The effect of low level lead exposure on the postnatal structuring of the rat cerebellum

Exposure of rat pups to lead (less than 45 micrograms/dl blood) caused no alterations in the rate of cerebellar cell acquisition, migration or final number when compared with age-matched controls. The rate of DNA biosynthesis was higher in the lead-exposed animals compared to controls and remained elevated until postnatal day 10. This observation suggests lengthening of the cell cycle. The expected increase in DNA biosynthetic rate was delayed in neuron-enriched fractions obtained from lead-exposed pups. This may have been due to the isolation procedure specifically selecting internal granular layer cells which migrated precociously during a protracted G1 phase in a lead-impaired cell cycle. Morphometric studies revealed no difference in the number, viability and migration of cells within and from the external granular layer of the cerebellum of lead-exposed animals. It is concluded that chronic low level lead exposure has no significant effect on the early structuring of the developing cerebellum.     

Traumatic internuclear ophthalmoplegia

Unilateral and bilateral internuclear ophthalmoplegia can rarely be caused by trauma. This article illustrates a traumatic pontine hemorrhage associated with bilateral internuclear ophthalmoplegia.     

The "in vitro skin test": a reliable and repeatable assay of immune competence in the surgical patient

In vitro blast transformation of human peripheral lymphocytes was tested using standard skin test antigens, the mitogens PHA and Con A, and the mixed lymphocytes reaction. The study group included 15 patients with multiple trauma, 40 with major burns, six following cholecystectomies, six following aortic reconstruction, and 30 normal volunteer controls. Repeated skin testing may sensitive patients to candida and streptokinase-streptodornase (SKSD), and desensitize them to mumps antigen. Blast transformation in response to PPD did not correlate with the clinical status of the patients; similarly, blast transformation in response to stimulation by the mitogens PHA and Con A could not reliably predict the occurrence of septic complications. Reactivity in response to stimulation by the soluble antigens SKSD and mumps and in the one-way mixed lymphocyte reaction accurately predicted the clinical course of patients. This method of "in vitro skin testing" is a reliable and repeatable method of monitoring the immunologic status of patients whose illness or injury requires longitudinal study.     

cbl-3: a new mammalian cbl family protein.

We have cloned a new human gene, cbl-3, which encodes a protein with marked homology to the cbl family of proteins. The predicted protein encoded by this gene retains the conserved phosphotyrosine binding domain (PTB) in the N-terminal and the zinc finger but is significantly shorter (MW 52.5 kDa) than the other mammalian cbl proteins. The protein lacks the extensive proline rich domain and leucine zipper seen in c-cbl and cbl-b and structurally most resembles the C. elegans and Drosophila cbl proteins. The gene is ubiquitously expressed with highest expression in the aerodigestive tract, prostate, adrenal gland, and salivary gland. The protein is phosphorylated and recruited to the EGFR upon EGF stimulation and inhibits EGF stimulated MAP kinase activation. In comparison to the other mammalian cbl proteins (e.g. cbl-b), cbl-3 interacts with a restricted range of proteins containing Src Homology 3 regions. An alternatively spliced form of the cbl-3 protein was also identified which deletes a critical region of the PTB domain and which does not interact with the EGFR nor inhibit EGF stimulated MAP kinase activation. These data demonstrate that cbl-3, a novel mammalian cbl protein, is a regulator of EGFR mediated signal transduction.     

Effects of nickel-oxide nanoparticle pre-exposure dispersion status on bioactivity in the mouse lung

Nanotechnology is emerging as one of the world's most promising new technologies. From a toxicology perspective, nanoparticles possess two features that promote their bioactivity. The first involves physical–chemical characteristics of the nanoparticle, which include the surface area of the nanoparticle. The second feature is the ability of the nanoparticle to traverse cell membranes. These two important nanoparticle characteristics are greatly influenced by placing nanoparticles in liquid medium prior to animal exposure. Nanoparticles tend to agglomerate and clump in suspension, making it difficult to reproducibly deliver them for in vivo or in vitro experiments, possibly affecting experimental variability. Thus, we hypothesize that nanoparticle dispersion status will correlate with the in vivo bioactivity/toxicity of the particle. To test our hypothesis, nano-sized nickel oxide was suspended in four different dispersion media (phosphate-buffered saline (PBS), dispersion medium (DM), a combination of dipalmitoyl-phosphatidyl choline (DPPC) and albumin in concentrations that mimic diluted alveolar lining fluid), Survanta®, or pluronic (Pluronic F-68). Well-dispersed and poorly dispersed suspensions were generated in each media by varying sonication time on ice utilizing a Branson Sonifer 450 (25W continuous output, 20?min or 5?min, respectively). Mice (male, C57BL/6J, 7-weeks-old) were given 0–80?µg/mouse of nano-sized nickel oxide in the different states of dispersion via pharyngeal aspiration. At 1 and 7 d post-exposure, mice underwent whole lung lavage to assess pulmonary inflammation and injury as a function of dispersion status, dose and time. The results show that pre-exposure dispersion status correlates with pulmonary inflammation and injury. These results indicate that a greater degree of pre-exposure dispersion increases pulmonary inflammation and cytotoxicity, as well as decreases in the integrity of the blood–gas barrier in the lung.     

Exploration of Sedentary Behavior in Residential Substance Abuse Populations: Results From an Intervention Study

Background: There is a growing body of research linking sedentary behavior with increased risk of chronic disease and all-cause mortality. It is increasingly recommended that service providers address the multiple behavioral risk factors associated with these chronic diseases as part of routine substance abuse treatment. Objectives: The study objective was to investigate rates of physical activity and sedentary behavior in a residential substance abuse population. In addition, efficacy of a sedentary behavior intervention, “Sit Switch,” was examined for feasibility in this context. Methods: Participants (n = 54) were residents of The Salvation Army Recovery Service Centres located in Canberra and on the Gold Coast, Australia. Actigraph GT3X+ accelerometers were used to measure rates and patterns of sedentariness and physical activity. A nonrandomized controlled study of a single-session group intervention aimed at decreasing prolonged sitting (“Sit Switch”) was conducted. Education, motivational-interviewing, and goal setting components underpinned the “Sit Switch” intervention. Results: Individuals were highly sedentary, spending 73% of daily activity at sedentary intensity engaged in inadequate levels of moderate physical activity (6.6%/day). The single session educational program did not lead to any significant changes in sedentary behavior. Conclusion/Importance: High levels of sedentariness and low levels of physical activity engagement are evident in residents in substance abuse treatment programs. It is strongly recommended that sedentariness, a modifiable risk behavior with independent consequences for cardiovascular disease and cancer, be addressed within residential programs.     

The Monitor Practice Programme: is non‐invasive management of dental caries in private practice effective?

Background: This paper reviews the efficacy of an intensive, preventive‐based, non‐invasive approach to the management of dental caries within a randomized controlled trial. Methods: The primary efficacy measure was the two‐year DMFS increment. Changes in risk status, fluoride history, number of emergency visits and toothaches, along with demographic variables such as age, gender, health problems, and the location of the dental practice attended were measured. Regression analysis was undertaken to adjust for potential confounding variables. Results: Nine hundred and two patients were recruited within 22 dental practices between May 2005 and March 2006. Baseline DMFS did not differ significantly between the control and study groups (p = 0.83). Age (p < 0.001), health status (p = 0.005), baseline risk (p < 0.001) and fluoride history (p < 0.001) were all independent significant predictors of two‐year DMFS increment. Gender approached significance (p = 0.08). There were no statistically significant differences between the groups in the incidence of toothaches (p = 0.1) or number of treatment visits required (p = 0.35). There was a significant difference in the two‐year incremental DMFS score in the study group compared to the control group (mean difference 2.2; p < 0.001). After adjusting for confounding variables the difference in the DMFS increment between the control and study groups remained significant (mean difference 1.7; p < 0.001). Conclusions: The results indicate efficacy of the preventive programme. Efficacy was independent of age, gender, medical concerns, fluoride history, or previous history of dental caries, in a population of patients attending for treatment in private dental practices, in a variety of locations, on a relatively short‐term basis (two years). While encouraging, it will be essential that these results are followed over a longer period of time in order to determine whether the benefits are maintained.     

Caries risk reduction in patients attending a caries management clinic

Background: A Caries Management Clinic was established for patients at high risk of caries aiming to reduce caries incidence to close to zero. That is, to prevent new lesions on existing sound surfaces, along the susceptible restoration margins, and to remineralize existing cavitated and non‐cavitated lesions. Twenty patients attended the clinic every two weeks from April to December 2005. Methods: The Caries Management System is a ten‐step non‐invasive strategy to arrest and remineralize early lesions and includes consideration of the patient at risk, the status of each individual lesion, patient management, clinical management, and monitoring. Results: After six months, there was a 42 per cent increase in gingival sites having Gingival Index scores of zero, and a 21 per cent decrease in sites having Gingival Index scores of 2 compared to baseline (χ² = 137.67, 4 df, p = 0.00001). Ready to change (RTC) patients had significantly fewer sites scored GI ≤ 2 compared to not‐RTC patients (p = 0.01). Compared with the not‐RTC patients, RTC patients were more than twice as likely to have fewer sites scored GI ≤ 2 (RR = 2.43, 95% CI (1.24, 4.71), p = 0.01). A total of 100 out of 146 smooth non‐cavitated carious surfaces at baseline have remineralized after six months, 99 per cent of sound surfaces remained sound, and 23 new lesions were observed in six of the 20 patients (α² = 292, 7 df, p = 0.00001). About half of proximal surfaces showing bitewing scores of grade 1 or 2 had regressed (α² = 86.66, 56 df, p = 0.0001) and 95 per cent of proximal sound surfaces at baseline, as diagnosed via bitewing radiographs, remained sound. Conclusions: This audit revealed that the implementation of the non‐invasive approach to caries management which combined intensive coaching in oral hygiene maintenance, special home care and intensive monitoring in a clinic for high‐risk patients was able to reduce gingival inflammation and maintain low plaque levels, at least within the scope of this short‐term review.