Cytotoxic effects on the midgut, hypopharyngeal, glands and brain of Apis mellifera honey bee workers exposed to chronic concentrations of lambda-cyhalothrin.

The honeybee, Apis mellifera is economically important for its products (honey, wax, and propolis) and for its role in pollination. This insect is threated due to high population losses in both agriculture and beekeeping. Within causes involved in the loss of honeybees is the increased pesticide use on agriculture. Although current testing for the regularization of insecticide use considers its acute toxic effects on pollinators, little is known about the effects of chronic exposure to sublethal concentrations that may persist in the environment. This study investigated the effect of chronic exposure to sublethal concentrations of lambda-cyhalothrin on the midgut, hypopharyngeal glands, and brain of A. mellifera. Honey bees were fed for eight days with LC50/100 insecticide. Subsequently, the midgut, hypopharyngeal glands, and brain were analyzed in light and transmission electron microscopies. The midgut was not affected after exposure, except in the posterior region with cell fragments in the lumen and changes in the mitochondria. The hypopharyngeal glands were severely affected by the insecticide with changes in the rough endoplasmic reticulum and cell death. The brain has extensive gaps in the neuropil as well as in the cellular bodies, especially in the corpora pedunculata. These resembled cellular alterations similar to those seen in death processes. The results of this study indicate that lambda-cyhalothrin is toxic to bees at sublethal concentrations and ingested chronically, causing damage to the midgut, hypopharyngeal glands, and brain, and may affect physiological and behavioral aspects of these insects.

Honey Bees and Environmental Stress: Toxicologic Pathology of a Superorganism.

As a eusocial species, Apis mellifera, the European honey bee, is effectively a superorganism-a group of genetically related individuals functioning as a collective unit. Because the unit of selection is the colony and not the individual, standard methods for assessing toxicologic pathology can miss colony-level responses to stress. For over a decade, US populations of honeybees have experienced severe annual losses attributed to a variety of environmental stressors varying temporally and geographically; differentiating among those stressors is accordingly a high priority. Social interactions among individuals in this social species, however, mean that the "footprint" of stressors such as pesticides, phytochemicals, pathogens, and parasites may be most discernible in individuals that did not themselves directly encounter the stressor. For example, neurotoxic effects of pesticides on nurse bees may impair their behavioral responses to queen-destined larvae, which may then emerge as adults with altered anatomy or physiology. Similarly, pesticide-induced size alterations in nurse hypopharyngeal glands, which produce royal jelly, the exclusive food of larval and adult queens, may disproportionately affect the queen's (and thus colony) health. Thus, evaluating toxicologic pathology in the honeybee requires a new perspective and development of assays that preserve the social context that ultimately determines colony health.

Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction.

Biliary reflux has been considered a potential risk factor in upper aerodigestive tract malignancies. It is not yet clearly known how pH affects the bile-induced activation of NF-κB and its related oncogenic pathway previously linked to hypopharyngeal carcinogenesis. In this study, repetitive applications of conjugated primary bile acids with unconjugated secondary bile acid, deoxycholic acid (DCA), on human hypopharyngeal primary cells reveal that strongly acidic pH (4.0) optimally enhances the tumorigenic effect of bile, by inducing activation of NF-κB, STAT3 nuclear translocation, bcl-2 overexpression and significant overexpression of the oncogenic mRNA phenotype, compared to weakly acidic pH (5.5) or neutral pH (7.0). As the pH becomes less acidic the partially activated primary bile acids and activated DCA begin to exert their influence; however, with significantly less intensity compared to bile acids at strongly acidic pH. Our findings suggest that biliary tumorigenic effect is strongly pH dependent. Controlling pH during reflux events may be therapeutically effective in reducing the potential risk of bile-induced hypopharyngeal cancer.

Treatment for postchemoradiotherapy hypopharyngeal stenosis: Pharyngoesophageal bypass using an anterolateral thigh flap-A case report.

Radiation-induced pharyngoesophageal stenosis is a frequent and unwanted consequence of nonsurgical treatment of hypopharyngeal carcinomas. Current treatment mainly includes endoscopic dilatations, but a poor response to this modality and/or a severe stenosis may lead to a radical resection (pharyngolaryngectomy) and reconstruction with tubed flaps, which allow oral feeding but fail to preserve speech. In this report, we present a case of radiation-induced hypopharyngeal stenosis treated with a pharyngoesophageal bypass using an anterolateral thigh (ALT) flap with the intention of preserving the larynx. We describe the case of a 59-year-old male with severe pharyngoesophageal stenosis after chemoradiotherapy due to a squamous cell carcinoma, where conventional dilatation treatment failed to restore pharyngoesophageal passage of solids or liquids. Since the patient rejected a pharyngolaryngectomy due the loss of speech entailed, a pharyngoesophageal bypass was performed using an ALT flap. The flap measured 13 × 20 cm, which ensured a 4-cm-diameter tube and enough length to communicate the lateral pharyngeal wall with the cervical esophagus. Endoscopy did not reveal flap failure, and during the immediate postoperative period, the patient had a small cervical leak detected only by imaging that did not affect the skin and resolved with antibiotic treatment. The patient also required a tracheostomy on day 4 and initially had no passage of saliva through the bypass; we attributed this to edema that resolved spontaneously after 1 month with complete liquid and solid passage and laryngeal competence that led to tracheal decannulation. Good functional results were achieved both for speech and swallowing at 5-year follow-up. We believe that this procedure may be considered before performing a pharyngolaryngectomy for the treatment of a persistent benign stenosis in patients with a functional larynx.

Curcumin prevents the bile reflux-induced NF-κB-related mRNA oncogenic phenotype, in human hypopharyngeal cells.

The presence of bile is not an uncommon finding in acidic oesophageal and extra-oesophageal refluxate, possibly affecting the hypopharyngeal mucosa and leading to neoplastic events. We recently demonstrated that acidic bile (pH ≤ 4.0) can induce NF-κB activation and oncogenic mRNA phenotype in normal hypopharyngeal cells and generate premalignant changes in treated hypopharyngeal mucosa. We hypothesize that curcumin, a dietary inhibitor of NF-κB, may effectively inhibit the acidic bile-induced cancer-related mRNA phenotype, in treated human hypopharyngeal primary cells (HHPC), supporting its potential preventive use in vivo. Luciferase assay, immunofluorescence, Western blot, qPCR and PCR microarray analysis were used to explore the effect of curcumin in HHPC exposed to bile (400 µmol/L) at acidic and neutral pH. Curcumin successfully inhibited the acidic bile-induced NF-κB signalling pathway (25% of analysed genes), and overexpression of NF-κB transcriptional factors, c-REL, RELA(p65), anti-apoptotic bcl-2, oncogenic TNF-α, EGFR, STAT3, WNT5A, ΔNp63 and cancer-related IL-6. Curcumin effectively reduced bile-induced bcl-2 overexpression at both acidic and neutral pH. Our novel findings suggest that, similar to pharmacologic NF-κB inhibitor, BAY 11-7082, curcumin can suppress acidic bile-induced oncogenic mRNA phenotype in hypopharyngeal cells, encouraging its future in vivo pre-clinical and clinical explorations in prevention of bile reflux-related pre-neoplastic events mediated by NF-κB.

In Vivo Short-Term Topical Application of BAY 11-7082 Prevents the Acidic Bile-Induced mRNA and miRNA Oncogenic Phenotypes in Exposed Murine Hypopharyngeal Mucosa.

PURPOSE: Bile-containing gastroesophageal reflux may promote cancer at extraesophageal sites. Acidic bile can accelerate NF-κB activation and molecular events, linked to premalignant changes in murine hypopharyngeal mucosa (HM). We hypothesize that short-term in vivo topical application of NF-κB inhibitor BAY 11-7082 can prevent acidic bile-induced early preneoplastic molecular events, suggesting its potential role in disease prevention. EXPERIMENTAL DESIGN: We topically exposed HM (C57Bl/6j wild-type) to a mixture of bile acids at pH 3.0 with and without BAY 11-7082 3 times/day for 7 days. We used immunofluorescence, Western blotting, immunohistochemistry, quantitative polymerase chain reaction, and polymerase chain reaction microarrays to identify NF-κB activation and its associated oncogenic mRNA and miRNA phenotypes, in murine hypopharyngeal cells in vitro and in murine HM in vivo. RESULTS: Short-term exposure of HM to acidic bile is a potent stimulus accelerating the expression of NF-κB signaling (70 out of 84 genes) and oncogenic molecules. Topical application of BAY 11-7082 sufficiently blocks the effect of acidic bile. BAY 11-7082 eliminates NF-κB activation in regenerating basal cells of acidic bile-treated HM and prevents overexpression of molecules central to head and neck cancer, including bcl-2, STAT3, EGFR, TNF-α, and WNT5A. NF-κB inhibitor reverses the upregulated "oncomirs" miR-155 and miR-192 and the downregulated "tumor suppressors" miR-451a and miR-375 phenotypes in HM affected by acidic bile. CONCLUSION: There is novel evidence that acidic bile-induced NF-κB-related oncogenic mRNA and miRNA phenotypes are generated after short-term 7-day mucosal exposure and that topical mucosal application of BAY 11-7082 can prevent the acidic bile-induced molecular alterations associated with unregulated cell growth and proliferation of hypopharyngeal cells.

Recurrent angioedema associated with pharmacological inhibition of dipeptidyl peptidase IV.

Angioedema (AE) of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to increased use of medications inhibiting the degradation of vasoactive peptides. Acquired angioedema related to angiotensin-converting enzyme inhibitors (ACEI-AAE) is well known, but other pharmaceutical agents also affect the degradation of bradykinin and substance P. We present a middle-aged man with recurrent episodes of severe AE of the oral cavity, hypopharynx and larynx due to pharmacological inhibition of dipeptidyl peptidase IV.

Ingestion of Bt rice pollen does not reduce the survival or hypopharyngeal gland development of Apis mellifera adults.

Because of its ecological and economic importance, the honey bee Apis mellifera is commonly used to assess the environmental risk of insect-resistant, genetically modified plants. In the present study, feeding-exposure experiments were used to determine whether pollen from transgenic rice harms A. mellifera worker bees. In 1 experiment, the survival and mean acinus diameter of hypopharyngeal glands of adult bees were similar when bees were fed on pollen from Bt rice lines or from a non-Bt rice line, but bee survival was significantly reduced when they received pollen that was mixed with potassium arsenate as a positive control. In a second experiment, bee survival and hypopharyngeal gland development were not reduced when adult bees were fed on non-Bt pollen and a sucrose solution supplemented with Cry2A at 400 µg/g, Cry1C at 50 µg/g, or bovine serum albumin (BSA) at 400 µg/g, but bee survival and hypopharyngeal gland development were reduced when the diet was supplemented with soybean trypsin inhibitor as a positive control. In both experiments, the uptake of Cry proteins by adult bees was confirmed. Overall, the results indicate that the planting of Bt rice lines expressing Cry2A or Cry1C protein poses a negligible risk to A. mellifera worker bees. Environ Toxicol Chem 2017;36:1243-1248. © 2016 SETAC.

Inhibition of CDK9 induces apoptosis and potentiates the effect of cisplatin in hypopharyngeal carcinoma cells.

Myeloid cell leukemia-1 (Mcl-1) plays an important role in survival, chemo- and radioresistance of head and neck squamous cell carcinoma (HNSCC). Cyclin-dependent kinase 9/cyclin T (CDK9) promotes excessive production of multiple pro-survival proteins including Mcl-1, leading to impaired apoptosis of cancer cells. As such, CDK9 is an emerging therapeutic target in cancer therapy. We herein report the first study of targeting CDK9 as a treatment strategy for hypopharyngeal squamous cell carcinoma (HSCC), an aggressive malignancy associated with one of the worst prognoses within HNSCC. We showed that mRNA levels of Mcl-1 were significantly higher in HSCC tumor tissues than in the adjacent non-tumor mucosae. In addition, the levels of Mcl-1 mRNA correlated with the tumor size and clinical stage of HSCC patients. CDKI-73, a potent CDK9 inhibitor, was capable of downregulating the expression of Mcl-1 in the HSCC cells by suppression of the CDK9 mediated phosphorylation of RNA polymerase II. CDKI-73 effectively induced apoptosis as a single agent and synergized anti-tumor activity of cisplatin in HSCC cells. Taken together, our study presents compelling evidence for developing CDK9 inhibitors, such as CDKI-73, as new therapeutic strategy for HSCC.

Honeybees Produce Millimolar Concentrations of Non-Neuronal Acetylcholine for Breeding: Possible Adverse Effects of Neonicotinoids.

The worldwide use of neonicotinoid pesticides has caused concern on account of their involvement in the decline of bee populations, which are key pollinators in most ecosystems. Here we describe a role of non-neuronal acetylcholine (ACh) for breeding of Apis mellifera carnica and a so far unknown effect of neonicotinoids on non-target insects. Royal jelly or larval food are produced by the hypopharyngeal gland of nursing bees and contain unusually high ACh concentrations (4-8 mM). ACh is extremely well conserved in royal jelly or brood food because of the acidic pH of 4.0. This condition protects ACh from degradation thus ensuring delivery of intact ACh to larvae. Raising the pH to ≥5.5 and applying cholinesterase reduced the content of ACh substantially (by 75-90%) in larval food. When this manipulated brood was tested in artificial larval breeding experiments, the survival rate was higher with food supplemented by 100% with ACh (6 mM) than with food not supplemented with ACh. ACh release from the hypopharyngeal gland and its content in brood food declined by 80%, when honeybee colonies were exposed for 4 weeks to high concentrations of the neonicotinoids clothianidin (100 parts per billion [ppb]) or thiacloprid (8,800 ppb). Under these conditions the secretory cells of the gland were markedly damaged and brood development was severely compromised. Even field-relevant low concentrations of thiacloprid (200 ppb) or clothianidin (1 and 10 ppb) reduced ACh level in the brood food and showed initial adverse effects on brood development. Our findings indicate a hitherto unknown target of neonicotinoids to induce adverse effects on non-neuronal ACh which should be considered when re-assessing the environmental risks of these compounds. To our knowledge this is a new biological mechanism, and we suggest that, in addition to their well documented neurotoxic effects, neonicotinoids may contribute to honeybee colony losses consecutive to a reduction of the ACh content in the brood food.

Changes in the Gene Expression Profiles of the Hypopharyngeal Gland of Worker Honeybees in Association with Worker Behavior and Hormonal Factors.

The hypopharyngeal glands (HPGs) of worker honeybees undergo physiological changes along with the age-dependent role change from nursing to foraging: nurse bee HPGs secrete mainly major royal jelly proteins, whereas forager HPGs secrete mainly α-glucosidase III, which converts the sucrose in the nectar into glucose and fructose. We previously identified two other genes, Apis mellifera buffy (Ambuffy) and Apis mellifera matrix metalloproteinase 1 (AmMMP1), with enriched expression in nurse bee and forager HPGs, respectively. In the present study, to clarify the molecular mechanisms that coordinate HPG physiology with worker behavior, we first analyzed whether Ambuffy, AmMMP1, mrjp2 (a gene encoding one of major royal jelly protein isoforms), and Hbg3 (a gene encoding α-glucosidase III) expression, is associated with worker behavior in 'single-cohort colonies' where workers of almost the same age perform different tasks. Expression of these genes correlated with the worker's role, while controlling for age, indicating their regulation associated with the worker's behavior. Associated gene expression suggested the possible involvement of some hormonal factors in its regulation. We therefore examined the relationship between ecdysone- and juvenile hormone (JH)-signaling, and the expression profiles of these 'indicator' genes (nurse bee HPG-selective genes: mrjp2 and Ambuffy, and forager HPG-selective genes: Hbg3 and AmMMP1). Expression of both ecdysone-regulated genes (ecdysone receptor, mushroom body large type Kenyon cell specific protein-1, and E74) and JH-regulated genes (Methoprene tolerant and Krüppel homolog 1) was higher in the forager HPGs than in the nurse bee HPGs, suggesting the possible roles of ecdysone- and JH-regulated genes in worker HPGs. Furthermore, 20-hydroxyecdysone-treatment repressed both nurse bee- and forager-selective gene expression, whereas methoprene-treatment enhanced the expression of forager-selective genes and repressed nurse bee-selective genes in the HPGs. Our findings suggest that both ecdysone- and JH-signaling cooperatively regulate the physiological state of the HPGs in association with the worker's behavior.

Synthesis and characterization of biodegradable polyurethane for hypopharyngeal tissue engineering.

Biodegradable crosslinked polyurethane (cPU) was synthesized using polyethylene glycol (PEG), L-lactide (L-LA), and hexamethylene diisocyanate (HDI), with iron acetylacetonate (Fe(acac)3) as the catalyst and PEG as the extender. Chemical components of the obtained polymers were characterized by FTIR spectroscopy, (1)H NMR spectra, and Gel Permeation Chromatography (GPC). The thermodynamic properties, mechanical behaviors, surface hydrophilicity, degradability, and cytotoxicity were tested via differential scanning calorimetry (DSC), tensile tests, contact angle measurements, and cell culture. The results show that the synthesized cPU possessed good flexibility with quite low glass transition temperature (T g , -22°C) and good wettability. Water uptake measured as high as 229.7 ± 18.7%. These properties make cPU a good candidate material for engineering soft tissues such as the hypopharynx. In vitro and in vivo tests showed that cPU has the ability to support the growth of human hypopharyngeal fibroblasts and angiogenesis was observed around cPU after it was implanted subcutaneously in SD rats.

Anesthesia and increased hypercarbic drive impair the coordination between breathing and swallowing.

BACKGROUND: Coordination between breathing and swallowing helps prevent aspiration of foreign material into the respiratory tract. The authors examined the effects of anesthesia and hypercapnia on swallowing-breathing coordination. METHODS: In a randomized controlled crossover study, general anesthesia with propofol or sevoflurane was titrated using an up-down method to identify the threshold for suppression of the motor response to electrical stimulation of the forearm. Additional measurements included bispectral index, genioglossus electromyogram, ventilation (pneumotachometer), and hypopharyngeal pressure. During wakefulness and at each level of anesthesia, carbon dioxide was added to increase the end-tidal pressure by 4 and 8 mmHg. A swallow was defined as increased genioglossus activity with deglutition apnea and an increase in hypopharyngeal pressure. Spontaneous swallows were categorized as physiological (during expiration or followed by expiration) or pathological (during inspiration or followed by an inspiration). RESULTS: A total of 224 swallows were analyzed. Anesthesia increased the proportion of pathological swallows (25.9% vs. 4.9%) and decreased the number of swallows per hour (1.7±3.3 vs. 28.0±22.3) compared to wakefulness. During anesthesia, hypercapnia decreased hypopharyngeal pressure during inspiration (-14.1±3.7 vs. -8.7±2 mmHg) and increased minute ventilation, the proportion of pathological swallows (19.1% vs. 12.3%), and the number of swallows per hour (5.5±17.0. vs. 1.3±5.5). CONCLUSIONS: Anesthesia impaired the coordination between swallowing and respiration. Mild hypercapnia increased the frequency of swallowing during anesthesia and the likelihood of pathological swallowing. During anesthesia, the risk for aspiration may be further increased when ventilatory drive is stimulated.

Concurrent chemoradiotherapy using cisplatin, tegafur, and leucovorin for advanced squamous cell carcinoma of the hypopharynx and oropharynx.

BACKGROUND: To evaluate the efficacy and adverse events of cisplatin, tegafur, and leucovorin concomitantly with radiotherapy for patients with advanced, non-metastatic squamous cell carcinoma (SCC) of the oropharynx and hypopharynx. METHODS: The PTL regimen consisted of cisplatin (P) 50 mg/m 2 on day 1, oral tegafur (T) 800 mg/day plus leucovorin (LV) 60 mg/day on days 1 through 14. It was repeated every 2 weeks through the radiotherapy course. Conventional radiotherapy with 1.8-2.0 Gy/day, 5 days per week, was delivered in a total dose of between 70 and 72 Gy. RESULTS: Sixty-five patients with stage III or IV of SCC of the head and neck were consecutively treated between May 2002 and November 2005. Forty-six (70.7%) patients had complete response after concomitant chemoradiotherapy (CCRT). With a median follow-up of 54.0 months (range 1-103 months), the 5-year locoregional control, progression-free survival, and overall survival rates were 50.6%, 40.7%, and 59.7%, respectively. Three (4.6%) patients had toxic death during treatment. Fifty-one (80.0%) patients experienced grade 3-4 mucositis which occurred in about 35% of the CCRT duration. The functional preservation rate among post-CCRT complete responders was 93.5% (43/46). The median cisplatin accumulated dosage was 150 mg, and the rate of hearing impairment among the survivors was 7.8%. CONCLUSION: CCRT with outpatient-based PTL for advanced SCC of oropharynx and hypopharynx is feasible and has comparative efficacy and acceptable adverse events.

Chronic pepsin exposure promotes anchorage-independent growth and migration of a hypopharyngeal squamous cell line.

OUTCOME OBJECTIVES: (1) Investigate the role of reflux, specifically pepsin, in laryngopharyngeal carcinogenesis. (2) Evaluate effects of chronic pepsin exposure on cell migration, apoptosis, and colony-forming ability in hypopharyngeal cells. STUDY DESIGN: Translation research. SETTING: Academic research laboratory. METHODS: Human hypopharyngeal squamous carcinoma FaDu cells were chronically exposed to nonacidic pepsin (exposed for 24 hours, 4 times over 2 weeks at the following concentrations: 0.01 mg/mL, 0.1 mg/mL, or 1 mg/mL). Precise wounds were created in confluent cell plates, and rates of cell migration into wounds were quantified. Separately, cell viability of chronic pepsin-exposed FaDu cells acutely treated with paclitaxel was measured. Finally, a clonogenic assay was performed on these cells to measure effects of chronic pepsin exposure on colony-forming ability. RESULTS: An increased rate of relative wound density was observed in chronic pepsin-treated (0.01 mg/mL, 0.1 mg/mL) cells compared with control (P < .001), suggesting greater rates of cell migration. Pepsin-treated (0.1 mg/mL) cells demonstrated on average greater cell viability compared with control after exposure to paclitaxel, suggesting possible apoptotic resistance; however, this was not statistically significant. Chronic pepsin exposure (0.1 mg/mL, 1 mg/mL) was associated with a dose-dependent increase in colony-forming ability relative to control (P < .001). CONCLUSION: Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration and colony-forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux.

Capsaicin-sensitive cough receptors in lower airway are responsible for cough hypersensitivity in patients with upper airway cough syndrome.

BACKGROUND: Cough hypersensitivity may be related to the pathogenesis of upper airway cough syndrome (UACS). The purpose of the study was to investigate the role of capsaicin-sensitive cough receptors on the laryngopharynx and lower airway in the cough hypersensitivity of patients with UACS. MATERIAL AND METHODS: 59 patients with UACS, 33 patients with rhinitis/sinusitis without cough, and 39 healthy volunteers were recruited for the study. Cough threshold C5, defined as the lowest concentration of capsaicin required for the induction of ≥ 5 coughs upon exposure to capsaicin, were determined at baseline and after laryngopharngeal anesthesia with lidocaine in all the subjects. After induced sputum cytology, the concentrations of histamine, prostaglandin E2 (PGE2), and calcitonin-gene-related peptide (CGPR) in the induced sputum were measured by ELISA. In 15 patients with UACS, sputum cytology and measurement of the above mediators were repeated after successful therapy. RESULTS: C5 response to capsaicin was significantly lower in the UACS group than in the rhinitis/sinusitis group and healthy control groups [3.9 (0.98, 7.8) µmol/L vs. 7.8 (3.9, 93.75) µmol/L vs. 31.2 (15.6, 62.5) µmol/L, H=40.12, P=0.000]. Laryngopharngeal anesthesia with lidocaine dramatically increased C5 to capsaicin in the subjects of all 3 groups by a similar degree, but the increase in the UACS group was still the lowest, with an increased level of histamine, PGE2, and CGRP in the induced sputum. When cough resolved with the treatment of cetirizine alone or in combination with erythromycin, the levels of CGRP and histamine in the induced sputum decreased significantly in 15 patients with UACS, with no obvious change in cell differential or concentration of PGE2 in the induced sputum. CONCLUSIONS: Laryngeal TRPV1 plays an important role in cough sensitivity, but sensitization of capsaicin-sensitive cough receptors in the lower airway may be more responsible for the cough hypersensitivity in patients with UACS.

[The application of laripront in the pediatric otorhinolaryngological practice].

The objective of the present study was to estimate the efficacy of laripront intended for the treatment of inflammatory diseases of the laryngopharynx in the children. Available for the observation were 50 patients aged between 4 and 14 years suffering from the following ENT pathologies: adenoiditis, lacunar tonsillitis, acute laryngitis, chronic tonsillitis, oropharyngeal candidiasis, chronic hypertrophic pharyngitis, atrophic pharyngolaryngitis after the chemical burn of the mouse cavity and laryngopharynx or in the case of gastroesophageal reflux disease. All the patients enjoyed the positive outcome of the treatment that was especially efficacions in the patients with acute pathologies. No adverse effects of the treatment were documented.

Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells.

OBJECTIVE/HYPOTHESIS: Laryngopharyngeal reflux (LPR) is thought to be a significant risk factor for laryngeal squamous cell carcinoma (SCC), but causality has never been proven. It is accepted that chronic reflux into the esophagus can induce metaplastic changes in esophageal mucosa with subsequent increased risk of esophageal adenocarcinoma, but no similar associations have been established for LPR and laryngopharyngeal SCC. The objective of this study was to test the hypothesis that reflux of pepsin into the laryngopharynx can promote carcinogenesis. STUDY DESIGN: Translational research study. METHODS: Normal human laryngeal primary epithelial cell cultures and hypopharyngeal FaDu SCC cells were exposed to human pepsin and analyzed by Human Cancer PathwayFinder and miRNA Superarrays, flow cytometry, and Western blot to determine the effect of pepsin on carcinogenesis. Laryngeal biopsy specimens taken from cancer patients and normal control subjects were analyzed for the presence of pepsin by Western blot. RESULTS: Microarray analysis demonstrated that pepsin significantly altered the expression of 27 genes implicated in carcinogenesis and also affected the expression of 22 microRNAs known to be altered in human head and neck cancers. Pepsin increased proliferation in both FaDu SCC cells and cultured normal laryngeal epithelial primary cells by increasing S phase distribution on flow cytometry analysis in a time- and dose-dependent manner. Furthermore, pepsin was detected in 60% (3/5) human laryngeal cancer biopsies, absent in all (0/5) normal control specimens. CONCLUSIONS: These data support a role for refluxed pepsin in the promotion of epithelial proliferation and carcinogenesis of the larynx and pharynx.

Iron pill-induced tumefactive mucosal injury of the hypopharynx.

Iron pill-induced mucosal injury of the airways with massive necrosis and stricture of the lower airways is known to occur, but symptomatic injury of the hypopharyngeal mucosa secondary to therapeutic oral iron ingestion has not been described. We report iron-sulfate-induced mucosal injury of the hypopharynx in a patient receiving therapeutic oral iron supplementation. The patient presented with dysphagia when swallowing pills, but not when eating or drinking. Imaging studies and clinical examination revealed an ulcerated and protuberant hypopharyngeal mass. Histology showed mucosal ulceration with deposits of extracellular crystalline iron particles. The histologic changes were identical to those seen in patients with "iron pill" gastritis.

Effect of stimulation of the laryngopharynx with water and salt solutions on voluntary swallowing in humans: characteristics of water receptors in the laryngopharyngeal mucosa.

Stimulation of water receptors in the laryngopharynx (LP) with water facilitates voluntary swallowing in humans. Based on measures of swallowing intervals (SIs) in repetitive swallowing, we investigated characteristics of laryngopharyngeal water receptors in humans. Healthy adult volunteers were instructed to perform repetitive swallowing as quickly as possible during infusion of a solution into the LP. Infusion of water shortened SI, suggesting that water excites water receptors. Infusion of 0.3 M NaCl solution prolonged SI, suggesting that the NaCl solution inhibits activity of water receptors. SI increased with increasing concentration of NaCl. Anion or cation substitutions indicated that excitation of water receptors is due to absence or reduced concentration of Cl(-). With diminution of peripheral inputs, cortical inputs would play a dominant role in voluntary swallowing. With infusion of a nonstimulating solution (0.3 M NaCl at 0.2 mL/min), SI varied greatly from subject to subject, suggesting that the ability of central regulation of swallowing to initiate repetitive voluntary swallowing varies among subjects. Facilitation of swallowing by chemosensory inputs from water receptors appeared strongly in subjects with longer SI with infusion of the nonstimulating solution. It appears that chemosensory activation compensates for the difficulty in initiating swallowing via the central neural mechanism.