Maxillary Mucinous Adenocarcinoma Mimicking a Lesion of Endodontic Origin: A Rare Case Report.

Periapical lesions of endodontic origin are fairly common in the oral cavity in association with tooth pulp infection. Most of these lesions will resolve with adequate root canal treatment and rarely cause suspicion of more insidious disease. Most clinicians tend to skip histopathological examination in cases where the lesion is excised or curetted. We present a rare case of mucinous adenocarcinoma in association an endodontically treated maxillary discoloured central incisor in a 38 year old patient with a history of root canal treatment about 15 years ago. Root canal re-treatment and wide excision was performed. Histology showed epithelial islands suggestive of a neoplasm. Immunohistochemistry was positive for CK7 and S100. Metastasis was ruled out and no evidence of recurrence has been noted in the 12-month follow up period. It is emphasized that any tissue removed from the surgical site should be analysed microscopically. (EEJ-2022-01-013).

Pulpal-anesthesia of a mandibular first molar with irreversible pulpitis by inferior alveolar nerve block plus buccal infiltration using articaine or lignocaine.

INTRODUCTION: This study aims to compare the efficacy of a combination of an inferior alveolar nerve block (IANB) plus buccal infiltration using 4% articaine versus 2% lignocaine in achieving anesthesia of lower first molar teeth with irreversible pulpitis. MATERIALS AND METHODS: Seventy adult patients were selected. A random sequence list was employed to administer IANB plus buccal infiltration. After the onset of lip numbness, cold test and electric pulp testing were performed. Five patients, four missed blocks and one no bleeding, were excluded. Heft Parker Visual Analog Scale scores during pulp extirpation were recorded. The data of sixty-five patients were statistically analyzed using Chi-square and Mann-Whitney U-test. RESULTS: The success rate after lip-numbness for articaine is 91.42% and for lignocaine is 94.28%. The difference is statistically, not significant (P = 0.6425). During access, the success rate for lignocaine is 96.87%, whereas 96.96% for articaine. This difference is also not significant (P = 0.982366). CONCLUSION: IANB plus buccal infiltration using articaine or lignocaine is equally effective in anesthetizing mandibular first molar with irreversible pulpitis.

Comparative evaluation of the effectiveness and fracture rate of three pathfinding nickel-titanium rotary instruments, Mtwo, OneG, and ProGlider, in mechanically negotiating moderately curved molar canals to the full working length.

AIM: To evaluate the scouting ability of three pathfinding nickel-titanium rotary instruments in moderately curved molar canals. MATERIALS AND METHODS: Ninety maxillary and mandibular molars were collected and were divided randomly into three groups each having 15 maxillary and 15 mandibular molars. The teeth were mounted on a specific apparatus for simulation of dento-alveolar socket. After access cavity preparation, the canals were negotiated with 08 K-file. Glide path preparation was performed using Mtwo or ProGlider or OneG instruments. The number of teeth in which the file reached the full working length (RFWL), number of passes required, and number of fractured instruments were recorded and subjected to statistical analysis using Chi-square, Kruskal-Wallis, and Mann-Whitney tests. RESULTS: There was a significant difference between the groups (P < 0.05). The RFWL of ProGlider was significantly higher than that of Mtwo (P = 0.005) and OneG (P = 0.037). The percentage of fracture with ProGlider was 6.67% and both Mtwo and OneG had 26.67% frequency. The difference was not statistically significant (P > 0.05). There was significant difference in the number of insertion passes in maxillary distobuccal (P < 0.05), mandibular mesiobuccal (P < 0.01), and distal (P < 0.01) canals. ProGlider was the most effective pathfinding instrument due to its file's design and a progressive taper of 2%-8%. This achieves a greater preflaring of the coronal and middle portions of the root canal, rendering the advance of the instrument toward the apex easier. CONCLUSION: ProGlider performed more efficiently and with less instrument breakage in scouting moderately curved canals of molar teeth.

γδ T-cell subsets in HIV controllers: potential role of Tγδ17 cells in the regulation of chronic immune activation.

OBJECTIVES: HIV controllers (HICs) are rare HIV-infected individuals able to maintain undetectable viremia in the absence of antiretroviral treatment. Although HIV-specific cytotoxic T cells have been well deciphered in HIC, γδ T lymphocytes remain largely uncharacterized. The aim of this study was to analyse phenotypic and functional characteristics of γδ T cells and their relationship with immune activation, which remains abnormally elevated and associated with comorbidities in HICs. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 16 HICs, 16 patients with untreated chronic HIV infection (UT-CHI) and 20 healthy donors. Surface marker expression and cytokine production by γδ T cells were analysed by flow cytometry. RESULTS: Despite normal frequencies of total γδ T cells, the Vδ2/Vδ2 ratio was significantly reduced in HIC, albeit to a lesser extent than UT-CHI patients. Of note, nine HICs showed elevated Vδ2 γδ T cells, as patients with UT-CHI, which was associated with higher CD8 T-cell activation. Interleukin (IL)-17-production by γδ T cells (Tγδ17) was better preserved in HIC than in UT-CHI patients. Proportion of total γδ T cells positively correlated with CD8 T-cell activation and HIV-DNA, IP-10 and sCD14 levels. Conversely, Tγδ17 cells negatively correlated with CD8 T-cell activation and plasma sCD14 levels. Moreover, transforming growth factor (TGF)-ß producing Vδ2 T cells were as dramatically depleted in HIC as in UT-CHI patients. CONCLUSION: The relative preservation of IL-17-producing γδ T cells in HIC and their negative association with immune activation raise the hypothesis that Tγδ17 cells - potentially through prevention of microbial translocation - may participate in the control of chronic systemic immune activation.

Potential Role of Vδ2+ γδ T Cells in Regulation of Immune Activation in Primary HIV Infection.

Although conventional regulatory T cells (Tregs) are sufficient in controlling low residual T-cell activation in ART-treated patients, they are not efficient in controlling exaggerated immune activation associated with high levels of HIV replication in primary HIV infection (PHI). Our previous data suggested that double negative (DN) T cells including mainly γδ DN T cells play a role in the control of immune activation in PHI. Since γδ T cells are capable of exerting regulatory functions, we investigated their implication as Tregs in PHI as well as chronic HIV infection (CHI). In a cross-sectional study of 58 HIV-infected patients, in the primary and the chronic phase either ART-treated or untreated (UT), we analyzed phenotype and cytokine production of γδ T cells using flow cytometry. Cytokine production was assessed following in vitro stimulation with isopentenyl pyrophosphate or plate-bound anti-CD3/anti-CD28 monoclonal antibodies. We found that the proportion of γδ T cells negatively correlated with CD8 T-cell activation in PHI patients. Furthermore, we found that in these patients, the Vδ2 receptor bearing (Vδ2+) γδ T cells were strongly activated, exhibited low terminal differentiation, and produced the anti-inflammatory cytokine, TGF-ß. In contrast, in UT-CHI, we observed a remarkable expansion of γδ T cells, where the Vδ2+ γδ T cells comprised of an elevated proportion of terminally differentiated cells producing high levels of IFN-γ but very low levels of TGF-ß. We also found that this loss of regulatory feature of γδ T cells in CHI was a lasting impairment as we did not find recovery of TGF-ß production even in ART-CHI patients successfully treated for more than 5 years. Our data therefore suggest that during the primary HIV infection, Vδ2+ γδ T cells may act as Tregs controlling immune activation through production of TGF-ß. However, in CHI, γδ T cells transform from an anti-inflammatory into pro-inflammatory cytokine profile and participate in sustenance of immune activation.

FcγRIII (CD16)-mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32).

Monocytes are known to engage in reciprocal crosstalk with NK cells but their influence on NK-cell-associated antibody-dependent cellular cytotoxicity (ADCC) is not well understood. We demonstrate that in humans FcγRIII (CD16)-dependent ADCC by NK cells is considerably enhanced by monocytes, and that this effect is regulated by FcγRII (CD32) crosslinking in healthy individuals. It is known that during HIV-1 infection, NK cells are known to express low levels of CD16 and exhibit reduced ADCC. We show that immune regulation of CD16-mediated NK-cell cytotoxicity by monocytes through CD32 engagement is substantially disturbed in chronic progressive HIV-1 infection. Expression of activating isoform of CD32 represented a compensatory mechanism for reduced expression of CD16 on NK cells during HIV-1 infection. As a result, the regulation of NK-cell-associated ADCC by monocytes is skewed and eventually constitutes a novel factor that contributes to HIV-1-associated immune deficiency, dysregulation and pathogenesis. Our data therefore provide evidence, for the first time, that in humans monocytes act as a rheostat for FcγRIII-mediated NK-cell functions maintaining a well-balanced immune response.

High frequencies of polyfunctional CD8+ NK cells in chronic HIV-1 infection are associated with slower disease progression.

UNLABELLED: Natural killer (NK) cells are effector and regulatory innate immune cells and play a critical role in the first line of defense against various viral infections. Although previous reports have indicated the vital contributions of NK cells to HIV-1 immune control, nongenetic NK cell parameters directly associated with slower disease progression have not been defined yet. In a longitudinal, retrospective study of 117 untreated HIV-infected subjects, we show that higher frequencies as well as the absolute numbers of CD8(+) CD3(-) lymphocytes are linked to delayed HIV-1 disease progression. We show that the majority of these cells are well-described blood NK cells. In a subsequent cross-sectional study, we demonstrate a significant loss of CD8(+) NK cells in untreated HIV-infected individuals, which correlated with HIV loads and inversely correlated with CD4(+) T cell counts. CD8(+) NK cells had modestly higher frequencies of CD57-expressing cells than CD8(-) cells, but CD8(+) and CD8(-) NK cells showed no differences in the expression of a number of activating and inhibiting NK cell receptors. However, CD8(+) NK cells exhibited a more functional profile, as detected by cytokine production and degranulation. IMPORTANCE: We demonstrate that the frequency of highly functional CD8(+) NK cells is inversely associated with HIV-related disease markers and linked with delayed disease progression. These results thus indicate that CD8(+) NK cells represent a novel NK cell-derived, innate immune correlate with an improved clinical outcome in HIV infection.

Loss of CCR7 expression on CD56(bright) NK cells is associated with a CD56(dim)CD16⁺ NK cell-like phenotype and correlates with HIV viral load.

NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell phenotype and functionality mainly focusing on CD56(dim)CD16⁺ and CD56⁻CD16⁺ NK cells. However, the impact of HIV-infection on CD56(bright) NK cells is less well understood. Here we report a rise of CD56(bright) NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. CCR7⁻CD56(bright) NK cells were characterized by increased cytolytic potential, higher activation states and a more differentiated phenotype. These cells thus acquired a number of features of CD56(dim)CD16⁺ NK cells. Furthermore, CD56(bright) NK cells from HIV patients exhibited higher degranulation levels compared to uninfected individuals. Thus, chronic HIV-infection is associated with a phenotypic and functional shift of CD56(bright) NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment.

Phenotypically and functionally distinct subsets contribute to the expansion of CD56-/CD16+ natural killer cells in HIV infection.

OBJECTIVE: Chronic HIV infection has been associated with activation and increased turnover of natural killer (NK) cells as well as with disturbed homeostasis of the NK cell compartment, including loss of CD56(+) NK cells and accumulation of dysfunctional CD56(-)/CD16(+) NK cells. We performed a comprehensive phenotypical and functional characterization of this population. DESIGN: A cross-sectional study was performed to analyze CD56(-)/CD16(+) NK cells from 34 untreated HIV-infected and 15 seronegative individuals. METHODS: NK cells were analyzed by flow cytometry. Degranulation was assessed by measuring their expression of CD107a after stimulation with K562 cells, interleukin-12 and interleukin-15. RESULTS: CD56(-)/CD16(+) NK cells are heterogeneous and composed of two populations, namely CD122(-)/CCR7(+) cells and CD122(-)/CCR7(+) cells. We show that expanded CD122(+) but not CCR7(+) cells in HIV-seropositive individuals are characterized by expression of senescence marker CD57 similarly to CD56(dim)/CD16(+) NK cells along with expression of KIRs, CD8, perforin and granzyme B. Despite expression of perforin and granzyme B, CD57 expressing cells exhibited less numbers of degranulating cells as measured by CD107a, indicating their functional impairment. However, there was no correlation between expansion of total CD56(-)/CD16(+) NK cells or the distinct subpopulations and viral load or CD4 cell count. CONCLUSION: These data indicate that expansion of CD56(-)/CD16(+) cells in HIV infection is driven by a distinct subset within this population with high expression of terminal differentiation marker with a phenotype resembling CD56(-)/CD16(+) NK cells.

Cytokine-activated NK cells inhibit PMN apoptosis and preserve their functional capacity.

Natural killer (NK) cells and polymorphonuclear cells (PMNs) play a critical role in the first line of defense against microorganisms. Upon host infection, PMNs phagocytose invading pathogens with subsequent killing by oxidative or nonoxidative mechanisms. NK cells are known to have immunoregulatory effects on T cells, B cells, dendritic cells (DCs), and monocytes through secretion of various soluble products and cell-cell contact. However, their impact on PMN survival and function is not well known. We found that soluble factors derived from cytokine-activated NK cells delay PMN apoptosis and preserve their ability to perform phagocytosis and produce reactive oxygen species (ROS). The expression patterns of CD11b and CD62L on PMNs differed according to the cytokine combination used for NK-cell stimulation. Irrespective of the NK-cell treatment, however, PMN survival was prolonged with sustained functional capacity. We found that interferon gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha produced by NK cells upon stimulation with cytokines played a crucial role in NK cell-mediated effects on PMNs. Our study demonstrates that soluble factors derived from cytokine-activated NK cells send survival signals to PMNs, which would promote their accumulation and function at the site of inflammation in vivo.

HIV infection is associated with a preferential decline in less-differentiated CD56dim CD16+ NK cells.

HIV-1 infection is characterized by loss of CD56(dim) CD16(+) NK cells and increased terminal differentiation on various lymphocyte subsets. We identified a decrease of CD57(-) and CD57(dim) cells but not of CD57(bright) cells on CD56(dim) CD16(+) NK cells in chronic HIV infection. Increasing CD57 expression was strongly associated with increasing frequencies of killer immunoglobulin-like receptors (KIRs) and granzyme B-expressing cells but decreasing percentages of cells expressing CD27(+), HLA-DR(+), Ki-67(+), and CD107a. Our data indicate that HIV leads to a decline of less-differentiated cells and suggest that CD57 is a useful marker for terminal differentiation on NK cells.

Exogenous HIV-1 Vpr disrupts IFN-alpha response by plasmacytoid dendritic cells (pDCs) and subsequent pDC/NK interplay.

HIV Vpr is known for its immunomodulatory capacities including its impairment of NK cell functions. However, the role of pDCs in this context remains elusive. We show that synthetic Vpr substantially inhibits type I IFN production by pDCs without inducing apoptosis in pDCs. Furthermore, we found that exogenous Vpr compromises subsequent pDC/NK interplay as shown by diminished IFN-gamma production by NK cells. Thus, Vpr-mediated dysregulation of IFN-alpha and IFN-gamma production affects key components of the innate immune response supporting an essential role of Vpr in HIV pathogenesis.

Host chemokine (C-C motif) ligand-2 (CCL2) is differentially regulated in HIV type 1 (HIV-1)-infected individuals.

Several cytokines and chemokines including chemokine (C-C motif) ligand-2 (CCL2) are induced in HIV-1 infection. However, the impact of HIV-1 viremia on CCL2 regulation is largely unknown. We utilized a DNA oligonucleotide microarray covering 110 inflammatory genes. Five genes were induced by at least 2-fold in PBMCs of HIV-1 viremic (>100,000 RNA copies ml(-1)) as compared with aviremic (<50 RNA copies ml(-1)) individuals. These genes were CCL2, CXC chemokine ligand-10, IFN-gamma, GTP-cyclohydrolase-1 and C-C chemokine receptor-1. In addition to microarray data verification by real-time PCR, analysis of independent patient samples revealed a similar expression pattern. CCL2 was the most strongly regulated gene at mRNA level and its serum concentration was significantly elevated in viremic compared with aviremic and HIV-1 seronegative controls, indicating a positive correlation between viremia and CCL2. Flow cytometric studies demonstrated a higher percentage of CCL2-expressing CD14(+) monocytes in viremic compared with aviremic individuals. These results suggest a highly restricted modulation of host inflammatory gene response by HIV. Genes up-regulated in the viremic state, in particular CCL2, presumably serve as potential enhancing factors in HIV-1 replication, represented by high viral load in HIV-1 viremic patients. Inhibition of increased CCL2 production could provide a new therapeutic intervention in HIV-1 infection.