Massive human ingestion of orpiment (arsenic trisulfide).

BACKGROUND: Because the toxicity of arsenic is well known, arsenic-containing compounds have frequently been ingested for suicidal purposes. We report a case of attempted suicide by massive ingestion of arsenic trisulfide, an arsenic mineral of low solubility, which resulted in minimal symptoms. CASE REPORT: An asymptomatic 57-year-old man presented to an Emergency Department 13h after his reported ingestion of approximately 84g of arsenic contained in a mineral specimen of orpiment (arsenic trisulfide) that had been crushed and mixed with an alcoholic beverage and food. His only symptom before presentation was nausea. Physical examination was unremarkable, and diagnostic tests included a normal electrolyte panel, a normal serum lactate, and a normal electrocardiogram. An abdominal radiograph revealed hyper-dense material scattered throughout the large intestine. As per the recommendations of the regional poison center, the patient was managed with whole bowel irrigation with a polyethylene glycol solution, maintenance intravenous hydration, and observation on a telemetry unit. Chelation was not performed. A spot urine specimen collected 12h after admission contained 1490µg of total arsenic per liter (background range<50µg per liter). The patient remained asymptomatic throughout his hospital course. Follow-up studies revealed a diminution in both intra-abdominal radiopacities and urine arsenic concentration. X-ray diffraction analysis of the specimen confirmed its identity as arsenic trisulfide. CONCLUSIONS: Our experience demonstrates that massive ingestion of a poorly soluble inorganic arsenic compound can be successfully managed with gastrointestinal decontamination alone without chelation, provided that the patient remains asymptomatic during close clinical monitoring.

Measurement of eotaxin (CCL11) in induced sputum supernatants: validation and detection in asthma.

BACKGROUND: Induced sputum is widely used in asthma research; however, for many mediators, the detection methods have not been validated. OBJECTIVE: We sought to optimize the method of detection of eotaxin, an important chemokine acting through the CCR3 receptor on eosinophils, basophils, and T(H)2 cells. METHODS: Induced sputum from normal and asthmatic subjects was processed with dithioerythritol (DTE) or PBS; recovery of eotaxin was assessed by means of ELISA before and after spiking with recombinant eotaxin. Furthermore, the effects of removing DTE by means of ultrafiltration or the addition of protease inhibitors and high-speed centrifugation on endogenous levels and spiking recovery of eotaxin were assessed. RESULTS: Endogenous eotaxin was undetectable in DTE-processed samples, with a mean of only 30% (SD, 13%) spike recovery. DTE had no effect on the immunoassay capture antibody but dramatically reduced the detection of recombinant eotaxin. Removal of DTE from sputum before immunoassay did not improve detection, although it restored the recovery of a subsequent eotaxin spike. In contrast, PBS-processed sputum resulted in an eotaxin spike recovery of 101% (SD, 20%). Addition of protease inhibitors or high-speed centrifugation had no effect on eotaxin detection. By using this optimized protocol, eotaxin levels in PBS-processed sputum samples were found to be significantly increased in asthmatic sputum (P<.05). CONCLUSION: Measurement of eotaxin by means of immunoassay is adversely affected by DTE, possibly through irreversible denaturation of epitopes, which makes eotaxin undetectable by using the immunoassay antibody. Sputum samples should be processed into PBS for assessment of eotaxin, which is present at increased levels in asthmatic sputum.

Sulphydryl blocker induced small intestinal inflammation in rats: a new model mimicking Crohn's disease.

BACKGROUND: Sulphydryl compounds are essential for maintaining mucosal integrity in the gastrointestinal tract. AIM: To characterise a model of experimental inflammation in the small intestine induced by a sulphydryl blocker. METHODS: Inflammation in the small intestine was induced in rats by intrajejunal administration of 0.1 ml 2% iodoacetamide. The possible amelioration of the damage induced was modulated by intragastric administration of TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; 50 mg/100 g body weight), ketotifen (200 micrograms/100 g body weight), or by addition of L-NAME (NG-nitro-L-arginine methyl ester; 0.1 mg/ml) or apocynin (120 micrograms/ml) to the drinking water. Rats were sacrificed at various time intervals, the small intestine resected, weighed, macroscopic lesions were assessed, and mucosal generation of inflammatory mediators and nitric oxide synthase activity were determined. RESULTS: Intrajejunal administration of iodoacetamide induced, after one week, multifocal mucosal erosions, ulcerations with granulomas and giant Langhans cells. At two weeks, the mucosa was almost macroscopically intact but histologically epithelial granuloma and giant cells were present. Myeloperoxidase activity was increased in the first 24 hours, one week later mucosal nitric oxide synthase activity and generation of leukotriene B4, leukotriene C4 and thromboxane B2 were increased, whereas prostaglandin E2 generation was decreased notably. Ketotifen and apocynin significantly decreased the extent of injury which was not affected by TEMPOL or L-NAME. CONCLUSIONS: Jejunal inflammation induced by the sulphydryl blocker, iodoacetamide, resembles the pathological changes in Crohn's disease. The protective effect of ketotifen and apocynin indicates the contribution of O2- and pro-inflammatory mediators to the pathogenesis of the damage, and may be a novel approach to the treatment of inflammatory bowel disease.

Abnormal effect of thiol groups on erythrocyte Na/Li countertransport kinetics in adult polycystic kidney disease.

BACKGROUND: Evidence suggests that in adult polycystic kidney disease (APCKD) there is abnormal membrane organisation that involves cytoskeletal proteins and affects ion-transport proteins. The possibility of detecting a membrane organisation defect in erythrocytes from APCKD patients was investigated. METHODS: Na/Li countertransport (CT) kinetics were measured in erythrocytes from APCKD patients compared with normal controls. The modulation of Na/Li CT kinetics by key membrane thiol groups and by dissociation of spectrin by heating was studied. RESULTS: In erythrocytes from APCKD compared to normal subjects the Km of Na/Li CT was lower (64 SEM 3v 90 SEM 3 mmol Na/l, P < 0.001) and Vmax/Km was higher (6.8 SEM 0.6v 5.3 SEM 0.4 (x 19(-3)), P < 0.05). In erythrocytes from normal subjects, after N-ethylmaleimide (NEM) treatment in choline medium, Km of Na/Li CT was reduced and Vmax/Km increased (59 SEM 5, 8.2 SEM 0.4 (x 10(-3)), P < 0.001) but there was no effect on these kinetic parameters in erythrocytes from APCKD. The effect of heating was similar to that of NEM in choline medium. In normal controls after NEM treatment in sodium medium both Km and Vmax were reduced whereas in APCKD Vmax was reduced but Km was unchanged. CONCLUSIONS: In APCKD the effect of a key membrane thiol group on Na association with Na/Li CT was absent and the effect of spectrin dissociation was similarily abnormal. A second thiol group effect on the Vmax of Na/Li CT was normal. The results are consistent with a thiol-protein linked to the spectrin cytoskeleton that modulates Na/Li CT and is abnormal in APCKD.