Exogenous activated NK cells enhance trafficking of endogenous NK cells to endometriotic lesions

Background: Endometriosis is defined as the presence of endometrial glands and stroma at ectopic locations. Although the prevalence of endometriosis is as high as 35 %-50 %, its pathogenesis remains controversial. An increasing number of studies suggest that changes in immune reactivity may be primarily involved in the development of endometriosis development. In this sense, it has been strongly suggested that a fundamental part of immunologic system, the natural killer cells (NK cells), are an important part of this process. NK cells, a component of the innate immune system, have been extensively studied for their ability to defend the organism against infections and malignancy. Recent studies have shown that IL-2-activated NK (A-NK) cells are able to attack and destroy tumors in lungs and livers of mice, demonstrating the therapeutic potential of these cells. Similarly to metastatic tumor cells, endometrial cells are able to adhere, infiltrate and proliferate at ectopic locations. Therefore, in this study, we evaluated the ability of adoptively transferred and endogenous NK cells to infiltrate endometriosis lesions. Methods: As NK cells donors were used C57BL/6 B6. PL- Thy 1.1 female mice. As uterine horns donors were used C57/BL6+GFP female mice and as endometriosis recipients C57BL/6 Thy1.2 female mice. Endometriosis induction was made by injection of endometrial tissue fragments. After 4 weeks, necessary for endometriosis lesions establishment the animals were divided in 3 experimental groups with 10 animals each. Group 1 received i.v doses of 5x106 A-NK in 200μl RPMI; Group 2 received i.p dose of 5x106 A-NK in 200μl RPMI and Group 3 received i.p dose of IL2 (0.5 mL RPMI containing 5.000U of IL2). Results: Our data show that exogenous A-NK cells injected via ip combined with endogenous A-NK cells seems to be the most efficient way for activated NK cells track and infiltrate endometriosis. Conclusion: For the first time, it was shown that both endogenous as exogenous A-NK cells are able to track, migrate and infiltrate endometriosis lesion. This seems to be a promising result, and if confirmed the efficiency of A-NK cells in killing endometriosis lesions, maybe in the future we could use this approach as an alternative treatment for women with endometriosis

Best practices in intercultural health: five case studies in Latin America

The practice of integrating western and traditional indigenous medicine is fast becoming an accepted and more widely used approach in health care systems throughout the world. However, debates about intercultural health approaches have raised significant concerns. This paper reports findings of five case studies on intercultural health in Chile, Colombia, Ecuador, Guatemala, and Suriname. It presents summary information on each case study, comparatively analyzes the initiatives following four main analytical themes, and examines the case studies against a series of the best practice criteria

Factors Affecting Infestation by Triatoma infestans in a Rural Area of the Humid Chaco in Argentina: A Multi-Model Inference Approach

Vector-borne transmission of Chagas disease remains a major public health problem in parts of Latin America. Triatoma infestans is the main vector in the countries located in the South American Cone, particularly in the Gran Chaco ecoregion where residual insecticide control has achieved only a moderate, irregular impact. To contribute to improved control strategies, we analyzed the factors associated with the presence and abundance of T. infestans in 327 inhabited houses in a well-defined rural area with no recent vector control interventions in the humid Argentine Chaco. Bugs were found mainly in domiciles, kitchens, storerooms, and chicken coops and nests, particularly where adequate refuge and animal hosts (humans, dogs, cats or poultry) were available. Domiciles constructed from mud were the most often infested, but brick-and-cement domiciles, even in good conditions, were also found infested. Availability of refuge and hosts for T. infestans are key targets for vector control. Ten-fold variations in domestic infestation observed across neighboring villages, and differences in the relevant factors for T. infestans presence with respect to other areas of the Gran Chaco region suggest that host management, building techniques and insecticide use need to be tailored to the local environment, socio-economic characteristics, and climatic conditions

An efficient approach to BAC based assembly of complex genomes

Background: There has been an exponential growth in the number of genome sequencing projects since the introduction of next generation DNA sequencing technologies. Genome projects have increasingly involved assembly of whole genome data which produces inferior assemblies compared to traditional Sanger sequencing of genomic fragments cloned into bacterial artificial chromosomes (BACs). While whole genome shotgun sequencing using next generation sequencing (NGS) is relatively fast and inexpensive, this method is extremely challenging for highly complex genomes, where polyploidy or high repeat content confounds accurate assembly, or where a highly accurate ‘gold’ reference is required. Several attempts have been made to improve genome sequencing approaches by incorporating NGS methods, to variable success. Results: We present the application of a novel BAC sequencing approach which combines indexed pools of BACs, Illumina paired read sequencing, a sequence assembler specifically designed for complex BAC assembly, and a custom bioinformatics pipeline. We demonstrate this method by sequencing and assembling BAC cloned fragments from bread wheat and sugarcane genomes. Conclusions: We demonstrate that our assembly approach is accurate, robust, cost effective and scalable, with applications for complete genome sequencing in large and complex genomes

IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni

Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4+CD44+CD25+GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni

Challenges and Pitfalls in the Management of Parathyroid Carcinoma: 17-Year Follow-Up of a Case and Review of the Literature

A 29-year-old man presented to his primary care physician with nausea, severe weight loss and muscle weakness. He had a hard, fixed neck swelling. He was severely hypercalcaemic with 10-fold increased parathyroid hormone (PTH) concentrations. A diagnosis of primary hyperparathyroidism was established and the patient was referred for parathyroidectomy. At neck exploration, an enlarged parathyroid gland with invasive growth into the thyroid gland was found and removed, lymph nodes were cleared and hemithyroidectomy was performed. A suspected diagnosis of parathyroid carcinoma was confirmed histologically. Serum calcium and PTH levels normalised post-operatively, but hyperparathyroidism recurred within 3 years of surgery. Over the following 17 years, control of hypercalcaemia represented the most difficult challenge despite variable success achieved with repeated surgical interventions, embolisations, radiofrequency ablation of metastases and treatment with calcimimetics, bisphosphonates and haemodialysis using low-dialysate calcium. In this paper, we report the challenges and pitfalls we encountered in the management of our patient over nearly two decades of follow-up and review recent literature on the topic