What Does It Take to Synergistically Combine Sub-Potent Natural Products into Drug-Level Potent Combinations?

10.1371/journal.pone.0049969PLoS ONE711

Coadministration of the Three Antigenic Leishmania infantum Poly (A) Binding Proteins as a DNA Vaccine Induces Protection against Leishmania major Infection in BALB/c Mice

Highly conserved intracellular proteins from Leishmania have been described as antigens in natural and experimental infected mammals. The present study aimed to evaluate the antigenicity and prophylactic properties of the Leishmania infantum Poly (A) binding proteins (LiPABPs). Three different members of the LiPABP family have been described. Recombinant tools based on these proteins were constructed: recombinant proteins and DNA vaccines. The three recombinant proteins were employed for coating ELISA plates. Sera from human and canine patients of visceral leishmaniasis and human patients of mucosal leishmaniasis recognized the three LiPABPs. In addition, the protective efficacy of a DNA vaccine based on the combination of the three Leishmania PABPs has been tested in a model of progressive murine leishmaniasis: BALB/c mice infected with Leishmania major. The induction of a Th1-like response against the LiPABP family by genetic vaccination was able to down-regulate the IL-10 predominant responses elicited by parasite LiPABPs after infection in this murine model. This modulation resulted in a partial protection against L. major infection. LiPABP vaccinated mice showed a reduction on the pathology that was accompanied by a decrease in parasite burdens, in antibody titers against Leishmania antigens and in the IL-4 and IL-10 parasite-specific mediated responses in comparison to control mice groups immunized with saline or with the non-recombinant plasmid. The results presented here demonstrate for the first time the prophylactic properties of a new family of Leishmania antigenic intracellular proteins, the LiPABPs. The redirection of the immune response elicited against the LiPABP family (from IL-10 towards IFN-γ mediated responses) by genetic vaccination was able to induce a partial protection against the development of the disease in a highly susceptible murine model of leishmaniasisThe study was supported in Spain by grants from Ministerio de Ciencia e Innovación FIS PI11/00095 and FISPI14/00366 from the Instituto de Salud Carlos III within the Network of TropicalDiseases Research (VI P I+D+I 2008-2011, ISCIII -Subdirección General de Redes y Centros de Investigación Cooperativa (RD12/0018/0009)). This work was also supported in Brazil by a grant from CNPq (Ciencia sem Fronteiras-PVE 300174/2014-4). A CBMSO institutional grant from Fundación Ramón Areces is also acknowledged. EAFC is a grant recipient of CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

Parasites and immunotherapy: with or against?

Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewe

In Vitro and In Vivo Activity of a Palladacycle Complex on Leishmania (Leishmania) amazonensis

Leishmaniasis is an important public health problem with an estimated annual incidence of 1.5 million of new human cases of cutaneous leishmaniasis and 500,000 of visceral leishmaniasis. Treatment of the diseases is limited by toxicity and parasite resistance to the drugs currently in use, validating the need to develop new leishmanicidal compounds. We evaluated the killing by the palladacycle complex DPPE 1.2 of Leishmania (Leishmania) amazonensis, an agent of human cutaneous leishmaniasis in the Amazon region, Brazil. DPPE 1.2 destroyed promastigotes of L. (L.) amazonensis in vitro at nanomolar concentrations, whereas intracellular amastigotes were killed at drug concentrations 10-fold less toxic than those displayed to macrophages. L. (L.) amazonensis-infected BALB/c mice treated by intralesional injection of DPPE 1.2 exhibited a significant decrease of foot lesion sizes and a 97% reduction of parasite burdens when compared to untreated controls. Additional experiments indicated the inhibition of the cathepsin B activity of L. (L.) amazonensis amastigotes by DPPE 1.2. Further studies are needed to explore the potential of DPPE 1.2 as an additional option for the chemotherapy of leishmaniasis

Óbitos e internações por tuberculose não notificados no município do Rio de Janeiro

OBJETIVO: Analisar a subnotificação de óbitos e internações por tuberculose no Sistema de Informação de Agravos de Notificação (Sinan). MÉTODOS: Foram selecionados os óbitos do Sistema de Informação sobre Mortalidade (SIM) com tuberculose como causa básica ou associada e as internações do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS) com causa principal ou secundária tuberculose de residentes no município do Rio de Janeiro em 2004. Foi realizada associação probabilística das bases de dados do SIM e SIH-SUS com a do Sinan, referentes aos anos de 2002 a 2004. RESULTADOS: Dos 542 óbitos por tuberculose no período, 234 (43,2%) não foram registrados no Sinan nos dois anos anteriores. Das 1.079 internações, 238 (22,1%) não foram notificadas. Foram relacionados às internações 71 óbitos: 47 ocorreram durante a internação por tuberculose, 24 após a internação. Sete não foram notificados no Sinan. Os idosos tiveram 1,6 vez (IC95% 1,074;2,516) a chance de não notificação dos mais jovens, e pessoas com nível superior ou mais escolaridade tiveram 3,6 vezes a chance (IC95% 1,384;11,022) daqueles com nenhum ano de estudo de não serem notificadas. Os menores de 15 anos tiveram 4,8 vezes a chance (IC95% 2,757;8,452) de não notificação daqueles entre 15 e 59 anos. Algumas divisões regionais de saúde apresentaram percentual de óbitos não notificados acima de 50% e esse percentual variou entre 37,8% e 12,7% para internações. CONCLUSÕES: Os dados sugerem problemas na detecção de casos e apontam barreiras de acesso ao tratamento oportuno e adequado e falhas na qualidade do sistema de informação, com diferenças entre as regiões do município.OBJETIVO: Analizar la subnotificación de óbitos e internaciones por tuberculosis en el Sistema de Información de Agravios de Notificación (Sinan). MÉTODOS: Se seleccionaron los óbitos del Sistema de Información sobre Mortalidad (SIM) con causa básica o asociada a tuberculosis y las internaciones del Sistema de Informaciones Hospitalarias del Sistema Único de Salud con causa principal o secundaria tuberculosis de residentes en el municipio de Rio de Janeiro (Sureste de Brasil) en 2004. Se realizó asociación probabilística de las bases de datos del SIM y SIH-SUS con la del Sinan, referentes a los años de 2002 a 2004. RESULTADOS: De los 542 óbitos por tuberculosis en el período, 234 (43,2%) no fueron registrados en el Sinan en los dos años anteriores. De las 1.079 internaciones, 238 (22,1%) no fueron notificadas. Se relacionaron a las internaciones 71 óbitos: 47 durante la internación por tuberculosis, 24 posterior a la internación. Siete no fueron notificados en el Sinan. Los ancianos presentaron 1,6 veces (IC 95% 1,074;2,516) la probabilidad de no notificación con relación a los más jóvenes, y personas con nivel superior o más de escolaridad presentaron 3,6 veces la probabilidad (IC 95% 1,384;11,022) de no ser notificados con relación a los que no tenían ningún año de estudio. Los menores de 15 años reflejaron 4,8 veces la probabilidad (IC 95% 2,757;8,452) de no notificación con respecto a los que tenían de 15 a 59 años. Algunas divisiones regionales de salud presentaron porcentaje de óbitos no notificados por encima del 50% y ese porcentaje varió entre 37,8% a 12,7% para internaciones. CONCLUSIONES: Los datos sugieren problemas en la detección de casos y apuntan barreras de acceso al tratamiento oportuno y adecuado y fallas en la calidad del sistema de información, con diferencias entre las regiones del municipio.OBJECTIVE: To analyze underreporting of deaths and hospital admissions from tuberculosis to the Information System for Notifiable Diseases (SINAN). METHODS: Cases with tuberculosis as basic or associated cause of death were selected from the Brazilian Mortality Information System (SIM) and hospital admissions for tuberculosis as main or secondary cause from the Hospital Information System of the Brazilian Unified Health System (SIH-SUS), for residents in the municipality of Rio de Janeiro in 2004. Probabilistic record linkage was carried out between the SIM and SIH-SUS databases and the SINAN for the years 2002 to 2004. RESULTS: Out of the 542 deaths from tuberculosis in the period, 234 (43.2%) were not registered in the SINAN for the two previous years. As for the 1,079 admissions, 238 (22.1%) failed to be notified. Seventy-one deaths were related to these admissions: 47 were registered out of the SIH-SUS by death, 24 occurred after discharge and seven remained unnotified in the SINAN. The elderly were 1.6 times (95%CI 1.074;2.516) less likely to be notified than younger patients, and those with at least a college education were 3.6 times (95%CI 1.384;11.022) less likely to be notified than those with no formal education. Patients under 15 were 4.8 times (95%CI 2.757;8.452) less likely to be notified than those aged between 15 and 59 years. Some regional health administration divisions showed a percentage of unnotified deaths of over 50% and this percentage ranged from 37.8% to 12.7% for hospital admissions. CONCLUSIONS: The data suggest problems in the detection of cases and point to obstacles in adequate and timely treatment, as well as to quality flaws in the information system, with differences among regions in the municipality

Between-day reliability of electromechanical delay of selected neck muscles during performance of maximal isometric efforts

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to assess the between-day reliability of the electromechanical delay (EMD) of selected neck muscles during the performance of maximal isometric contractions in five different directions.</p> <p>Methods</p> <p>Twenty-one physically active males participated in two testing sessions separated by seven to eight days. Using a custom-made fixed frame dynamometer, cervical force and surface electromyography (EMG) were recorded bilaterally from the splenius capitis, upper trapezius and sternocleidomastoid muscles during the performance of efforts in extension, flexion, left and right lateral bending, and protraction. The EMD was extracted using the Teager-Kaiser Energy Operator. Reliability indices calculated for each muscle in each testing direction were: the difference in scores between the two testing sessions and corresponding 95% confidence intervals, the standard error of measurement (SEM) and intra-class correlation coefficients (ICC).</p> <p>Results</p> <p>EMD values showed no evidence of systematic difference between the two testing sessions across all muscles and testing directions. The SEM for extension, flexion and lateral bending efforts ranged between 2.5 ms to 4.8 ms, indicating a good level of measurement precision. For protraction, SEM values were higher and considered to be imprecise for research and clinical purposes. ICC values for all muscles across all testing directions ranged from 0.23 to 0.79.</p> <p>Conclusion</p> <p>EMD of selected neck muscles can be measured with sufficient precision for the assessment of neck muscle function in an athletic population in the majority of directions tested.</p