Infectome: A platform to trace infectious triggers of autoimmunity

The “exposome” is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the “infectome”, which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regard to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the “immunome” and “microbiome” projects.     

Tracing environmental markers of autoimmunity: introducing the infectome

We recently introduced the concept of the infectome as a means of studying all infectious factors which contribute to the development of autoimmune disease. It forms the infectious part of the exposome, which collates all environmental factors contributing to the development of disease and studies the sum total of burden which leads to the loss of adaptive mechanisms in the body. These studies complement genome-wide association studies, which establish the genetic predisposition to disease. The infectome is a component which spans the whole life and may begin at the earliest stages right up to the time when the first symptoms manifest, and may thus contribute to the understanding of the pathogenesis of autoimmunity at the prodromal/asymptomatic stages. We provide practical examples and research tools as to how we can investigate disease-specific infectomes, using laboratory approaches employed from projects studying the “immunome” and “microbiome”. It is envisioned that an understanding of the infectome and the environmental factors that affect it will allow for earlier patient-specific intervention by clinicians, through the possible treatment of infectious agents as well as other compounding factors, and hence slowing or preventing disease development.     

The effects of diode laser (660 nm) on the rate of tooth movements: an animal study

Lasers in Medical Science - Low-level laser has been indicated to have the capability to facilitate the differentiation of the osteoclastic and osteoblastic cells which are responsible for the bone...     

An economic model of 2-hour post-dose ciclosporin monitoring in renal transplantation

BACKGROUND: Monitoring of microemulsion ciclosporin (cyclosporine; Neoral) by 2-hour post-dose drug concentrations (C2) is an accurate measure of ciclosporin absorption efficiency and exposure, and appears superior to trough (C0) monitoring for prediction of rejection risk. A predictive decision model was used to determine if this approach also reduces total treatment costs in the first 12 months after renal transplantation. METHODS: Parameter estimates for key clinical events were derived from the literature and from prospective pharmacokinetic studies comprising 234 adult HLA-non-identical renal graft recipients at seven Canadian centres. Patients were treated with microemulsion ciclosporin (Neoral), corticosteroids and azathioprine or mycophenolate mofetil. Using the perspective of the Canadian healthcare provider, total treatment costs for the C2 versus the C0 strategy were modelled over 12 months, and then remodelled using conservative estimates to extend the timeframe to 5 years. Health resources were valued in 1999 Canadian dollars. RESULTS: The incidence of acute rejection was estimated to be 25% at 1 year in patients monitored by C0 and 18% in those monitored by C2. Patient survival was considered to be independent of monitoring strategy, and graft loss was predicted to be 1.4% lower in the C2 group. The studies suggested no important differences in comorbidity and the costs of C0 and C2 monitoring and ambulatory-based adverse events were held equivalent. Using these inputs, the average cost per patient for the first year post-transplant was Can dollars 46,857 for C0 monitoring and Can dollars 45,306 for C2 monitoring, rising to Can dollars 146,879 and Can dollars 142,569 after 5 years. The predicted cost for initial hospitalisation was Can dollars 11,280 for C0 and Can dollars 10,806 for C2 monitoring. The cost of maintenance immunosuppressive drug use, graft loss and dialysis was Can dollars 19,098 in the C0 group and Can dollars 18,612 in the C2 group, while acute rejection treatment costs were Can dollars 2169 and Can dollars 1577, respectively. An additional Can dollars 14,310 was consumed by other events, including repeat hospitalisation, for each group. Sensitivity analysis indicated that the most influential parameters affecting savings due to C2 monitoring were a reduction in the duration of initial and follow-up hospitalisations and reduced risks of acute rejection and subsequent graft loss. CONCLUSIONS: Compared with traditional trough concentration monitoring, ciclosporin monitoring at 2 hours post-dose produced a predicted saving of Can dollars 1551 during the first year after renal transplant. Although modelling assumptions become more restrictive over time, this projection allows a preliminary assessment of the long-term economic impact of the routine use of C2 monitoring.     

5' exonuclease assay for detection of serogroup Y Neisseria meningitidis

The incidence of serogroup Y meningococcal disease has increased recently in the United States. Here, we describe the development of a 5' exonuclease assay for the detection of serogroup Y Neisseria meningitidis and demonstrate the usefulness of this assay for resolving serogroup identification of strains that are resistant to conventional serogrouping and for the nonculture identification of serogroup Y meningococcal disease.     

Determination of sensitivity of male Wistar rats to an equal dose of ketamine/xylazine injection at anesthetic dose in a chronic model of hypernatremia in comparison with control group

OBJECTIVE: To determine the sensitivity to an equal dose of ketamine/xylazine injection at anesthetic dose in a chronic model of hypernatremia. METHODS: This study was conducted at the Department of Physiology, Zanjan University of Medical Science, Zanjan, Iran in 2004. Sixty male Wistar rats, weighing 250 +/- 20 g were randomly allocated to 3 groups. The control group was provided with tap water, and first and second test groups consumed 1% and 2% salt concentrations for 144 hours. One hundred mg/kg ketamine and 10 mg/kg xylazine were used as an anesthetic agent. The measured anesthetic parameters comprises of righting reflex latency, required time for establishment of animal's immobility, immobility period, required time for appearance of animal's mobility and complete re-establishment of the righting reflex. RESULTS: The required time for inhibition of the righting reflex and animal's mobility in the second group was significantly shorter than the first and control groups. Immobility period, required time for appearance of animal's mobility and complete re-establishment of the righting reflex in the second group were significantly longer than the first and control groups. CONCLUSION: Hypernatremia increases the speed of transition from different steps of ketamine/xylazine anesthesia with significant delay in immobility period and recovery from anesthesia in rats, hence, anesthetic dose reduction in hypernatremia is necessary.