Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial.

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.

Immediate and long-term impact of the COVID-19 pandemic on delivery of surgical services.

BACKGROUND: The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients. Very little is known about pandemic management and effects on other services, including delivery of surgery. METHODS: This was a scoping review of all available literature pertaining to COVID-19 and surgery, using electronic databases, society websites, webinars and preprint repositories. RESULTS: Several perioperative guidelines have been issued within a short time. Many suggestions are contradictory and based on anecdotal data at best. As regions with the highest volume of operations per capita are being hit, an unprecedented number of operations are being cancelled or deferred. No major stakeholder seems to have considered how a pandemic deprives patients with a surgical condition of resources, with patients disproportionally affected owing to the nature of treatment (use of anaesthesia, operating rooms, protective equipment, physical invasion and need for perioperative care). No recommendations exist regarding how to reopen surgical delivery. The postpandemic evaluation and future planning should involve surgical services as an essential part to maintain appropriate surgical care for the population during an outbreak. Surgical delivery, owing to its cross-cutting nature and synergistic effects on health systems at large, needs to be built into the WHO agenda for national health planning. CONCLUSION: Patients are being deprived of surgical access, with uncertain loss of function and risk of adverse prognosis as a collateral effect of the pandemic. Surgical services need a contingency plan for maintaining surgical care in an ongoing or postpandemic phase.

ANTECEDENTES: La pandemia en curso tiene un efecto colateral sobre la salud en la prestación de atención quirúrgica a millones de pacientes. Se sabe muy poco sobre el manejo de la pandemia y sus efectos colaterales en otros servicios, incluida la prestación de servicios quirúrgicos. MÉTODOS: Se ha realizado una revisión de alcance de toda la literatura disponible relacionada con COVID-19 y cirugía utilizando bases de datos electrónicas, páginas web de sociedades, seminarios online y repositorios de pre-publicaciones. RESULTADOS: Se han publicado varias guías perioperatorias en un corto período de tiempo. Muchas recomendaciones son contradictorias y, en el mejor de los casos, se basan en datos anecdóticos. A medida que las regiones con el mayor volumen de operaciones per cápita se ven afectadas, se cancela o difiere un número sin precedentes de operaciones. Ninguna de las principales partes interesadas parece haber considerado cómo una pandemia priva de recursos a los pacientes que necesitan una intervención quirúrgica, con pacientes afectados de manera desproporcionada debido a la naturaleza del tratamiento (uso de anestesia, quirófanos, equipo de protección, contacto físico y necesidad de atención perioperatoria). No existen recomendaciones sobre cómo reanudar la actividad quirúrgica. La evaluación tras la pandemia y la planificación futura deben incluir a los servicios quirúrgicos como una parte esencial para mantener la atención quirúrgica adecuada para la población también durante un brote epidémico. La prestación de servicios quirúrgicos, debido a su naturaleza transversal y a sus efectos sinérgicos en los sistemas de salud en general, debe incorporarse a la agenda de la OMS para la planificación nacional de la salud. CONCLUSIÓN: Los pacientes se ven privados de acceso a la cirugía con una pérdida de función incierta y riesgo de un pronóstico adverso como efecto colateral de la pandemia. Los servicios quirúrgicos necesitan un plan de contingencia para mantener la atención quirúrgica durante la pandemia y en la fase post-pandemia.

Cigarette smoke modifies neutrophil chemotaxis, neutrophil extracellular trap formation and inflammatory response-related gene expression.

BACKGROUND AND OBJECTIVE: Cigarette smoking is a major risk factor for periodontitis, and smoking perturbs neutrophil reactive oxygen species production. This study tested the hypothesis that cigarette smoke extract (CSE) and its components/metabolites nicotine, cotinine and thiocyanate (SCN-), may influence neutrophil functions. MATERIAL AND METHODS: Chemotaxis was assessed in neutrophils pre-treated with CSE using real-time video microscopy. Neutrophil extracellular trap (NET) release in response to CSE, nicotine, cotinine, SCN- as well as to phorbol 12-myristate-13-acetate and hypochlorous acid following pre-treatment with CSE, nicotine, cotinine or SCN- was assessed using fluorescence-based assays. The impact of CSE and SCN- treatment on neutrophil respiratory burst- and inflammation-related gene expression (NFKBIE, DNAJB1, CXCL8, NCF1, NCF2, CYBB) was determined by real-time polymerase chain reaction. RESULTS: Both CSE and SCN- pre-treatment inhibited phorbol 12-myristate-13-acetate-stimulated NET release. Additionally, SCN- inhibited hypochlorous acid-stimulated NET formation, while SCN- alone stimulated NET release. Overall, neutrophils pre-treated with CSE exhibited reduced speed, velocity and directionality relative to untreated neutrophils. Although CSE and SCN- promoted DNAJB1 expression, increased redox-related gene expression was only detected in response to SCN-. CONCLUSION: These results suggest that CSE can alter ex vivo neutrophil activation by mechanisms independent of SCN- and nicotine, and SCN- may contribute to the perturbed innate immune responses observed in smokers.

Progress in the development of subunit vaccines for gastrointestinal nematodes of ruminants.

The global increase in anthelmintic resistant nematodes of ruminants, together with consumer concerns about chemicals in food, necessitates the development of alternative methods of control for these pathogens. Subunit recombinant vaccines are ideally placed to fill this gap. Indeed, they are probably the only valid option for the long-term control of ruminant parasitic nematodes given the increasing ubiquity of multidrug resistance in a range of worm species across the world. The development of a subunit multicellular parasite vaccine to the point of practical application would be a groundbreaking step in the control of these important endemic infections of livestock. This review summarizes the current status of subunit vaccine development for a number of important gastrointestinal nematodes of cattle and sheep, with a focus on the limitations and problems encountered thus far, and suggestions as to how these hurdles might be overcome.

Marker genes for activation of the RNA interference (RNAi) pathway in the free-living nematode Caenorhabditis elegans and RNAi development in the ovine nematode Teladorsagia circumcincta.

The nematode Teladorsagia circumcincta is a major cause of parasitic gastroenteritis in sheep in temperate regions. The development of resistance to the major anthelmintic classes used for its control is a threat to small ruminant farming sustainability. Vaccination is a potential alternative control method for this nematode. Gene datasets can be exploited to identify potential vaccine candidates and these validated further by methods such as RNA interference (RNAi) prior to vaccine trials. Previous reports indicate that RNAi in parasitic nematodes is inconsistent and, to date, there are no internal controls that indicate activation of the RNAi pathway in response to double-stranded RNA (dsRNA). The present aims were to determine whether or not the transcription levels of potential marker genes in the RNAi pathway could indicate activation of the pathway in Caenorhabditis elegans and to develop an RNAi platform in T. circumcincta. In C. elegans, transcript levels of three candidate marker genes, Ce-dcr-1 (Dicer), Ce-ego-1 (Enhancer of Glp-One family member) and Ce-rsd-3 (RNAi Spreading Defective), were analysed and results indicated that activation of the pathway had no effect on transcript levels of these genes. In T. circumcincta, two vaccine candidate genes from the Activation-associated Secreted Protein (ASP) family were targets for knockdown. RNAi experiments showed successful silencing of both targets, although inconsistencies in efficacy were observed. After testing a number of parameters that might affect variability, it was found that the length of the storage period of the larvae plays an important role in the consistency of the RNAi results.

Helminth egg excretion with regard to age, gender and management practices on UK Thoroughbred studs.

Few studies have described the combined effect of age, gender, management and control programmes on helminth prevalence and egg shedding in grazing equines. Here, fecal samples collected from 1221 Thoroughbred horses, residing at 22 studs in the UK, were analysed. The distribution of strongyle eggs amongst individuals in relation to age, gender and management practices was investigated. Fecal worm egg counts (FWECs), described as the number of eggs per gramme (epg) of feces, were determined using a modification of the salt flotation method. The FWEC prevalence (mean%) of strongyles, Parascaris equorum, tapeworm spp. and Strongyloides westeri was 56, 9, 4 and 8%, respectively. Strongyle, P. equorum, tapeworm spp. and S. westeri infections were detected on 22 (100%), 11 (50%), 9 (41%) and 8 (36%) of studs, respectively. Within all age and gender categories, strongyle FWECs were highly over-dispersed (arithmetic mean = 95 epg, aggregation parameter k=0·111) amongst horses. Animal age, last anthelmintic type administered and management practices (for example, group rotation on grazing) most strongly influenced strongyle prevalence and level of egg shedding (P < 0·05). Overall, 11% of equines (range: 234-2565 epg) were responsible for excreting 80% of the strongyle eggs detected on FWEC analysis. The results confirm that the judicious application of targeted treatments has potential to control equine strongyle populations by protecting individual horses from high burdens, whilst promoting refugia for anthelmintic susceptible genotypes.

Variation in fecal egg counts in horses managed for conservation purposes: individual egg shedding consistency, age effects and seasonal variation.

Cyathostomins are the most prevalent equine intestinal parasites and resistance has been reported in these nematodes against all 3 licensed anthelmintic classes. Strategies need to be developed that are less dependent upon drugs and more reliant on management-based control. To develop these we need to understand natural transmission patterns better. Here, we analysed longitudinal fecal egg count (FEC) data from 5 pony populations used for conservation purposes. We tested how egg excretion varied amongst populations and individuals, and how this was affected by age and climate. There was evidence for consistency in FECs over time at the individual level; this was generally weak and accounted for <10% of the total variance. Animals <5 years old had higher FECs and there was profound seasonal variation in FECs, with highest levels recorded in spring/summer. Effects of monthly temperature and rainfall explained most, but not all, of the observed seasonal variation and associations between climate measures and FECs were stronger in younger versus adult animals. One population was occasionally treated with anthelmintics and analysis of this population suggested that treatment substantially altered the seasonal dynamics. This paper highlights the variability in strongyle egg excretion amongst individuals and the factors involved in this variation.

Phage-display library biopanning as a novel approach to identifying nematode vaccine antigens.

Infections with parasitic nematodes are of significant welfare and economic importance worldwide, and because of the emergence of anthelmintic resistance, this has lead to alternative methods of parasite control being required. Vaccination offers a feasible alternative control, and the majority of research has focused on the production of recombinant versions of native antigens previously identified as protective in vaccinated animals. Attempts at the production of protective recombinant subunit vaccines have been hindered, however, as these antigens have invariably failed to replicate the same level of protective immune response as seen with the native versions. It has been proposed that these failures are owing to the fact that the recombinant proteins do not contain the appropriate post-translational modifications to retain the protective capacity of the native molecules. In this review, we discuss a novel approach to vaccine antigen identification through the application of random peptide phage-display libraries and their use to identify peptide sequences that potentially mimic the structure(s) of antigenic epitopes. This area of research is still relatively novel with respect to parasites, and the current state of the art will be discussed here.

New insights into sequence variation in the IGS region of 21 cyathostomin species and the implication for molecular identification.

Cyathostomins comprise a group of 50 species of parasitic nematodes that infect equids. Ribosomal DNA sequences, in particular the intergenic spacer (IGS) region, have been utilized via several methodologies to identify pre-parasitic stages of the commonest species that affect horses. These methods rely on the availability of accurate sequence information for each species, as well as detailed knowledge of the levels of intra- and inter-specific variation. Here, the IGS DNA region was amplified and sequenced from 10 cyathostomin species for which sequence was not previously available. Also, additional IGS DNA sequences were generated from individual worms of 8 species already studied. Comparative analysis of these sequences revealed a greater range of intra-specific variation than previously reported (up to 23%); whilst the level of inter-specific variation (3-62%) was similar to that identified in earlier studies. The reverse line blot (RLB) method has been used to exploit the cyathostomin IGS DNA region for species identification. Here, we report validation of novel and existing DNA probes for identification of cyathostomins using this method and highlight their application in differentiating life-cycle stages such as third-stage larvae that cannot be identified to species by morphological means.

A calcium-activated apyrase from Teladorsagia circumcincta: an excretory/secretory antigen capable of modulating host immune responses?

A cDNA representing the gene Teladorsagia circumcincta apyrase-1 (Tci-apy-1) was isolated, by PCR, from a T. circumcincta fourth-stage larval (L4) cDNA library. The closest orthologue of this gene is a Ca(2+)-dependent apyrase from Ostertagia ostertagi, with 92% amino acid identity across all 339 residues. Tci-apy-1 is transcribed in a stage-specific manner, the transcript being predominant in L4, detectable in the adult cDNA, but absent from eggs and infective third-stage larvae (L3). The protein, Tci-APY-1, was detected by immunoblotting in extracts of L4 nematodes and was present in excretory/secretory products from the same developmental stage. A recombinant version of Tci-APY-1 was expressed in bacteria as an active enzyme that hydrolysed nucleoside triphosphate substrates with a preference of ATP over other nucleoside triphosphates. Recombinant Tci-APY-1 hydrolysed ATP and ADP but not AMP. Apyrase activity was divalent cation-dependent, with no hydrolysis in the presence of Mg(2+), but activation in the presence of Ca(2+). Recombinant Tci-APY-1 was bound by IgG present in serum and both IgG and IgA present in abomasal mucus from trickle-infected, immune sheep but not in material derived from lambs exposed to a single infection. The potential immunomodulatory roles of this Tci-APY-1 are discussed in relation to purinergic signalling.

Fusobacterium nucleatum regulation of neutrophil transcription.

BACKGROUND AND OBJECTIVE: Abnormal neutrophil responses have been observed in periodontitis patients, including hyper-reactivity in terms of production of reactive oxygen species (ROS) following exposure to the key quorum-sensing plaque bacterium, Fusobacterium nucleatum. This study was designed to characterize the transcriptional response of neutrophils to F. nucleatum. MATERIAL AND METHODS: Peripheral blood neutrophils were exposed to F. nucleatum, and gene expression was analysed using high-throughput transcriptomics. RESULTS: Microarray technology demonstrated differential expression of 208 genes (163 increased and 43 decreased relative to control genes), which identified regulation of several ontological classes, including signal transduction (13%), transcription regulation (7%) and ROS response (14%). Individual gene expression analysis of selected transcripts, including CSF, CXCL3, FOS, HMOX1, HSP40, SOD2, NFKB2 and GP91, in individual and pooled RNA samples from control and F. nucleatum-exposed neutrophils corroborated microarray data. Analysis of ROS generation, combined with transcript analysis, in response to a panel of proinflammatory stimuli (F. nucleatum, Porphyromonas gingivalis, Escherichia coli lipopolysaccharide and opsonized Staphylococcus aureus) identified significant differences in ROS and transcript regulatory control. Further analyses of neutrophils from periodontitis patients and periodontally healthy control subjects stimulated with F. nucleatum indicated significant differential induction of several ROS response-related transcripts. CONCLUSION: These data demonstrate that neutrophils are transcriptionally active in response to the periodontal pathogen F. nucleatum and that these changes in gene expression are likely to affect neutrophil function. The differential response of neutrophils to a range of stimuli combined with data demonstrating differences between patient and control neutrophils indicate the importance of this cell and its interaction with the local tissue environment in the pathogenesis of periodontitis.

Facing the threat of equine parasitic disease.

Horses worldwide are exposed to a complex mixture of intestinal parasitic helminths. When burdens are high, these parasites can seriously compromise health and welfare. Some helminth species have an extremely high prevalence and are difficult to control, not least because there is a limited understanding of their most basic biology. Furthermore, levels of resistance to some of the commonly used anthelmintics are widespread and increasing. The cyathostomins are the most common nematode species affecting equids worldwide. Within this group of parasites are more than 50 different species. Until recent research activities, little was known about the contribution that individual species make to clinical disease, parasite epidemiology and anthelmintic resistance. This review describes some of the recent research advances in the understanding of cyathostomins in these areas. As part of the research effort, molecular tools were developed to facilitate identification of the non-parasitic stages of cyathostomins. These tools have proved invaluable in the investigation of the relative contributions that individual species make to the pathology and epidemiology of mixed infections. At the more applied level, research has also progressed in the development of a diagnostic test that will allow numbers of cyathostomin encysted larvae to be estimated. This test utilises cyathostomin-specific serum antibody responses as markers of infection. As anthelmintic resistance will be the major constraint on parasite control in future, researchers are actively investigating mechanisms of drug resistance and how to improve the detection of resistance in the field. Recent developments in these areas are also outlined.

Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN-JDRF Type 1 Diabetes Combination Therapy Assessment Group.

Like many other complex human disorders of unknown aetiology, autoimmune-mediated type 1 diabetes may ultimately be controlled via a therapeutic approach that combines multiple agents, each with differing modes of action. The numerous advantages of such a strategy include the ability to minimize toxicities and realize synergies to enhance and prolong efficacy. The recognition that combinations might offer far-reaching benefits, at a time when few single agents have yet proved themselves in well-powered trials, represents a significant challenge to our ability to conceive and implement rational treatment designs. As a first step in this process, the Immune Tolerance Network, in collaboration with the Juvenile Diabetes Research Foundation, convened a Type 1 Diabetes Combination Therapy Assessment Group, the recommendations of which are discussed in this Perspective paper.

A macrophage migration inhibitory factor-like tautomerase from Teladorsagia circumcincta (Nematoda: Strongylida).

A macrophage migration inhibitory factor (MIF)-like molecule, Tci-MIF-1, was isolated from Teladorsagia circumcincta and subjected to detailed characterization. A cDNA representing Tci-mif-1 was isolated following its identification in third-stage larvae (L3)-enriched cDNA population. Sequencing of the cDNA indicated a 348-bp open reading frame (ORF) with the closest orthologue being a MIF derived from the human hookworm Ancylostoma ceylanicum. Messenger RNA (mRNA) representing the Tci-MIF-1 transcript was detected in eggs, L3 and adult stages of T. circumcincta. The transcript was also present, but to a lesser extent in fourth-stage larvae (L4). Detection of Tci-MIF-1 protein in T. circumcincta developmental stages reflected the transcript levels identified by reverse transcriptase-PCR. Using immunohistochemistry, the Tci-MIF-1 protein was shown to have a diffuse distribution in L3 tissue, and in L4 and adult stages, the protein was localized to the nematode gut. A recombinant version of Tci-MIF-1 was produced, and enzymic assays indicated that this recombinant protein and a somatic extract of L3 possessed dopachrome tautomerase activity as has been observed previously in other MIF-like molecules. Neither native, purified Tci-MIF nor recombinant Tci-MIF-1 dramatically influenced the in vitro migration of sheep monocytes.

MMP-13 expression in keratocyst odontogenic tumour associated with NBCCS and sporadic keratocysts.

OBJECTIVE: To investigate the matrix metalloproteinase (MMP)-13 expression in associated and non-nevoid basal cell carcinoma syndrome (NBCCS) Odontogenic Keratocysts (OCKs) in order to contribute to a better understanding of the differences in the growth pattern between them. MATERIALS AND METHODS: Thirty-nine paraffin-embedded blocks of OCKs, 26 sporadic OCKs and 11 NBCCS-associated KCOTs were studied by immunohistochemistry to evaluate MMP-13 expression both in epithelial and stromal layers. A semi-quantitative scale was used to evaluate immunostaining. Obtained data were compared between the two groups, using Fischer's exact test and the chi-square test. RESULTS: Only 13 of 26 sporadic OCKs showed a positive immunostaining, whilst 11 KCOTs resulted in positive labelling for MMP-13 expression. Moreover, syndromic cysts displayed a more intense and diffuse MMP-13 labelling of the stromal tissue. Instead, in non-syndromic forms, the staining pattern of MMP-13 in stromal tissue was completely absent. Fisher's exact test showed a statistically significant greater prevalence of KCOTs-immunolabelled cysts with respect to sporadic OCKs. CONCLUSIONS: Results from this study point out that the biological behaviour of these cysts could be related not only to the epithelial layer but also to stromal tissue in that... MMP-13 overexpression in stromal tissue of NBCCS-associated KCOTs could clarify the higher aggressiveness of these cysts.

Teladorsagia circumcincta: activation-associated secreted proteins in excretory/secretory products of fourth stage larvae are targets of early IgA responses in infected sheep.

A detailed proteomic analysis of excreted/secretory (ES) proteins derived from fourth stage larvae (L4) of Teladorsagia circumcincta identified a number of components, including N-type and C-type single domain activation-associated secreted proteins (ASPs). Immunoblotting of L4 ES extracts with abomasal mucus derived from infected, immune sheep demonstrated the immunogenicity of some of these components, including an N-type single-domain ASP, designated Tci-ASP-1. The full-length cDNA encoding this protein was isolated and sequenced. Homology searches using the inferred amino acid sequence of Tci-ASP-1 showed that it had highest identity (75% over 231 residues) to, a N-type, single-domain ASP from Ostertagia ostertagi. Phylogenetic analysis confirmed the relationship of Tci-ASP-1 with other N-type ASPs. Reverse-transcriptase (RT)-PCR experiments demonstrated the presence of transcript encoding Tci-ASP-1 in L4 and adult stage T. circumcincta but not in pre-parasitic stages such as eggs and third stage larvae. A recombinant version of Tci-ASP-1 was expressed in Escherichia coli and the purified protein was reactive with IgA present in abomasal mucus derived from immune sheep.

Teladorsagia circumcincta in the sheep abomasum: defining the role of dendritic cells in T cell regulation and protective immunity.

Parasitic nematodes of the small-ruminant gastrointestinal tract pose a problem worldwide. The impact of these pathogens is worsened by the emergence of anthelmintic resistance to all three available classes of drugs. In addition to causing considerable economic loss, these parasites are detrimental to the health and welfare of sheep and goats. Vaccination offers an alternative approach to drug-based control and a great deal of investment has gone into the investigation of protective antigens for some of these nematode species. However, attempts at vaccination are hindered by a lack of understanding of how best to promote protective immunity to nematode species, such as Teladorsagia circumcincta, which inhabits the abomasum of sheep. This situation contrasts with that in murine models of gastrointestinal nematode infection, where the basis of protective immunity is increasingly well understood. In this review, we discuss the current knowledge of the immune effector mechanisms elicited by T. circumcincta and consider the probable role of dendritic cells in the initiation of both effector and regulatory responses in the abomasum.

Proteomic analysis of excretory/secretory products released by Teladorsagia circumcincta larvae early post-infection.

Teladorsagia circumcincta is an important parasitic nematode of domestic small ruminants. Drug resistance in this species is common so alternative methods of control are required. As animals develop immunity to T. circumcincta, vaccination is a valid option. Little is known about the antigens that play a role in stimulating immunity at this host/parasite interface. As responses generated between 1 and 5 dpi are known to affect development of these nematodes in their gastric niche, we focused on proteins released during the early stages of infection. To identify molecules potentially involved in immunity, we undertook a proteomics analysis of proteins released from larvae harvested at 1-, 3- and 5-days post-infection (dpi). This analysis produced peptide sequence data that was used to search information available in T. circumcincta expressed sequence tag (EST) databases and enabled identification of a number of excretory/secretory (ES) proteins. Immunoblots were performed to assess the relative molecular weight of ES antigens that were targets of local IgA responses in mucus from sheep rendered immune to infection. ELISA was performed to assess antigen-specific mucus IgA levels in individual sheep. These experiments provided preliminary evidence that the proteins identified in the larval secretome were subject to these antibody responses.

Immune recognition of the surface associated antigen, Tc-SAA-1, from infective larvae of Teladorsagia circumcincta.

A cDNA encoding a surface-associated antigen was amplified by reverse transcriptase polymerase chain reaction (PCR) from RNA extracted from Teladorsagia circumcincta exsheathed third stage larvae (xL3). The protein encoded by this cDNA, Tc-SAA-1, displays 77% identity over 162 amino acid residues to a surface associated antigen from Ancylostoma caninum (Ac-SAA-1). Antiserum raised against a bacterially-expressed recombinant form of Tc-SAA-1 reacted with a native protein in somatic and surface extracts of xL3 but not with L4 or adult parasites. Limited binding of anti-Tc-SAA-1 antibody was observed on the cuticular surface of xL3 s, however, regions of localization underlying the cuticle were observed. Incubation of xL3 T. circumcincta with anti-SAA rabbit serum failed to significantly inhibit penetration of the abomasal mucosa in vitro. IgA in abomasal mucus derived from sheep that had received a trickle infection of T. circumcincta bound recombinant Tc-SAA-1.

Periodontitis and type 2 diabetes: is oxidative stress the mechanistic link?

Periodontitis is a common, chronic inflammatory disease initiated by bacteria which has an increased prevalence and severity in patients with type 2 diabetes. Recent studies indicate that the co-morbid presence of periodontitis can, in turn, adversely affect diabetic status and the treatment of periodontitis can lead to improved metabolic control in diabetes patients. Current evidence points to a bidirectional interrelationship between diabetes and inflammatory periodontitis. The importance of oxidative stress-inflammatory pathways in the pathogenesis of type 2 diabetes and periodontitis has recently received attention. Given the bidirectional relationship between these two conditions, this review discusses the potential synergistic interactions along the oxidative stress-inflammation axis common to both type 2 diabetes and periodontitis, and the implications of this relationship for diabetic patients.