THE MUTATOR PHENOTYPE IS A FEATURE OF IMMUNODEFICIENCY-RELATED LYMPHOMAS

The mutator phenotype caused by defects in the mismatch repair system is observed in a subset of solid neoplasms characterized by widespread microsatellite instability-high (MSI-H). It is known to be very rare in non-Hodgkin lymphomas (NHL), whereas mutator NHL is the most frequent tumor subtype in mismatch repair-deficient mice. By screening a series of 603 human NHL with specific markers of the mutator phenotype, we found here 12 MSI-H cases (12/603, 2%). Of interest, we demonstrated that this phenotype was specifically associated with immunodeficiency-related lymphomas (ID-RL), because it was observed in both posttransplant lymphoproliferative disorders (9/111, 8.1%) and HIV infection-related lymphomas (3/128, 2.3%) but not in a large series of NHL arising in the general population (0/364) (P < 0.0001). The MSI pathway is known to lead to the production of hundreds of abnormal protein neoantigens that are generated in MSI-H neoplasms by frameshift mutations of a number of genes containing coding microsatellite sequences. As expected, MSI-H ID-RL were found to harbor such genetic alterations in 12 target genes with a putative role in lymphomagenesis. The observation that the MSI-H phenotype was restricted to HIV infection-related lymphomas and posttransplant lymphoproliferative disorders suggests the existence of the highly immunogenic mutator pathway as a novel oncogenic process in lymphomagenesis whose role is favored when host immunosurveillance is reduced. Because MSI-H-positive cases were found to be either Epstein-Barr virus-positive or -negative, the mutator pathway should act synergistically or not with this other oncogenic factor, playing an important role in ID-RL

Effect of betamethasone and diclofenac sodium on serum and tissue concentration of amoxicillin: in vivo study in rats Efeito da betametasona e do diclofenaco sódico na concentração sérica e tecidual da amoxicilina: estudo in vivo em ratos

OBJECTIVE: Antimicrobial agents in combination with anti-inflammatory drugs have been usually prescribed in both Medicine and Dentistry. However, few scientific reports support this clinical practice. The aim of this study was to evaluate the effect of betamethasone and diclofenac sodium on serum and tissue concentration of amoxicillin in rats. METHODS: Four polyurethane sponges were implanted in the back skin of 48 rats. After seven days the animals were divided into 6 groups (n=8). Group 1: amoxicillin (25 mg/kg); G2: diclofenac sodium (2.5 mg/kg); G3: betamethasone (0.1 mg/kg); G4: diclofenac sodium and amoxicillin; G5: betamethasone and amoxicillin; and G6: 0.9% sodium chloride solution (1.0 mL - control group). All drugs were administered in a single dose. After 90 minutes, the granulomatous tissues of each animal were surgically removed and weighed. Blood was collected from cervical plexus, centrifuged and 10µL of serum was placed on paper discs. In order to estimate amoxicillin concentration, serum and granulomatous tissues were separately submitted to microbiological assay, which used 10(8)cfu/mL of Staphylococcus aureus ATCC 25923 (penicillin-susceptible strain). After incubation (18 hours, 37ºC) the inhibition zones were measured and compared to a regression curve. RESULTS: No inhibition zones were observed for groups 2, 3 and 6. Tissue and serum concentrations of both G1 (4.14µg/g and 2.06µg/mL, respectively) and G5 (3.87µg/g and 1.70µg/mL, respectively) showed statistically significant differences (Kruskal-Wallis, p<0.05) in comparison to G4 (1.45µg/g and 0.41µg/mL, respectively). G1 and G5 did not differ significantly (p>0.05). CONCLUSION: Considering single doses, betamethasone did not interfere with amoxicillin levels but diclofenac sodium reduced both tissue and serum levels of amoxicillin in rats.<br>OBJETIVO: A prescrição de antimicrobianos associados a antiinflamatórios é uma prática comum em odontologia, embora na maioria das vezes não haja justificativa para tal conduta. O objetivo deste trabalho foi avaliar, em um estudo in vivo em ratos, os efeitos da betametasona e do diclofenaco sódico nas concentrações sérica e tecidual da amoxicilina. MÉTODOS: Foram utilizados 48 ratos Wistar machos (6 grupos, n=8), com idade de 60 dias. Esponjas de PVC (policlorovinil) foram implantadas em quatro pontos no dorso de cada animal. Após sete dias, foram administrados por via intragástrica ou intramuscular: Grupo 1: amoxicilina (25 mg/kg); G2: diclofenaco sódico (2,5 mg/kg/i.m.); G3: betametasona (0,1 mg/kg/i.m.); G4: diclofenaco sódico e amoxicilina; G5: betametasona e amoxicilina; e G6: solução de cloreto de sódio a 0,9% (1,0 mL - grupo controle). Após 90 minutos, foram colhidos 2 tecidos granulomatosos e amostras séricas de cada animal e colocados em meios de cultura inoculados com 10(8) ufc/mL de Staphylococcus aureus ATCC 25923. Os halos de inibição foram medidos após 18 horas de incubação (37ºC), e através do teste microbiológico foram obtidas as concentrações séricas e teciduais da amoxicilina. RESULTADOS: Não foram observados halos de inibição para os grupos 2, 3 e 6. As concentrações séricas e teciduais de G1 (4,14µg/g e 2,06µg/mL, respectivamente) e G5 (3,87µg/g e 1,70µg/mL, respectivamente) demonstraram diferenças estatisticamente significantes (Kruskal-Wallis, p<0,05) em comparação a G4 (1,45µg/g e 0,41µg/mL, respectivamente). G1 e G5 não apresentaram diferença estatística (p>0,05). CONCLUSÃO: Considerando uma dose única, a betametasona não interferiu nas concentrações sérica e tecidual de amoxicilina, enquanto o diclofenaco sódico reduziu as concentrações sérica e tecidual de amoxicilina em ratos

Determining the degradation efficiency and mechanisms of ethyl violet using HPLC-PDA-ESI-MS and GC-MS

<p>Abstract</p> <p>Background</p> <p>The discharge of wastewater that contains high concentrations of reactive dyes is a well-known problem associated with dyestuff activities. In recent years, semiconductor photocatalysis has become more and more attractive and important since it has a great potential to contribute to such environmental problems. One of the most important aspects of environmental photocatalysis is in the selection of semiconductor materials like ZnO and TiO₂, which are close to being two of the ideal photocatalysts in several respects. For example, they are relatively inexpensive, and they provide photo-generated holes with high oxidizing power due to their wide band gap energy. In this work, nanostructural ZnO film on the Zn foil of the Alkaline-Manganese Dioxide-Zinc Cell was fabricated to degrade EV dye. The major innovation of this paper is to obtain the degradation mechanism of ethyl violet dyes resulting from the HPLC-PDA-ESI-MS analyses.</p> <p>Results</p> <p>The fabrication of ZnO nanostructures on zinc foils with a simple solution-based corrosion strategy and the synthesis, characterization, application, and implication of Zn would be reported in this study. Other objectives of this research are to identify the reaction intermediates and to understand the detailed degradation mechanism of EV dye, as model compound of triphenylmethane dye, with active Zn metal, by HPLC-ESI-MS and GC-MS.</p> <p>Conclusions</p> <p>ZnO nanostructure/Zn-foils had an excellent potential for future applications on the photocatalytic degradation of the organic dye in the environmental remediation. The intermediates of the degradation process were separated and characterized by the HPLC-PDA-ESI-MS and GC-MS, and twenty-six intermediates were characterized in this study. Based on the variation of the amount of intermediates, possible degradation pathways for the decolorization of dyes are also proposed and discussed.</p