Immunogenicity of a Promiscuous T Cell Epitope Peptide Based Conjugate Vaccine against Benzo[a]pyrene: Redirecting Antibodies to the Hapten

The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142–51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15–56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted

Effect of spinal manipulation on sensorimotor functions in back pain patients: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Low back pain (LBP) is a recognized public health problem, impacting up to 80% of US adults at some point in their lives. Patients with LBP are utilizing integrative health care such as spinal manipulation (SM). SM is the therapeutic application of a load to specific body tissues or structures and can be divided into two broad categories: SM with a high-velocity low-amplitude load, or an impulse "thrust", (HVLA-SM) and SM with a low-velocity variable-amplitude load (LVVA-SM). There is evidence that sensorimotor function in people with LBP is altered. This study evaluates the sensorimotor function in the lumbopelvic region, as measured by postural sway, response to sudden load and repositioning accuracy, following SM to the lumbar and pelvic region when compared to a sham treatment.</p> <p>Methods/Design</p> <p>A total of 219 participants with acute, subacute or chronic low back pain are being recruited from the Quad Cities area located in Iowa and Illinois. They are allocated through a minimization algorithm in a 1:1:1 ratio to receive either 13 HVLA-SM treatments over 6 weeks, 13 LVVA-SM treatments over 6 weeks or 2 weeks of a sham treatment followed by 4 weeks of full spine "doctor's choice" SM. Sensorimotor function tests are performed before and immediately after treatment at baseline, week 2 and week 6. Self-report outcome assessments are also collected. The primary aims of this study are to 1) determine immediate pre to post changes in sensorimotor function as measured by postural sway following delivery of a single HVLA-SM or LVVA-SM treatment when compared to a sham treatment and 2) to determine changes from baseline to 2 weeks (4 treatments) of HVLA-SM or LVVA-SM compared to a sham treatment. Secondary aims include changes in response to sudden loads and lumbar repositioning accuracy at these endpoints, estimating sensorimotor function in the SM groups after 6 weeks of treatment, and exploring if changes in sensorimotor function are associated with changes in self-report outcome assessments.</p> <p>Discussion</p> <p>This study may provide clues to the sensorimotor mechanisms that explain observed functional deficits associated with LBP, as well as the mechanism of action of SM.</p> <p>Trial registration</p> <p>This trial is registered in ClinicalTrials.gov, with the ID number of <a href="http://www.clinicaltrials.gov/ct2/show/NCT00830596">NCT00830596</a>, registered on January 27, 2009. The first participant was allocated on 30 January 2009 and the final participant was allocated on 17 March 2011.</p

Postural control in patients with lumbar disc herniation in the early postoperative period

Chronic spinal disc disease leads to disorders in postural movement coordination. An incorrect asymmetrical movement pattern for the lower limbs loading impairs proprioception and deteriorates postural stability, particularly when the vision is occluded. The standard surgical treatment improves biomechanical conditions in the lumbar spine, reduces pain, yet does it reduce the stability deficit in the upright position? An answer to the latter question would help work out targeted therapy to improve postural stability. We hypothesized that the standard surgical treatment would improve postural stability reflected by decreased sway variability accounting for better use of proprioceptive inputs postoperatively. Thirty-nine patients with lumbar disc herniation participated in the study. Their postural sway was recorded in anterior/posterior and medial/lateral planes with their eyes open or closed (EC) before and after surgery. The variability, range, mean velocity of the recorded time series and the area of the ellipse enclosed by the statokinesiogram were used as measures of postural stability. Preoperatively, EC condition resulted in an increased variability and mean velocity of postural sway, while postoperatively it caused an increase in sway mean velocity and sway area only with no effect on sway variability and range. The comparison of the balance before and after the surgery in the EC condition showed significant decrease in all parameters. In the early postoperative period, the patients recover the ability to control their postural sway in EC within normal limits, however, at the expense of significantly increased frequency of corrective torques. It is probably a transient short-term strategy needed to compensate for the recovery phase when the normal weighting factors for all afferents are being reestablished. We propose that this transient postoperative period may be the best timing of therapeutic intervention targeted at facilitating and reinforcing the acquisition of correct motor patterns

BRIEF REPORT: Nutrition and Weight Loss Information in a Popular Diet Book: Is It Fact, Fiction, or Something in Between?

BACKGROUND/OBJECTIVE: Diet books dominate the New York Times Advice Best Seller list and consumers cite such books as an important source of nutrition information. However, the scientific support for nutrition claims presented as fact (nutrition facts) in diet books is not known. DESIGN/MEASUREMENTS: We assessed the quality of nutrition facts in the best-selling South Beach Diet using support in peer-reviewed literature as a measure of quality. We performed structured literature searches on nutrition facts located in the books\u27 text, and then assigned each fact to 1 of 4 categories (1) fact supported, (2) fact not supported, (3) fact both supported and not supported, and (4) no related papers. A panel of expert reviewers adjudicated the findings. RESULTS: Forty-two nutrition facts were included. Fourteen (33%) facts were supported, 7 (17%) were not supported, 18 (43%) were both supported and not supported, and 3 (7%) had no related papers, including the fact that the diet had been scientifically studied and proven effective. CONCLUSIONS: Consumers obtain nutrition information from diet books. We found that over 67% of nutrition facts in a best-seller diet book may not be supported in the peer-reviewed literature. These findings have important implications for educating consumers about nutrition information sources