The intracellular As-protein binding in cytosol and methanol–water extract of the auricle and saphene tissues of As impacted people was evaluated by bidimensional size exclusion FPLC-UV-ICP-MS. The ...fractionation of cytosol using Superdex, Phenomenex and MonoQ HR 5/5 columns, shows that As is distributed in a wide range of contiguous fractions of each column, being 8, 25, 50 % the percentages of As in the collected fractions, respectively. In the methanol: water extracts a similar study than performed with the cytosol using preparative gel chromatography on Sephadex G-75 and Shephadex G-100 columns and the MonoQ HR 5/5 anion protein exchange was carried out. A very low As (<1 % of total As) and protein contain were found in the different fractions of both SEC fractionating series. A similar As–protein association to that found in the cytosol after fractionating with MonoQ HR 5/5 was observed for auricle and saphene. Inorganic and methylated As speciation in the 20 – 26 cytosol fractions obtained within the Phenomenex column was performed by HPLC–ICP–MS using the Hamilton PRP-X100 column. Only As (III) and As (V) were present and the results obtained shows that the As (III)/As(V) ratio is constant in most cases. Direct evidence of the existence of As–binding peptides in auricle and saphene vein from arsenic impacted human beings has have been obtained which was previously reported by means of novo peptide synthesis.
Gamma-ray bursts (GRBs) and their afterglows are the most brilliant transient events in the Universe. Both the bursts themselves and their afterglows have been predicted to be visible out to ...redshifts of z 20, and therefore to be powerful probes of the early Universe. The burst GRB 000131, at z = 4.50, was hitherto the most distant such event identified. Here we report the discovery of the bright near-infrared afterglow of GRB 050904 (ref. 4). From our measurements of the near-infrared afterglow, and our failure to detect the optical afterglow, we determine the photometric redshift of the burst to be z = 6.39 - 0.12 + 0.11 (refs 5-7). Subsequently, it was measured spectroscopically to be z = 6.29 ± 0.01, in agreement with our photometric estimate. These results demonstrate that GRBs can be used to trace the star formation, metallicity, and reionization histories of the early Universe.
Leachables from single-use bioprocess containers (BPCs) are a source of process-related impurities that have the potential to alter product quality of biotherapeutics and affect patient health. ...Leachables often exist at very low concentrations, making it difficult to detect their presence and challenging to assess their impact on protein quality. A small-scale stress model based on assessing protein stability was developed to evaluate the potential risks associated with storing biotherapeutics in disposable bags caused by the presence of leachables. Small-scale BPCs were filled with protein solution at high surface area-to-volume ratios (≥3× the surface area-to-volume ratio of manufacturing-scale BPCs) and incubated at stress temperatures (e.g., 25 °C or 30 °C for up to 12 weeks) along with an appropriate storage vessel (e.g., glass vial or stainless steel) as a control for side-by-side comparison. Changes in protein size variants measured by size exclusion chromatography, capillary electrophoresis, and particle formation for two monoclonal antibodies using both the small-scale stress model and a control revealed a detrimental effect of gamma-irradiated BPCs on protein aggregation and significant BPC difference between earlier and later batches. It was found that preincubation of the empty BPCs prior to protein storage improved protein stability, suggesting the presence of volatile or heat-sensitive leachables (heat-labile or thermally degraded). In addition, increasing the polysorbate 20 concentration lowered, but did not completely mitigate, the leachable-protein interactions, indicating the presence of a hydrophobic leachable. Overall, this model can inform the risk of BPC leachables on biotherapeutics during routine manufacturing and assist in making decisions on the selection of a suitable BPC for the manufacturing process by assessing changes in product quality.
Leachables from single-use systems often exist in small quantities and are difficult to detect with existing analytical methods. The presence of relevant detrimental leachables from single-use bioprocess containers (BPCs) can be indirectly detected by studying the stability of monoclonal antibodies via changes by size exclusion chromatography, capillary electrophoresis sodium dodecyl sulfate, and visible/sub-visible particles using a small-scale stress model containing high surface area-to-volume ratio at elevated temperature alongside with an appropriate control (e.g., glass vials or stainless steel containers). These changes in protein quality attributes allowed the evaluation of potential risks associated with adopting single-use bioprocess containers for storage as well as bag quality and bag differences between earlier and later batches. These leachables appear to be generated during the bag sterilization process by gamma irradiation. Improvements in protein stability after storage in "preheated" bags indicated that these leachables may be thermally unstable or volatile. The effect of surfactant levels, storage temperatures, surface area-to-volume ratios, filtration, and buffer exchange on leachables and protein stability were also assessed.
To determine the efficacy of danazol for refractory autoimmune thrombocytopenia or Evans' syndrome complicating systemic lupus erythematosus (SLE).
We studied 16 consecutive patients with SLE and ...corticosteroid refractory autoimmune thrombocytopenia; 3 patients had coexisting autoimmune hemolysis (Evans' syndrome). Five patients had undergone splenectomy. Danazol was commenced at 200 mg/day, and increased stepwise (maximum 1200 mg/day) until benefit or toxicity was observed. After remission the danazol dose was gradually reduced to 200-400 mg/day.
All 16 patients achieved a complete remission (platelet count >100 x 10(9)/l, hematocrit >39%) 2 months after starting danazol (range 6 weeks-8 months). Remission persisted during continued danazol therapy (mean followup 18.2 months, range 2-49 months). One patient with Evans' syndrome required discontinuation of danazol because of jaundice and biopsy proven minimal hepatic necrosis: hemolysis recurred after discontinuation of danazol.
Danazol is effective for the treatment of autoimmune thrombocytopenia or Evans' syndrome complicating SLE irrespective of splenectomy status. Longer followup will be needed to determine whether the remission persists after withdrawal of danazol.
El dolor lumbar es muy frecuente en la población y disminuye la calidad de vida de los pacientes que lo sufren. En los últimos años se ha sugerido la ozonoterapia como tratamiento alternativo debido ...a su efecto antiinflamatorio y analgésico. Los resultados mostraron que la ozonoterapia es confiable y efectiva para el tratamiento de la hernia de disco lumbar, dolor radicular y dolor de espalda mecánico debido al dolor lumbar.Tras examinar los resultados de los estudios descritos realizados en los últimos años en diversos países se puede comprobar la eficacia y seguridad de la ozonoterapia para reducir el dolor lumbar a corto y largo plazo cuando no funciona el tratamiento conservador, y su poder para retrasar la cirugía. A raíz de estos favorables resultados resulta imprescindible trasmitir esta novedosa terapia a los profesionales sanitarios para que puedan incorporarla en su trabajo diario y así poder ofrecer a los pacientes los mejores tratamientos basados en las últimas evidencias científicas demostradas.
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