Soluble forms of Toll-like receptor 4 are present in human saliva and modulate tumour necrosis factor-alpha secretion by macrophage-like cells.

In health, mucosal inflammation is prevented by tightly regulated responses via Toll-like receptors (TLR) that interact with specific microbe associated molecular patterns. Currently, 13 TLRs have been identified. Based on the specificity of ligand recognition, TLR-2 and TLR-4 can recognize most oral commensal microorganisms. Recent identification of some soluble TLRs (sTLRs) suggests additional regulatory roles for these receptors. We report here the presence of sTLR-4 polypeptides in adult human saliva. Functionally, the salivary sTLR-4 suppressed cytokine secretion by activated macrophages. The sTLR-4 levels were elevated significantly in oral lichen planus (OLP), a chronic inflammatory condition of the oral mucosa characterized by clinical persistence. In contrast, the epithelial cells in the saliva of OLP subjects expressed significantly reduced TLR-2 and TLR-4 mRNA that correlated with fewer bacteria/salivary epithelial cells. Investigating the soluble and cellular components of saliva is useful in identifying potential biomarkers for oral mucosal lesions.

Differential innervation of protruder and retractor muscles of the tongue in rat.

Protrusion and retraction of the tongue are essential components of such orofacial behaviors as mastication, respiration, and swallowing. Stimulation of the medial branch of the hypoglossal nerve yields tongue protrusion, while stimulation of the lateral branch yields tongue retraction in rat. We exploited the transsynaptic transport capabilities of pseudorabies virus to determine specific circuits that innervate protruder and retractor muscles of the rat tongue. Each group of muscles is innervated by distinct populations of hypoglossal motoneurons: caudal ventral and ventrolateral motoneurons form the largest proportion of those innervating protruders, whereas rostral dorsal motoneurons innervate retractors. Our primary finding was differential innervation of protruder and retractor motoneurons by premotoneurons in the lateral tegmental field: premotoneurons innervating protruder motoneurons were more ventral and ventromedial than those innervating retractor motoneurons. In addition, protruder motoneurons received projections from the ipsilateral lateral parabrachial nucleus but not spinal trigeminal nucleus or medial and ventral subnuclei of the solitary tract; the converse was true for retractor motoneurons. These results suggest segregation of functional networks that control hypoglossal motoneurons. The dorsal medulla, in or around the solitary tract, contains neurons specific to retractor motoneurons, and the region ventrolateral to the hypoglossal nucleus contains circuitry specific to protruder motoneurons. Common innervation of medial and lateral branch motoneurons is provided by premotoneurons in the raphe and gigantocellular reticular formation of the medial medulla. The midline medullary nuclei with diverse projections may coordinate complex behavior or modulate general motoneuron excitability, whereas the lateral reticular formation, with anatomically discrete projections, may control motoneurons that contribute to distinct orofacial behaviors.

Brainstem network controlling descending drive to phrenic motoneurons in rat.

Contraction of the diaphragm is controlled by phrenic motoneurons that receive input from sources that are not fully established. Bulbospinal (second-order) neurons projecting to phrenic motoneurons and propriobulbar (third-order) neurons projecting to these bulbspinal neurons were investigated in rat by transsynaptic transport of the neuroinvasive pseudorabies virus. Bulbospinal neurons were located predominantly in the medullary lateral tegmental field in two functionally described regions, the ventral respiratory group and Bötzinger complex. An intervening region, the pre-Bötzinger complex, contained essentially no phrenic premotoneurons. Bulbospinal neurons were also located in ventral, interstitial, and ventrolateral subnuclei of the solitary tract, and gigantocellular, Kölliker-Fuse, parabrachial, and medullary raphe nuclei. A monosynaptic pathway to phrenic motoneurons from the nucleus of the solitary tract was confirmed; monosynaptic pathways from upper cervical spinal cord, spinal trigeminal nucleus, medical and lateral vestibular nuclei, and medial pontine tegmentum were not verified. Locations of third-order neurons were consistent with described projections to the ventral respiratory group, from contralateral ventral respiratory group, Bötzinger complex, A5 noradrenergic cell group, and the following nuclei; solitary, raphe, Kölliker-Fuse, parabrachial, retrotrapezoid, and paragigantocellular. Novel findings included a projection from locus coeruleus to respiratory premotoneurons and the lack of previously described pathways from area postrema and spinal trigeminal nucleus. These second- and third-order neurons from the output network for diphragm motor control which includes numerous behaviors (e.g., respiration, phonation, defecation). Of the premotoneurons, the rostral ventral respiratory group is the primary population controlling phrenic motoneurons.

Pre-Bötzinger complex in cats: respiratory neuronal discharge patterns.

Patterns of respiratory neuronal discharge in the pre-Bötzinger complex, hypothesized as a brainstem site generating respiratory rhythm, are described in adult cats. Signals were recorded from neurons in the Bötzinger complex, pre-Bötzinger complex and rostral ventral respiratory group (rVRG) of anesthetized adult cats. The pre-Bötzinger complex, located caudal to expiratory-modulated Bötzinger neurons, contained a mix of neurons with inspiratory-modulated, expiratory-modulated, or phase-spanning patterns of impulse activity, in contrast to the more homogenous neuronal distributions characteristic of adjacent Bötzinger and rVRG regions.

Organotin implications in anticarcinogenesis. Effects of several organotins on tumour growth rate in mice.

Several cohorts of cancerous mice were continuously dosed with 2,2'-bipyridyl dibutyltin dichloride, 1,10-phenanthroline dibutyltin and histidine dibutyltin; presented at 1 ppm and 10 ppm in drinking water. Tumour growth rates were significantly reduced. Tributyltin fluoride (TBTF) applied dermally, using dimethyl sulfoxide (DMSO) as the carrier, over the tumour site was ineffective. Variation in thymus and spleen weight between controls and tin-exposed mice indicates a lymphatic involvement. Analysis of mouse tissue for total tin content showed high tin concentrations in the thymus and spleen.

Organotin implications in anticarcinogenesis. Background and thymus involvement.

A comprehensive study of the scientific literature regarding tin content in normal and pathogenic human tissue has disclosed that various organotin materials retard both the onset and growth of cancer in laboratory animals, and decreased tissue tin in humans may be associated with tumour development. Initial studies by the authors have shown that the thymus gland of the mouse possesses a relatively high concentration of tin and is also the major site of accumulation for 14C-labelled tri-n-butyltin fluoride (TBTF). When mammary cancer-prone mice with transplanted tumours were orally dosed continuously with this agent in their drinking water, the tumour growth rate was significantly reduced. Both mouse mammary tumours and human lung tumours show low tin content compared to normal body tissue.