The P2X7 receptor (P2X7R) is a nonselective cation channel that is activated by extracellular ATP and triggers the secretion of several proinflammatory substances, such as IL-1β, IL-18, TNF-α, and nitric oxide. Recently, several preclinical studies have demonstrated that this receptor participates in inflammation and pain mechanisms. Taken together, these results indicate that P2X7R is a promising pharmacological target, and compounds that modulate the function of this receptor show potential as new anti-inflammatory medicines. In this review, we discuss aspects of P2X7R pharmacology and the participation of this protein in inflammation and pain and provide an overview of some promising compounds that have been tested as antagonists of P2X7R, with clinical applicability.
Medical Education 2011:
45
: 748–755
Context Research activity is not a mandatory component of medical education in many developing countries, including Brazil, although such experiences can have a positive impact on the quality of medical education. The interest and involvement of medical students in research and the barriers they face in accessing research training in developing countries have not been adequately addressed. Objectives We sought to assess the availability of scientific training programmes in Brazilian medical schools, the degree of involvement of medical students in these programmes, the main barriers to student involvement in research and possible reasons for the lack of scientific training programmes. Methods This study examined 13 medical programmes conducted in six Brazilian states. A total of 1004 medical students were interviewed. We evaluated the availability of scientific training in the institutions attended by these students, the participation of the students in such activities and students’ reasons for not joining such programmes based on student answers to our questionnaire. Results Although only 7% of the medical students expressed no interest in research, only 60% of them were involved in research training. Students regarded a lack of institutional incentive as the most significant barrier to their participation in research activities. Other significant barriers included defective infrastructure and insufficient time available for professors to mentor undergraduate students. According to the feedback from the students, eight of the 13 schools investigated featured structured programmes for scientific training. However, a mean of only 47% of students participated in scientific training programmes on their campuses and 13% of students were compelled to pursue such activities off‐campus. Conclusions Although scientific training during medical education in Brazil is still less frequent than expected, most of the students were interested in research activities. The barriers to undergraduate scientific training described in this paper may help the Brazilian government improve research training in medical schools. These issues might also be explored in other developing countries.
Photodynamic therapy (PDT) combines light, a photosensitizing chemical substance, and molecular oxygen to elicit cell death and is employed in the treatment of a variety of diseases, including cancer. The development of PDT treatment strategies requires in vitro assays to develop new photosensitizers. One such assay is the MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide developed in 1983 and widely used in PDT studies. Despite the exponential growth in the number of publications, a uniform MTT protocol for use in the PDT area is lacking. Herein, we list and standardize the conditions to evaluate the photosensitizer methylene blue (MB) in glioblastoma and neuroblastoma cell lines. In addition, we review technical pitfalls and identify several variables that must be taken into consideration in order to provide accurate results with MTT. We conclude that for each cell line we must have a dose-response curve using the MTT assay and good controls for the standardization. Additionally, the optimal values of the time and cell density must be in the linear range of the curve to avoid errors. We describe all relevant points and outline the best normalization techniques to observe the differences between treatments.