Human apolipoprotein A-I binds amyloid-beta and prevents A beta-induced neurotoxicity

Aggregates of the amyloid-P peptide (A beta) play a central role in the pathogenesis of Alzheimer`s disease (AD). Identification of proteins that physiologically bind A beta and modulate its aggregation and neurotoxicity could lead to the development of novel disease-modifying approaches in AD. By screening a phage display peptide library for high affinity ligands of aggregated A beta(1-42), We isolated a peptide homologous to a highly conserved amino acid sequence present in the N-terminus of apolipoprotein A-I (apoA-I). We show that purified human apoA-I and A beta form non-covalent complexes and that interaction with apoA-I affects the morphology of amyloid aggregates formed by A beta. Significantly, A beta/apoA-I complexes were also detected in cerebrospinal fluid from AD patients. Interestingly, apoA-I and apoA-I-containing reconstituted high density lipoprotein particles protect hippocampal neuronal cultures from A beta-induced oxidative stress and neurodegeneration. These results suggest that human apoA-I modulates A beta aggregation and A beta-induced neuronal damage and that the A beta-binding domain in apoA-I may constitute a novel framework for the design of inhibitors of A beta toxicity. (C) 2009 Published by Elsevier Ltd.

Cisplatin and Etoposide in Childhood Germ Cell Tumor: Brazilian Pediatric Oncology Society Protocol GCT-91

Purpose In 1988, we formed a consortium of Brazilian institutions to develop uniform standards for the diagnostic assessment and multidisciplinary treatment of children and adolescents with germ cell tumors. We also implemented the first childhood Brazilian germ cell tumor protocol, GCT-91, evaluating two-agent chemotherapy with cisplatin and etoposide (PE). We now report on the clinical characteristics and survival of children and adolescents with germ cell tumors treated on this protocol. Patients and Methods From May 1991 to April 2000, 115 patients (106 assessable patients) were enrolled onto the Brazilian protocol with a diagnosis of germ cell tumor. Results Patients were treated with surgery only (n = 35) and chemotherapy (n = 71). Important prognostic factors included stage (P = .025), surgical procedure at diagnosis according to resectability (P = .032), and abnormal lactate dehydrogenase value at diagnosis (P = .001). Conclusion The improvement in survival by the introduction of a standard protocol is an important achievement. This is of particular importance for smaller institutions with previous limited experience in the treatment of childhood germ cell tumors. In addition, the results of a two-agent regimen with PE were favorable (5-year overall survival rate is 83.3% for patients in the high-risk group [n = 36] who received PE v 58.8% for patients in the high-risk patients group who received PE plus ifosfamide, vinblastine, and bleomycin [n = 17; P = .017]). Thus for selected patients, complex three-agent regimens may not be necessary to achieve long-term survival, even for some patients with advanced disease.

Prognostic Impact of MYCN, DDX1, TrkA, and TrkC Gene Transcripts Expression in Neuroblastoma

Background. The aims of this study were to define the mRNA expression profiles of MYCN, DDX1, TrkA, and TrkC in biopsy tumor samples from 64 Brazilian patients with neuroblastomas of different risk stages and to correlate altered expression with prognostic values. Procedure. Patients were retrospectively classified into low- (n = 11), intermediate- (n = 18), and high-risk (n = 35) groups using standard criteria. The mRNA levels of the above genes were measured by quantitative real-time polymerase chain reaction. Univariate analyses were performed and survival curves were plotted by the Kaplan-Meier method. Results. Of the 64 patients, 53% were female and 62.5% were older than 18 months. The 5-year overall survival (OS) for the entire cohort was 40.3%, with inferior median OS in patients identified in the intermediate- and high-risk groups. A significant difference in OS with respect to TrkA mRNA expression was found for the high-risk group vs. either the low- or intermediate-risk groups (P < 0.01, log rank test). Within the intermediate-risk group, neuroblastoma patients with positive TrkA mRNA expression had better clinical outcomes than patients with no TrkA transcript expression (P = 0.004). Another difference in OS was only found between the intermediate- and high-risk groups (P < 0.027, log rank test). No significant correlation of mRNA expression and survival outcome could be detected for the MYCN, DDX1. Conclusions. Positive expression of TrkA mRNA may be a clinically useful addition to the current risk classification system, allowing the identification of NB tumors with favorable prognosis. Pediatr Blood Cancer 2011; 56: 749-756. (c) 2010 Wiley-Liss, Inc.

Intravenous cisplatin administration in sulphur-crested cockatoos (Cacatua galerita): Clinical and pathologic observations

The prevalence of neoplasia in birds is generally low; however, in some species of companion and aviary birds, the incidence is high and neoplasia is a common cause of death. Surgical excision or limb amputation has been performed as the therapeutic plan. Chemotherapy in the treatment of avian neoplasia is largely empirical and poorly documented. For example, cisplatin has been used intralesionally in macaws (Ara species) with limited clinical success. Eight sulphur-crested cockatoos (Cacatua galerita), under general isoflurane anesthesia, were infused intravenously with cisplatin at 6.4 or 1.0 mg/kg over 1 hour and hydrated with lactated Ringer's solution for 1 hour before and 2 hours after cisplatin infusion. Birds were euthanatized 96 hours after infusion, except for 2 birds given the low cisplatin dose, which were euthanatized on day 35 after dosing. All birds tolerated the study procedure while under anesthesia. Blood pressure, heart rate, and respiratory rate did not change significantly. In the low-dose group, the mean cloacal temperature decreased significantly during the infusion period (P < .001) and then rose progressively to preinfusion values by 24 hours. Also in this group, the mean body weight tended to increase during the infusion period before significantly decreasing (P < .05) by 5% at 96 hours after dosing. At 24 hours after dosing, all birds were bright and eating. However, intermittent regurgitation and fecal changes (moist, dark green feces and yellow urates) occurred in 3 of 8 birds, especially those given the high dose. By 72 hours after dosing, droppings in the low-dose group were normal in appearance. One bird in the high-dose group died by 94 hours after dosing. Myelosuppression was not observed in any bird and at necropsy, no evidence of cisplatin toxicity was found except in 1 bird given the high cisplatin dose. On histology, this bird showed nephrotoxicity, and its serum uric acid levels and mean estimated white blood cell count increased significantly by 24 hours after dosing. This paper reports for the first time the effect of systemic cisplatin administration in birds and provides veterinarians data for formulating efficacious and safe protocols for platinum-containing compounds when treating neoplasia in parrots and other companion birds.

Parathyroid hormone (1-34): A major advance in the treatment of osteoporosis?

Osteoporosis is a major public health problem for older women and men. Parathyroid hormone (PTH) (1-34), which produces similar biological activity to the parent hormone, was tested in postmenopausal women with prior vertebral fractures. In 18 months, PTH (1-34) caused a dramatic 65% decrease in the risk of new vertebral fractures with a 10% increase in bone mineral density with few side effects. PTH (1-34) represents an exciting new therapy for this high risk group.

Being attuned to intergroup differences in mergers: The role of aligned leaders for low-status groups

The present research focused on responses of low-status group members to a merger with a high-status group. A study was conducted (N = 153) in which the alignment of the leader for the merged group (ingroup vs. outgroup) and leader behavior (equality, outgroup favoritism, ingroup favoritism, complementarity) were manipulated. The authors predicted that the leader, by his or her behavior, would play an important role in defining the new relationship between premerger groups. Overall, low-status ingroup leaders were evaluated more positively than high-status outgroup leaders. Ingroup leaders were evaluated more favorably and were more likely to engender a common identity in the merged group than were outgroup leaders when leaders behaved in an ingroup-favoring or complementary fashion. In contrast, evaluations of ingroup and outgroup leaders did not differ when the leader stressed equality or was outgroup favoring. The findings demonstrate the important role leaders can play in accentuating or de-emphasizing premerger status differences.

Children and sand play: screening of potential harmful microorganisms in sandboxes, parks, and beaches

Sand serves as a reservoir for potentially pathogenic microorganisms. Children, a high-risk group, can acquire infections from sand in sandboxes, recreational areas, and beaches. This paper reviews the microbes in sands, with an emphasis on fungi. Recreational areas and beach sands have been found to harbor many types of fungi and microbes. A newly emerging group of fungi of concern include the black yeast-like fungi. After establishing that sand is a reservoir for fungi, clinical manifestations of fungal infections are described with an emphasis on ocular and ear infections. Overall, we recommend environmental studies to develop monitoring strategies for sand and studies to evaluate the link between fungi exposure in sand and human health impacts.

Unlimited or disrupted communication? How does the development of the mobile phone effect our ability of social action?

The aim of this essay is to discuss the thesis of the German Sociologist Günter Burkhart that in modern societies a phenomenon appeared which he calls “handymania”, an excessive and nearly addictive use of the mobile phones especially from adolescents. After a short overview about the history of the cell phone, I will relate this development to Jürgen Habermas “theory of communicative action”, more precisely to his diagnosis of a pathological society (“lifeworld”) to find out if the “handymania” could be one expression of it. Adjacent I will present social-psychological theories from E.H.Erikson and Tilmann Habermas to ascertain whether juveniles could really be a high-risk group for this kind of addiction. I will focus on the ability to communicate in an Habermasian way that could be seriously harmed by the unregulated usage of cell phones.

Nanoparticles based Permeable Reactive Barriers as an Eco-efficient Technology for nitrate remediation in soil and groundwater

The need to increase agricultural yield led, among others, to an increase in the consumption of nitrogen based fertilizers. As a consequence, there are excessive concentrations of nitrates, the most abundant of the reactive nitrogen (Nr) species, in several areas of the world. The demographic changes and projected population growth for the next decades, and the economic shifts which are already shaping the near future are powerful drivers for a further intensification in the use of fertilizers, with a predicted increase of the nitrogen loads in soils. Nitrate easily diffuses in the subsurface environments, portraying high mobility in soils. Moreover, the presence of high nitrate loads in water has the potential to cause an array of health dysfunctions, such as methemoglobinemia and several cancers. Permeable Reactive Barriers (PRB) placed strategically relatively to the nitrate source constitute an effective technology to tackle nitrate pollution. Ergo, PRB avoid various adverse impacts resulting from the displacement of reactive nitrogen downstream along water bodies. A four stages literature review was carried out in 34 databases. Initially, a set of pertinent key words were identified to perform the initial databases searches. Then, the synonyms of those initial key words were used to carry out a second set of databases searches. The third stage comprised the identification of other additional relevant terms from the research papers identified in the previous two stages. Again, databases searches were performed with this third set of key words. The final step consisted of the identification of relevant papers from the bibliography of the relevant papers identified in the previous three stages of the literature review process. The set of papers identified as relevant for in-depth analysis were assessed considering a set of relevant characterization variables.

The role of functional polymorphisms in immune response genes as biomarkers of BCG Immunotherapy outcome in bladder cancer: Establishment of a predictive profile in a Southern Europe population

OBJECTIVE: To evaluate the predictive value of genetic polymorphisms in the context of BCG immunotherapy outcome and create a predictive profile that may allow discriminating the risk of recurrence. MATERIAL AND METHODS: In a dataset of 204 patients treated with BCG, we evaluate 42 genetic polymorphisms in 38 genes involved in the BCG mechanism of action, using Sequenom MassARRAY technology. Stepwise multivariate Cox Regression was used for data mining. RESULTS: In agreement with previous studies we observed that gender, age, tumor multiplicity and treatment scheme were associated with BCG failure. Using stepwise multivariate Cox Regression analysis we propose the first predictive profile of BCG immunotherapy outcome and a risk score based on polymorphisms in immune system molecules (SNPs in TNFA-1031T/C (rs1799964), IL2RA rs2104286 T/C, IL17A-197G/A (rs2275913), IL17RA-809A/G (rs4819554), IL18R1 rs3771171 T/C, ICAM1 K469E (rs5498), FASL-844T/C (rs763110) and TRAILR1-397T/G (rs79037040) in association with clinicopathological variables. This risk score allows the categorization of patients into risk groups: patients within the Low Risk group have a 90% chance of successful treatment, whereas patients in the High Risk group present 75% chance of recurrence after BCG treatment. CONCLUSION: We have established the first predictive score of BCG immunotherapy outcome combining clinicopathological characteristics and a panel of genetic polymorphisms. Further studies using an independent cohort are warranted. Moreover, the inclusion of other biomarkers may help to improve the proposed model.

Epidemiological and clinical aspects of snAkebite in Belo Horizonte, Southeast Brazil

Epidemiologic and clinical aspects of 310 hospitalized snakebite patients and 310 matched controls were described, over a seven years period, from an emergency hospital in Belo Horizonte, Southeast Brazil. The diagnosis was based upon clinical picture or actual snake identification. Fifty six percent of victims were bitten by the snakes of genus Bothrops, 32.0% by Crotalus, 1.0% by Lachesis and 10.0% undetermined. During the study period, stable number of cases and marked seasonal variation were noted. In comparing cases of snakebite and controls, those from a rural area or who were involved in agricultural labor activity were identified as a high risk group, with an odds ratio (OR) of 14.7 and 6.7, respectively, in favor of being bitten. Upon treatment, snakebite patients were 13.5 times more likely to have had early anaphylactic reactions than their controls, with a higher association in the age group ³ 20 years (OR = 30.3). Increased risks were also detected for pyrexia (OR = 11.7), with a marked association in the group under 19 years old (OR = 16.6). Severe cases of snakebite are an important treatable cause of morbidity in Brazil but therapy may be potentially life threatening. The higher case-fatality ratio encountered, compared to national statistics may be due the representativeness of the more severe cases who sought hospitalization. Preventing snakebite and early referral of those who are bitten is proposed

Adequate Seal and No Endoleak on the First Postoperative Computed Tomography Angiography as Criteria for No Additional Imaging Up to 5 Years after Endovascular Aneurysm Repair

OBJECTIVE: Intensive image surveillance after endovascular aneurysm repair is generally recommended due to continued risk of complications. However, patients at lower risk may not benefit from this strategy. We evaluated the predictive value of the first postoperative computed tomography angiography (CTA) characteristics for aneurysm-related adverse events as a means of patient selection for risk-adapted surveillance. METHODS: All patients treated with the Low-Permeability Excluder Endoprosthesis (W. L. Gore & Assoc, Flagstaff, Ariz) at a tertiary institution from 2004 to 2011 were included. First postoperative CTAs were analyzed for the presence of endoleaks, endograft kinking, distance from the lowermost renal artery to the start of the endograft, and for proximal and distal sealing length using center lumen line reconstructions. The primary end point was freedom from aneurysm-related adverse events. Multivariable Cox regression was used to test postoperative CTA characteristics as independent risk factors, which were subsequently used as selection criteria for low-risk and high-risk groups. Estimates for freedom from adverse events were obtained using Kaplan-Meier survival curves. RESULTS: Included were 131 patients. The median follow-up was 4.1 years (interquartile range, 2.1-6.1). During this period, 30 patients (23%) sustained aneurysm-related adverse events. Seal length <10 mm and presence of endoleak were significant risk factors for this end point. Patients were subsequently categorized as low-risk (proximal and distal seal length ≥10 mm and no endoleak, n = 62) or high-risk (seal length <10 mm or presence of endoleak, or both; n = 69). During follow-up, four low-risk patients (3%) and 26 high-risk patients (19%) sustained events (P < .001). Four secondary interventions were required in three low-risk patients, and 31 secondary interventions in 23 high-risk patients. Sac growth was observed in two low-risk patients and in 15 high-risk patients. The 5-year estimates for freedom from aneurysm-related adverse events were 98% for the low-risk group and 52% for the high-risk group. For each diagnosis, 81.7 image examinations were necessary in the low-risk group and 8.2 in the high-risk group. CONCLUSIONS: Our results suggest that the first postoperative CTA provides important information for risk stratification after endovascular aneurysm repair when the Excluder endoprosthesis is used. In patients with adequate seal and no endoleaks, the risk of aneurysm-related adverse events was significantly reduced, resulting in a large number of unnecessary image examinations. Adjusting the imaging protocol beyond 30 days and up to 5 years, based on individual patients' risk, may result in a more efficient and rational postoperative surveillance.

Prophylactic Use of Liposomal Amphotericin B in Preventing Fungal Infections Early After Liver Transplantation: a Retrospective, Single-Center Study

In this study the authors evaluated the efficacy of prophylaxis with liposomal amphotericin B (L-AmB) in the incidence of fungal infections (FI) during the first 3 months after liver transplant (LT). The study was retrospective and accessed a 4-year period from 2008 to 2011. All patients who died in the first 48 hours after LT were excluded. Patients were divided by the risk groups for FI: Group 1, high-risk (at least 1 of the following conditions: urgent LT; serum creatinine >2 mg/dL; early acute kidney injury [AKI] after LT; retransplantation; surgical exploration early post-LT; transfused cellular blood components [>40 U]); and Group 2, low-risk patients. Group 1 patients were further separated into those who received antifungal prophylaxis with L-AmB and those who did not. Prophylaxis with L-AmB consisted of intravenous administration of L-AmB, 100 mg daily for 14 days. Four hundred ninety-two patients underwent LT; 31 died in the first 48 hours after LT. From the remaining 461 patients, 104 presented with high-risk factors for FI (Group 1); of these, 66 patients received antifungal prophylaxis and 38 did not. In this group 8 FI were observed, 5 in patients without antifungal prophylaxis (P = .011). Three more FI were identified in Group 2. By logistic regression analysis, the categorical variable high-risk group was independently related to the occurrence of invasive FI (P = .006). We conclude that prophylaxis with L-AmB after LT was effective in reducing the incidence of FI. No influence on mortality was detected.

Prevalence of HIV-1/2, HTLV-I/II, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and Trypanosoma cruzi among prison inmates at Manhuaçu, Minas Gerais State, Brazil

The purpose of this study was to determine the seroprevalence of human immunodeficiency virus (HIV-1/2), human T-cell lymphotropic virus (HTLV-I/II), hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and Trypanosoma cruzi among 63 male prisoners in Manhuaçu, Minas Gerais, Brazil and to compare this with data from eligible blood donors. The positive results were as follows: 11/63 (17.5%) for HBV, 5/63 (7.4%) for syphilis, 4/63 (6.3%) for HCV, 3/63 (4.8%) for Chagas' disease, 2/63 (3.2%) for HIV-1/2 and 1/63 (1.6%) for HTLV-I/II. The seroprevalence in prisoners was higher than among blood donors, mainly for antibodies to HIV-1/2, HCV and HBV. This is probably due to low social economic level, illiteracy, higher proportion with a prior history of intravenous drug use and/or unsafe sexual behavior. Therefore, these prisoners constitute a high risk group and routine screening and counseling are recommended.

Standardization of an ELISA test using a recombinant nucleoprotein from the Junin virus as the antigen and serological screening for arenavirus among the population of Nova Xavantina, State of Mato Grosso

INTRODUCTION: Arenavirus hemorrhagic fever is a severe emerging disease. METHODS: Considering that the levels of antibodies against arenavirus in the Brazilian population are completely unknown, we have standardized an ELISA test for detecting IgG antibodies using a recombinant nucleoprotein from the Junin virus as the antigen. This protein was obtained by inserting the gene of the Junin virus nucleoprotein into the genome of Autographa californica nucleopolyhedrovirus, using the Bac-to-Bac baculovirus expression system. This recombinant baculovirus was used to infect S. frugiperda cells (SF9). RESULTS: The infection resulted in synthesis of high concentrations of recombinant protein. This protein was detected on 12.5% polyacrylamide gel and by means of Western blot. Using the standardized ELISA test, 343 samples from the population of Nova Xavantina were analyzed. We observed that 1.4% of the serum samples (five samples) presented antibody titers against arenavirus. CONCLUSIONS: These results show the population studied may present exposure to arenavirus infection.