Modulation of the pharmacological effects of enzymatically-active PLA2 by BTL-2, an isolectin isolated from the Bryothamnion triquetrum red alga

<p>Abstract</p> <p>Background</p> <p>An interaction between lectins from marine algae and PLA₂from rattlesnake was suggested some years ago. We, herein, studied the effects elicited by a small isolectin (BTL-2), isolated from <it>Bryothamnion triquetrum</it>, on the pharmacological and biological activities of a PLA₂isolated from rattlesnake venom (<it>Crotalus durissus cascavella</it>), to better understand the enzymatic and pharmacological mechanisms of the PLA₂and its complex.</p> <p>Results</p> <p>This PLA₂consisted of 122 amino acids (approximate molecular mass of 14 kDa), its pI was estimated to be 8.3, and its amino acid sequence shared a high degree of similarity with that of other neurotoxic and enzymatically-active PLA₂s. BTL-2 had a molecular mass estimated in approximately 9 kDa and was characterized as a basic protein. In addition, BTL-2 did not exhibit any enzymatic activity.</p> <p>The PLA₂and BTL-2 formed a stable heterodimer with a molecular mass of approximately 24–26 kDa, estimated by molecular exclusion HPLC. In the presence of BTL-2, we observed a significant increase in PLA₂activity, 23% higher than that of PLA₂alone. BTL-2 demonstrated an inhibition of 98% in the growth of the Gram-positive bacterial strain, <it>Clavibacter michiganensis michiganensis </it>(Cmm), but only 9.8% inhibition of the Gram-negative bacterial strain, <it>Xanthomonas axonopodis </it>pv <it>passiflorae </it>(Xap). PLA₂decreased bacterial growth by 27.3% and 98.5% for Xap and Cmm, respectively, while incubating these two proteins with PLA₂-BTL-2 inhibited their growths by 36.2% for Xap and 98.5% for Cmm.</p> <p>PLA₂significantly induced platelet aggregation in washed platelets, whereas BTL-2 did not induce significant platelet aggregation in any assay. However, BTL-2 significantly inhibited platelet aggregation induced by PLA₂. In addition, PLA₂exhibited strong oedematogenic activity, which was decreased in the presence of BTL-2. BTL-2 alone did not induce oedema and did not decrease or abolish the oedema induced by the 48/80 compound.</p> <p>Conclusion</p> <p>The unexpected results observed for the PLA₂-BTL-2 complex strongly suggest that the pharmacological activity of this PLA₂is not solely dependent on the presence of enzymatic activity, and that other pharmacological regions may also be involved. In addition, we describe for the first time an interaction between two different molecules, which form a stable complex with significant changes in their original biological action. This opens new possibilities for understanding the function and action of crude venom, an extremely complex mixture of different molecules.</p

Neurogranin as a predictor of memory and executive function decline in MCI patients

Objective To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Methods Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. Results High levels of CSF Ng were associated with poor baseline memory scores (β = −0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = −0.0313, p = 0.0068 and β = −0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ42) were controlled for in these analyses. Conclusions High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD

Comparative serology techniques for the diagnosis of Trypanosoma cruzi infection in a rural population from the state of Querétaro, Mexico

Immunological diagnostic methods for Trypanosoma cruzi depend specifically on the presence of antibodies and parasitological methods lack sensitivity during the chronic and “indeterminate” stages of the disease. This study performed a serological survey of 1,033 subjects from 52 rural communities in 12 of the 18 municipalities in the state of Querétaro, Mexico. We detected anti-T. cruzi antibodies using the following tests: indirect haemagglutination assay (IHA), indirect immunofluorescence assay (IFA), ELISA and recombinant ELISA (rELISA). We also performed Western blot (WB) analysis using iron superoxide dismutase (FeSOD), a detoxifying enzyme excreted by the parasite, as the antigen. Positive test results were distributed as follows: ELISA 8%, rELISA 6.2%, IFA and IHA 5.4% in both cases and FeSOD 8%. A comparative study of the five tests was undertaken. Sensitivity levels, specificity, positive and negative predictive values, concordance percentage and kappa index were considered. Living with animals, trips to other communities, gender, age, type of housing and symptomatology at the time of the survey were statistically analysed using SPSS software v.11.5. Detection of the FeSOD enzyme that was secreted by the parasite and used as an antigenic fraction in WBs showed a 100% correlation with traditional ELISA tests

The impact of hypertension, hemorrhage, and other maternal morbidities on functioning in the postpartum period as assessed by the WHODAS 2.0 36-item tool

© 2018 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics. Objective: To assess the scores of postpartum women using the WHO Disability Assessment Schedule 2.0 36-item tool (WHODAS-36), considering different morbidities. Methods: Secondary analysis of a retrospective cohort of women who delivered at a referral maternity in Brazil and were classified with and without severe maternal morbidity (SMM). WHODAS-36 was used to assess functioning in postpartum women. Percentile distribution of total WHODAS score was compared across three groups: Percentile (P)90. Cases of SMM were categorized and WHODAS-36 score was assessed according to hypertension, hemorrhage, or other conditions. Results: A total of 638 women were enrolled: 64 had mean scores below P90 (41.3). Of women scoring above P>90, those with morbidity had a higher mean score than those without (44.6% vs 36.8%, P=0.879). Women with higher WHODAS-36 scores presented more complications during pregnancy, especially hypertension (47.0% vs 37.5%, P=0.09). Mean scores among women with any complication were higher than those with no morbidity (19.0 vs 14.2, P=0.01). WHODAS-36 scores were higher among women with hypertensive complications (19.9 vs 16.0, P=0.004), but lower among those with hemorrhagic complications (13.8 vs 17.7, P=0.09). Conclusions: Complications during pregnancy, childbirth, and the puerperium increase long-term WHODAS-36 scores, demonstrating a persistent impact on functioning among women, up to 5 years postpartum

Domain choice in an experimental nested modeling prediction system for South America

The purposes of this paper are to evaluate the new version of the regional model, RegCM3, over South America for two test seasons, and to select a domain for use in an experimental nested prediction system, which incorporates RegCM3 and the European Community-Hamburg (ECHAM) general circulation model (GCM). To evaluate RegCM3, control experiments were completed with RegCM3 driven by both the NCEP/NCAR Reanalysis (NNRP) and ECHAM, using a small control domain (D-CTRL) and integration periods of January–March 1983 (El Niño) and January–March 1985 (La Niña). The new version of the regional model captures the primary circulation and rainfall differences between the two years over tropical and subtropical South America. Both the NNRP-driven and ECHAM-driven RegCM3 improve the simulation of the Atlantic intertropical convergence zone (ITCZ) compared to the GCM. However, there are some simulation errors. Irrespective of the driving fields, weak northeasterlies associated with reduced precipitation are observed over the Amazon. The simulation of the South Atlantic convergence zone is poor due to errors in the boundary condition forcing which appear to be amplified by the regional model. To select a domain for use in an experimental prediction system, sensitivity tests were performed for three domains, each of which includes important regional features and processes of the climate system. The domain sensitivity experiments were designed to determine how domain size and the location of the GCM boundary forcing affect the regional circulation, moisture transport, and rainfall in two years with different large scale conditions. First, the control domain was extended southward to include the exit region of the Andes low level jet (D-LLJ), then eastward to include the South Atlantic subtropical high (D-ATL), and finally westward to include the subsidence region of the South Pacific subtropical high and to permit the regional model more freedom to respond to the increased resolution of the Andes Mountains (D-PAC). In order to quantify differences between the domain experiments, measures of bias, root mean square error, and the spatial correlation pattern were calculated between the model results and the observed data for the seasonal average fields. The results show the GCM driving fields have remarkable control over the RegCM3 simulations. Although no single domain clearly outperforms the others in both seasons, the control domain, D-CTRL, compares most favorably with observations. Over the ITCZ region, the simulations were improved by including a large portion of the South Atlantic subtropical high (D-ATL). The methodology presented here provides a quantitative basis for evaluating domain choice in future studies

Validation of the WHO Disability Assessment Schedule (WHODAS 2.0) 12-item tool against the 36-item version for measuring functioning and disability associated with pregnancy and history of severe maternal morbidity

© 2018 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics. Objective: To validate the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item tool against the 36-item version for measuring functioning and disability associated with pregnancy and the occurrence of maternal morbidity. Methods: This is a secondary analysis of the Brazilian retrospective cohort study on long-term repercussions of severe maternal morbidity (SMM) among women who delivered at a tertiary facility (COMMAG study). We compared WHODAS-12 and WHODAS-36 scores of women with and without SMM using measures of central tendency and variability, tests for instruments’ agreement (Bland-Altman plot), confirmatory factor analysis (CFA), and Cronbach alpha coefficient for internal consistency. Results: The COMMAG study enrolled 638 women up to 5 years postpartum. Although the median WHODAS-36 and -12 scores for all women were statistically different (13.04 and 11.76, respectively; P<0.001), there was a strong linear correlation between them. Furthermore, the mean difference and the differences in variance analyses demonstrated agreement of total scores between the two versions. CFA demonstrated how the WHODAS-12 questions are divided into six previously defined factors and Cronbach alpha showed good internal consistency. Conclusion: WHODAS-12 demonstrated agreement with WHODAS-36 for total score and was a good instrument for screening functioning and disability among postpartum women, with and without SMM

Chagas Disease Risk in Texas

Chagas disease is endemic in Texas and spread through triatomine insect vectors known as kissing bugs, assassin bugs, or cone–nosed bugs, which transmit the protozoan parasite, Trypanosoma cruzi. We examined the threat of Chagas disease due to the three most prevalent vector species and from human case occurrences and human population data at the county level. We modeled the distribution of each vector species using occurrence data from México and the United States and environmental variables. We then computed the ecological risk from the distribution models and combined it with disease incidence data to produce a composite risk map which was subsequently used to calculate the populations expected to be at risk for the disease. South Texas had the highest relative risk. We recommend mandatory reporting of Chagas disease in Texas, testing of blood donations in high risk counties, human and canine testing for Chagas disease antibodies in high risk counties, and that a joint initiative be developed between the United States and México to combat Chagas disease