Efficacy and safety of leflunomide as an adjuvant drug in refractory dermatomyositis with primarily cutaneous activity.

OBJECTIVES: To evaluate leflunomide as an adjuvant drug in refractory dermatomyositis (DM) with primarily cutaneous activity. METHODS: A retrospective, single-centre, cohort study including 18 adult patients with DM (classical or clinically amyopathic DM) and cutaneous activity from 2001 to 2016 was conducted. Patients were dependent on glucocorticoid and refractory to at least two full-dose immunosuppressants/immunomodulators or presented previous adverse events with immunobiological drugs. One immunosuppressant was maintained and leflunomide added to the treatment. Patients were followed for six consecutive months. RESULTS: Leflunomide proved effective and safe in 12 (66.6%) out of the 18 patients. There was total control of cutaneous activity and prednisone was tapered from 17.5 to 6.0 mg/day (p<0.001). In addition, two of these patients that also had muscle involvement improved muscle strength after leflunomide treatment. Side effects or inefficacy were observed in six patients. There were no cases of serious infection or death. CONCLUSIONS: Leflunomide therapy appears to be effective and safe as an adjuvant drug in refractory DM with primarily cutaneous activity. Further studies are needed to confirm this data.

Undergraduate research in medical education: a descriptive study of students' views.

BACKGROUND: Medical students engage in curricular and extracurricular activities, including undergraduate research (UR). The advantages, difficulties and motivations for medical students pursuing research activities during their studies have rarely been addressed. In Brazil, some medical schools have included undergraduate research into their curriculum. The present study aimed to understand the reality of scientific practice among medical students at a well-established Brazilian medical school, analyzing this context from the students' viewpoint. METHODS: A cross-sectional survey based on a questionnaire applied to students from years one to six enrolled in an established Brazilian medical school that currently has no curricular UR program. RESULTS: The questionnaire was answered by 415 students, 47.2% of whom were involved in research activities, with greater participation in UR in the second half of the course. Independent of student involvement in research activities, time constraints were cited as the main obstacle to participation. Among students not involved in UR, 91.1% said they favored its inclusion in the curriculum, since this would facilitate the development of such activity. This approach could signify an approximation between the axes of teaching and research. Among students who had completed at least one UR project, 87.7% said they would recommend the activity to students entering the course. CONCLUSION: Even without an undergraduate research program, students of this medical school report strong involvement in research activities, but discussion of the difficulties inherent in its practice is important to future developments.

Antiplasmodial, beta-haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolines.

A novel series of 4-aminoquinoline-containing 2-imidazolines were synthesized via a one-pot 3-component condensation reaction of amine, aldehyde and isocyanoacetate. The products were obtained in high yield as well as purity and were evaluated directly against two strains of Plasmodium falciparum and Trypanosoma brucei. Compound was the most active across all parasites with ED(50) = 3.3 nM against a chloroquine (CQ)-sensitive 3D7 strain, ED(50) = 33 nM against a CQ-resistant K1 strain and ED(50) = 70 nM against T. brucei. Several compounds were able to inhibit formation of beta-haematin in vitro, suggesting haemozoin formation in the malaria parasite as a possible target. On the other hand, evaluation against a human KB cell line revealed that the compounds were generally non-cytotoxic to the host cells.

Application of multicomponent reactions to antimalarial drug discovery. Part 2: New antiplasmodial and antitrypanosomal 4-aminoquinoline gamma- and delta-lactams via a 'catch and release' protocol.

A parallel synthesis of a new series of 4-aminoquinoline gamma- and delta-lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.