Sublingual Tissue Research Articles

Neutrophils negatively regulate induction of mucosal IgA antibody responses to sublingual immunization (MUC4P.835)

Abstract Secretory IgA antibody plays an important role in the protection of mucosal surfaces against microbial pathogens. Induction of the IgA antibody has been known to be largely dependent upon the cytokine milieu. However, the importance of innate immune cell subsets for IgA responses has not been fully appreciated yet. We investigated the role of myeloid cell-subsets on IgA responses to sublingual immunization. In contrast with cholera toxin as an adjuvant which promotes IgA responses, sublingual application of the Bacillus anthracis edema toxin (EdTx) to C57BL/6 mice transiently increased the frequencies of neutrophils in sublingual tissue and cervical lymph nodes (CLNs), and promoted antigen-specific serum IgG, but not serum or mucosal IgA responses. However, EdTx as an adjuvant failed to increase frequencies of neutrophils in sublingual tissue and CLNs of mice lacking IKKβ in myeloid cells (IKKβΔMye), and these mice developed antigen-specific mucosal IgA responses. Interestingly, depletion of neutrophils in C57BL/6 mice promoted antigen-specific fecal and serum IgA responses, similar to those of IKKβΔMye mice, and this effect was associated with increased frequencies of surface IgA expressing plasma cells, α4β7+CCR9+ B cells in lamina propria and number of Peyer’s patch. Our results show that the presence of neutrophils at mucosal inductive sites negatively influences induction of IgA responses and underlying mechanisms are under investigations.

Impact of fluid resuscitation with hypertonic-hydroxyethyl starch versus lactated ringer on hemorheology and microcirculation in hemorrhagic shock

The choice of volume expander for fluid resuscitation in hemorrhagic shock is still debated. Changes in plasma viscosity (PV) are barely investigated while PV modulates functional capillary density, microcirculation and organ function. The present study evaluated the impact of 2 strategies of fluid resuscitation in hemorrhagic shock in pigs. Ten pigs were subjected to hemorrhagic shock and randomly assigned to a low viscosity fluid regimen (Lactated Ringer's, LR) group or a high viscosity regimen (hypertonic-hydroxyethyl starch, HES) for volume resuscitation. Sublingual microcirculatory flow and tissue oxygen tension were assessed together with macro- and microcirculatory, biochemical and rheological variables at baseline, 30 minutes after hemorrhagic shock, immediately after reaching resuscitation endpoints (R-0), and 60 minutes after resuscitation (R-60). PV decreased similarly in both groups following resuscitation (from 1.36 [1.32-1.38] to 1.21 [1.21-1.23] for LR, and from 1.32 [1.31-1.32] to 1.20 [1.17-1.21] mPa.s for HES). No differences were found between the groups for other rheological variables, microcirculatory flow or tissue oxygen tension at R-0 and R-60. Despite a 6-fold difference in the volumes required to achieve blood flow endpoints, commercially available volume expanders had similar effects on rheological and microcirculatory variables, irrespective of their viscosity. Our findings are consistent with the absence of clinically relevant differences between crystalloid and colloid resuscitation of hemorrhagic shock.

Dynamic sonography and CT findings of unilateral submandibular gland agenesis associated with herniated hypertrophic sublingual gland

Congenital agenesis of the submandibular gland is uncommon. We report dynamic sonography and CT findings of the unilateral submandibular gland agenesis associated with herniated hypertrophic sublingual gland tissue through the mylohyoid gap. The dynamic sonography examination applied at rest and during the modified Valsalva maneuver demonstrated hypertrophied sublingual gland prolapsing to the anterior part through the mylohyoid gap. This may be the first reported case describing dynamic sonography findings of this entity. CT confirmed the agenesis of the left submandibular gland and compensatory hypertrophy of the ipsilateral sublingual gland.

Dynamic sonography and CT findings of unilateral submandibular gland agenesis associated with herniated hypertrophic sublingual gland

Congenital agenesis of the submandibular gland is uncommon. We report dynamic sonography and CT findings of the unilateral submandibular gland agenesis associated with herniated hypertrophic sublingual gland tissue through the mylohyoid gap. The dynamic sonography examination applied at rest and during the modified Valsalva maneuver demonstrated hypertrophied sublingual gland prolapsing to the anterior part through the mylohyoid gap. This may be the first reported case describing dynamic sonography findings of this entity. CT confirmed the agenesis of the left submandibular gland and compensatory hypertrophy of the ipsilateral sublingual gland.

OP168: Compartmental tongue surgery: A 10 years story

Analyzing the cancer invasion pattern into the tongue we observed that the front of invasion follow the muscle fibers, horizontally into the intrinsic muscles and changing to a vertical direction when the extrinsic muscles are reached. The median tongue septum separating the genioglossus was almost never breached; when controlateral invasion occurred, it was via invasion of the intrinsic muscles above genioglossus. Other observed paths of tumour spread were: the fibrous and fatty tissue between genioglossus and hyoglossus muscles, the soft tissue between the hyoglossus muscle, the connective tissue of the floor of the mouth and the sublingual adipose tissue. We identify an anatomical (and functional) area into the tongue that can be at risk of being involved by cancer. We called this area tongue compartment and developed a rational surgical approach to tongue cancer resection: the compartmental surgery (CTS). This technique provides the complete removal of the involved muscle and sublingual tissues as to remove the path of disease spread and sites of potential residual foci. We perform CTS on 198 patients with primary untreated advanced tongue cancer from August 1999 to December 2009. After surgery, patients were followed in an outpatients up to 10 years. Their data of survival and functional recover were collected in a database and then statistically analyzed. 20 patients (10%) had local recurrences after 10 months (2–75 months). 18 patients (9%), had lymph node recurrences after 7 months (2–16 months); 24 patients (12%) had distant metastases after 13 months (1–87 months). Overall 5-yrs OS was 70.6% and 5-yrs DFS was 65.7%. The markedly improved outcomes in CTS patients, compared to those treated by standard surgery, suggest that CTS could be an anatomic approach to the surgical management of tongue cancer and provides better oncologic outcomes.

Tunneling Under the Digastricus Muscle Increases Salivary Duct Exposure and Completeness of Excision in Mandibular and Sublingual Sialoadenectomy in Dogs

To document the extent of rostral salivary duct and glandular tissue excision achieved through a conventional lateral approach before and after tunneling under the digastricus muscle. Experimental cadaveric study. Dog cadavers (n = 8). Bilateral mandibular and sublingual sialoadenectomy was performed in 8 cadavers using a conventional lateral approach and the point of proposed salivary duct transection was marked with Evans blue dye. Remaining salivary duct was then tunneled under the digastricus muscle and dissection continued rostrally. The most rostral point of the gland/duct complex was marked before transection of the salivary duct. Once removed, the distance between the 2 marks was measured and recorded. Completeness of glandular tissue excision was confirmed by dissection and gross examination. The tunneling technique improved rostral exposure and increased the median (IQR) length of salivary duct excision by 1.8 (0.35) cm. Residual polystomatic sublingual salivary tissue remained in all cadavers after simulated resection without tunneling under the digastricus muscle. After tunneling, complete removal of rostral salivary tissue was achieved in 13 of 15 procedures. Tunneling under the digastricus muscle increases the length of rostral salivary duct and glandular tissue that can be removed through a conventional lateral approach.

A Pragmatic Contouring Guideline for Salivary Gland Structures in Head and Neck Radiation Oncology

One of the main normal tissue toxicities in head and neck radiation oncology is xerostomia. In several studies, reduced radiation dose to the salivary glands has been shown to diminish the effects of gland dysfunction. However, no clear guidelines exist to define the anatomic location of the involved glands on cross-sectional imaging in a pragmatic manner. This study presents an anatomic, computed tomography (CT)-based definition of the major and minor salivary glands. On the basis of information from normal structure anatomy, the location of major and minor salivary glands was identified and translated into a cross-sectional CT-based description of the salivary glands. The major salivary glands include the parotids and submandibular glands. The minor salivary glands are presented as a part of a surrogate structure (the Minor Oral Including Sublingual Salivary Tissue target), including the minor glands located in the oral mucosa of the tongue, hard and soft palate, buccal mucosa, and inner surface of the lips. Clinical implementation of CT-based delineations of the salivary glands according to the proposed guideline should reduce interobserver variability. This may lead to an improved understanding of the relationship between radiation dose and volume and effects on salivary function.

Persistent peripheral and microcirculatory perfusion alterations after out-of-hospital cardiac arrest are associated with poor survival*

To evaluate sublingual microcirculatory and peripheral tissue perfusion parameters in relation to systemic hemodynamics during and after therapeutic hypothermia following out-of-hospital cardiac arrest. Prospective observational study. Intensive cardiac care unit at a university teaching hospital. We followed 80 patients, of whom 25 were included after out-of-hospital cardiac arrest. In all patients, we induced therapeutic hypothermia to 33°C during the first 24 hrs of admission. Complete hemodynamic measurements were obtained directly on intensive cardiac care unit admission (baseline), during induced hypothermia (T1), directly after rewarming (T2), and another 24 hrs later (T3). In addition, the sublingual microcirculation was observed using sidestream dark-field imaging, and peripheral tissue perfusion was monitored with the peripheral perfusion index, capillary refill time, tissue oxygen saturation, and forearm-to-fingertip skin temperature gradient. During hypothermia, all sublingual microcirculatory parameters decreased significantly together with peripheral capillary refill time and the peripheral perfusion index, followed by a significant increase at T2. Changes in sublingual and peripheral tissue perfusion parameters were significantly related to changes in central body temperature, but not to changes in systemic hemodynamic variables such as cardiac index or mean arterial pressure. Surprisingly, these parameters were significantly lower in nonsurvivors (n=6) at admission and after rewarming. Persistent alterations in these parameters were related with the prevalence of organ dysfunction and were highly predictive of mortality. Following out-of-hospital cardiac arrest, the early postresuscitation phase is characterized by abnormalities in sublingual microcirculation and peripheral tissue perfusion, which are caused by vasoconstriction due to induced systemic hypothermia and not by impaired systemic blood flow. Persistence of these alterations is associated with organ failure and death, independent of systemic hemodynamics.

Assessment of the mutagenic potential of arecoline in gpt delta transgenic mice

Chewing the areca nut is carcinogenic to humans. Arecoline, a major alkaloid in areca nut, is suspected to be a carcinogenic component. It has been shown to have genotoxic potential in various in vitro systems; but information on its in vivo genotoxicity is limited. To investigate the organ-specific mutagenic potential of arecoline, we employed gpt delta transgenic mice to analyze the mutagenicity of arecoline in the oral tissues and liver. Male gpt delta mice were given arecoline hydrobromide in drinking water at 300 and 700μg/mL for 6 weeks. 4-Nitroquinoline-1 (4-NQO) was used as a positive control. Two weeks after the last treatment, mutation frequencies in the oral tissues (a mixture of gingival, buccal, pharyngeal and sublingual tissue) and liver were detected and mutation spectra were analyzed. There were no statistically significant differences in the average mutation frequencies between arecoline-treated and untreated groups in both the oral tissues and liver. However, in the oral tissues, one mouse in arecoline-300μg/mL group and two mice in arecoline-700μg/mL group showed more than 2.5-fold higher mutation frequencies than the untreated group; they also exhibited unique mutation spectra compared to spontaneous mutation types. In these three mice, all mutations occurred at G:C sites, where G:C→T:A transversions were most frequent, followed by G:C→A:T transitions and G:C→C:G transversions. The main type of spontaneous mutation in both the oral tissues and liver was G:C→A:T transition. These results suggest that arecoline poses a mutagenic hazard in the oral tissues of gpt delta transgenic mice.

An IKKβ-IL-17 axis fine-tunes Ab responses to sublingual immunization (120.7)

Abstract The nature of immune cells recruited at the sites of antigen exposure and the cytokine microenvironment play a key role at shaping immune responses. Using a model sublingual vaccine with Bacillus anthracis edema toxin as an adjuvant, we show that alteration of IKKβ signaling in myeloid cells (IKKβΔMye) enhanced the magnitude of Ab and T cell responses, compared to control mice. While this model vaccine failed to induce S-IgA Abs in control mice, significant S-IgA Ab responses were induced in mucosal secretions of IKKβΔMye mice. We also established that the sublingual vaccine recruited lower numbers of CD11b+F4/80+Gr1high and CD11b+F4/80-Gr1high, but higher number of CD11b+F4/80+Gr1- cells in the sublingual tissues of IKKβΔMye mice. In contrast, higher numbers of CD11b+F4/80+Gr1high and CD11b+F4/80-Gr1high, but lower number of CD11b+F4/80+Gr1- cells were recruited in the sublingual tissues of control and IL-17A KO mice. Lack of IL-17A signaling did not affect the magnitude of Ab responses to the sublingual vaccine. However, the profile of B cell epitope responses was affected in IL-17A KO mice. Furthermore, CD11b+ cells isolated from IKKβΔMye mice assisted B cell-differentiation and induced production of IgA Abs by IL-17Rhigh B lymphocytes in vitro. Our results support the existence of an IKKβ-IL-17 axis for regulation of mucosal immunity and identify IKKβ signaling as a potential target for improving induction of mucosal immunity by sublingual vaccines.

Oral tonsil in the floor of mouth: Ectopic oral tonsillar tissue simulating benign neoplasms

Oral tonsils, ectopic sublingual tonsillar tissue, manifest as an asymptomatic, nonulcerated, freely movable nodule. We present a case of a 28-year-old female with ectopic tonsillar tissue in the anterior floor of the mouth. The lesion was totally removed under local anesthesia. The microscopic examination showed well demarcated and encapsulated lymphoid tissue with lymphoid follicles and central lacuna-like squamous epithelium covering space. These findings are similar to tonsillar tissue, and the case was finally diagnosed as sublingual oral tonsil. This article underlines that oral tonsils occur more frequently than is generally recognized, and the importance of differential diagnosis of soft tissue nodules in the oral floor.

Recording ‘Sublingual Crescents’ in Lower Complete Dentures: A Technique so Effective but still Esoteric and Arcane

To achieve retention in severely resorbed mandibular ridges during impression making and to maintain the retention and stability of these dentures during function. No good method with adequate clinical photographs that will empower the dentist with the necessary skill has been reported in the literature. The technique involves making a preliminary impression in alginate to record the denture bearing area clearly, doing a border moulding procedure with excess width to fill the wide sulcus present; except in the area of anterior lingual flange from second premolar to second premolar area. The anterior lingual border of the impression is then extended sublingually without interfering with the tongue function or blocking the opening of the ducts of the sublingual gland; to maintain contact with the surrounding sublingual tissue in both protruded and retruded positions of the tongue, thereby creating good peripheral seal in the most vulnerable area in the lower denture, where the seal is easily broken during tongue movements. This impression technique, combined with arrangement of teeth on the center of the ridge in the posterior part, use of flattened cusp posterior teeth and contoured polish surface of denture base (Fisch concept) provide sufficient retention and stability to the dentures made on these severely resorbed ridges. Patients with severely resorbed ridges cannot be rehabilitated with implants also and so normally suffer with loose lower denture fabricated with normal border moulding procedures. These patients can be rehabilitated to a great extent properly.

In VitroPermeation of Mesembrine Alkaloids fromSceletium tortuosumacross Porcine Buccal, Sublingual, and Intestinal Mucosa

Sceletium tortuosum is an indigenous South African plant that has traditionally been used for its mood-enhancing properties. Recently, products containing S. tortuosum have become increasingly popular and are commonly administered as tablets, capsules, teas, decoctions, or tinctures, while traditionally the dried plant material has been masticated. This study evaluated the in vitro permeability of the four major S. tortuosum alkaloids (i.e., mesembrine, mesembrenone, mesembrenol, and mesembranol) across porcine intestinal, sublingual, and buccal tissues in their pure form and in the form of three different crude plant extracts, namely water, methanol, and an acid-base alkaloid-enriched extract. The permeability of mesembrine across intestinal tissue was higher than that of the highly permeable reference compound caffeine (which served as a positive control for membrane permeability) both in its pure form, as well as in the form of crude extracts. The intestinal permeability of mesembranol was similar to that of caffeine, while those of mesembrenol and mesembrenone were lower than that of caffeine, but much higher than that of the poorly permeable reference compound atenolol (which served as a negative control for membrane permeability). In general, the permeabilities of the alkaloids were lower across the sublingual and the buccal tissues than across the intestinal tissue. However, comparing the transport of the alkaloids with that of the reference compounds, there are indications that transport across the membranes of the oral cavity may contribute considerably to the overall bioavailability of the alkaloids, depending on pre-systemic metabolism, when the plant material is chewed and kept in the mouth for prolonged periods. The results from this study confirmed the ability of the alkaloids of S. tortuosum in purified or crude extract form to permeate across intestinal, buccal, and sublingual mucosal tissues.

Cardiac displacement during off-pump coronary artery bypass grafting surgery: effect on sublingual microcirculation and cerebral oxygenation

Cardiac displacement during off-pump coronary artery bypass (OPCAB) surgery causes a fall in cardiac output. Here, we investigate how this drop in systemic perfusion is transferred to the oxygenation of sublingual and cerebral tissue. Sublingual microcirculatory perfusion or microcirculatory hemoglobin oxygen saturation (μHbSO(2)) measurements were performed using sidestream dark-field imaging and reflectance spectrophotometry, respectively (both n = 12). The cerebral tissue oxygenation index was measured by near-infrared spectrophotometry (n = 12). Cardiac output was calculated by pulse contour analysis of arterial pressure. Cardiac displacement reduced the cardiac output from 4.3 ± 0.8 to 1.2 ± 0.3 l/min (P < 0.05), paralleled by a decrease in μHbSO(2) from 64.2 ± 9.1 to 48.6 ± 8.7% (P < 0.01). Cardiac displacement did not change functional capillary density, while red blood cell velocity decreased from 895 ± 209 to 396 ± 178 μm/s (P<0.01). Cerebral tissue oxygenation index decreased from 69.5 ± 4.0 to 57.4 ± 8.5% (P<0.01) during cardiac displacement. After repositioning of the heart, all the values returned to baseline. Our data suggest that systemic hemodynamic alterations during cardiac displacement in OPCAB surgery reduce sublingual and cerebral tissue oxygenation. These findings are particularly important for patients at risk for the consequences of cerebral ischemia.

Red blood cell transfusions and tissue oxygenation in anemic hematology outpatients

There is little clinical evidence that red blood cell (RBC) transfusions improve oxygen availability at the microcirculatory level. We tested the hypotheses that anemia in chronically anemic patients with relatively healthy microcirculation would be associated with low tissue hemoglobin (Hb) and tissue oxygenation levels and that these conditions would be improved after RBC transfusions. Near-infrared spectroscopy (NIRS) was used to determine tissue oxygen saturation (StO(2)) and tissue Hb index (THI; an index of the amount of Hb in the NIRS measurement volume) in the thenar eminence and sublingual tissue before and 30 minutes after RBC transfusions in 20 chronically anemic hematology outpatients. Data are presented as median (25%-75%). The patients received three (two to three) bags of RBCs in saline-adenine-glucose-mannitol with an age of 21 (7-21) days, which was infused intravenously at the rate of 0.7 bag/hr. RBC transfusions significantly increased hematocrit level from 26% (24%-28%) to 32% (30%-34%; p < 0.0001), Hb level from 8.2 (7.6-8.9) g/dL to 11.0 (9.9-11.8) g/dL (p < 0.0001), whole blood viscosity from 3.4 (3.1-3.5) mPa/sec to 4.2 (4.0-4.5) mPa/sec (p < 0.0001), thenar StO(2) from 81% (80%-84%) to 86% (81%-89%; p = 0.002), thenar THI from 11.2 (9.3-13.3) AU to 13.7 (9.7-15.3) AU (p = 0.024), sublingual StO(2) from 86% (81%-89%) to 91% (86%-92%; p < 0.0001), and sublingual THI from 15.2 (13.0-17.4) AU to 17.2 (13.5-19.7) AU (p = 0.040). Although anemia in chronically anemic hematology outpatients was not associated with low StO(2) and THI levels, RBC transfusions were successful in improving these variables.

Sublingual tissue perfusion improves during emergency treatment of acute decompensated heart failure

ObjectivesThe aim of this study was to measure sublingual perfused capillary density (PCD) to assess sublingual microvascular perfusion during emergency department (ED) treatment of acute decompensated heart failure (ADHF). MethodsThis prospective, observational study enrolled ED patients with ADHF, measuring pre- and post-ED treatment PCD. Sidestream dark-field imaging was analyzed by 3 investigators blinded to patient identifiers and time points. Patient demographics, ADHF etiology, serum brain natriuretic peptide, and hemoglobin were measured along with a visual analogue scale (VAS), which assessed patient baseline characteristics and response to ED treatment. A paired t test analyzed changes in PCD, mean arterial pressure (MAP), and patient assessment. Interrater variability was assessed with an intraclass correlation coefficient (ICC), with a P value <.05 considered significant for all testing. ResultsThirty-six patients were enrolled with a mean time between pretreatment and posttreatment PCD (±SD) of 138 ± 59 minutes and a hospital length of stay of 4.0 ± 4.1 days. During this time, PCD increased (difference, 1.3 mm/mm2; 95% confidence interval, 0.4-2.1; P = .004), as did the MAP (P = .002), patient VAS score (P < .001), and observer VAS score (P < .001). There was no correlation between the change in PCD and time (R2 = .016, P = .47), MAP (R2 = .013, P = .54), or VAS scores. The ICC was 0.954. ConclusionsSublingual tissue perfusion is diminished in ADHF but increases with treatment. It may represent a quantitative way to evaluate ADHF in the ED setting.

Schwannoma arising from the sublingual gland

Sublingual gland tumors, especially mesenchymal tumors, are extremely rare. We describe the first reported case of schwannoma arising from the sublingual gland with details of the histopathologic and immunohistochemical features. A 70-year-old woman developed a painless swelling on the floor of the mouth. The excised material was sublingual gland tissue with an ovoid, grayish-yellow solid tumorous mass at the cut surface. The tumor was composed of proliferated spindle-shaped tumor cells exhibiting palisading patterns. In the center of the tumor, a small salivary gland component was recognized. Immunohistochemically, the tumor cells were strongly positive for S-100 protein but negative for neurofilament protein. The Ki-67 labeling index was 4.58. The clear presence of a remnant sublingual gland lobule in the present tumor provided convincing evidence that it was a schwannoma arising from the sublingual gland and thus the first of its type to be reported.

Immunological mechanisms of sublingual allergen-specific immunotherapy

Within the last 100 years of allergen-specific immunotherapy, many clinical and scientific efforts have been made to establish alternative noninvasive allergen application strategies. Thus, intra-oral allergen delivery to the sublingual mucosa has been proven to be safe and effective. As a consequence, to date, sublingual immunotherapy (SLIT) is widely accepted by most allergists as an alternative to conventional subcutaneous immunotherapy. Although immunological mechanisms remain to be elucidated in detail, several studies in mice and humans within recent years provided deeper insights into local as well as systemic immunological features in response to SLIT. First of all, it was shown that the target organ, the oral mucosa, harbours a sophisticated immunological network as an important prerequisite for SLIT, which contains among other cells, local antigen-presenting cells (APC), such as dendritic cells (DCs), with a constitutive disposition to enforce tolerogenic mechanisms. Further on, basic research on local DCs within the oral mucosa gave rise to possible alternative strategies to deliver the allergens to other mucosal regions than sublingual tissue, such as the vestibulum oris. Moreover, characterization of oral DCs led to the identification of target structures for both allergens as well as adjuvants, which could be applied during SLIT. Altogether, SLIT came a long way since its very beginning in the last century and some, but not all questions about SLIT could be answered so far. However, recent research efforts as well as clinical approaches paved the way for another exciting 100 years of SLIT.

Mucosal Immune System in Neonatal Period and Early Infancy

The major mechanisms of mucosal defense in the neonate consist of a variety of nonspecific barriers, and innate and specific adaptive immune responses. The functions of innate immunity in the mucosal surfaces are mediated by host-specific microbial–pathogen recognition receptors, designed to recognize unique microbial-associated molecular patterns integral to the structure of most microorganisms. Other mechanisms include many antimicrobial peptides, macrophages, dendritic cells, complement components and host-derived cellular and soluble products. The important elements of neonatal mucosal adaptive immunity include the inductive sites, such as the Peyer’s patches and other lymphoid structures in the respiratory and gastrointestinal tracts, the nasopharyngeal and sublingual tissues, the subepithelial and intraepithelial sites in most external mucosal surfaces, including the genital tract and the mammary glands. These sites contain lymphoid cells derived by the homing of antigen-activated cells from the inductive sites. Activated B cells, mostly IgA (up to 80%) are detected in the mucosal tissues shortly after birth. However, IgA-producing plasma cells are generally detected in the mucosa approximately 7–10 days of age. With progressive environmental antigenic stimulation, the number of circulating IgA cells increase significantly by 1 month of age. The postnatal development of mucosal immunity is critically influenced by the acquisition and nature of mucosal microflora, and the temporal nature and qualitative and quantitative aspects of dietary antigens and other environmental agents introduced in the neonatal period. Mucosal immune responses are generally protective against disease-producing organisms and environmental macromolecules. The mucosal immune responses may also be pathologic and foster the induction of immunologically mediated disease states and autoimmunity. The development of secretory IgA and other antimicrobial mucosal responses as well as the induction of tolerance in the neonatal period and early infancy are essential for the maintenance of mucosal homeostasis in early childhood and prevention of disease later in life.

Tongue Tie and Frenotomy in the Breastfeeding Newborn

Tongue tie or ankyloglossia has been the subject of much controversy. As defined in this review, tongue tie occurs when a common minor embryologic tissue remnant—persistence of midline sublingual tissue that usually undergoes apoptosis during embryonic development—causes restriction of normal tongue movement. Effective breastfeeding requires newborns to fine-tune their tongue movements to adapt to their mothers' particular nipple and breast anatomy and physiology. In the presence of tongue tie, two categories of signs/symptoms arise: those related to nipple trauma and those related to ineffective breast emptying and low infant intake. Untreated tongue tie can lead to untimely weaning and its attendant health risks. Frenotomy is a safe and effective procedure to release tongue tie and improve tongue function and breastfeeding outcomes.