1859年11月24日，达尔文(Charles Robert Darwin，1809～1882)发表《物种起源》一书，从而创立了生物进化论，否认了地球上人的特殊中心地位及"上帝造人"的观点，奠定了具有深刻意 义的思想变革基础，成为现代生命科学的基石.150余年来，随着现代生命科学研究的深入，人类频繁震惊于生命体构造的"精妙"与"完美"，而每一新的科学 发现也在令人类慨叹认识的局限性，诚然，在医学领域我们对生命体的认识亦仅是"冰山一角".正基于此，在微创外科迅猛发展的今天，本文从进化论角度分析外 科治疗原则的变迁，旨在探讨进化论思维模式对外科决策的指导意义.
Identification of potential T-cell epitopes in the peanut major allergens is essential for development of peptide-based immunotherapy. Traditional methods of T-cell epitope discovery use overlapping short peptides spanning the full length of the protein in T-cell proliferation assays. Because large proteins， such as Ara h 1， require a large number of peptides， this limits screening to a small number of allergic subject–derived T-cell lines.We sought to identify candidate peptides of Ara h 1 that display promiscuous binding to MHC class II and induce T2 cytokine production by T cells.MHC class II binding prediction was performed with NetMHCIIpan 2.0 (peptide length， 15; 1-mer offset) and the most abundant class II alleles in the North American population and with anMHC class II peptide reporter assay performed in parallel， which used synthetic 15-mer peptides offset by 5 mer spanning the protein. High-resolution MHC class II typing and a T-cell proliferation assay using preselected peptides were performed with PBMCs from 98 subjects with peanut allergy and 14 healthy control subjects. IL-4， IL-13， IL-5， IFN-γ， and TNF-α levels were measured in culture supernatants.Thirty-six Ara h 1 peptides were identified by usingpredictions and MHC class II binding assays. In combination with T-cell proliferation and cytokines secreted in T-cell assays， we have identified 4 vaccine candidate Ara h 1 peptides.Preselection of peptides by usingandapproaches in combination with conventional methods appears to be an effective strategy for identifying peanut T-cell peptide vaccine candidates.
Background： The consumption of hyperlipidic and hypercaloric diet is considered a major factor to promote obesity and the consumption of food with antioxidant properties， like JuÃ§ara (Euterpe edulis Mart)， could be a tool to prevent the deleterious effect of high white adipose deposition. The aim of the present study was to evaluate the effect of administration of juÃ§ara pulp in mice fed a high-fat， high-calorie diet on glucose tolerance and adipose tissue inflammatory status. Methods： Mice were distributed into the following groups： control diet; control diet plus 0.5 % of juÃ§ara; control diet plus 2 % of juÃ§ara; hypercaloric and hyperlipidic diet; hypercaloric and hyperlipidic diet plus 0.5 % of juÃ§ara and hypercaloric and hyperlipidic diet plus 2 % of juÃ§ara. Treatments started when mice were 8 weeks old and carried on for a total period of 10 weeks. The serum glucose， triacylglycerol， total cholesterol， insulin， adiponectin， lipopolysaccharides and free fatty acids concentrations were measured. Oral glucose tolerance test was performed. TNF-Î±， IL-6， and IL-10 protein level were determined by ELISA on mesenteric and epididymal white adipose tissues. Determination of catalase activity was realized in the same tissues. Data were analysed using one-way analysis of variance and post hoc analysis was performed with the Tukey's test. Results： The addition of 0.5 % juÃ§ara improved glycemic response in animals that consumed normocaloric as well as hypercaloric and hyperlipidic diets (HC). Supplementation with 0.5 and 2 % did not change the body composition of animals that received the HC diet; however， the animals fed the normocaloric diet with 2 % juÃ§ara gained body mass. An intake of 2 % juÃ§ara in the HC diet promoted a reduction of catalase activity and IL-10 level in epididymal adipose tissue. Conclusions： These results suggest that with the administration of 0.5 % juÃ§ara， the beneficial effects of polyphenols overcome the deleterious effects of macronutrient composition of juÃ§ara， whereas with the administration of 2 % juÃ§ara promotes damage by the composition of the fruit and overshadows the beneficial effects of polyphenols on glucose metabolism. On the other hand， higher juÃ§ara supplementation improves the inflammatory status targeted by the HC diet.
Prospective investigation on the transfer of Ara h 2, the most potent peanut allergen, in human breast milk
Abstract Background Peanut allergy is one of the most severe food allergies. Whether breast feeding induces tolerance to peanuts or on the contrary， predisposes at risk-babies to occult allergic sensitization to peanuts is still a matter of discussion. We sought to investigate the transfer of the most potent peanut allergen Ara h 2 into human breast milk in a German breast milk study and to shed light on the time kinetics of Ara h 2 appearance. Methods We recruited 32 lactating， non-peanut allergic women， and collected breast milk samples at different time points after consumption of 100 g dry roasted peanuts. Breast milk samples were investigated for Ara h 2 with different immunological methods： by 2D immunoblotting with a patient′s serum， by affinity enrichment using a monoclonal antibody against Ara h 2 followed by LC-MS/MS based detection and by a competitive inhibition ELISA for the detection of Ara h 2 and its digestion resistant peptides (DRP-Ara h 2). Results In a qualitative analysis Ara h 2 could be identified in a breast milk sample by 2D immunoblot by means of a patient′s serum and furthermore by immunoaffinity enrichment followed by LC-MS/MS analysis. In a semi-quantitative analysis Ara h 2 and its digestion-resistant peptides were detected in the breast milk of 9 out of 32 subjects. Evidence suggests that Ara h 2 is excreted individually either rapidly (after 1 h， 2 h， 3 h or 4 h) or delayed (after 8 h or 12 h) and in different concentrations. Conclusions Time and concentration of secreted Ara h 2 in breast milk appears to be individually regulated. The identification of Ara h 2 in breast milk is the prerequisite for the investigation of its sensitizing or tolerogenic properties. This article is protected by copyright. All rights reserved.
Background：Specific immunoglobulin E to Ara h 2 (sIgE to Ara h 2) is described as an upcoming predicting factor for diagnosing peanut allergy in children. The gold standard for diagnosing peanut allergy is a double blind placebo controlled food challenge， however this is time consuming and potentially harmful. We investigate Ara h 2 as a preliminary less invasive diagnostic tool for diagnosing peanut allergy in a general population of peanut sensitized children. Methods：Children (n=52) with peanut sensitization were retrospectively included. An oral food challenge (OFC) confirmed peanut allergy or tolerance， as primary outcome. Individual candidate predictors were identified by univariate regression analysis and used in a prediction model. Different cut-off values were obtained and receiver operating characteristic curves were plotted. Results：Multivariate analyses resulted in Ara h 2 as best predictor， with a discriminative ability of 0.87 (95% confidence interval， 0.77–0.97). Sensitivity and specificity of 55% and 95%， respectively， were found for a sIgE to Ara h 2 cut-off value of 4.25 kU/L. The highest positive predictive value of 100% was reached at 5.61 kU/L. No absolute relation was found between the value of Ara h 2 and the severity of the reaction during OFC. Conclusion：This study developed a prediction model in which sIgE to Ara h 2 was the best predictor for peanut allergy in sensitized children in a general hospital. Therefore depending on the history and the Ara h 2 results， an OFC is not always needed to confirm the diagnosis.
Removal of peanut allergen Ara h 1 from common hospital surfaces, toys and books using standard cleaning methods
Background In children， a diagnosis of peanut allergy causes concern about accidental exposure because even small amounts of peanut protein could trigger an allergic reaction. Contamination of toys， books or other items by peanut butter in areas where individuals have eaten may occur in hospital waiting rooms and cafeterias. It is not known if hospital cleaning wipes are effective in removing peanut allergen. Objectives The purpose of this study was to determine whether cleaning peanut contaminated items with common household and hospital cleaning wipes would remove peanut allergen. Methods 5 mL of peanut butter was evenly smeared on a 12 inch by 12 inch (30.5 by 30.5 cm) square on a nonporous (laminated plastic) table surface， a plastic doll， and a textured plastic ball， and 2.5 mL was applied to smooth and textured book covers. Samples for measurement of Ara h 1 were collected prior to the application of the peanut butter (baseline)， and after cleaning with a common household wipe and two commercial hospital wipes. A monoclonal-based ELISA for arachis hypogaea allergen 1 (Ara h 1)， range of detection 1.95-2000 ng/mL， was used to assess peanut allergen on each item. The samples were diluted 1：50 for testing. Results At baseline， there was no detectable Ara h 1 allergen on any item at baseline. Detectable Ara h 1 was detected on all products after applying peanut butter (range 1.2-19.0 micrograms/mL). After cleaning with any product， no Ara h 1 was detected on any item. Conclusions Table surfaces， book covers and plastic toys can be cleaned to remove peanut allergen Ara h 1 using common household and hospital cleaning wipes. Regular cleaning of these products or cleaning prior to their use should be promoted to reduce the risk of accidental peanut exposure， especially in areas where they have been used by many children.
Notas acerca de las guacamayas (Psittacidae: Ara) introducidas en el municipio de Medellín, Colombia
In the 90s， organizations in charge of wildlife management in Medellín， released macaws (Psittacidae： Ara) in the city. We report Ara severa， A. chloroptera and A. macao in the city. A group of eight individuals， belonging to the latter two species was observed flocking together in the urban area of Medellin. Nest site availability is limited because of urban expansion and logging of old dangerous trees. These macaws are out of their natural range but have shown considerable adaptability. Strategies to manage wildlife in this urban area have been limited. Further work is needed to guarantee the continued survival of these macaws.
Ara h 2 and Ara 6 are the best predictors of severe peanut allergy: A double-blind placebo-controlled study
Abstract Background Component-resolved diagnostics offers a modern tool in peanut allergy， but studies applying consistently double-blind placebo-controlled challenges are lacking. We aimed to optimize diagnostics for moderate-to-severe peanut allergy in a birch-endemic region， and to create an oral-peanut challenge with its allergen activity characterized. Methods We performed double-blind placebo-controlled peanut challenges for a referred sample of 6- to18-year-olds with peanut-sensitization or a high suspicion of peanut allergy， including anaphylaxis. We measured specific-IgE (sIgE) to Ara h 1， 2， 3， 6， 8， and 9. Testing of allergen activity of the challenge products was by IgE-microarray inhibition. Results Of the 102 patients， 69 were challenge-positive： 25 (36%) had severe， 36 (52%) moderate， and 8 (12%) mild symptoms; 38 (37%) received adrenalin. SIgE to Ara h 6 AUC 0.98 (95%CI， 0.96-1.00) was the best marker of moderate-to-severe allergy. When sIgE to Ara h 2 and Ara h 6 were measured together， all (100%) severe reactions at low doses were successfully diagnosable. SIgE to Ara h 8 had no diagnostic value， AUC 0.42 (95%CI， 0.30-0.52). Both non-roasted and roasted peanut inhibited 100% of IgE-binding to Ara h 1， 2， 3， and 6. Non-roasted peanut inhibited 87% of IgE-binding to Ara h 8， roasted inhibited 30%. The products lacked Ara h 9 activity. Conclusion Co-sensitization to Ara h 2 and Ara h 6 was associated with severe reactions distinguishing severe allergy from mild symptoms. SIgE to Ara h 8 added no diagnostic value. Component-resolved diagnostics reduce the need for oral challenges in peanut allergy. This article is protected by copyright. All rights reserved.
In the past decade， there has been an increase in allergic reactions to peanut proteins， sometimes resulting in fatal anaphylaxis. The development of improved methods for diagnosis and treatment of peanut allergies requires a better understanding of the structure of the allergens. Ara h 1， a major peanut allergen belonging to the vicilin family of seed storage proteins， is recognized by serum IgE from >90% of peanut-allergic patients. In this communication， Ara h 1 was shown to form a highly stable homotrimer. Hydrophobic interactions were determined to be the main molecular force holding monomers together. A molecular model of the Ara h 1 trimer was constructed to view the stabilizing hydrophobic residues in the three dimensional structure. Hydrophobic amino acids that contribute to trimer formation are at the distal ends of the three dimensional structure where monomer-monomer contacts occur. Coincidentally， the majority of the IgE-binding epitopes are also located in this region， suggesting that they may be protected from digestion by the monomer-monomer contacts. On incubation of Ara h 1 with digestive enzymes， various protease-resistant fragments containing IgE-binding sites were identified. The highly stable nature of the Ara h 1 trimer， the presence of digestion resistant fragments， and the strategic location of the IgE-binding epitopes indicate that the quaternary structure of a protein may play a significant role in overall allergenicity.