Quantitative analysis of MRP-8 in gingival crevicular fluid in periodontal health and disease using microbore HPLC.

BACKGROUND:

The protein components of GCF can be separated by reverse-phase microbore HPLC on a C18 column with detection on the basis of 214 nm absorbance. A single major symmetrical protein peak eluting with a retention time of 26 min (50% acetonitrile) was evident in gingival crevicular fluid (GCF) from periodontitis patients but not in healthy GCF. This protein was identified as human MRP-8 by N-terminal amino acid sequencing and liquid chromatography quadropole mass spectrometry.

AIMS:

To quantify the amount of MRP-8 detectable in GCF from individual healthy, gingivitis and periodontitis affected sites and to study the relationship, if any, between the levels of this responsive protein and periodontal health and disease.

METHODS:

GCF was sampled (30 s) from healthy, gingivitis, and periodontitis sites in peridontitis subjects (n=15) and from controls (n=5) with clinically healthy gingiva and no periodontitis. Purified MRP-8 was sequenced by Edmann degradation and the phenylthiohydantoin (PTH) amino acid yield determined (by comparison of peak area with external PTH amino acid standards). This value was subsequently used to calculate the relative amount of protein in the peak eluting with a retention time of 26.0 min (MRP-8) in individual GCF chromatograms.

RESULTS:

Higher levels of MRP-8 were detected in inflammatory sites: periodontitis 457.0 (281.0) ng; gingivitis 413.5 (394.5) ng compared with periodontally healthy sites in diseased subjects 14.6 (14.3) ng and in controls 18.6 (18.5) ng, p=0.003. There was at least 20-fold more MRP-8 in the inflammatory compared with the healthy sites studied.

CONCLUSIONS:

The preliminary data indicate that MRP-8 is present in GCF, with significantly greater amounts present at diseased than healthy sites. A systematic study of the relationship of this protein to periodontal disease could prove useful in further clarifying whether MRP-8 could be a reliable GCF biomarker of gingivitis and periodontitis.

Increased anti-tumour efficacy of doxorubicin when combined with sulindac in a xenograft model of an MRP-1-positive human lung cancer

Background: A number of cellular proteins, including P-glycoprotein (P-gp) and Multiple drug Resistance Protein (MRP-1), act as drug efflux pumps and are important in the resistance of many cancers to chemotherapy. We previously reported that a small number of NSAIDs could inhibit the activity of MRP-1. Materials and Methods: We chose sulindac as a candidate agent for further investigation as it has the most favourable efficacy and toxicity profile of the agents available for a potential specific MRP-1 inhibitor. NCI H460 cells expressed MRP-1 protein (by Western blot) and also the toxicity, of doxorubicin (a substrate of MRP-1) could be potentiated in this line using non-toxic concentrations of the MRP-1 substrate/inhibitor sulindac. These cells were implanted in nude mice and the animals divided into various groups which were administered doxorubicin and/or sulindac. Results: Sulindac was shown to significantly potentiate the tumour growth inhibitor activity of doxorubicin in this MRP-1-overexpressing human tumour xenograft model. Conclusion: Sulindac may be clinically useful as an inhibitor of the MRP-1 cancer resistance mechanism.

Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma.

Background Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease. Methods In this retrospective study the expression of two of these transporter efflux pumps, namely MDR-1 P-gp (ABCB1) and MRP-1 (ABCC1) were studied by immunohistochemistry in archival material from 95 renal cell carcinoma patients. Results In the first study investigating MDR-1 P-gp and MRP-1 protein expression patterns in renal cell carcinoma patients, high levels of expression of both efflux pumps are observed with 100% of tumours studied showing MDR-1 P-gp and MRP-1 positivity. Conclusion Although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type.

Identification of MRP-8 (calgranulin A) as a major responsive protein in chronic periodontitis

The purpose of the study was to analyse how the protein composition of the inflammatory exudate associated with chronic periodontitis differed from the exudate in periodontal health. Gingival crevicular fluid (GCF) was collected from sites with chronic periodontal inflammation and from non-diseased sites in healthy control subjects. Microbore HPLC analysis revealed one major difference in GCF protein profiles between healthy controls and periodontitis patients. The protein enhanced in periodontitis patients was identified as migration inhibitory factor-related protein-8 (MRP-8) by a combination of N-terminal amino acid sequencing, mass spectrometry, and SDS-PAGE. Together, these data demonstrate, for the first time, the presence of monomeric MRP-8 in an inflammatory exudate. Whether monomeric MRP-8 is a unique feature of chronic periodontal inflammation is not yet clear, but the chemotactic properties of this peptide support a functional role for MRP-8 in periodontal inflammation. Copyright (C) 2000 John Wiley & Sons, Ltd.

Construir la escuela desde la diversidad y para la igualdad : conclusiones generales del Congreso Estatal de MRP (Madrid, 26-28 enero 2001).

Se presentan las conclusiones del Congreso Estatal de Movimientos de Renovación Pedagógica. Estas conclusiones se centran en la consecución de la igualdad social y educativa y en la relación entre ambas, consecuencia de la relación existente entre escuela y sociedad. Se resalta la responsabilidad que esta última tiene sobre el funcionamiento del sistema educativo y de ello se deriva la defensa que se hace de la escuela pública. Otro eje central en estas conclusiones es el de la atención a la diversidad, exponiendo medidas sobre cómo realizarla en los diferentes niveles. Otros temas secundarios que también se tratan son la visión androcéntrica en la escuela, la educación intercultural o el fracas o escolar.

¿Qué son los MRP?

Resumen tomado de la revista

MRP' s : la escuela p??blica y las redes para construirla

Resumen tomado de la publicaci??n

El profesorado : su trabajo y la renovación de la escuela : XIII encuentro de MRP : El Paular Madrid. Mayo 1992.

Resumen de las ponencias presentadas en el XIII encuentro de Movimientos de Renovación Pedagógica que en esta ocasión se centró en el perfil y la formación del profesor..

Cr??tica y nostalgia de los Movimientos de Renovaci??n Pedag??gica : el MRP "Tamonante"

Monogr??fico con el t??tulo: La Libreta. ???Extra 25 a??os???

MRP-production planning in agile manufacturing

Over the years many researchers have been investigating the area of MRP production planning and still is an area of high interest today. This paper look at production planning where there is unpredictable demands due to the type of product and market a company produces for. Production planning becomes difficult when demand fluctuates unpredictably, and hence a historical sales forecast is used as the initial data for production planning. The sales from previous years, especially in a seasonal market, don't necessarily correlate well to the current and future sales for the next year. A planner working in such environment would have himself frustrating to create a feasible production plan that not only needs to meet customer's demands but also to built up the 'correct' amount of stock for that peak sell season. To overcome some of these problems, This work describes a production planning methodology that can be implemented robustly and quickly. This paper has studied two multi-item lot-sizing problems. We detailed the development of the planning problem mathematically and highlight some solutions to initial problems investigated.

MRP-production planning in agile manufacturing

The research studied a production planning problem in a manufacturing firm. Some production planning software was developed that enabled the efficient and rapid reproduction of an optimum production forecast. Not only was the production cost reduced but a significant length of planning time cn be saved using the software.