Railway Regulation In Portugal: Lessons From Experience

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Chloroquine diphosphate: a risk factor for herpes zoster in patients with dermatomyositis/polymyositis

OBJECTIVES: Herpes zoster has been widely described in the context of different systemic autoimmune diseases but not dermatomyositis/polymyositis. Therefore, we analyzed the prevalence, risk factors and herpes zoster outcomes in this population. METHOD: A retrospective cohort study of herpes zoster infections in dermatomyositis/polymyositis patients was performed. The patients were followed at a tertiary center from 1991 to 2012. For the control group, each patient with herpes zoster was paired with two patients without herpes zoster. Patients were matched by gender and the type of myositis, age at myositis onset and disease duration. RESULTS: Of 230 patients, 24 (10.4%) had a histories of herpes zoster (19 with dermatomyositis and five with polymyositis, two-thirds female). The mean age of the patients with herpes zoster was 44.6±16.8 years. No difference between the groups was found regarding cumulative clinical manifestations. Disease activity, autoantibody, muscle and leukogram parameters were also comparable between the groups. No differences in immunosuppressive (alone or in association with other immunosuppressive therapies) or glucocorticoid (current use, medium dose and cumulative dose in the last two months) therapies were found between patients with and without herpes zoster. However, a higher proportion of patients in the herpes zoster group received chloroquine diphosphate compared to the control group. All of the patients received acyclovir; 58.3% of patients had postherpetic neuralgia and no cases of recurrence were reported. Furthermore, individuals who were taking high prednisone doses at the time of the herpes zoster diagnosis had reduced levels of postherpetic neuralgia. CONCLUSIONS: These data suggest that chloroquine diphosphate could predispose patients with dermatomyositis/polymyositis to developing herpes zoster, particularly women and dermatomyositis patients

Trypsin-Like Serine Proteases in Lutzomyia longipalpis – Expression, Activity and Possible Modulation by Leishmania infantum chagasi

Background: Midgut enzymatic activity is one of the obstacles that Leishmania must surpass to succeed in establishing infection. Trypsins are abundant digestive enzymes in most insects. We have previously described two trypsin cDNAs of L. longipalpis: one (Lltryp1) with a bloodmeal induced transcription pattern, the other (Lltryp2) with a constitutive transcription pattern. We have now characterized the expression and activity of trypsin-like proteases of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in Brazil. Methodology and Principal Findings: In order to study trypsin expression profiles we produced antibodies against peptides specific for Lltryp1 and Lltryp2. The anti-Lltryp1-peptide antibody revealed a band of 28 kDa between 6 and 48 hours. The anti-Lltryp2 peptide antibody did not evidence any band. When proteinaceous substrates (gelatin, hemoglobin, casein or albumin) were co-polymerized in polyacrylamide gels, insect midguts obtained at 12 hours after feeding showed a unique proteolytic pattern for each substrate. All activity bands were strongly inhibited by TLCK, benzamidine and 4-amino-benzamidine, indicating that they are trypsin-like proteases. The trypsin-like activity was also measured in vitro at different time points after ingestion of blood or blood containing Leishmania infantum chagasi, using the chromogenic substrate BArNA. L. longipalpis females fed on blood infected with L. i. chagasi had lower levels of trypsin activity after 12 and 48 hours than non-infected insects, suggesting that the parasite may have a role in this modulation. Conclusions and Significance: Trypsins are important and abundant digestive enzymes in L. longipalpis. Protein production and enzymatic activity followed previously identified gene expression of a blood modulated trypsin gene. A decrease of enzymatic activity upon the parasite infection, previously detected mostly in Old World vectors, was detected for the first time in the natural vector-parasite pair L. longipalpis-L. i. chagasi