms; a five years retrospective analysis]. / Polymorphisme clinique de la myasthénie à point de départ oculaire; analyse rétrospective sur cinq ans.

INTRODUCTION: myasthenia gravis is a neuromuscular junction disorder that can jeopardize the patient's life and has a high clinical polymorphism that makes it difficult to diagnose. PATIENTS AND METHODS: after reviewing the disease physiology, its clinical symptoms, and the different means to diagnose and treat it, we present a 15-patient series that we cared for at the Rothschild ophthalmologic foundation from 2002 to 2007 for myasthenia gravis that began with isolated ocular symptoms, so as to highlight the clinical diversity of this pathology. RESULTS: when the disease was diagnosed, 11 patients out of 15 had a ptosis with diplopia, two had an isolated ptosis, and two had isolated diplopia. After investigations, we discovered that three patients had a malignant thymoma and one had thymic hyperplasia. An autoimmune disease association was found in two patients: the first one had Hashimoto thyroiditis and the second one developed optical neuromyelitis a few years after his myasthenia gravis. Only three patients secondarily developed a generalized myasthenia gravis. DISCUSSION: our series of patients has a low disease generalization rate in comparison with the published data in the medical literature, indicating that two-thirds of patients with ocular myasthenia gravis should develop generalized myasthenia gravis within approximately 2 years after the beginning of their illness. This could be explained by the early consultation of these patients and the common prescription of an immunosuppressive therapy, reducing the risk of secondarily generalized myasthenia gravis according to some studies. CONCLUSION: despite the small number of patients, this study underlines the clinical polymorphism of ocular myasthenia gravis and the risks it may cause. Close collaboration between ophthalmologists and neurologists is needed to ensure good care for these patients.

Sphenoid and optic nerve sheath meningioma revealed by recurrent brain infarctions.

Meningioma, though benign, may invade adjacent structures such as bone, soft tissues, dural sinuses and arteries. However brain infarctions secondary to meningioma involving the cavernous sinus and encasing and narrowing the intracranial carotid artery are rare. We report the case of a young man with recurrent left carotid artery infarctions due to a left sphenoid meningioma infiltrating the posterior optic nerve sheath through the optic canal and circumscribing the intracranial carotid artery. The patient had a gradually progressive occlusion of the middle cerebral artery, the distal internal carotid artery and finally the anterior cerebral artery ipsilateral to the sphenoid meningioma.

Toll-like receptor 2 is critical for induction of Reg3 beta expression and intestinal clearance of Yersinia pseudotuberculosis.

OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer's patches that are positioned in the terminal ileum. Whereas toll-like-receptor 2 (TLR2) controls mucosal inflammation by detecting certain microbiota-derived signals, its exact role in protecting Peyer's patches against bacterial invasion has not been defined. DESIGN: Wild-type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y pseudotuberculosis via the oral or systemic route. The role of microbiota in conditioning Peyer's patches against Yersinia through TLR2 was assessed by delivering, ad libitum, exogenous TLR2 agonists in drinking water to germ-free and streptomycin-treated animals. Bacterial eradication from Peyer's patches was measured by using a colony-forming unit assay. Expression of cryptdins and the c-type lectin Reg3 beta was quantified by quantitative reverse transcriptase polymerase chain reaction analysis. RESULTS: Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the Peyer's patches and succumbed to sepsis independently of nucleotide-binding and oligomerisation domain 2 (NOD2). Recognition of both microbiota-derived and myeloid differentiation factor 88 (MyD88)-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3 beta requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3 beta expression in Peyer's patches. Importantly, oral treatment with exogenous TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced expression of Reg3 beta and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3 beta resulted in impaired clearance of the bacterial load in Peyer's patches. CONCLUSIONS: TLR2/REG3 beta is thus an essential component in conditioning epithelial defence signalling pathways against bacterial invasion.

The complication of retained intraocular recipient corneal button after penetrating keratoplasty.

PURPOSE: To describe the complication of retained intraocular recipient corneal button after penetrating keratoplasty. METHOD: Case report. A 27-year-old man was referred to us because of complications after penetrating keratoplasty on the right eye. Slit-lamp examination disclosed a clear graft with a second clear corneal button behind. RESULTS: A second penetrating keratoplasty was performed successfully on the right eye. Histologic examination showed an intact epithelium and stroma vascularization of the recipient corneal button. Immunochemistry of the recipient corneal button and the first donor corneal button was performed. CONCLUSION: Although the recipient corneal button remained inside the anterior chamber for 5 months, no epithelial ingrowth occurred.

Tratamento da superdosagem de anticoagulantes orais / Reversal of excessive oral anticoagulation

OBJETIVO - Verificar a resposta de 73 pacientes com superdosagem de droga anti-vitamina K (AVK) a 3 esquemas de tratamento. MÉTODOS - Os 73 pacientes foram avaliadois em 94 ocasiöes e divididos em 3 grupos: grupo A (N=32), suspensäo por dois dias e introduçäo de dose menor; grupo B (N=37), suspensÝo do AVK e reavaliaçäo em 4 dias; grupo C (N=25), vitamina K por via oral. A razäo normalizada internacional (RNI) final foi considerada adequada quando entre 2,0 e 4,0. RESULTADOS - Näo houve diferença entre os tratamentos (x2=2,352, p=0,671) para 61 pacientes com RNI inicial menor que 8. Houve mais pacientes com RNI menor que 2 no grupo C (x2=9,998, p=0,007) entre 33 pacientes com RNI maior que 8. Cinco dos 7 pacientes do grupo B que continuaram com superdosagem tinham RNI menor que 4,5 e pequeno risco de hemorragia. Entretanto 6, dos 10 pacientes do grupo C com anticoagulaçäo insuficiente tinham RNI menor que 1,6 e risco de trombose. Treze pacientes sangraram, mas sem necessidade de transfusäo. Conclusäo - A reversäo da superdosagem de AVK pode ser feita pela suspensäo de transfusÝo da droga Administraçäo de vitamina K, por via oral, deve ser restringir a pacientes com RNI mais elevado para se evitar anticoagulaçäo insuficiente.

Avaliaçäo clínica e laboratorial de pacientes em uso de anticoagulantes orais / Clinical and Laboratory Management of Patients Under Oral Anticoagulation

Objetivo - Avaliar o acompanhamento clínico e laboratorial de pacientes em uso de drogas antivitamina K(AVK). MÉTODOS - Foram avaliados, retrospectivamente, 952 consultas ambulatoriais de 100 pacientes em uso de AVK, durante 7,6 meses. Havia 56 homens e 44 mulheres, 54 pacientes com obstruçäo arterial aguda, 34 com troboembolismo venoso e 12 com cardiopatia. O nível de anticoagulaçäo foi medido pelo tempo de protrombina expresso em razäo normalizada internacional (RNI). RESULTADOS - Nível adequado de anticoagulaçäo foi observado em 59 "por cento" das consultas dos 73 pacientes considerados estáveis, com intervalo entre consultas maior do que 3 semanas. Os 27 pacientes instáveis tinham 36 "por cento" das consultas com RNI adequado. Anticoagulaçäo insuficiente ocorreu por uso irregular (22 por cento), dieta rica em vitamina (19 por cento) e dose insuficiente (16 por cento). Quatro pacientes tiveram sangramento sem gravidade e näo houve recorrência da trombose durante o período de observaçäo. CONCLUSÄO - O controle clínico e laboratorial, através do RNI, é fundamental para evitar complicaçöes hemorrágicas ou trombóticas em pacientes que necessitam de anticoagulaçäo oral.

Hemorrhagic and thrombotic complications in patients with myeloproliferative diseases.

OBJECTIVE: To correlate the incidence of hemorrhage and thrombosis to bleeding time (BT) and platelet aggregation in 27 consecutive patients with myeloproliferative diseases (MPD). DESIGN: Retrospective study. SETTING: Public tertiary referral center. PATIENTS: Eighteen patients with chronic myelogenous leukemia (CML), 5 with polycytemia vera (PV), 2 with essential thrombocytemia (ET) and 2 with idiopathic myelofibrosis (MF). Duke's BT and epinephrine-induced platelet aggregation were performed on the patients and on 10 healthy individuals. RESULTS: Eleven patients presented symptoms (41%):9 with hemorrhage (33%) and 5 with thrombosis (19%). There were less symptomatic patients in the CML group (28%) than in the other MPD (67%), without statistical significance (Fisher, p = 0.06). Duke's BT was longer in symptomatic patients (Mann-Whitney, p < 0.05). Platelet aggregation was abnormal in 7 patients (26%) and 71% of them were symptomatic (Fisher, p = 0.07). CONCLUSIONS: The high incidence of bleeding and thrombosis in patients with MPD was related to prolonged BT, but not to platelet aggregation abnormalities.