Decreased phagocytic function in neutrophils and monocytes from peripheral blood in periodontal disease

Phagocytosis by neutrophils and monocytes constitutes the main defense mechanism against bacterial challenges in periodontitis. Phagocytosis by neutrophils has already been evaluated, whereas phagocytic function of monocytes has hardly been addressed so far.

Objectives

The aim of this study was to assess phagocytosis by neutrophils and monocytes in periodontitis.

Material and Methods

The sample included 30 subjects with severe periodontitis and 27 control subjects without periodontal disease. The phagocytic index (PhI) was calculated as the mean number of adhered/ingested Saccharomyces cerevisiae per phagocytozing monocyte or neutrophil multiplied by the percentage of phagocytes involved in phagocytosis.

Results

A significant reduction in phagocyte functions was observed in individuals with periodontitis. The median of PhI of neutrophils using non-sensitized S. cerevisiae was 3 for the control group, and 1.5 for the periodontitis group (p=0.01, Mann-Whitney test). The median of PhI of monocytes with non-sensitized S. cerevisiae was 26.13 for the control group, and 13.23 for the periodontitis group (p=0.03, Mann Whitney test). The median of PhI of monocytes assessed with sensitized S. cerevisiae was 97.92 for the control group and 60.1 for the periodontitis group (p=0.005, t-test).

Conclusion

The data demonstrated a reduction in the function of phagocytes, suggesting a decrease in immune defenses in periodontitis.     

Low expression of MSH2 DNA repair protein is associated with poor prognosis in head and neck squamous cell carcinoma

Objective

This study aimed to investigate the expression of the MSH2 DNA repair protein in head and neck squamous cell carcinoma (HNSCC) in order to analyze its association with clinicopathologic factors and overall survival of patients.

Material and Methods

Clinical data and primary lesions of HNSSC were collected from 55 patients who underwent surgical resection with postoperative radiotherapy in Montes Claros, state of Minas Gerais, Brazil, between 2000 and 2008. Immunohistochemical reactions were performed to analyze MSH2 protein expression.

Results

Bivariate analysis showed no significant correlation or association between MSH2 expression and clinicopathologic parameters by Mann-Whitney and Kruskal-Wallis tests. Patients with locoregional metastatic disease (OR=4.949, p<0.001) and lower MSH2 immunohistochemical expressions (OR=2.943, p=0.032) presented poorer survival for HNSCC by Cox regression models.

Conclusions

Our data demonstrated that lower MSH2 expression might contribute to a higher clinic aggressiveness of HNSCC by promoting an unfavorable outcome.     

Nicotinic acetylcholine receptor antagonistic property of the selective dopamine uptake inhibitor, GBR-12909 in rat hippocampal slices

Previously we found that inhibitors of noradrenaline (NA) and/or 5-HT reuptake are able to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) in the CNS most probably by a channel blocker-type mechanism. The aim of our study was to clarify whether selective dopamine uptake inhibitors also possess this property, therefore we investigated the effect of GBR-12909 on the nicotine-evoked release of [3H]NA from rat hippocampal slices. GBR-12909, similar to selective NA and 5-HT uptake blockers, inhibited the nicotine-evoked release with an IC50 of 2.32 microM. The ability of monoamine uptake blockers to inhibit nicotine-evoked [3H]NA release (IC50) and NA reuptake (Ki) showed no correlation, indicating that the NA uptake system is not involved in the inhibition of the response to nicotine. Previously we have shown in whole cell patch clamp experiments, that GBR-12909, depending on the stimulation pattern, inhibits Na+-currents with an IC50 in the 6-35 microM concentration range [Mike A, Karoly R, Vizi ES, Kiss JP (2003) Inhibitory effect of the DA uptake blocker GBR-12909 on sodium channels of hippocampal neurons. Neuroreport 14:1945-1949]. To study whether the inhibition of Na+-channels is involved in the action of GBR-12909 on the nicotine-evoked [(3)H]NA release, we compared the effect of GBR-12909 and the Na(+)-channel blocker tetrodotoxin (TTX) on the electrical stimulation- and nicotine-evoked response. TTX prevented the release of [3H]NA induced by both types of stimulation, whereas GBR-12909 inhibited only the nicotine-induced response, indicating that under our experimental conditions the target of GBR-12909 is not the Na+-channel. These data indicate that the selective DA uptake inhibitor GBR-12909 is able to inhibit nAChRs, that is, the nAChR antagonistic property of monoamine uptake inhibitors is independent of their selectivity. The fact that monoamine uptake inhibitors with different chemical structure and selectivity are able to inhibit nAChRs may reveal some common properties of nicotinic receptors and monoamine uptake carriers.     

Purinergic modulation of glutamate release under ischemic-like conditions in the hippocampus

The aim of the present study was to explore whether endogenous activation of different purine receptors by ATP and adenosine contributes to or inhibits excess glutamate release evoked by ischemic-like conditions in rat hippocampal slices. Combined oxygen-glucose deprivation (OGD) elicited a substantial, [Ca(2+)](o)-independent release of [(3)H]glutamate, which was tetrodotoxin (1 microM)-sensitive and temperature-dependent. The P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 0.1-10 microM), and the selective P2X(7) receptor antagonist Brilliant Blue G (1-100 nM), decreased OGD-evoked [(3)H]glutamate efflux indicating that endogenous ATP facilitates ischemia-evoked glutamate release. The selective A(1)-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1-250 nM) and the selective A(2A) receptor antagonists 4-(2-[7-amino-2-)2-furyl(triazolo-[1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385, 0.1-20 nM) and 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261, 2-100 nM) decreased OGD-evoked [(3)H]glutamate efflux, indicating that endogenous adenosine also facilitates glutamate release under these conditions. The effect of DPCPX and ZM241385 was reversed, whereas the action of P2 receptor antagonists was potentiated by the selective ecto-ATPase inhibitor 6-N,N-diethyl-D-beta,gamma-dibromomethyleneATP (ARL67156, 50 microM). The binding characteristic of the A(2A) ligand [(3)H]CGS21680 to hippocampal membranes did not change significantly in response to OGD. Taken together these data suggest that while A(1) receptors might became desensitized, A(2A) and P2X receptor-mediated facilitation of glutamate release by endogenous ATP and its breakdown product adenosine remains operational under long-term OGD. Therefore the inhibition of P2X/A(2A) receptors rather than the stimulation of A(1) adenosine receptors could be an effective approach to attenuate glutamatergic excitotoxicity and thereby counteract ischemia-induced neurodegeneration.     

Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a −0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (−4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection

Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge.     

Characteristics of cholinergic neuroeffector transmission of ganglionic and aganglionic colon in Hirschsprung's disease.

Differences in the release and content of acetylcholine and the alpha 2 adrenoceptor mediated interaction between noradrenergic and cholinergic neurons were investigated by neurochemical and pharmacological methods in aganglionic and ganglionic segments of isolated human colon taken from children suffering from Hirschsprung's disease. Both at rest and during transmural stimulation the release of acetylcholine was significantly higher in the spastic (aganglionic) segment than in the proximal dilated bowel. Significant differences were found in the tissue concentration of acetylcholine between ganglionic and aganglionic specimens. The pattern of response to transmural stimulation was also different in the spastic and dilated bowel. Transmural stimulation induced relaxation and contraction in ganglionic specimens but only contractions in aganglionic specimens. The sensitivity of the smooth muscle in the aganglionic portion to exogenous acetylcholine and to field stimulation was found to be higher than in the ganglionic portion. While noradrenaline added to the organ bath reduced the stimulation-evoked release of acetylcholine from spastic segments, via an alpha 2 adrenoceptor mediated process, yohimbine did not enhance the release. It is suggested that in Hirschsprung's disease the increased acetylcholine release, the enhanced sensitivity of smooth muscle cells to acetylcholine, and the lack of alpha 2 adrenoceptor mediated noradrenergic modulation of acetylcholine release from cholinergic interneurons might be responsible for the spasm of aganglionic segments.     

Piecemeal degranulation of mast cells in the inflammatory eyelid lesions of interleukin-4 transgenic mice. Evidence of mast cell histamine release in vivo by diamine oxidase-gold enzyme-affinity ultrastructural cytochemistry

We used light and electron microscopy to analyze the eyelid inflammation that develops in transgenic mice that overexpress interleukin-4 (IL-4; Tepper et al, Cell 62:457, 1990). Analysis of alkaline Giemsa-stained plastic sections examined by light microscopy (Dvorak et al, J Exp Med 132:558, 1970), as well as by routine transmission electron microscopy, indicated that the mast cells in the inflammatory eyelid lesions were undergoing piecemeal degranulation, a form of secretion in which the cells' cytoplasmic granules exhibit characteristic morphologic changes that are thought to be associated with the prolonged, vesicle-mediated release of the granules' constituents. Moreover, by using a newly reported enzyme affinity-gold method, which stains histamine based on binding to diamine oxidase-gold (Dvorak et al, J Histochem Cytochem 41:787, 1993), we show that these activated mast cells had released much of their histamine content. The eyelid lesions also exhibited increased numbers of mast cells; interstitial fibrosis, particularly around cutaneous nerves and blood vessels; activated fibroblasts; focal axonal damage; venules with endothelial cells containing numerous vesiculo-vacuolar organelles; and infiltrates of neutrophils and eosinophils. Our findings illustrate that overexpression of the IL-4 gene in vivo can result in eyelid lesions associated with piecemeal degranulation of mast cells, as well as tissue fibrosis and a variety of other pathologic changes. These results also represent the first direct morphologic evidence for histamine secretion by mast cells in vivo.