Alterations in the cortical thymic epithelium of rats after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): an (immuno)histological study.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces thymic atrophy in rats. The present study was initiated to provide (immuno)histological data on the mechanism of action. Juvenile male Wistar rats were orally intubated once with 50 or 150 micrograms/kg TCDD. They were euthanized 4 or 10 days thereafter, or were allowed to stay alive until Day 20 or 26. Growth retardation occurred rapidly in all TCDD-treated animals. Lethality was demonstrated within 20-21 days after administration. At Days 4 and 10 after intubation, thymic atrophy was shown by reduction of thymic weight and cortex/medulla ratio. Staining patterns for T-cell markers in the atrophic thymuses coincided with the reduction of cortical areas. There was no evidence indicating that the effects were indirectly caused by stress. TCDD-induced thymic atrophy persisted until Day 26 after administration. Immunohistochemical analysis revealed prominent changes in the cortical thymic epithelium at the 150-micrograms/kg dose level. First, in the cortex epithelial cell aggregates were observed both at Day 4 and at Day 10 after administration. Apparently, the architecture of the epithelium had changed in these animals. Second, at 10 days after administration epithelial cells were found with the simultaneous expression of markers that in the normal uninvoluted thymus only occur either in the subcapsular/medullary area or in the cortex. This phenotype points to an unusual stage of differentiation. We conclude that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Apparently, it disturbs the epithelial network and interfers with the differentiation of epithelial cells.     

Prevention of work‐related airway allergies; summary of the advice from the Health Council of the Netherlands

The Health Council of the Netherlands published a report in which the best procedure and method for recommending health‐based occupational exposure limits (OELs) for inhaled allergens were identified by evaluating the scientific state of the art. Many respiratory disorders in the workplace arise from inhalation of substances which can cause allergy. To protect workers against respiratory allergy, various preventive measures are taken, one of them being reduction of exposure by setting legally binding standards. These are based on health‐based OELs that specify a level of exposure to an airborne substance, a threshold level, below which it may reasonably be expected that there is no risk of adverse health effects. The Council is of the opinion that an OEL should prevent against allergic sensitization, as sensitization plays a crucial biological role and is a prerequisite for the development of allergy. Furthermore, the Council considers it most likely that the exposure level below which no allergic sensitization develops for most allergens is so low, that OELs are difficult to set with the current knowledge and technical feasibilities. An alternative approach is to accept exposure, which carries a small predefined risk in developing allergic sensitization. In addition, it is worth considering periodic screening of exposed workers on allergic sensitization, because timely intervention can prevent worse. The feasibility of periodic screening and what else is needed to comply with the most important criteria, should however be judged case‐by‐case.     

Localization of motoneurons innervating the stylopharyngeus muscle in the cat

Recent investigations of the nucleus ambiguus (NA) have attempted to identify motoneurons associated with muscles of the larynx and pharynx. However, relatively little attention has been directed to the stylopharyngeus muscle, which is important in elevation of the pharynx in swallowing and speech. The present study was designed to identify the specific location of stylopharyngeus motoneurons within the brainstem. Horseradish peroxidase or fluorescent dye was injected into the stylopharyngeus muscle of 12 cats. Retrogradely labeled cells were located ipsilateral in the rostral NA and retrofacial nucleus. This is the first report to definitively localize stylopharyngeus motoneurons.     

Sequential activity of gamma-delta T-cell receptor bearing lymphocytes, specific T-cell factors, and alpha-beta T-cell receptor bearing T-cells: a hypothesis

The cell-mediated immune response against cell-bound antigens are biphasic responses. The 'classical' components of cell-mediated immunity such as delayed type hypersensitivity (DTH) and cytotoxic T-cells, are preceded by antigen-specific T-cell factor production. These antigen-specific T-cell factors can be detected in the serum 1-2 days after immunization, which suggests that these antigen-specific T-cell factors play an important role in the initiation of cell-mediated immune responses. Factor-producing lymphocytes can be detected already 1 day after immunization at the site of the antigen challenge, and at first 4-5 days after immunization in the peripheral lymphoid organs. The phenotype of these factor-producing lymphocytes is Thy-1+, CD3+, L3T4 (CD4)-, Lyt2 (CD8)-, whereas the T-lymphocytes inducing the DTH response are Thy 1+, CD3+, L3T4 (CD4)+, Lyt2 (CD8)-. This suggests that these factor-producing lymphocytes are gamma-delta bearing T-lymphocytes. gamma-delta TCR bearing T-cells can develop independently of the thymus, and are present in athymic nude mice. Immunization of athymic (nude) mice induces antigen-specific T-cell factor production as well. This suggests that the gamma-delta bearing T lymphocytes present in nude mice can react to cell-bound antigens and produce these factors.     

Involvement of serotonin in intestinal mastocytopoiesis and inflammation during a Trichinella spiralis infection in mice

The involvement of serotonin in the regulation of intestinal mastocytopoiesis and inflammation has been investigated in mice infected with Trichinella spiralis. Two serotonin antagonists, methysergide and ketanserin, were examined for their ability to interfere with jejunal pathology comprising the influx of mucosal mast cells and other inflammatory cells during an infection with T. spiralis and with worm expulsion. In vitro analysis of the frequency of mast cell precursors in bone marrow, blood, spleen and intestinal tissue suggested that the mucosal mast cell response during a T. spiralis infection is probably due to invasion and local maturation in the gut of mast cell precursors, and may be mediated by T-cell-derived mast cell growth factors. Since both serotonin antagonists inhibited the mucosal mast cell response in T. spiralis-infected mice and diminished the influx of eosinophilic granulocytes, goblet cell hyperplasia, and villous atrophy, it was concluded that during a T. spiralis infection in mice release of serotonin may provide an environment that facilitates the local influx in the gut of inflammatory cells. Since worm expulsion was not affected by the serotonin antagonists, these results suggest that worm expulsion can occur without a mast cell and or eosinophilic granulocyte influx. The role of serotonin release by as yet unidentified serotonin-containing cells in the gut in relation with T cell regulation is discussed.     

Three cases of dural arteriovenous fistula of the anterior condylar vein within the hypoglossal canal

Dural arteriovenous fistulas (DAVFs) of the anterior condylar vein are an uncommon but important subset of fistulas occurring at the skull base that can be confused with DAVFs of the marginal sinus on angiography. MR angiography source images can document the intraosseous extent and the relationship to the hypoglossal canal of this type of fistula, which can have significant clinical implications. We present the imaging features of angiography, CT, and MR angiography of three cases of DAVFs localized to the anterior condylar vein and within the hypoglossal canal, which were confirmed by source images from MR angiography. Transvenous coil embolization was curative in two of three cases and would seem to be the treatment of choice when venous access is available.     

Exhaled Nitric Oxide: A Novel Biomarker of Adverse Respiratory Health Effects in Epidemiological Studies

The sampling of exhaled breath is a noninvasive procedure that can be performed easily in adults, children, and patients with respiratory disease. Several studies have demonstrated increased exhaled nitric oxide in patients with pulmonary disease, including asthma. In addition, exhaled nitric oxide may be an elegant tool for monitoring of environmental health effects of air pollution and the prevalence of atopy in epidemiological surveys. Recent literature about exhaled nitric oxide is presented in this article. Technical, physiological, and behavioral confounding factors of exhaled nitric oxide measurement are outlined.