Chemical characterization of inks in skin reactions to tattoo

Skin reactions are well described complications of tattooing, usually provoked by red inks. Chemical characterizations of these inks are usually based on limited subjects and techniques. This study aimed to determine the organic and inorganic composition of inks using X-ray fluorescence spectroscopy (XRF), X-ray absorption spectroscopy (XANES) and Raman spectroscopy, in a cohort of patients with cutaneous hypersensitivity reactions to tattoo. A retrospective multicenter study was performed, including 15 patients diagnosed with skin reactions to tattoos. Almost half of these patients developed skin reactions on black inks. XRF identified known allergenic metals - titanium, chromium, manganese, nickel and copper - in almost all cases. XANES spectroscopy distinguished zinc and iron present in ink from these elements in endogenous biomolecules. Raman spectroscopy showed the presence of both reported (azo pigments, quinacridone) and unreported (carbon black, phtalocyanine) putative organic sensitizer compounds, and also defined the phase in which Ti was engaged. To the best of the authors' knowledge, this paper reports the largest cohort of skin hypersensitivity reactions analyzed by multiple complementary techniques. With almost half the patients presenting skin reaction on black tattoo, the study suggests that black modern inks should also be considered to provoke skin reactions, probably because of the common association of carbon black with potential allergenic metals within these inks. Analysis of more skin reactions to tattoos is needed to identify the relevant chemical compounds and help render tattoo ink composition safer.Peer reviewe

How to assess the role of Pt and Zn in the nephrotoxicity of Pt anti-cancer drugs?: An investigation combining μXRF and statistical analysis. Part II: Clinical application

International audienceIn this contribution, an approach developed previously for mice is used for human biopsy. In the case of patient 1, Pt detection is performed 6 days after the last oxaliplatin infusion, while for patient 2, the biopsy was performed more than 15 days after his first platin infusion and several dialysis. Even for these biological samples, experiments show that synchrotron mediated mXRF is a suitable tool to detect Pt in kidney biopsy, and thus probably for any organ exposed to Pt. Therefore, mXRF could also be of major interest to decipher the mechanism beyond Pt induced neurotoxicity, ototoxicity on human biopsy. Pharmacoavailability of chemotherapies is a major concern because some treatment failures are explained by poor tumor penetration of the active molecule. mXRF could be an elegant way to map the distribution of Pt inside cancerous cells at the micrometer scale. Pt and Zn are only two of the numerous trace elements that mXRF can detect; heavy metal intoxication diagnosis and the toxicity mechanism probably could also benefit from this innovative technique

Precise identification of crystal deposits in the kidney tissue

International audienceBackgroundBiopsies of native or transplanted kidneys in patients suffering chronic or acute renal failure are commonly stained for tissue examination and search for possible crystal deposits which are then identified by polarizing microscopy and staining by von Kossa’s method revealing mainly calcium deposits. Aim of the studyRevisiting the nature of crystal deposits in kidney tissue sections by infrared microscopy. Method 205 renal biopsies presumably containing crystal deposits were analyzed with the Spotlight 400 FTIR imaging System in the mid infrared spectral range to obtain infrared maps of tissue slides at high spatial resolution, down to 10 microns.Results Based on infrared analysis, we identified crystals in all biopsies including 78.8% calcium-containing crystals, 15.3% purine crystals of which 90.5% of 2,8-dihydroxyadenine, and 5.9% drugs crystals. Among birefringent crystals observed under polarized light, we identified 60.2% of calcium oxalate monohydrate, 2.6% of lipids, 13.1% of 2,8-dihydroxyadenine, 7.8% of uric acids and urates, 5.9% of drug crystals (triamterene, N-acetylsulfadiazine, ciprofloxacine, indinavir monohydrate, atazanavir); and among non refringent crystals: 27% of carbapatite, 14.6% of amorphous carbonated calcium phosphate, 3.9% of drug crystals (foscarnet, vancomycine) and 1.5% of other phosphates. Overall, we identified 26 different types of crystals. Surprisingly, we found mixtures of crystalline phases in a high proportion (23.8%) of biopsy samples.DiscussionCrystals may be related to various pathological conditions. Identification of dihydroxyadenine prompt to treat the patient with allopurinol. In transplanted patients, we found a negative correlation between the amount of calcium phosphate deposits and the graft survival. The high occurrence of mixed crystals may be a marker for successive episodes of kidney dysfunction related to different mechanisms. We therefore suggest that FTIR microspectroscopy is a major diagnostic tool for crystal identification and should be proposed to any patient with a past history of stone disease and presenting with an unexplained renal failure of the native or grafted kidney.Conclusion A precise identification of crystal deposits in the kidney tissue may totally modify the diagnosis of an unexplained kidney dysfunction. Common histological procedures clearly fail to identify accurately crystals deposits and should be completed by infrared analysis

Nephrotoxicity induced by drugs: The case of foscarnet and atazanavirdA SEM and mFTIR investigation

International audienceBiopsies of native or transplanted kidneys in patients suffering chronic or acute renal failure are commonly stained for tissue examination and search for possible crystal deposits which are then identified by polarizing microscopy and staining by von Kossa's method revealing mainly calcium deposits. Renal biopsies presumably containing crystal deposits were analyzed with a Spotlight 400 μFTIR (Fourier Transform Infra Red) imaging system in the mid-infrared spectral range to obtain infrared maps of tissue slides at high spatial resolution, down to 10 microns. When required, an optional ATR imaging accessory was used, improving the spatial resolution by a factor four, down to 3 microns at 1000 cm−1. Among the 685 renal biopsies, 72% contained abnormal non-proteic material. Among them, 2.16% contained drug crystals (triamterene, N-acetylsulfadiazine, ciprofloxacine, indinavir, atazanavir, foscarnet, and vancomycine). We focused on foscarnet and atazanavir deposits. In the case of foscarnet-induced renal failure, two types of crystals were found in one patient. They were located in different parts of the nephron: sodium and/or calcium phosphonoformate crystals within glomerules and carbapatite in the proximal tubular cells. By contrast, atazanavir was only found in the tubular lumen of the nephron

Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy.

International audienceRecent findings in idiopathic membranous nephropathy (MN) suggest that in most patients, the disease is because of anti-phospholipase A(2) receptor (PLA(2) R1) autoantibodies. Our aim was to analyze the prevalence and significance of anti-PLA(2) R1 antibodies in recurrent and de novo MN after transplantation. We assessed circulating PLA(2) R1 autoantibodies by a direct immunofluorescence assay based on human embryonic kidney cells transfected with a PLA(2) R1 cDNA, and the presence of PLA(2) R1 antigen in immune deposits. We showed that PLA(2) R1 was involved in 5 of 10 patients with recurrent MN, but in none of the 9 patients with de novo MN. We also showed a marked heterogeneity in the kinetics and titers of anti-PLA(2) R1, which may relate to different pathogenic potential. We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence. Because PLA(2) R1 autoantibody was not always associated with recurrence, its predictive value should be carefully analyzed in prospective studies

Expression of the transcriptional regulator snail1 in kidney transplants displaying epithelial-to-mesenchymal transition features

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Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric obstruction.

International audienceThrombospondin-1 (TSP-1) is an endogenous activator of transforming growth factor-β (TGF-β), and an anti-angiogenic factor, which may prevent kidney repair. Here we investigated whether TSP-1 is involved in the development of chronic kidney disease using rats with unilateral ureteral obstruction, a well-known model to study renal fibrosis. Obstruction of 10 days duration induced inflammation, tubular cell atrophy, dilation, apoptosis, and proliferation, leading to interstitial fibrosis. TSP-1 expression was increased in parallel to that of collagen III and TGF-β. Relief of the obstruction at day 10 produced a gradual improvement in renal structure and function, the reappearance of peritubular capillaries, and restoration of renal VEGF content over a 7- to 15-day post-relief period. TSP-1 expression decreased in parallel with that of TGF-β1 and collagen III. Mice in which the TSP-1 gene was knocked out displayed less inflammation and had better preservation of renal tissue and the peritubular capillary network compared to wild-type mice. Additional studies showed that the inflammatory effect of TSP-1 was mediated, at least in part, by monocyte chemoattractant protein-1 and activation of the Th17 pathway. Thus, TSP-1 is an important profibrotic and inflammatory mediator of renal disease. Blockade of its action may be a treatment against the development of chronic kidney disease

Nanometric chemical speciation of abnormal deposits in kidney biopsy: Infrared-nanospectroscopy reveals heterogeneities within vancomycin casts.

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Detection of silica and calcium carbonate deposits in granulomatous areas of skin sarcoidosis by μFourier transform infrared spectroscopy and Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy analysis

International audienceSarcoidosis is a multisystem inflammatory disease affecting different organs particularly lung, skin, eyes and joints. Characterized by noncaseating epithelioid granulomas, sarcoidosis is considered to be caused by a complex interplay between genetics and environmental agents while it still remains a disease of unknown etiology. 10 skin biopsies from patients with cutaneous sarcoidosis were included in the study. After polarized light examination (PLE) through optical microscopy, these skin biopsies have been investigated through mFourier transform (FTIR) infrared spectroscopy and Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (FE-SEM/EDX). Three biopsies showed a refractive material at PLE. FTIR and FE-SEM/EDX analyses indicate the presence of silica at the center of the granulomas in these three biopsies. Another striking result is related to the presence of calcite, a calcium carbonate at the periphery of the granulomas. To our best knowledge, this is the first time that the presence of this calcium carbonate has been reported. Such description at the submicrometer scale paves the way for a better understanding of the physicochemical processes related to sarcoidosis and will help clinicians to develop new diagnostic tools

Genetic inhibition of discoidin domain receptor 1 protects mice against crescentic glomerulonephritis.

International audienceThis study investigated the role of discoidin domain receptor 1 (DDR1), a collagen receptor that displays tyrosine-kinase activity, in the development of glomerulonephritis. Crescentic glomerulonephritis was induced in DDR1-deficient mice and their wild-type (WT) littermates as controls, by injection of alloimmune sheep nephrotoxic serum (NTS). Histological, functional and transcriptomic studies were performed. Glomerulonephritis produced a 17-fold increase of DDR1 expression, predominantly in glomeruli. DDR1 deletion protected NTS-treated mice against glomerular disease (proteinuria/creatininuria 5.5±1.1 vs. 13.2±0.8 g/mmol in WT, crescents 12±2 vs. 24±2% of glomeruli, urea 16±2 vs. 28±5 mM), hypertension (123±11 vs. 157±8 mmHg), and premature death (70 vs. 10% survival) (all P<0.05). Reciprocal stimulation between DDR1 and interleukin-1b expression in vivo and in cultured podocytes suggested a positive feed-back loop between DDR1 and inflammation. In NTS-treated WT mice, administration of DDR1-specific antisense oligodeoxynucleotides decreased DDR1 expression (-56%) and protected renal function and structure, including nephrin expression (4.2±1.4 vs. 0.9±0.4 arbitrary units, P<0.05), compared to control mice receiving scrambled oligodeoxynucleotides. The therapeutic potential of this approach was reinforced by the observation of increased DDR1 expression in glomeruli of patients with lupus nephritis and Goodpasture's syndrome. These results prompt further interest in DDR1 blockade strategies, especially in the treatment of glomerulonephritis