Not All Worms Were Created Equal

[Extract] Whilst we support the need to report safety outcomes from experimental therapy of any kind, including the use of helminths as therapy, we believe that it is important to critically examine the causal relationship of the reported event to the proposed etiology so that a balanced view of the cause and effect be arrived at. This is particularly the case in an uncontrolled setting where formal processes for documenting and reporting experimental therapy may not be in place. Recent reviews of studies with one of the most widely used helminths, the anthropophilic hookworm, Necator americanus, have shown this helminth to be safe and well tolerated in hundreds of individuals by numerous research groups across Australia, the US and Europe (1–3). In BMC Pulmonary Medicine (4), Zeynalyan and colleagues report rapidly progressive respiratory failure in a patient with significant comorbidities, including systemic sclerosis, interstitial lung disease and pulmonary hypertension after self-administration of N. americanus larvae that were purchased over the internet. Here we raise some concerns about this report

Hydrogen producing microbial communities of the biocathode in a microbial electrolysis cell

In the search for alternatives for fossil fuels and the reuse of the energy from waste streams, the microbial electrolysis cell is a promising technique. The microbial electrolysis cell is a two electrode system in which at the anode organic substances, including waste water, are used by microorganisms that release the terminal electrons to the electrode. These electrons are subsequently used at the cathode resulting in the production of a current. By addition of a small voltage, hydrogen gas can be produced by combining electrons and protons at the cathode. To catalyse the hydrogen evolution reaction at the cathode, expensive catalysts such as platinum are required. Recently, the use of biocathodes has shown great potential as an alternative for platinum. The microbial community responsible for the hydrogen evolution in such systems is, however, not well understood. In this study we focused on the characterization of the microbial communities of the microbial electrolysis cell biocathode using molecular techniques. The results show that the microbial community consists of 44% Proteobacteria, 27% Firmicutes, 18% Bacteriodetes and 12% related to other phyla. Within the major phylogenetic groups we found several clusters of uncultured species belonging to novel taxonomic groups at genus level. These novel taxonomic groups developed under environmentally unusual conditions and might have properties that have not been described before. Therefore it is of great interest to study those novel groups further. Within the Proteobacteria a major cluster belonged to the Deltaproteobacteria and based on the known characteristics of the closest related cultured species, we suggest a mechanism for microbial electron transfer for the production of hydrogen at the cathode

Suppression of inflammation and tissue damage by a hookworm recombinant protein in experimental colitis

Gastrointestinal parasites, hookworms in particular, have evolved to cause minimal harm to their hosts when present in small numbers, allowing them to establish chronic infections for decades. They do so by creating an immunoregulatory environment that promotes their own survival, but paradoxically also benefits the host by protecting against the onset of many inflammatory diseases. To harness the therapeutic value of hookworms without using live parasites, we have examined the protective properties of the recombinant protein anti-inflammatory protein (AIP)-1, secreted in abundance by hookworms within the intestinal mucosa, in experimental colitis. Colitic inflammation assessed by weight loss, colon atrophy, oedema, ulceration and necrosis, as well as abdominal adhesion was significantly suppressed in mice treated with a single intraperitoneal dose of AIP-1 at 1 mg kg(-1). Local infiltration of inflammatory cells was also significantly reduced, with minimal goblet cell loss and preserved mucosal architecture. Treatment with AIP-1 promoted the production of colon interleukin (IL)-10, transforming growth factor (TGF)-beta and thymic stromal lymphopoietin (TSLP), resulting in the suppression of tumour necrosis factor (TNF)-alpha, IL-13 and IL-17 A cytokines and granulocyte macrophage colony-stimulating factor (GM-CSF), CX motif chemokine ( CXCL)-11 and cyclooxygenase synthase (COX)-2 mRNA transcripts. AIP-1 promoted the accumulation of regulatory T cells in the colon likely allowing rapid healing of the colon mucosa. Hookworm recombinant AIP-1 is a novel therapeutic candidate for the treatment of inflammatory bowel diseases that can be explored for the prevention of acute inflammatory relapses, an important cause of colorectal cancer

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease

A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders.This work was supported by grants 613718 to P.G., and 1037304 and 1020114 to A.L. from the National Health and Medical Research Council of Australia (NHMRC), and by the Royal Society and the Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grants Scheme to C.C. T.J. is supported by scholarships from the Biotechnology and Biological Sciences Research Council (BBSRC) Doctoral Training Partnerships program

Effect of Hookworm Infection on Wheat Challenge in Celiac Disease – A Randomised Double-Blinded Placebo Controlled Trial

Background and Aims: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten

Effects of the glucolipid synthase inhibitor, P4, on functional and phenotypic parameters of murine myeloma cells

This study describes the effects of the glucolipid synthase inhibitor P4, (DL-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol), on various functional and phenotypic parameters of 5T33 murine myeloma cells. Cell recovery was reduced by >85% following incubation of the cells for 3 days in the presence of 4 μM P4 (the IC50 concentration). Both cytostatic and cytotoxic inhibition was observed with tumour cell metabolic activity and clonogenic potential reduced to 42% and 14% of controls, respectively, and viability reduced to 52%. A dose-dependent increase in cells undergoing apoptosis (from 7% to 26%) was also found. P4 induced a decrease in the number of cells expressing H-2 Class I and CD44, and a large increase in cells expressing H-2 Class II and the IgG2b paraprotein. It did not affect surface expression of CD45 or CD54 (ICAM-1). Based on these alterations in tumour cell growth, adhesion molecule expression and potential immunogenicity, it is anticipated that P4 will provide a novel therapeutic approach for the treatment of multiple myeloma. In addition, given that essentially all tumours rely heavily on overexpressed or abnormal glucosphingolipids for growth, development and metastasis, glucolipid synthase inhibitors may prove to be universally effective anti-cancer agents. © 1999 Cancer Research Campaig

Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases

Magnetic moments of short-lived nuclei with part-per-million accuracy: Towards novel applications of β\beta-detected NMR in physics, chemistry and biology

We determine for the first time the magnetic dipole moment of a short-lived nucleus with part-per-million (ppm) accuracy. To achieve this two orders of magnitude improvement over previous studies, we implement a number of innovations into our $\beta$-detected Nuclear Magnetic Resonance ($\beta$-NMR) setup at ISOLDE/CERN. Using liquid samples as hosts we obtain narrow, sub-kHz linewidth, resonances, while a simultaneous in-situ $^1$H NMR measurement allows us to calibrate and stabilize the magnetic field to ppm precision, thus eliminating the need for additional $\beta$-NMR reference measurements. Furthermore, we use ab initio calculations of NMR shielding constants to improve the accuracy of the reference magnetic moment, thus removing a large systematic error. We demonstrate the potential of this combined approach with the 1.1 s half-life radioactive nucleus $^{26}$Na, which is relevant for biochemical studies. Our technique can be readily extended to other isotopic chains, providing accurate magnetic moments for many short-lived nuclei. Furthermore, we discuss how our approach can open the path towards a wide range of applications of the ultra-sensitive $\beta$-NMR in physics, chemistry, and biology.Comment: re-submitte

Eosinophilic Enteritis Confined to an Ileostomy Site

Eosinophilic enteritis is a rather rare condition that can manifest anywhere from esophagus to rectum. Its description in the literature is sparse, but associations have been made with collagen vascular disease, malignancy, food allergy, parasitic or viral infections, inflammatory bowel disease, and drug sensitivity. We present the case of a 41-year-old male diagnosed with ulcerative colitis who underwent proctocolectomy with ileal pouch anal anastomosis and loop ileostomy formation utilizing Seprafilm®, who later developed eosinophilic enteritis of the loop ileostomy site. This is the first report of eosinophilic enteritis and its possible link to the use of bioabsorbable adhesion barriers