Medioevo, cultura materiale e storia: qualche osservazione

Nel contributo si discute il lavoro di Andrea Augenti, recente manuale di archeologia medievale. L\u2019attenzione si rivolge prevalentemente all\u2019impostazione teorica, ad alcune note sui temi e al rapporto con il pubblico

Mycophenolate mofetil for methotrexate-resistant juvenile localized scleroderma

Objectives: To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma. Methods: Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan-Meier analysis. Results: MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P = 0.008 and P = 0.029, respectively), and linear scleroderma of the face in the MTX-group (P = 0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4 years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P = 0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy. Conclusion: The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment

Mechanism of action of the monosialoganglioside GM1 as a modulator of CD4 expression. Evidence that GM1-CD4 interaction triggers dissociation of p56lck from CD4, and CD4 internalization and degradation.

Analyzing the mechanisms underlying the capability of the monosialoganglioside GM1 to induce CD4 modulation we observed that GM1 has a dual effect on the CD4 molecule. GM1 treatment of the lymphoma cell line MOLT-3 and CD4-transfected HeLa cells for times shorter than 30 min prevented binding of monoclonal antibodies (mAbs) recognizing epitopes located within the first NH2-terminal domains of CD4, but not of the OKT4 mAb, which binds to the region of CD4 proximal to the transmembrane domain. However, no binding of the OKT4 mAb was observed after a few hours of treatment with GM1 in both MOLT-3 cells and HeLa cells transfected with an intact CD4 molecule, but not in HeLa cells transfected with a CD4 molecule lacking the bulk of the cytoplasmic domain, suggesting that modulation of CD4 by GM1 depends on the integrity of the cytoplasmic domain. GM1 treatment blocked binding of several mAbs which recognize epitopes located within the first two NH2-terminal domains of CD4 and did not induce CD4 down-modulation if MOLT-3 cells were preincubated with the OKT4A or the OKT4 mAbs. Immunoprecipitation studies with [35S]methionine-labeled MOLT-3 cells showed that GM1-induced CD4 down-modulation was accompanied by CD4 degradation, and this was preceded by dissociation of p56lck from CD4. GM1-induced CD4 down-modulation, dissociation of p56lck from CD4, and CD4 degradation were unaffected by staurosporine, which, on the contrary, blocked these events in response to phorbol 12-myristate 13-acetate. These observations demonstrate that the first action of GM1 is to mask epitopes located within the first two NH2-terminal domains; then, GM1 triggers protein kinase C-independent signals which cause p56lck dissociation from CD4 and the delivery of the molecule to an intracellular compartment where it is eventually degraded

Advanced oxidation processes for remediation of azo dyes used in the textile industry

O objectivo deste trabalho visa avaliar a degradação fotocatalitica dos corantes azo Remazol Amarelo Ouro, Azul e Carbon RGB. Para tal foram avaliados os seguintes parâmetros: concentração de TiO2, concentração do corante, efeito do H2O2, efeito do pH e da reciclagem de TiO2. TiO2 Degussa P25 foi testado em concentrações a partir de 0gL-1 a 1 gL-1. A concentração do corante foi de 30 mgL-1 a 120 mgL-1 e a concentração do peróxido de hidrogénio foi de 0.3x10-3 a 6x10-2 mol L-1. A variação do pH foi de 2 a 11 e de reciclagem de TiO2 foi feita com 5 ciclos. As amostras foram tratadas durante duas horas com irradiação artificial (lâmpada de vapor mercúrio, 125W) e as amostras foram recolhidas aos 0, 15, 30, 45, 60, 90 e 120 minutos. A fotodegradação das amostras foi seguida por espectroscopia UV-Vis. A eficiência da degradação fotocatalítica aumentou com o aumento da quantidade de TiO2. O efeito do H2O2 foi benéfico para a degradação dos 3 corantes. Os resultados indicam que a degradação fotocatalítica depende da concentração de corante, da quantidade de fotocatalisador utilizado, irradiação UV vs tempo, do pH da solução e da concentração de peróxido de hidrogénio adicionado

Sudan Black B treatment reduces autofluorescence and improves resolution of in situ hybridization specific fluorescent signals of brain sections

Interference by autofluorescence is one of the major concerns of immunofluorescence analysis of in situ hybridization-based diagnostic assays. We present a useful technique that reduces autofluorescent background without affecting the tissue integrity or direct immunofluorescence signals in brain sections. Using six different protocols, such as ammonia/ethanol, Sudan Black B (SBB) in 70% ethanol, photobleaching with UV light and different combinations of them in both formalin-fixed paraffin-embedded and frozen human brain tissue sections, we have found that tissue treatment of SBB in a concentration of 0.1% in 70% ethanol is the best approach to reduce/eliminate tissue autofluorescence and background, while preserving the specific fluorescence hybridization signals. This strategy is a feasible, non-time consuming method that provides a reasonable compromise between total reduction of the tissue autofluorescence and maintenance of specific fluorescent labels.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2007/56146-2]Comissao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)[1429/08-6

Mechanism of action of probiotics

The modern diet doesn't provide the required amount of beneficial bacteria. Maintenance of a proper microbial ecology in the host is the main criteria to be met for a healthy growth. Probiotics are one such alternative that are supplemented to the host where by and large species of Lactobacillus, Bifidobacterium and Saccharomyces are considered as main probiotics. The field of probiotics has made stupendous strides though there is no major break through in the identification of their mechanism of action. They exert their activity primarily by strengthening the intestinal barrier and immunomodulation. The main objective of the study was to provide a deep insight into the effect of probiotics against the diseases, their applications and proposed mechanism of action

Contamination and oxidative stress biomarkers in estuarine fish following a mine tailing disaster

Background The Rio Doce estuary, in Brazil, was impacted by the deposition of iron mine tailings, caused by the collapse of a dam in 2015. Based on published baseline datasets, the estuary has been experiencing chronic trace metal contamination effects since 2017, with potential bioaccumulation in fishes and human health risks. As metal and metalloid concentrations in aquatic ecosystems pose severe threats to the aquatic biota, we hypothesized that the trace metals in estuarine sediments nearly two years after the disaster would lead to bioaccumulation in demersal fishes and result in the biosynthesis of metal-responsive proteins. Methods We measured As, Cd, Cr, Cu, Fe, Mn, Pb, Se and Zn concentrations in sediment samples in August 2017 and compared to published baseline levels. Also, trace metals (As, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Se and Zn) and protein (metallothionein and reduced glutathione) concentrations were quantified in the liver and muscle tissues of five fish species (Cathorops spixii, Genidens genidens, Eugerres brasilianus, Diapterus rhombeus and Mugil sp.) from the estuary, commonly used as food sources by local populations. Results Our results revealed high trace metal concentrations in estuarine sediments, when compared to published baseline values for the same estuary. The demersal fish species C. spixii and G. genidens had the highest concentrations of As, Cr, Mn, Hg, and Se in both, hepatic and muscle, tissues. Trace metal bioaccumulation in fish was correlated with the biosynthesis of metallothionein and reduced glutathione in both, liver and muscle, tissues, suggesting active physiological responses to contamination sources. The trace metal concentrations determined in fish tissues were also present in the estuarine sediments at the time of this study. Some elements had concentrations above the maximum permissible limits for human consumption in fish muscles (e.g., As, Cr, Mn, Se and Zn), suggesting potential human health risks that require further studies. Our study supports the high biogeochemical mobility of toxic elements between sediments and the bottom-dwelling biota in estuarine ecosystems

Immunohistochemistry Analysis of Proteins Related with Apoptosis as Prognostic Factor in Epidermoid Carcinoma of Penis

The aim was to analyze the protein expression of apoptotic genes caspase-3, caspase-8 and bcl-2 with the immunohistochemistry technique, correlating with tumor grade (I, II and III) and with the patient survival in order to understand the basic mechanism of tumoral transformation. The immunohistochemistry reactions on 50 samples of squamous cell carcinoma were carried out with the avidin-biotin immunoperoxidase method and antigen recovery. The analyses were made using the graduation method "in crosses" (0 to 4 crosses - no stain to more than 75% of positives cells) and in categories (low, intermediate, high) of the cytoplasm immunoreactivity of the epidermoid penile carcinoma cells. It was observed a statistically significant difference when the expression of caspase-3 were compared with the grades land II of the tumor (p=0.0010) and when comparing the patient survival with the grades I and II of the tumor (p=0.0212). The protein bcl-2 was more expressed than caspase-3 and caspase-8 proteins, suggesting that the apoptotic rate in this carcinoma is low. The higher expression of the anti-apoptotic protein bcl-2 suggests a higher preservation of the tumoral cells

Immunohistochemistry Analysis of Proteins Related with Apoptosis as Prognostic Factor in Epidermoid Carcinoma of Penis

The aim was to analyze the protein expression of apoptotic genes caspase-3, caspase-8 and bcl-2 with the immunohistochemistry technique, correlating with tumor grade (I, II and III) and with the patient survival in order to understand the basic mechanism of tumoral transformation. The immunohistochemistry reactions on 50 samples of squamous cell carcinoma were carried out with the avidin-biotin immunoperoxidase method and antigen recovery. The analyses were made using the graduation method "in crosses" (0 to 4 crosses - no stain to more than 75% of positives cells) and in categories (low, intermediate, high) of the cytoplasm immunoreactivity of the epidermoid penile carcinoma cells. It was observed a statistically significant difference when the expression of caspase-3 were compared with the grades land II of the tumor (p=0.0010) and when comparing the patient survival with the grades I and II of the tumor (p=0.0212). The protein bcl-2 was more expressed than caspase-3 and caspase-8 proteins, suggesting that the apoptotic rate in this carcinoma is low. The higher expression of the anti-apoptotic protein bcl-2 suggests a higher preservation of the tumoral cells

Patient-derived glioblastoma cells show significant heterogeneity in treatment responses to the inhibitor-of-apoptosis-protein antagonist birinapant.

BACKGROUND: Resistance to temozolomide (TMZ) greatly limits chemotherapeutic effectiveness in glioblastoma (GBM). Here we analysed the ability of the Inhibitor-of-apoptosis-protein (IAP) antagonist birinapant to enhance treatment responses to TMZ in both commercially available and patient-derived GBM cells. METHODS: Responses to TMZ and birinapant were analysed in a panel of commercial and patient-derived GBM cell lines using colorimetric viability assays, flow cytometry, morphological analysis and protein expression profiling of pro- and antiapoptotic proteins. Responses in vivo were analysed in an orthotopic xenograft GBM model. RESULTS: Single-agent treatment experiments categorised GBM cells into TMZ-sensitive cells, birinapant-sensitive cells, and cells that were insensitive to either treatment. Combination treatment allowed sensitisation to therapy in only a subset of resistant GBM cells. Cell death analysis identified three principal response patterns: Type A cells that readily activated caspase-8 and cell death in response to TMZ while addition of birinapant further sensitised the cells to TMZ-induced cell death; Type B cells that readily activated caspase-8 and cell death in response to birinapant but did not show further sensitisation with TMZ; and Type C cells that showed no significant cell death or moderately enhanced cell death in the combined treatment paradigm. Furthermore, in vivo, a Type C patient-derived cell line that was TMZ-insensitive in vitro and showed a strong sensitivity to TMZ and TMZ plus birinapant treatments. CONCLUSIONS: Our results demonstrate remarkable differences in responses of patient-derived GBM cells to birinapant single and combination treatments, and suggest that therapeutic responses in vivo may be greatly affected by the tumour microenvironment