Glomerular Endothelial Cell-Derived microRNA-192 Regulates Nephronectin Expression in Idiopathic Membranous Glomerulonephritis.

BACKGROUND: Autoantibodies binding to podocyte antigens cause idiopathic membranous glomerulonephritis (iMGN). However, it remains elusive how autoantibodies reach the subepithelial space because the glomerular filtration barrier (GFB) is size selective and almost impermeable for antibodies. METHODS: Kidney biopsies from patients with iMGN, cell culture, zebrafish, and mouse models were used to investigate the role of nephronectin (NPNT) regulating microRNAs (miRs) for the GFB. RESULTS: Glomerular endothelial cell (GEC)-derived miR-192-5p and podocyte-derived miR-378a-3p are upregulated in urine and glomeruli of patients with iMGN, whereas glomerular NPNT is reduced. Overexpression of miR-192-5p and morpholino-mediated npnt knockdown induced edema, proteinuria, and podocyte effacement similar to podocyte-derived miR-378a-3p in zebrafish. Structural changes of the glomerular basement membrane (GBM) with increased lucidity, splitting, and lamellation, especially of the lamina rara interna, similar to ultrastructural findings seen in advanced stages of iMGN, were found. IgG-size nanoparticles accumulated in lucidity areas of the lamina rara interna and lamina densa of the GBM in npnt-knockdown zebrafish models. Loss of slit diaphragm proteins and severe structural impairment of the GBM were further confirmed in podocyte-specific Npnt knockout mice. GECs downregulate podocyte NPNT by transfer of miR-192-5p-containing exosomes in a paracrine manner. CONCLUSIONS: Podocyte NPNT is important for proper glomerular filter function and GBM structure and is regulated by GEC-derived miR-192-5p and podocyte-derived miR-378a-3p. We hypothesize that loss of NPNT in the GBM is an important part of the initial pathophysiology of iMGN and enables autoantigenicity of podocyte antigens and subepithelial immune complex deposition in iMGN.

Increased Recovery of Gold Thiosulfate Alkaline Solutions by Adding Thiol Groups in the Porous Structure of Activated Carbon.

Thiosulfate leaching combined with ion-exchange resins is an innovative alternative for gold recovery. According to the properties of activated carbon, it could replace resins in the gold recovery process, improve efficiency, and reduce operating cost. In this research, the adsorption process of gold thiosulfate complex on thiol-modified activated carbon was studied. Thioglycolic acid (ATG) was impregnated in activated carbon, and its adsorption ability was tested with synthetic solutions of gold and sodium thiosulfate (Au 10 mg·L-1, Na2S2O3 0.1 mol·L-1, pH = 10.0). Carbon was characterized by infrared spectroscopy, SEM-EDS, PZC titration, hardness number measures, and proximal analysis. Synthetic solutions were also characterized by UV-vis spectroscopy and cyclic voltammetry. The percentage of volatile material increased from 10.0 to 13.9% due to the impregnation process of ATG. Infrared spectra show characteristic bands of C-H, S-H, and C-S bonds. In the adsorption tests, the ATG-impregnated carbon achieved 91% of gold recovery, while the same amount of ATG in the liquid phase stirred with unmodified activated carbon reached 90% of gold recovery. The 44.9% of gold recovered with activated carbon impregnated with ATG was eluted with sodium cyanide ([NaCN] = 0.2 mol·L-1; [NaOH] = 0.25 mol·L-1; [CH3CH2OH] = 30% V/V; pH = 12.0; t = 24 h). These results suggest the gold transferred from the thiosulfate complex to a new gold thiolate complex.

Patch Testing With an Extended Metal Allergen Series at the Massachusetts General Hospital (2006-2017).

BACKGROUND: Reports of patch test data with an extended metal series that includes rare metals are limited. OBJECTIVE: The aims of the study were to analyze and report patch testing results from an extended metal series, examine associations with sex and age, and highlight concomitant metal reactions. METHODS: This study is a retrospective review of 150 patients referred for suspected metal allergy from January 1, 2007, to December 31, 2016. RESULTS: The most common indications for evaluation referral were those having symptoms after implantation of a metal device (55.3%) and those with a history and concern of metal allergy before implantation of a metal device (22.0%). One or more positive patch test reactions were observed in 87 patients (58.0%). Metals with the highest frequencies were nickel sulfate 2.5% (26.2%), gold sodium thiosulfate 0.5% (23.0%), gold sodium thiosulfate 2.0% (20.7%), palladium chloride 2.0% (19.6%), cobalt chloride 1.0% (12.0%), and manganese chloride 2.0% (10.1%). Of the 45 metals tested, 15 caused no patch test reactions. Female patients were more likely to be sensitized to nickel, gold, and palladium (P < 0.05). Younger patients (≤40 years) had higher reaction rates to nickel, mercury, palladium, and cobalt. Concomitant reactions of the top metals (nickel, palladium, gold, and cobalt) were statistically associated bidirectionally (P < 0.05), except for cobalt and gold. CONCLUSIONS: Allergy to metals, including those not included in standard series, may be more prevalent than previously suspected. Results may help guide future testing for suspected metal allergy, although future studies are warranted.

Screening for Gold Sensitization in Consecutive Eczema Patients: Prevalence, Relevance, and Sources of Exposure.

BACKGROUND: Since the 1990s, gold has been recognized as an important contact allergen. OBJECTIVES: Based on our results with gold sodium thiosulfate (GST) in the TRUE Test patch test system in the baseline series, the aims of the study were to evaluate baseline testing with gold salts worldwide and to discuss relevance. METHODS: Patients with positive patch test reactions to GST were questioned on exposure at day 7 reading. RESULTS: In a 1-year period, 89 (18.5%) of 480 patients tested positive to GST, making this the most frequent contact allergy. The 89 patients comprised 18 males and 71 females. The reaction was considered relevant in 21%; this is a minimum figure because 2 patients were withdrawn because of unknown relevance and because clinical features suggestive of gold contact allergy at distant sites, such as the face, were not taken into account. Altogether, 88% had been exposed. Worldwide, the prevalence of gold sensitization ranges between 0.78% and 30.7%, and relevance, in larger studies, has been between 15% and 20% of patients. The use of earrings and the presence of dental gold were important sources of exposure. CONCLUSIONS: Because it may be difficult to diagnose gold allergy, screening may be recommended when history taken suggests gold exposure.

Experience in patch testing: A 6-year retrospective review from a single academic allergy practice.

BACKGROUND: Patch testing is the "gold standard" to identify culprit allergen(s) causing allergic contact dermatitis (ACD), but there are limited studies of patch testing from allergy practice settings. OBJECTIVE: We sought to explore patch test findings in a large academic allergy practice, including patch testing results, history of atopy, location of dermatitis, and referral source. We also wanted to determine whether patch testing using an extended panel, such as the North American screening series, compared with a limited series, such as the Thin-Layer Rapid-Use Epicutaneous (T.R.U.E.) Test, increased the sensitivity. METHODS: A retrospective chart review was conducted of patients referred for patch testing over a 6-year period. RESULTS: A total of 585 patients (mean age 48.7 years, 71.6 % female) underwent patch testing over the 6-year period, of which 369 (63%) had a positive test. Of those who tested positive, 202 (55%) reported a history of atopy. The extremities were the most commonly involved site, followed by the head/neck and trunk. The 5 most common positive allergens were nickel sulfate, gold sodium thiosulfate, methylchloroisothiazolinone, thimerosal, and bacitracin. Three hundred fourteen (53.6%) patients were positive to at least 1 allergen on TRUE testing. Extended screening series identified an additional 10.8% of patients with positive tests who were negative to T.R.U.E. test allergens. CONCLUSION: Patch testing is a valuable diagnostic tool for the practicing allergist and provides early identification of culprit allergens in ACD. Performing an extended screening series such as the North American Contact Dermatitis Group (NACDG) or supplemental panel of allergens increased sensitivity when compared with a limited series.

Positive reactions to gold sodium thiosulfate in patch test panels (TRUE Test) in Japan: A multicentre study.

BACKGROUND: The proportion of positive test results with gold sodium thiosulfate included in a patch test panel (P-GST) had been found to be greater than that with gold sodium thiosulfate 0.5% pet. by allergEAZE (A-GST). OBJECTIVES: To compare positive reactions to P-GST and A-GST, and to evaluate late reactions after the day (D) 7 reading. METHODS: A retrospective analysis was performed of 588 patients at participating departments (119 males; 469 females) who were patch tested with P-GST and A-GST in May 2015 to March 2016. RESULTS: Positive test reactions to P-GST and A-GST were observed in 15% and 6% of patients, respectively. Three patients reported a positive reaction occurring after the D7 reading. CONCLUSIONS: Gold sodium thiosulfate often gives a positive reaction after 2 to 3 weeks, and, in such cases, the positive reaction may be sustained, so it is recommended to assess the reaction for up to 1 month after application.

De la historia antigua de los métodos iodométricos: de Robert Bunsen a Karoly Tham / Ancient history of the iodometric methods: from Robert Bunsen to Karoly Tham

La contribución más importante en el ámbito de la iodometría se debe a Bunsen, quien describe la determinación de una amplia variedad de sustancias oxidantes liberando el yodo a partir del ioduro potasio, y valorándolo con ácido sulfuroso. Bunsen tenía predilección por el trabajo cuantitativo y era un genio en el diseño de la ciencia aplicada aunque no patenta los dispositivos que idea. Da un impulso decisivo a la institucionalización de la farmacia alemana en el siglo XIX, interesándose por el desarrollo de la educación farmacéutica. Heinrich Schwarz tras estudiar en de Halle y pasar por Giessen marcha al laboratorio de Pelouze en París, donde se familiariza con los métodos volumétricos de análisis, trabajando a su regreso a Alemania en este campo. Propone reemplazar el ácido sulfuroso utilizado por Bunsen en las valoraciones con yodo por tiosulfato sódico, lo que supuso un gran avance. Theophile Pelouze, farmacéutico, es fundamental para entender las conexiones con Schwarz y también con Bunsen. El trabajo concluye con la determinación de azúcares propuesta por Arthur Barreswill modificada por Fehling, y con la determinación de la pureza del ioduro de potasio del comercio

The most important contribution in the field of iodometry is due to Bunsen, who describes the determination of a wide variety of oxidizing substances by releasing iodine from iodide potassium, and assessing it with sulphurous acid. Bunsen had a predilection for quantitative work and was a genius in the design of applied science, although he does not patent the devices that idea. It gives a decisive impulse to the institutionalization of the German pharmacy in the 19th century, taking an interest in the development of pharmaceutical education. Heinrich Schwarz after studying in Halle and going through Giessen goes to the Pelouze laboratory in Paris, where he becomes familiar with the volumetric methods of analysis, working on his return to Germany in this field. It proposes to replace the sulphurous acid used by Bunsen in the evaluations with iodine by sodium thiosulphate, which represented a great advance. Theophile Pelouze, pharmacist, is essential to understand the connections with Schwarz and also with Bunsen. The work concludes with the determination of sugars proposed by Arthur Barres will modified by Fehling, and with the determination of the purity of the potassium iodide of the trade

Planarians as models to investigate the bioactivity of gold(I) complexes in vivo.

Gold(I)-containing complexes are used in drug discovery research for rheumatoid arthritis, cancer, and parasitic infections. In this study, we tested the bioactivity of gold(I) complexes in vivo using planarians. The planarian Schmidtea mediterranea possesses orthologues of tumor suppressor genes, such as p53, that, when silenced, cause deregulation of cell proliferation and apoptosis. In this context, we tested two triethylphosphine-gold(I) complexes (AdO and AdT) to determine if they can attenuate phenotypes that result from p53 inhibition. First, we identified the drug concentration that did not affect survival or regeneration and evaluated the drug's effect on cell division and apoptosis. We found that AdT treatment decreased the number of mitotic cells and that all drug treatments increased the number of apoptotic cells. We then performed p53(RNAi) and drug treatments concomitantly and observed the phenotype progression. Drug treatment increased survival three-fold and decreased apoptosis, which resulted in an attenuated phenotype. Our results indicate that planarians can be treated with gold(I) complexes, and that this treatment can diminish the p53(RNAi) phenotype and extend survival. In this work we show that planarians can be used as a model to study the in vivo effect of gold(I) complexes and to further investigate their mechanisms of action.

Excipient and Dose per Unit Area Affect Sensitivity When Patch Testing With Gold Sodium Thiosulfate.

BACKGROUND: Dose/area and reading paradigms for gold patch testing are controversial and not standardized worldwide. OBJECTIVES: The aims of this study were to determine the optimum patch test dose of gold sodium thiosulfate (GST) in a hydrogel (HYD) and to establish GST HYD safety/efficacy and further characterize normal morphology and time course of GST reactions. METHODS: Twenty gold-allergic patients were patch tested with a dilution series of GST HYD and with GST 2% petrolatum (pet). Furthermore, this previously determined optimal dose was compared with GST 0.5% pet in 19 known-allergic and 216 consecutive subjects. RESULTS: The optimal GST HYD dose was 0.075 mg/cm, not statistically different from GST 2% pet (P = 0.4795). Gold sodium thiosulfate HYD outperformed GST 0.5% pet in both known-allergic subjects (79% vs 63%, P = 0.2482) and consecutive subjects (30% vs 9%, P < 0.0001). Late reactions were common in consecutive patients with both HYD and pet. Significantly more persistent reactions were associated with GST HYD than with GST 0.5% pet. CONCLUSIONS: Gold sodium thiosulfate HYD 0.075 mg/cm is the optimal dose for diagnosis of gold contact allergy with GST. Gold sodium thiosulfate 0.5% pet yielded false-negatives in some patients, suggesting inadequate dose per centimeter squared. Late reads are normal, expected, and necessary for diagnosis of gold contact allergy in this cohort.

Tiosulfato sódico a bajas dosis en el tratamiento de la arteriolopatía urémica calcificante / Sodium thiosulfate in the treatment of calcific uremic arteriolopathy (calciphylaxis)

No disponible

Calcifilaxis no urémica mediada por acenocumarol / Non-uremic calciphylaxis due to acenocoumarol

No disponible