Vaccines for papillomavirus infection

Vaccines to prevent PV infection, utilising PV L1 virus like particles (VLPs) to induce neutralising antibody, are in clinical trial and show all the characteristics likely to be associated with success. Results warrant global planning for the deployment of VLP vaccines within a decade, as part of a program to prevent cervical cancer. Vaccines designed to treat existing PV infection by inducing therapeutic cellular immunity targeted to PV proteins are at a much earlier stage of development. The wide choice of potential and proposed antigens, routes and mechanisms of delivery, and possible treatment regimens suggest that, to move the field forward, surrogate markers allowing comparison of the relative efficacy of different vaccine approaches are required. These should be based on reduction in load of virus infection, and need to be validated in animal models or in man. (C) 2002 Published by Elsevier Science B.V.

Association between HIV-1 infection, the etiology of genital ulcer disease, and response to syndromic management

Background: Reports on the effect of HIV-1 infection on healing rates of ulcers are conflicting. Goal: The goal was to determine the etiology and response to treatment of genital ulcer disease (GUD) in relation to HIV-1 infection. Study Design: This was a cohort study of patients with GUD treated with local syndromic management protocols. Results: Among the 587 recruited, the prevalences of infections due to HSV, Treponema pallidum, Chlamydia trachomatis (lymphogranuloma venereum [LGV]), Haemophilus ducreyi, Calymmatobacterium granulomatis, and HIV-1 were 48%, 14%, 11%, 10%, 1%, and 75%, respectively. The prevalence of T pallidum was higher among men (P = 0.03), and an association was seen among HIV-1-seronegatives on univariate and multivariate analyses (P < 0.001; P = 0.01). The prevalence of C trachomatis (LGV) was higher among females (P = 0.004), and an association was seen among HIV-1-seropositives on univariate analysis (P = 0.04). At follow-up, 40/407 (10%) showed a decreased healing tendency, not associated with ulcer etiology or HIV-1 seropositivity. Conclusion: Response to syndromic management of GUD was acceptable and not associated with HIV-1 coinfection.

The prevalence, intensities and risk factors associated with geohelminth infection in tea-growing communities of Assam, India

OBJECTIVE To determine the prevalence, intensity and associated risk factors for infection with Ascaris, hookworms and Trichuris in three tea-growing communities in Assam, India. METHODS Single faecal samples were collected from 328 individuals and subjected to centrifugal floatation and the Kato Katz quantitation technique and prevalence and intensities of infection with each parasite calculated. Associations between parasite prevalence, intensity and host and environmental factors were then made using both univariate and multivariate analysis. RESULTS The overall prevalence of Ascaris was 38% [95% confidence interval (CI): 33, 43], and the individual prevalence of hookworm and Trichuris was 43% (95% CI: 38, 49). The strongest predictors for the intensity of one or more geohelminths using multiple regression (P less than or equal to 0.10) were socioeconomic status, age, household crowding, level of education, religion, use of footwear when outdoors, defecation practices, pig ownership and water source. CONCLUSION A universal blanket treatment with broad-spectrum anthelmintics together with promotion of scholastic and health education and improvements in sanitation is recommended for helminth control in the communities under study.

Protection against Paracoccidioides brasiliensis infection conferred by the prophylactic administration of native and recombinant ArtinM

We determined the prophylactic effect of both the d-mannose-binding lectin ArtinM extracted from the seeds of Artocarpus integrifolia (jackfruit) and its recombinant counterpart during the course of experimental paracoccidioidomycosis induced in BALB/c mice. Four experimental protocols of prophylaxis were employed to evaluate the most protective regimen of ArtinM administration. It was demonstrated that the best effect was obtained by administration of two ArtinM doses on days 10 and 3 before the challenge with Paracoccidioides brasiliensis. By following this protocol, the lungs of mice that received native or recombinant ArtinM exhibited reduced fungal burden and granuloma incidence. In addition, the protocol augmented contents of IL-12, IFN-gamma, TNF-alpha and NO. On the other hand, the control group consisting of untreated infected mice had higher pulmonary levels of IL-4 and IL-10. In conclusion, prophylaxis with ArtinM significantly reproduces the effect of its therapeutic administration, i.e, it confers resistance to P. brasiliensis infection in mouse models by promoting IL-12 production and favours Th1-immunity.

Incorporation of antigenic GPI-proteins from Leishmania amazonensis to membrane mimetic systems: Influence of DPPC/cholesterol ratio

The reconstitution of membrane proteins into liposomes is a useful tool to prepare antigenic components that induce immunity. We have investigated the influence of the dipalmitoylphosphatidylcholine (DPPC)/cholesterol molar ratio on the incorporation of a GPI-protein from Leishmania amazonensis on liposomes and Langmuir monolayers. The latter system is a well behaved and practical model, for understanding the effect of variables such as surface composition and lipid packing on protein incorporation. We have found that the DPPC/cholesterol molar ratio significantly alters the incorporation of the GPI-protein. In the absence of cholesterol, reconstitution is more difficult and proteoliposomes cannot be prepared, which we correlated with disruption of the DPPC layer. Our results provide important information that Could be employed in the development of a vaccine system for this disease or be used to produce other GPI-systems for biotechnological application. (c) 2009 Elsevier Inc. All rights reserved.

Molecular adaptability of nucleoside diphosphate kinase b from trypanosomatid parasites: stability, oligomerization and structural determinants of nucleotide binding

Nucleoside diphosphate kinases play a crucial role in the purine-salvage pathway of trypanosomatid protozoa and have been found in the secretome of Leishmania sp., suggesting a function related to host-cell integrity for the benefit of the parasite. Due to their importance for housekeeping functions in the parasite and by prolonging the life of host cells in infection, they become an attractive target for drug discovery and design. In this work, we describe the first structural characterization of nucleoside diphosphate kinases b from trypanosomatid parasites (tNDKbs) providing insights into their oligomerization, stability and structural determinants for nucleotide binding. Crystallographic studies of LmNDKb when complexed with phosphate, AMP and ADP showed that the crucial hydrogen-bonding residues involved in the nucleotide interaction are fully conserved in tNDKbs. Depending on the nature of the ligand, the nucleotide-binding pocket undergoes conformational changes, which leads to different cavity volumes. SAXS experiments showed that tNDKbs, like other eukaryotic NDKs, form a hexamer in solution and their oligomeric state does not rely on the presence of nucleotides or mimetics. Fluorescence-based thermal-shift assays demonstrated slightly higher stability of tNDKbs compared to human NDKb (HsNDKb), which is in agreement with the fact that tNDKbs are secreted and subjected to variations of temperature in the host cells during infection and disease development. Moreover, tNDKbs were stabilized upon nucleotide binding, whereas HsNDKb was not influenced. Contrasts on the surface electrostatic potential around the nucleotide-binding pocket might be a determinant for nucleotide affinity and protein stability differentiation. All these together demonstrated the molecular adaptation of parasite NDKbs in order to exert their biological functions intra-parasite and when secreted by regulating ATP levels of host cells.

Dermaseptin 01 as antimicrobial peptide with rich biotechnological potential: study of peptide interaction with membranes containing Leishmania amazonensis lipid-rich extract and membrane models

This article addresses the interactions of the synthetic antimicrobial peptide dermaseptin 01 (GLWSTIKQKGKEAAIAAA-KAAGQAALGAL-NH(2), DS 01) with phospholipid (PL) monolayers comprising (i) a lipid-rich extract of Leishmania amazonensis (LRE-La), (ii) zwitterionic PL (dipalmitoylphosphatidylcholine, DPPC), and (iii) negatively charged PL (dipalmitoylphosphatidylglycerol, DPPG). The degree of interaction of DS 01 with the different biomembrane models was quantified from equilibrium and dynamic liquid-air interface parameters. At low peptide concentrations, interactions between DS 01 and zwitterionic PL, as well as with the LRE-La monolayers were very weak, whereas with negatively charged PLs the interactions were stronger. For peptide concentrations above 1 mu g/ml, a considerable expansion of negatively charged monolayers occurred. In the case of DPPC, it was possible to return to the original lipid area in the condensed phase, suggesting that the peptide was expelled from the monolayer. However, in the case of DPPG, the average area per lipid molecule in the presence of DS 01 was higher than pure PLs even at high surface pressures, suggesting that at least part of DS 01 remained incorporated in the monolayer. For the LRE-La monolayers, DS 01 also remained in the monolayer. This is the first report on the antiparasitic activity of AMPs using Langmuir monolayers of a natural lipid extract from L. amazonensis. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd.

Lipid microspheres loaded with antigenic membrane proteins of the Leishmania amazonensis as a potential biotechnology application

Lipid microspheres (LM) are excellent drug delivery or vaccines adjuvant systems and are relatively stable. The aim of this work is to develop and characterize a system that is able to encapsulate and present antigenic membrane proteins from Leishmania amazonensis. Membrane proteins are important for vaccine`s formulation because these proteins come in contact with the host cell first, triggering the cell mediated immune response. This is a useful tool to avoid or inactivate the parasite invasion. The LM are constituted by soybean oil (SO), dipalmitoylphosphatidilcholine (DPPC), cholesterol and solubilized protein extract (SPE). The particles formed presented an average diameter of 200 run, low polydispersion and good stability for a period of 30 days, according to dynamic light scattering assays. Isopycnic density gradient centrifugation of LM-protein showed that proteins and lipids floated in the sucrose gradient (5-50%w/v) suggesting that the LM-protein preparation was homogeneous and that the proteins are interacting with the system. The results show that 85% of SPE proteins were encapsulated in the LM. Studies of cellular viability of murine peritoneal macrophages show that our system does not present cytotoxic effect for the macrophages and still stimulates their NO production (which makes its application as a vaccine adjuvant possible). LM-protein loaded with antigenic membrane proteins from L. amazonensis seems to be a promising vaccine system for immunization against leishmaniasis. (C) 2009 Elsevier Inc. All rights reserved.

Endoscopic removal of eroded adjustable gastric band: lessons learned after 5 years and 78 cases

Background: One of the complications of laparoscopic adjustable gastric banding is intragastric erosion, leading to a revisional procedure to remove the band. Our aim was to present the procedure and results of endoscopic band removal in a 5-year multicenter experience from the Gastro Obeso Center and Universidade de Sao Paulo, Sao Paulo, and Universidade Federal de Pernambuco, Recite, Brazil. Methods: From 2003 to 2008, 82 patients were diagnosed with band erosion. The clinical data concerning the endoscopic procedure were prospectively recorded and retrospectively reviewed. Results: The average preoperative body mass index was 43.2 kg/m(2) (range 34-50). At the diagnosis of intragastric erosion, the body mass index was 24-41 kg/m(2) (average 31.8). The erosion occurred an average of 16.3 months (range 6-36) postoperatively. The symptoms included pain in 25 (31%), port infection in 21 patients (27%), and weight regain in 20 (25%), and 12 patients (15%) were asymptomatic. Endoscopic removal was possible for 78 patients (95%). In 85% of patients, the band was removed in the first session, with an average duration of 55 minutes (range 25-150). Five cases of pneumoperitoneum occurred after the procedure. Of these, 3 were treated conservatively, 1 was treated by laparoscopy, and I was treated by abdominal puncture using the Veress needle. Conclusion: Endoscopic removal of eroded laparoscopic adjustable gastric banding is safe and effective. It can be used as a first choice procedure in clinical practice. (Surg Obes Relat Dis 2010; 6:423-428.) (C) 2010 American Society for Metabolic and Bariatric Surgery. All rights reserved.

In situ immune responses to interstitial pneumonitis in human visceral leishmaniasis

Lung disease during active human visceral leishmaniasis is frequently reported. As such, studies have associated pulmonary symptoms to interstitial pneumonitis with a mononuclear infiltrate. However, the immune response in this condition has never been described before. The aim of this study was to determine the immunophenotypic pattern and cytokine profile of lung involvement (IPL) in human visceral leishmaniasis. Quantitative methods of analysis were performed using immunohistochemistry, and were compared with a control group of normal lung. Interstitial macrophages and cd8 cells were increased in IPL, and IL-4 as well as TNF-alpha displayed increased expression when compared to the control group. This inflammatory process with a Th2 pattern, as suggested by increased IL-4 and low IFN-gamma expression, is consistent with the immune response in other organs of visceral leishmaniasis. The microenvironment of the immune response in this condition is associated with lung disease in patients with interstitial pneumonitis related to visceral leishmaniasis, increasing the chance of bacterial infection.