Pyromellitic dianhydride crosslinked cyclodextrin nanosponges for curcumin controlled release; formulation, physicochemical characterization and cytotoxicity investigations

Aim: In this study, a nanosponge structure was synthesised with capability of encapsulating curcumin as a model polyphenolic compound and one of the herbal remedies that have widely been considered due to its ability to treat cancer. Methods: FTIR, DSC and XRD techniques were performed to confirm the formation of the inclusion complex of the nanosponge-drug. Results: DSC and XRD patterns showed an increasing stability and a decreasing crystallinity of curcumin after formation of inclusion complex. Encapsulation efficiency was 98% (w/w) and a significant increase was observed in loading capacity (184% w/w). The results of cytotoxicity assessments demonstrated no cell toxicity on the healthy cell line, while being toxic against cancer cells. Haemolysis test was performed to evaluate the blood-compatibility characteristic of nanosponge and complex and the results showed 0.54% haemolysis in the lowest complex concentration (50μgml−1) and 5.09% at the highest concentration (200μgml−1). Conclusions: Thus, the introduced system could be widely considered in cancer treatment as a drug delivery system

C-Terminal Domain Deletion Enhances the Protective Activity of cpa/cpb Loaded Solid Lipid Nanoparticles against Leishmania major in BALB/c Mice

Cutaneous leishmaniasis (CL) is the most common form of leishmaniasis with an annual incidence of approximately 2 million cases and is endemic in 88 countries, including Iran. CL's continued spread, along with rather ineffectual treatments and drug-resistant variants emergence has increased the need for advanced preventive strategies. We studied Type II cysteine proteinase (CPA) and Type I (CPB) with its C-terminal extension (CTE) as cocktail DNA vaccine against murine and canine leishmaniasis. However, adjuvants' success in enhancing immune responses to selected antigens led us to refocus our vaccine development programs. Herein, we discuss cationic solid lipid nanoparticles' (cSLN) ability to improve vaccine-induced protective efficacy against CL and subsequent lesion size and parasite load reduction in BALB/c mice. For this work, we evaluated five different conventional as well as novel parasite detection techniques, i.e., footpad imaging, footpad flowcytometry and lymph node flowcytometry for disease progression assessments. Vaccination with cSLN-cpa/cpb-CTE formulation showed highest parasite inhibition at 3-month post vaccination. Immunized mice showed reduced IL-5 level and significant IFN-ã increase, compared to control groups. We think our study represents a potential future and a major step forward in vaccine development against leishmaniasis

Pulmonary arterial pressure detects functional mitral stenosis after annuloplasty for primary mitral regurgitation: An exercise stress echocardiographic study

Introduction: The restrictive mitral valve annuloplasty (RMA) is the treatment of choice for degenerative mitral regurgitation (MR), but postoperative functional mitral stenosis remains a matter of debate. In this study, we sought to determine the impact of mitral stenosis on the functional capacity of patients. Methods: In a cross-sectional study, 32 patients with degenerative MR who underwent RMA using a complete ring were evaluated. All participants performed treadmill exercise test and underwent echocardiographic examinations before and after exercise. Results: The patients� mean age was 50.1 ± 12.5 years. After a mean follow-up of 14.1 ± 5.9 months (6�32 months), the number of patients with a mitral valve peak gradient >7.5 mm Hg, a mitral valve mean gradient >3 mm Hg, and a pulmonary arterial pressure (PAP) �25 mm Hg at rest were 50, 40.6, and 62.5, respectively. 13 patients (40.6) had incomplete treadmill exercise test. All hemodynamic parameters were higher at peak exercise compared with at rest levels (all P <.05). The PAP at rest and at peak exercise as well as peak transmitral gradient at peak exercise were higher in patients with incomplete exercise compared with complete exercise test (all P <.05). The PAP at rest (a sensitivity and a specificity of 84.6 and 52.6, respectively; area under the curve AUC =.755) and at peak exercise (a sensitivity and a specificity of 100% and 47.4%, respectively; AUC =.755) discriminated incomplete exercise test. Conclusion: The RMA for degenerative MR was associated with a functional stenosis and the PAP at rest and at peak exercise discriminated low exercise capacity. © 2017, Wiley Periodicals, Inc

Pulmonary arterial pressure detects functional mitral stenosis after annuloplasty for primary mitral regurgitation: An exercise stress echocardiographic study

Introduction: The restrictive mitral valve annuloplasty (RMA) is the treatment of choice for degenerative mitral regurgitation (MR), but postoperative functional mitral stenosis remains a matter of debate. In this study, we sought to determine the impact of mitral stenosis on the functional capacity of patients. Methods: In a cross-sectional study, 32 patients with degenerative MR who underwent RMA using a complete ring were evaluated. All participants performed treadmill exercise test and underwent echocardiographic examinations before and after exercise. Results: The patients� mean age was 50.1 ± 12.5 years. After a mean follow-up of 14.1 ± 5.9 months (6�32 months), the number of patients with a mitral valve peak gradient >7.5 mm Hg, a mitral valve mean gradient >3 mm Hg, and a pulmonary arterial pressure (PAP) �25 mm Hg at rest were 50, 40.6, and 62.5, respectively. 13 patients (40.6) had incomplete treadmill exercise test. All hemodynamic parameters were higher at peak exercise compared with at rest levels (all P <.05). The PAP at rest and at peak exercise as well as peak transmitral gradient at peak exercise were higher in patients with incomplete exercise compared with complete exercise test (all P <.05). The PAP at rest (a sensitivity and a specificity of 84.6 and 52.6, respectively; area under the curve AUC =.755) and at peak exercise (a sensitivity and a specificity of 100% and 47.4%, respectively; AUC =.755) discriminated incomplete exercise test. Conclusion: The RMA for degenerative MR was associated with a functional stenosis and the PAP at rest and at peak exercise discriminated low exercise capacity. © 2017, Wiley Periodicals, Inc

Combination of (M)DSC and surface analysis to study the phase behaviour and drug distribution of ternary solid dispersions

Purpose: Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix. Methods: MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed. Results: The distribution of the API in the ternary solid dispersions depended on formulation parameters. The extent of API surface coverage and therefore the distribution of the API over both polymeric phases differed significantly for the three formulations. Conclusions: Combining (M)DSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions

DNA plasmid coding for Phlebotomus sergenti salivary protein PsSP9, a member of the SP15 family of proteins, protects against Leishmania tropica

Background: The vector-borne disease leishmaniasis is transmitted to humans by infected female sand flies, which transmits Leishmania parasites together with saliva during blood feeding. In Iran, cutaneous leishmaniasis (CL) is caused by Leishmania (L.) major and L. tropica, and their main vectors are Phlebotomus (Ph.) papatasi and Ph. sergenti, respectively. Previous studies have demonstrated that mice immunized with the salivary gland homogenate (SGH) of Ph. papatasi or subjected to bites from uninfected sand flies are protected against L. major infection. Methods and results: In this work we tested the immune response in BALB/c mice to 14 different plasmids coding for the most abundant salivary proteins of Ph. sergenti. The plasmid coding for the salivary protein PsSP9 induced a DTH response in the presence of a significant increase of IFN-γ expression in draining lymph nodes (dLN) as compared to control plasmid and no detectable PsSP9 antibody response. Animals immunized with whole Ph. sergenti SGH developed only a saliva-specific antibody response and no DTH response. Mice immunized with whole Ph. sergenti saliva and challenged intradermally with L. tropica plus Ph. sergenti SGH in their ears, exhibited no protective effect. In contrast, PsSP9-immunized mice showed protection against L. tropica infection resulting in a reduction in nodule size, disease burden and parasite burden compared to controls. Two months post infection, protection was associated with a significant increase in the ratio of IFN-γ to IL-5 expression in the dLN compared to controls. Conclusion: This study demonstrates that while immunity to the whole Ph. sergenti saliva does not induce a protective response against cutaneous leishmaniasis in BALB/c mice, PsSP9, a member of the PpSP15 family of Ph. sergenti salivary proteins, provides protection against L. tropica infection. These results suggest that this family of proteins in Ph. sergenti, Ph. duboscqi and Ph. papatasi may have similar immunogenic and protective properties against different Leishmania species. Indeed, this anti-saliva immunity may act as an adjuvant to accelerate the cell-mediated immune response to co-administered Leishmania antigens, or even cause the activation of infected macrophages to remove parasites more efficiently. These findings highlight the idea of applying arthropod saliva components in vaccination approaches for diseases caused by vector-borne pathogens. © 2019, Public Library of Science. All rights reserved

Removal of cationic pollutants from water by xanthated corn cob: optimization, kinetics, thermodynamics, and prediction of purification process

The removal of Cr(III) ions and methylene blue (MB) from aqueous solutions by xanthated corn cob (xCC) in batch conditions was investigated. The sorption capacity of xCC strongly depended of the pH, and increase when the pH rises. The kinetics was well fitted by pseudo-second order and Chrastil’s model. Sorption of Cr(III) ions and MB on xCC was rapid during the first 20 min of contact time and, thereafter, the biosorption rate decrease gradually until reaching equilibrium. The maximum sorption capacity of 17.13 and 83.89 mg g-1 for Cr(III) ions and MB, respectively was obtained at 40 °C, pH 5 and sorbent dose 4 g dm-3 for removal of Cr(III) ions and 1 g dm-3 for removal of MB. The prediction of purification process was successfully carried out and the verification of theoretically calculated amounts of sorbent was confirmed by using packed-bed column laboratory system with recirculation of the aqueous phase. The wastewater from chrome plating industry was successfully purified, i.e. after 40 min concentration of Cr(III) ions was decreased lower than 0.1 mg dm-3. Also, removal of MB from the river water was successfully carried out and after 40 min removal efficiency was about 94 %

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Cationic Liposomes Formulated with Synthetic Mycobacterial Cordfactor (CAF01): A Versatile Adjuvant for Vaccines with Different Immunological Requirements

It is now emerging that for vaccines against a range of diseases including influenza, malaria and HIV, the induction of a humoral response is insufficient and a substantial complementary cell-mediated immune response is necessary for adequate protection. Furthermore, for some diseases such as tuberculosis, a cellular response seems to be the sole effector mechanism required for protection. The development of new adjuvants capable of inducing highly complex immune responses with strong antigen-specific T-cell responses in addition to antibodies is therefore urgently needed. (cell-mediated/humoral) and malaria (humoral) immunization with CAF01-based vaccines elicited significant protective immunity against challenge.CAF01 is potentially a suitable adjuvant for a wide range of diseases including targets requiring both CMI and humoral immune responses for protection

Recent updates and perspectives on approaches for the development of vaccines against visceral leishmaniasis

All rights reserved. Visceral leishmaniasis (VL) is one of the most important tropical diseases worldwide. Although chemotherapy has been widely used to treat this disease, problems related to the development of parasite resistance and side effects associated with the compounds used have been noted. Hence, alternative approaches for VL control are desirable. Some methods, such as vector control and culling of infected dogs, are insufficiently effective, with the latter not ethically recommended. The development of vaccines to prevent VL is a feasible and desirable measure for disease control, for example, some vaccines designed to protect dogs against VL have recently been brought to market. These vaccines are based on the combination of parasite fractions or recombinant proteins with adjuvants that are able to induce cellular immune responses, however, their partial efficacy and the absence of a vaccine to protect against human leishmaniasis underline the need for characterization of new vaccine candidates. This review presents recent advances in control measures for VL based on vaccine development, describing extensively studied antigens, as well as new antigenic proteins recently identified using immuno-proteomic techniquesThis work was supported by grants from Instituto Nacional de Ciência e Tecnologia em Nano-Biofarmacêutica, Rede Nanobiotec/Brasil-Universidade Federal de Uberlândia/CAPES, PRONEX-FAPEMIG (APQ-01019-09), FAPEMIG (CBB-APQ-00819-12 and CBB-APQ-01778-2014), and CNPq (APQ-482976/2012-8, APQ-488237/2013-0, and APQ-467640/2014-9). EAFC and LRG are recipients of the grant from CNPq. MACF is the recipient of grants from FAPEMIG/CAPE