Immunotoxicology: an overview

It is now known that chemicals and drugs may induce selective toxicity which may alter the interactions between immunocompetent cells, especially if the toxicity occurs during proliferation and differentiation. Hence, a flexible panel of sensitive in vivo and in vitro assays has been developed and validated to assess the immunotoxicity or immunopharmacology of suspect agents in rodents. The combined use of such sequential analysis methods with host resistance assays can effectively define immunomodulation following exposure to xenobiotics. Methods development, refinement and validation will be an ongoing requirement because of our rapidly expanding knowledge of the cell biology of the immune system. Classic studies of the comparative preclinical toxicology of several immunosuppressive drugs have substantiated species similarities and have contributed significantly to the development of predictive rodent models for extrapolation to humans. Studies of immunopharmacology and immunotoxicity of cyclosporin A, for example, produced both the desired pharmacology and the undesired toxicity at similar doses in both rodents and humans. When species differences are observed during toxicology studies they are most probably due to differences in absorption, disposition, metabolism, excretion, or delivered dose at the target tissue, rather than major species differences in cellular targets or cell physiology. This assumption is the basis for using rodent species to predict the toxicity of chemicals and drugs under development.(ABSTRACT TRUNCATED AT 250 WORDS)     

The neck

This article describes the clinical and imaging roles of MR with respect to the following: neck masses of known or uncertain etiology; staging of cervical metastatic disease; thyroid and parathyroid; and evaluation of the thoracic inlet. Pertinent normal anatomy is highlighted when appropriate.     

Anti-inflammatory effect of β2-agonists: Inhibition of TNF-α release from human mast cells

β₂-Agonists inhibit the release of preformed mediators such as histamine and newly synthesized mediators such as prostaglandin D₂ from mast cells. However, although mast cells have been identified as an important source of several cytokines including tumor necrosis factor-α (TNF-α), there is no information about their regulation by β₂-agonists. Thus given the importance of TNF-α in inflammation and the widespread use of β₂-agonists, we investigated the effect of long-acting (salmeterol) and short-acting (salbutamol) β₂-agonists on the secretion of TNF-α from human skin mast cells. Treatment of mast cells with salmeterol or salbutamol (100 nmol/L) inhibited the IgE-dependent release of TNF-α (82% and 74%, respectively). Moreover, 2-hour treatment with salmeterol, isoproterenol, or salbutamol inhibited mast cell cytotoxicity against a TNF-α–sensitive cell line, WEHI-164, with an IC₅₀ of 71, 50, and 29 nmol/L, respectively. Specificity for β-adrenergic receptors was shown with propranolol. The inhibitory effect of β₂-agonists was observed after only 20 minutes of treatment but was lost by 24 hours after removal of salbutamol and isoproterenol (7% and 11% inhibition remaining, respectively). In contrast, the inhibition of TNF-α release was increased 1 hour after removal of salmeterol and remained significant 24 hours later. Furthermore, β₂-agonists did not show tachyphylaxis for the inhibition of TNF-α release. Thus selective β₂-agonists demonstrate anti-inflammatory activity by inhibiting the release of TNF-α from mast cells stimulated through their IgE receptor or by a tumor target cell. This inhibitory effect of β-agonists may be important in their mode of action in the treatment of allergic diseases. (J Allergy Clin Immunol 1997;100:825-31.)     

Pilomatrix carcinoma. A new case

We present a new case of Pilomatrix Carcinoma after having review the 22 cases previously published. The tumor arisen in a 74 years old male, in the left preauricular region. The lesion was excised with wide margins. A year after there is not any evidence of recurrence or metastases.     

Measurement of Perceived Disruption During Rebuilding Following Hurricane Andrew

The purpose of this study was to develop and evaluate a measure of perceived disruption during rebuilding following a disaster. Two eight-item scales, which measured intensity of disruption during the entire repair phase (Intensity-RP) and intensity of disruption during the past month (Intensity-PM) were developed and administered to 135 survivors of Hurricane Andrew. At 9 to 12 months postdisaster, Intensity-RP and Intensity-PM were both significantly associated with scores on the Global Severity Index of the SCL-90-R, and with scores on the Impact of Event-Intrusion Scale; Intensity-PM alone was significantly associated with PTSD scores. Regression analyses indicated that each scale contributed significant unique variance in predicting mental health symptoms, even after controlling for relevant demographic and initial disaster exposure variables.     

Vagus Nerve Stimulation Induces a Sustained Anticonvulsant Effect

Summary: Purpose: Stimulation of the vagus nerve can effectively abort several types of experimentally induced seizures in animals when administered near the time of seizure onset. Indirect evidence from human trials and animal studies suggests that the anticonvulsant effects of vagus nerve stimulation (VNS) extend beyond the duration of stimulation. We used the pentylenetetrazol model to determine whether VNS exerts a persistent anticonvulsant effect.
Methods: VNS (1 mA, 30 Hz, 500 μs pulse width) was administered continuously for 0, 1, or 60 min, or intermittently (30 s on, 5 min off) for 60 min, to awake and freely moving animals. After the end of stimulation, pentylenetetrazol (50 mg/kg i.p.) was administered to induce seizures. Time-course studies were also performed, consisting of 60 min of VNS followed by pentylenetetrazol injection after 0, 3-, 5-, and 10-min intervals.
Results: The greatest anticonvulsant effect occurred after 60 min of continuous VNS, which prevented convulsions in four of 12 rats and reduced significantly seizure duration, the total number of seizures, and number of tonic seizures. Intermittent VNS was less effective than continuous stimulation for 60 min, but more effective than that for 1 min. The anticonvulsant effect declined in a time-dependent fashion after discontinuation of VNS, with return to nonstimulated control values by 10 min.
Conclusions: The results of this study verify a persistent VNS-induced anticonvulsant effect and indicate that its efficacy is dependent on the cumulative stimulus duration.     

Laterality, torque and personality

Evidence accumulating from a variety of methodological approaches suggests that unusual laterality is often a concomitant feature of emotional pathology. In the present study both torque and a multifaceted measure of laterality were examined with respect to personality variables measured by the 16 PF in a normal population. Interestingly, a pattern of emotionality for subjects with a more confused laterality was revealed in a normal population which is notably similar to reported aberrant personality factors and laterality in more pathological groups. The existence of a cohesive continuum of emotional expression in relation to confused laterality is suggested. In addition, both torque and the multifactored measure of laterality are critiqued as research measures and for their clinical potential.