Proteome analysis of Leishmania (Viannia) braziliensis by two-dimensional gel electrophoresis and mass spectrometry

Leishmania (Viannia) braziliensis, a protozoan parasite widespread in the New World, is responsible for the infection of different mammal orders, including humans. This species is considered to be a major etiological agent of American cutaneous leishmaniasis. A proteomic study was carried out to identify proteins expressed by L. (V.) braziliensis. One hundred and one spots representing 75 protein entries were identified by MALDI-TOF-TOF. Isoelectric point values estimated by gel electrophoresis matched closely with predicted values, although some discrepancies existed suggesting that post-translational protein modifications may be common in L. braziliensis. Moreover, 20 hypothetical proteins were experimentally identified. Identified proteins were classified into 15 groups according to biological process. Among the proteins identified, approximately 40% have not been previously reported in a proteomic map of Leishmania. In addition, a number of potential virulence factors and drug targets were identified in this protein map, including some proteins associated with the metastatic phenotype. This study describes the first compilation of a proteomic reference map for L. braziliensis (pI 4-7, M(r) 10-130 kDa) and provides a very useful tool for comparative studies of strains isolated from patients presenting different clinical manifestations of leishmaniasis as well as a potential tool to identify markers for clinical diagnosis, therapeutics, and prognosis.     

From transit hub to major supplier of illicit cigarettes to Argentina and Brazil: the changing role of domestic production and transnational tobacco companies in Paraguay between 1960 and 2003

Background

Paraguay has reportedly been a major transit hub for illicit tobacco products since the 1960s, initially to supply markets in Argentina and Brazil and, more recently, other regional markets and beyond. However, to date there has been no systematic analysis, notably independent of the tobacco industry, of this trade including the roles of domestic production and transnational tobacco companies (TTCs). This article fills that gap by detailing the history of Paraguay’s illicit cigarette trade to Brazil and Argentina of TTC products and Paraguayan production between 1960 and 2003. The effective control of illicit cigarette flows, under Article 15 of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) and the Protocol to Eliminate the Illicit Trade in Tobacco Products, requires fuller understanding of the changing nature of the illicit trade.

Methods

We systematically searched internal industry documents to understand the activities and strategies of leading TTCs in Paraguay and subregion over time. We also mapped illicit trade volume and patterns using US government and UN data on the cigarette trade involving Paraguay. We then estimated Paraguay’s cigarette production from 1989 to 2003 using tobacco leaf flows from the United Nations Commodity Trade Statistics Database (UN Comtrade).

Results

We identify four phases in the illicit tobacco trade involving Paraguay: 1) Paraguay as a transit hub to smuggle BAT and PMI cigarettes from the U.S. into Argentina and Brazil (from the 1960s to the mid-1970s); 2) BAT and PMI competing in north-east Argentina (1989–1994); 3) BAT and PMI competing in southern and southern-east Brazil (mid to late 1990s); and 4) the growth in the illicit trade of Paraguayan manufactured cigarettes (from the mid- 1990s onwards). These phases suggest the illicit trade was seeded by TTCs, and that the system of supply and demand on lower priced brands they developed in the 1990s created a business opportunity for manufacturing in Paraguay. Brazil’s efforts to fight this trade, with a 150% tax on exports to Latin American countries in 1999, further prompted supply of the illicit trade to shift from TTCs to Paraguayan manufacturers.

Conclusion

This paper extends evidence of the longstanding complicity of TTCs in the illicit trade to this region and the consequent growth of Paraguayan production in the 1990s. Our findings confirm the need to better understand the factors influencing how the illicit tobacco trade has changed over time, in specific regional contexts, and amid tobacco industry globalization. In Paraguay, the changing roles of TTC and domestic production have been central to shifting patterns of illicit supply and distribution since the 1960s. Important questions are raised, in turn, about TTCs efforts to participate as legitimate partners in global efforts to combat the problem, including a leading role in data gathering and analysis.

     

Structural imaging of conjunctival filtering blebs in XEN gel implantation and trabeculectomy: a confocal and anterior segment optical coherence tomography study

Graefe's Archive for Clinical and Experimental Ophthalmology - To describe and compare the conjunctival filtering bleb features after XEN gel implantation and trabeculectomy using anterior...     

Smile—It's in your blood!

Emotions and feelings are the bricks of our social life and yet we often forget that they have a significant impact on our physical wellbeing. Indeed, a growing number of studies have shown that both an imbalanced or improved emotional state can significantly influence the way our immune system responds. In this commentary, we have summarized the most recent studies on the effects of different types of emotional states on the immune system and we have also explored the effects of mood modulator approaches on the immune response. We hope this commentary will prompt scientists and clinicians to think about the therapeutic value and potential of emotions and feelings in immune-related diseases. At the same time, we think that this commentary will shed some light on the scientific truth behind the very famous expression “It's in my blood” when we talk about feelings and personality.     

The additive prognostic value of restrictive pattern and dipyridamole-induced contractile reserve in idiopathic dilated cardiomyopathy

BACKGROUND: Diastolic dysfunction and lack of contractile reserve are unfavorable prognostic predictors in patients with dilated cardiomyopathy (DCM). AIMS: This study aims to assess whether diastolic dysfunction and lack of dipyridamole-induced contractile reserve were additive predictors of poor outcome in patients with DCM. METHODS: A total of 116 patients with DCM and ejection fraction (EF<35%) were studied by dipyridamole echo (0.84 mg/kg over 10 min). At rest, a restrictive filling pattern was defined as: E/A ratio >2 and an E-wave deceleration time of <140 ms on transmitral flow velocity profile. RESULTS: Rest wall motion score index (WMSI) was 2.2+/-0.3 and decreased to 1.9+/-0.41 after dipyridamole (p<0.001). During follow-up (median 26.5 months), 22 cardiac deaths occurred. At multivariate analysis, dipyridamole-induced contractile reserve yielded significant incremental prognostic value (RR=0.275, p<0.006) over NYHA class (RR=1.971, p<0.03), angiotensin-converting enzyme inhibitor therapy (RR=0.173, p<0.001), and left ventricular end-diastolic diameter (RR=1.131, p<0.001). The worst prognostic combination was the presence of restrictive pattern at rest and the absence of contractile reserve (deltaWMSI<0.15). CONCLUSION: In patients with DCM, the ominous combination of restrictive transmitral flow pattern and lack of contractile reserve during dipyridamole stress predicts an unfavourable outcome.     

Current management of late onset neonatal bacterial sepsis in five European countries

Late onset neonatal sepsis (LOS) has a high mortality and the optimal management is poorly defined. We aimed to evaluate new expert panel-derived criteria to define LOS and characterize the current management and antibiotic susceptibility of LOS-causing organisms in Europe. A prospective observational study enrolled infants aged 4 to 90 days in five European countries. Clinical and laboratory findings as well as empiric treatment were recorded and patients were followed until the end of antibiotic therapy. Failure was defined as a change of primary antibiotic, no resolution of clinical signs, appearance of new signs/pathogens or death. Antibiotic therapy was considered appropriate if the organism was susceptible to at least one empiric antibiotic. 113 infants (median age 14 days, 62 % ≤1500 g) were recruited; 61 % were culture proven cases (28 CoNS, 24 Enterobacteriaceae, 11 other Gram-positives and 6 Gram-negative non-fermentative organisms). The predictive value of the expert-panel criteria to identify patients with a culture proven LOS was 61 % (95 % CI 52 % to 70 %). Around one third of Enterobacteriaceae were resistant to ampicillin + or cefotaxime + gentamicin but only 10 % to meropenem. Empiric treatment contained a total of 43 different antibiotic regimens. All-cause mortality was 8 % with an additional 45 % classified as failure of empiric therapy, mainly due to change of primary antibiotics (42/60). Conclusions: The expert panel—derived diagnostic criteria performed well identifying a high rate of culture proven sepsis. Current management of LOS in Europe is extremely variable suggesting an urgent need of evidence-based guidelines.