Modification of the brain proteome of Africanized honeybees (Apis mellifera) exposed to a sub-lethal doses of the insecticide fipronil.

Fipronil is a phenylpyrazole insecticide that is widely used in Brazilian agriculture for pest control. Although honeybees are not targets of fipronil, studies indicate that this pesticide can be harmful to honeybees. To assess the effects of fipronil in the brain of Africanized Apis mellifera workers, this study focused on the toxico-proteome profiling of the brain of newly emerged and aged honeybee workers that were exposed to a sub-lethal dose (10 pg fipronil per day. i.e. (1)/100 of LD50/bee/day during 5 days) of the insecticide. Proteomic analysis identified 25 proteins that were differentially up-regulated or down-regulated when the fipronil-exposed and non-exposed groups were compared. These proteins are potentially related to pathogen susceptibility, neuronal chemical stress, neuronal protein misfolding, and occurrence of apoptosis, ischemia, visual impairment, damaged synapse formation, brain degeneration, memory and learning impairment. The exposure of honeybees to a very low dose of fipronil, even for a short period of time (5 days), was sufficient to cause a series of important neuroproteomic changes in the brains of honeybees.

Myosin cross-bridges do not form precise rigor bonds in hypertrophic heart muscle carrying troponin T mutations.

Distribution of orientations of myosin was examined in ex-vivo myofibrils from hearts of transgenic (Tg) mice expressing Familial Hypertrophic Cardiomyopathy (FHC) troponin T (TnT) mutations I79N, F110I and R278C. Humans are heterozygous for sarcomeric FHC mutations and so hypertrophic myocardium contains a mixture of the wild-type (WT) and mutated (MUT) TnT. If mutations are expressed at a low level there may not be a significant change in the global properties of heart muscle. In contrast, measurements from a few molecules avoid averaging inherent in the global measurements. It is thus important to examine the properties of only a few molecules of muscle. To this end, the lever arm of one out of every 60,000 myosin molecules was labeled with a fluorescent dye and a small volume within the A-band (~1 fL) was observed by confocal microscopy. This volume contained on average 5 fluorescent myosin molecules. The lever arm assumes different orientations reflecting different stages of acto-myosin enzymatic cycle. We measured the distribution of these orientations by recording polarization of fluorescent light emitted by myosin-bound fluorophore during rigor and contraction. The distribution of orientations of rigor WT and MUT myofibrils was significantly different. There was a large difference in the width and of skewness and kurtosis of rigor distributions. These findings suggest that the hypertrophic phenotype associated with the TnT mutations can be characterized by a significant increase in disorder of rigor cross-bridges.

Chronic allograft dysfunction-is there a treatment?

BACKGROUND: The major causes of renal transplant loss are death and chronic allograft dysfunction (CAD). The aims of this study were to determine the incidence of CAD in our population and the relation between allograft survival and immunosuppressive regimens. METHODS: We studied retrospectively 473 patients who received deceased donor kidney transplants with at least 1 allograft biopsy between January 1990 and May 2007. Clinical data included age, gender, biopsy data, and immunosuppression before and after kidney biopsy. Mean age was 45.4 +/- 12.7 years including 65% males with a mean follow-up of 6.7 +/- 4.5 years. CAD was observed in 177 of 473 biopsies: 48 patients showed interstitial fibrosis (IF); 101 chronic rejection (CR); 16 transplant glomerulopathy (TG); and 12, CR and TG. Mean follow-up since the discovery of the histologic feature was 60.5 +/- 50.5 months for IF; 38.3 +/- 40.8 for CR, and 18.2 +/- 19.2 for TG. RESULTS: CAD, which was more common in younger patients (P = .03), correlated upon univariate and multivariate analysis with CKD stage 5d development (P < .001). Deposition of C4d in peritubular capillaries was more frequent among CAD patients (P = .004), an association with particular relevance to recipients with CR (P = .02) and TG (P < .001). When we analyzed CAD subpopulation, we observed a positive correlation between allograft survival and immunosuppression modification after biopsy. Substitution of sirolimus (40/177) was shown in univariate, multivariate and Cox regression analyses to be a renal protector (P < .002). Allograft survival was also correlated with initial mycophenolate mofetil versus azathioprine, (62/177) immunosuppression (P < .001). CONCLUSION: CAD, a frequent histologic feature, may benefit from sirolimus conversion.

Sirolimus-induced drug fever in a renal transplant patient: a case report.

Herein we have described the case of a male renal transplant recipient who developed drug fever apparently related to sirolimus. He had been stable under an immunosuppressive regimen of tacrolimus and mycophenolate mofetil, but developed acute cellular rejection at 5 years after transplantation due to noncompliance. Renal biopsy showed marked interstitial fibrosis, and immunosuppression was switched from mycophenolate to sirolimus, maintaining low tacrolimus levels. One month later he was admitted to our hospital for investigation of intermittently high fever, fatigue, myalgias, and diarrhea. Physical examination was unremarkable and drug levels were not increased. Lactic dehydrogenase and C-reactive protein were increased. The blood cell count and chest radiographic findings were normal. After extensive cultures, he was started on broad-spectrum antibiotics. Inflammatory markers and fever worsened, but diarrhea resolved. All serologic and imaging tests excluded infection, immune-mediated diseases, and malignancy. After 12 days antibiotics were stopped as no clinical improvement was achieved. Drug fever was suspected; sirolimus was replaced by mycophenolate mofetil. Fever and other symptoms disappeared after 24 hours; inflammatory markers normalized in a few days. After 1 month the patient was in good health with stable renal function. Although infrequent, the recognition of drug fever as a potential side effect of sirolimus may avoid unnecessary invasive diagnostic procedures. Nevertheless, exclusion of other common causes of fever is essential.

Leukopenia in kidney transplant patients with the association of valganciclovir and mycophenolate mofetil.

Cytomegalovirus (CMV) is the most common viral infection after transplantation. Valganciclovir (VGC) is established for prophylaxis and treatment of CMV infections, but leukopenia which appears in 10% to 13% (severe in 4.9%) is the principal side effect. We have recently noted an increased incidence of leukopenia and severe neutropenia among our renal transplant patients and thought to identify the associated factors. We conducted a retrospective analysis of all kidney transplantations performed between January 2005 and December 2006. All patients received mycophenolate mofetil (MMF), tacrolimus, and steroids. VGC was used for targeted prophylaxis and preemptive therapy of CMV infection, with doses adjusted to renal function. Of the 64 patients undergoing renal transplantation 13 (20.3%) developed leukopenia within 3 +/- 2 months after transplantation with severe neutropenia in 5 (7.8%). All patients were on MMF and VGC (VGC 605 +/- 296 mg/d). Leukopenia was significantly associated with simultaneous liver-kidney transplantation and with second kidney transplantations (P < .01). The incidence of leukopenia was higher among patients under VGC since day 1 of transplantation (P = .008) with maximal incidence observed among patients prescribed 900 mg/d as opposed to those on lower doses (P < .01). There was no increase in CMV infection among patients with a low dose of VGC. No patient developed clinical CMV disease. In conclusion, VGC prophylaxis was associated with an increased frequency of leukopenia on MMF-tacrolimus treated patients or regimens. Low-dose VGC for CMV prophylaxis appeared to be as effective as high-dose treatment, and associated less frequently with leukopenia and neutropenia.

Landsat phenological metrics and their relation to aboveground carbon in the Brazilian Savanna.

BACKGROUND: The quantification and spatially explicit mapping of carbon stocks in terrestrial ecosystems is important to better understand the global carbon cycle and to monitor and report change processes, especially in the context of international policy mechanisms such as REDD+ or the implementation of Nationally Determined Contributions (NDCs) and the UN Sustainable Development Goals (SDGs). Especially in heterogeneous ecosystems, such as Savannas, accurate carbon quantifications are still lacking, where highly variable vegetation densities occur and a strong seasonality hinders consistent data acquisition. In order to account for these challenges we analyzed the potential of land surface phenological metrics derived from gap-filled 8-day Landsat time series for carbon mapping. We selected three areas located in different subregions in the central Brazil region, which is a prominent example of a Savanna with significant carbon stocks that has been undergoing extensive land cover conversions. Here phenological metrics from the season 2014/2015 were combined with aboveground carbon field samples of cerrado sensu stricto vegetation using Random Forest regression models to map the regional carbon distribution and to analyze the relation between phenological metrics and aboveground carbon. RESULTS: The gap filling approach enabled to accurately approximate the original Landsat ETM+ and OLI EVI values and the subsequent derivation of annual phenological metrics. Random Forest model performances varied between the three study areas with RMSE values of 1.64 t/ha (mean relative RMSE 30%), 2.35 t/ha (46%) and 2.18 t/ha (45%). Comparable relationships between remote sensing based land surface phenological metrics and aboveground carbon were observed in all study areas. Aboveground carbon distributions could be mapped and revealed comprehensible spatial patterns. CONCLUSION: Phenological metrics were derived from 8-day Landsat time series with a spatial resolution that is sufficient to capture gradual changes in carbon stocks of heterogeneous Savanna ecosystems. These metrics revealed the relationship between aboveground carbon and the phenology of the observed vegetation. Our results suggest that metrics relating to the seasonal minimum and maximum values were the most influential variables and bear potential to improve spatially explicit mapping approaches in heterogeneous ecosystems, where both spatial and temporal resolutions are critical.

Long-term effect of lovastatin on lipoprotein profile in patients with primary nephrotic syndrome.

Eight patients with biopsy-proven primary nephrotic syndrome were included in an open, prospective, two-year study of lovastatin. One patients was withdrawn after 6 months due to an asymptomatic rise in creatinine phosphokinase, which was rapidly reversed after interruption of lovastatin. In the remaining patients, treatment was well-tolerated and produced no side effects. After 2 years of treatment, these 7 patients had decreases in total cholesterol from 446 +/- 165 to 250 +/- 57 mg/dl (p < 0.001), LDL cholesterol from 343 +/- 121 to 174 +/- 49 mg/dl (p < 0.001), Apo B lipoprotein from 162 +/- 60 to 108 +/- 42 mg/dl (p < 0.05), triglycerides from 336 +/- 273 to 182 +/- 71 mg/dl (p < 0.04). There was no change in HDL cholesterol. The LDL/HDL cholesterol and the total/HDL cholesterol ratios fell from 15.0 +/- 12.1 and 19.1 +/- 17.2 mg/dl before the study to 4.4 +/- 1.2 and 6.3 +/- 1.6 mg/dl, respectively, at 2 years. A decrease in proteinuria from 8.6 +/- 4.6 to 5.0 +/- 3.7 g/24 h (p < 0.02) was noted in 4 patients on concomitant ACE inhibitor therapy. Renal function remained stable in all patients throughout the study, except for one whose moderate impairment progressed to end-stage renal failure requiring dialysis 3 months poststudy. We conclude that long-term lovastatin in patients with primary nephrotic syndrome is an effective and generally safe treatment for accompanying dyslipidemia.

Bronchial asthma in children: clinical and epidemiologic approach in different Portuguese speaking countries.

BACKGROUND: Geographical differences in asthma prevalence are currently accepted, but evidence is sparse due to the lack of multicentre studies using the same protocol. OBJECTIVES: To compare the prevalence of asthma and atopy among schoolchildren from Portuguese speaking countries (ISAAC and Portuguese Study) and evaluate some environmental variables, such as house dust mite exposure. MATERIAL AND METHODS: Significant random samples of schoolchildren studied with standard validated methods--questionnaires, skin prick tests, methacholine bronchial challenge tests; dust bed sampling for analysis of mite antigens. RESULTS: In the ISAAC study, in the 13-14 year-old age group, statistical significant differences were found, with higher wheezing prevalence in Brazil than in Portugal (two-fold). In the Portuguese Study, atopy prevalence ranged between 6.0 and 11.9% in Sal and S. Vicente (Cape Verde), up to 48.6 and 54.1% in Macau and Madeira. Active asthma had the higher values in Madeira (14.6%), and the lower in Macau (1.3%). Cape Verde had intermediate asthma prevalence (10.6 and 7.0%). The bronchial challenge test was positive in 25, 66 and 70% of asthmatic children from Sal, S. Vicente and Madeira respectively. Significant HDM antigen concentrations (Der p1) were found in Cape Verde and Madeira. CONCLUSIONS: There are significant variations in asthma and atopy prevalence between these pediatric populations. The reasons remain under discussion, but genetics linked to race, seem to play a central role, modulated by environmental and lifestyle variables.

[Sporadic amyotrophic lateral sclerosis. Diagnostic criteria]. / Esclerose lateral amiotrófica esporádica. Critérios diagnósticos.

The authors report two cases of amyotrophic lateral sclerosis (ALS) misdiagnosis (a craniocervical junction disorder, and a cervical spinal cord ependymoma). They review some causes of ALS-like syndrome and propose a protocol to be adopted for the study of all patients who present clinical abnormalities suggesting ALS.

[Intracranial saccular aneurysm: report of 3 cases in a same family]. / Aneurisma sacular intracraniano. Apresentação de trés casos em uma mesma família.

The authors report the cases of three patients from the same family, all with intracranial saccular aneurysm (left carotid artery, anterior communicating artery, and middle cerebral artery). All three patients were operated on with good recovery and no complications. The authors call attention for some etiopathogenic aspects of familial saccular aneurysms.

Atopy and enteroparasites.

UNLABELLED: There are not many studies about the intestinal parasitosis (IP) and atopic asthma (AA) relationship, and these show discordant results, possibly due to different studies design and differences in population selection. On the basis of personal results obtained by an epidemiological inquiry designed to estimate the prevalence of enteroparasitoses in asthmatic children and vice vesa, the aim of this study was to compare the prevalence of IP in AA and in a control group (CG) by a cross sectional study using clinical and laboratorial parameters, applied to 63 children (47 with AA and 16 in CG) aged 6 to 11 years, 37 males and 26 females, Caucasians, with the same socioeconomical conditions, consecutively selected in our Hospital. The results showed: The IP in AA children was 21.3%; the IP in CG was 25%; in the group with AA and IP, 40% of them had symptomology of IP; in the CG with IP, 100% had symptoms. CONCLUSIONS: The IP prevalence in AA was not statistically different from the IP in CG (p > 0.05) More data are needed to clarify the significant differences between the symptomatology rates of IP in asthmatic and non asthmatics; the reduced number of patients with symptoms in AA may reflect modulation of IP in AA and/or different parasite load.

Ocorrência de cochonilhas em espinheira-santa (Maytenus ilicifolia Mart. ex Reissek) / Occurrence of mealybugs in "espinheira-santa" (Maytenus ilicifolia Mart. ex Reissek)

Maytenus ilicifolia é uma espécie medicinal nativa do Brasil que vem sendo cultivada para atender a crescente demanda do mercado. Os fatores que interferem na produção, tal como a incidência de pragas e doenças, devem ser estudados para garantir o incremento na produtividade. O objetivo deste trabalho foi registrar a ocorrência e a identificação de cochonilhas associadas a 15 acessos de espinheira-santa (Maytenus ilicifolia) do Banco Ativo de Germoplasma da Embrapa Clima Temperado e do Instituto Federal Sul-rio-grandense. Foi registrada a quantidade de plantas infestadas em cada acesso e identificado, em laboratório, as espécies de cochonilhas infestantes. O número de plantas infestadas variou entre os acessos. Foram identificadas as cochonilhas Ceroplastes sp. e Saissetia oleae, família Coccidae. Dos 10 acessos infestados, 23 (11,3%) plantas apresentaram infestação com Ceroplastes sp. e, apenas uma (0,5%), com Saissetia oleae. O acesso 133 mostrou a maior incidência de Ceroplastes sp. (33,3%), seguido do acesso 130 (25,0%). O acesso 123 foi o que apresentou menor quantidade de plantas infestadas (4,8%). Saissetia oleae ocorreu em apenas uma planta, pertencente ao acesso 136 (5,6%).

Maytenus ilicifolia is a medicinal species native to Brazil which has been cultivated to meet the growing market demand. Factors that interfere with the production, such as the incidence of pests and diseases, should be studied to ensure increased productivity. The aim of this study was to record the occurrence and the identification of mealybugs associated with 15 "espinheira-santa" (Maytenus ilicifolia) accessions from the Active Germplasm Bank of "Embrapa Clima Temperado" and "Instituto Federal Sul-rio-grandense". The quantity of infested plants in each accession was recorded and the species of infested mealybugs were identified in the laboratory. The number of infested plants varied among accessions. The identified mealybugs were Ceroplastes sp. and Saissetia oleae, family Coccidae. Of 10 infested accessions, 23 plants (11.3%) showed infestation with Ceroplastes sp., and only one (0.5%) with Saissetia oleae. Accession 133 showed the highest incidence of Ceroplastes sp. (33.3%), followed by accession 130 (25.0%). Accession 123 had the least amount of infested plants (4.8%). Saissetia oleae occurred in only one plant, belonging to accession 136 (5.6%).

A new scenario of bioprospecting of Hymenoptera venoms through proteomic approach

Venoms represent a huge and essentially unexplored reservoir of bioactive components that may cure diseases that do not respond to currently available therapies. This review select advances reported in the literature from 2000 to the present about the new scenario of Hymenoptera venom composition. On account of new technologies in the proteomic approach, which presents high resolution and sensitivity, the combination of developments in new instruments, fragmentation methods, strategic analysis, and mass spectrometry have become indispensable tools for interrogation of protein expression, molecule interaction, and post- translational modifications. Thus, the biochemical characterization of Hymenoptera venom has become a major subject of research in the area of allergy and immunology, in which proteomics has been an excellent alternative to assist the development of more specific extracts for diagnosis and treatment of hypersensitive patients to Hymenoptera venoms.

Effect of low protein diet on the renal response to meat ingestion in diabetic nephropathy.

We measured the renal haemodynamic and proteinuric response to a meat meal (MM) in ten persistently proteinuric insulin-dependent diabetic patients in a randomized cross-over study of 3 weeks on low protein diet (LPD) or normal protein intake (NPD). On LPD, protein intake (0.64 +/- 0.05 vs 1.15 +/- 0.09 g kg-1 body weight (BW) per day, P less than 0.001), plasma urea (6.6 +/- 1.3 vs 11.0 +/- 2.0 mmol l-1, P less than 0.01) and urea appearance (0.06 +/- 0.01 vs 0.16 +/- 0.03 gN kg-1 body weight per day, P less than 0.001) were lower. Baseline glomerular filtration rate (GFR), renal plasma flow (RPF) and renal vascular resistance (RVR) were similar on the two diets and there were no significant average changes in these variables after the meat meal on either diet (NPD, before vs after MM: GFR: 67 +/- 11 vs 71 +/- 13 ml min-1 1.73 m-2; RPF: 479 +/- 70 vs 512 +/- 81 ml min-1 1.73 m-2; RVR: 181 +/- 45 vs 179 +/- 52 mmHg min-1 l-1); (LPD, before vs after MM: GFR: 64 +/- 10 vs 67 +/- 11 ml min-1 1.73 m-2; RPF: 506 +/- 60 vs 533 + 52 ml min-1 1.73 m-2; RVR: 151 +/- 28 vs 146 +/- 32 mmHg min-1 l-1). However, all patients with baseline GFR above 60 ml min-1 1.73 m-2 showed a GFR rise in response to the meat meal on both diets, while patients with lower baseline values tended to reduce their GRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Autosomal dominant polycystic kidney disease: evidence for the existence of a third locus in a Portuguese family.

Autosomal dominant polycystic kidney disease is characterized by clinical and genetic heterogeneity. Two loci implicated in the disease have previously been mapped (PKD1 on chromosome 16 and PKD2 on chromosome 4). By two point and multipoint linkage analysis, negative lod scores have been found for both chromosome 16 and chromosome 4 markers in a large Portuguese family, indicating that a third PKD locus is involved in the development of the disease.