Oral manifestations of diabetes mellitus in complete denture wearers.

PubMed

Cristina de Lima, Danielle; Nakata, Gislaine Cristina; Balducci, Ivan; Almeida, Janete Dias

2008-01-01

The oral mucosa has been reported to show a variety of changes in subjects with diabetes mellitus. The purpose of this study was to compare diabetic and nondiabetic subjects wearing complete dentures with regard to salivary flow, salivary buffering capacity, denture retention, and oral mucosal lesions. Sixty subjects, 30 with and 30 without a diagnosis of diabetes, were matched for gender, race, and age. Salivary flow, salivary buffering capacity, glycemia, blood pressure, presence of mucosal lesions, denture retention, use of medications, and behavioral factors (controlled or uncontrolled diet, alcohol consumption, and smoking) reported by the subjects, were evaluated. For the salivary buffering capacity test, 1 mL of saliva was pipetted into a test tube containing 3 mL 0.005 N of hydrochloric acid, and the pH was measured with indicator strips. Group differences were statistically analyzed using the Student t test and the Mann-Whitney test for quantitative variables and the chi-square test for qualitative variables (alpha =.05). Mean (SD) salivary flow was 1.14 (0.87) mL/min in the nondiabetic subjects and 0.95 (0.61) mL/min in the diabetic subjects. Evaluation of self-reported denture retention revealed no significant difference between groups. Denture retention was observed in 66.7% (20/30) of the control group and in 50% (15/30) of the diabetic group. The prevalence of mucosal lesions was 90% (27/30) in the control group and 83.3% (25/30) in the diabetic group. Salivary buffering capacity was 5.80 (0.85) in the control group and 5.26 (0.83) in the diabetic group (P=.017). Within the limitations of this study, no significant differences were observed in salivary flow, denture retention, or oral lesions in diabetic and nondiabetic subjects.

Surface-Modified P(HEMA-co-MAA) Nanogel Carriers for Oral Vaccine Delivery: Design, Characterization, and In Vitro Targeting Evaluation

PubMed Central

Durán-Lobato, Matilde; Carrillo-Conde, Brenda; Khairandish, Yasmine; Peppas, Nicholas A.

2015-01-01

Oral drug delivery is a route of choice for vaccine administration because of its noninvasive nature and thus efforts have focused on efficient delivery of vaccine antigens to mucosal sites. An effective oral vaccine delivery system must protect the antigen from degradation upon mucosal delivery, penetrate mucosal barriers, and control the release of the antigen and costimulatory and immunomodulatory agents to specific immune cells (i.e., APCs). In this paper, mannan-modified pH-responsive P(HEMA-co-MAA) nanogels were synthesized and assessed as carriers for oral vaccination. The nanogels showed pH-sensitive properties, entrapping and protecting the loaded cargo at low pH values, and triggered protein release after switching to intestinal pH values. Surface decoration with mannan as carbohydrate moieties resulted in enhanced internalization by macrophages as well as increasing the expression of relevant costimulatory molecules. These findings indicate that mannan-modified P(HEMA-co-MAA) nanogels are a promising approach to a more efficacious oral vaccination regimen. PMID:24955658

Proteomics Analysis of the Adhesion Activity of Lactobacillus acidophilus ATCC 4356 Upon Growth in an Intestine-Like pH Environment.

PubMed

Wu, Zhen; Wang, Gang; Wang, Wenwen; Pan, Daodong; Peng, Liuyang; Lian, Liwei

2018-03-01

Many health effects of Lactobacillus acidophilus are desirable among these the adhesion ability is vital to enhance the possibility of colonization and stabilization associated with the gut mucosal barrier. In this study, the growth characteristics and the adhesion activity of L. acidophilus in the intestine-like pH environment (pH 7.5) are identified. The number of bacteria adhering to the HT-29 cells is found with a gradual increase trend (pH 5.5-7.5). This also leads to the morphological changes of L. acidophilus after exposure to different pH environments. Furthermore, with the help of the isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis, 207 proteins are detected differentially expressed at pH of 7.5. The use of GO analysis and KEGG analysis indicates three essential pathways related to the cell envelope peptide-glycan biosynthesis, carbohydrate metabolism, and amino acid metabolism are obviously changed. Adhesion related surface protein fmtB and PrtP are upregulated in pH 7.5 group. While the moonlight proteins like pyruvate kinase, which binds specifically to the mucin layer and inhibits the adhesive activity of L. acidophilus, is found downregulated. These results could be useful to understand the adhesion mechanism of L. acidophilus adapting for the gut mucosal barrier in the intestinal environment. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis

PubMed Central

Reda, Rana Ihab; Wen, Ming Ming; El-Kamel, Amal Hassan

2017-01-01

Purpose The purpose of this study was to formulate ketoprofen (KET)-loaded Eudragit L and Eudragit S nanofibers (NFs) by the electrospinning technique for buccal administration to treat oral mucositis as a safe alternative to orally administered KET, which causes gastrointestinal tract (GIT) side effects. Materials and methods NFs were prepared by electrospinning using Eudragit L and Eudragit S. Several variables were evaluated to optimize NF formulation, such as polymer types and concentrations, applied voltage, flow rate and drug concentrations. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) and analyses of drug contents, hydration capacity, surface pH, drug release and ex vivo permeation were performed to evaluate the NFs. The selected formulation (F1) was evaluated in vivo on induced oral mucositis in rabbits. Results SEM revealed that 20% polymer formed smooth and bead-free NFs. DSC results confirmed the amorphous nature of KET in the NFs. FTIR confirmed hydrogen bond formation between the drug and polymer, which stabilized the NFs. Both formulations (F1 and F2) had an acceptable surface pH. The drug loading was >90%. The amount of KET released from NF formulations was statistically significantly higher (P≤0.001) than that released from the corresponding solvent-casted films. The complete release of KET from F1 occurred within 2 hours. Ex vivo permeation study revealed that only a small fraction of drug permeated from F1, which was a better candidate than F2 for local buccal delivery. In vivo evaluation of F1 on oral mucositis induced in rabbits demonstrated that F1 reduced the clinical severity of mucositis in rabbits under the current experimental conditions. The attenuated clinical severity was accompanied by a marked reduction in inflammatory infiltrate and re-epithelization of the epithelial layer. Conclusion Eudragit L100 nanofibers (EL-NF) loaded with KET (F1) suppressed the inflammatory response associated with mucositis, which confirmed the efficacy of local buccal delivery of KET-loaded EL-NF in treating oral mucositis. PMID:28392691

A High Grain Diet Dynamically Shifted the Composition of Mucosa-Associated Microbiota and Induced Mucosal Injuries in the Colon of Sheep.

PubMed

Wang, Yue; Xu, Lei; Liu, Junhua; Zhu, Weiyun; Mao, Shengyong

2017-01-01

This study investigated the dynamic shifts in mucosa-associated microbiota composition and mucosal morphology in the colon of sheep fed a high grain (HG) diet. A total of 20 male sheep were randomly assigned to four groups ( n = 5 for each). The sheep in first group received hay diet. The animals in other 3 groups were fed an HG diet for 7 (HG7), 14 (HG14), or 28 (HG28) days, respectively. Colonic digesta samples were collected to determine the pH and the concentrations of volatile fatty acid (VFA) and lactate. The colonic mucosa was sampled to characterize the bacterial communities using Illumina MiSeq sequencing and to determine mRNA expression levels of cytokines and tight junction protein genes using quantitative real-time PCR. As time advanced, results revealed that colonic pH linearly decreased ( P = 0.007), and the concentrations of total VFA linearly increased ( P < 0.001). Microbial analysis showed that an HG diet linearly reduced ( P < 0.050) the diversity and richness of the colonic microbiota. The principal coordinate analysis results showed that the colonic mucosa-associated bacterial communities of the four groups significantly shifted with number of days fed an HG diet. At the genus level, HG feeding significantly increased the relative abundance of some taxa including Prevotella , Coprococcus , Roseburia , and Clostridium_sensu_stricto_1 , and decreased the proportion of Treponema, and the percentage of these taxa was not affected by days fed an HG diet. The microscopic examination showed that HG feeding caused the mucosal epithelial injury. The RT-PCR results showed that the mRNA expression of claudin-1 ( P = 0.038), IL-1β ( P = 0.045), IL-6 ( P = 0.050), and TNF-α ( P = 0.020) increased linearly with number of days fed an HG diet. The correlation analysis revealed significant correlation between the colonic mucosal mRNA expression of cytokines and mucosal bacterial composition. Generally, HG feeding increased colonic fermentation and altered colonic mucosal bacterial communities, which eventually caused colonic mucosal damage and led to colonic dysfunction, and these changes occurred gradually over at least 4 weeks.

A High Grain Diet Dynamically Shifted the Composition of Mucosa-Associated Microbiota and Induced Mucosal Injuries in the Colon of Sheep

PubMed Central

Wang, Yue; Xu, Lei; Liu, Junhua; Zhu, Weiyun; Mao, Shengyong

2017-01-01

This study investigated the dynamic shifts in mucosa-associated microbiota composition and mucosal morphology in the colon of sheep fed a high grain (HG) diet. A total of 20 male sheep were randomly assigned to four groups (n = 5 for each). The sheep in first group received hay diet. The animals in other 3 groups were fed an HG diet for 7 (HG7), 14 (HG14), or 28 (HG28) days, respectively. Colonic digesta samples were collected to determine the pH and the concentrations of volatile fatty acid (VFA) and lactate. The colonic mucosa was sampled to characterize the bacterial communities using Illumina MiSeq sequencing and to determine mRNA expression levels of cytokines and tight junction protein genes using quantitative real-time PCR. As time advanced, results revealed that colonic pH linearly decreased (P = 0.007), and the concentrations of total VFA linearly increased (P < 0.001). Microbial analysis showed that an HG diet linearly reduced (P < 0.050) the diversity and richness of the colonic microbiota. The principal coordinate analysis results showed that the colonic mucosa-associated bacterial communities of the four groups significantly shifted with number of days fed an HG diet. At the genus level, HG feeding significantly increased the relative abundance of some taxa including Prevotella, Coprococcus, Roseburia, and Clostridium_sensu_stricto_1, and decreased the proportion of Treponema, and the percentage of these taxa was not affected by days fed an HG diet. The microscopic examination showed that HG feeding caused the mucosal epithelial injury. The RT-PCR results showed that the mRNA expression of claudin-1 (P = 0.038), IL-1β (P = 0.045), IL-6 (P = 0.050), and TNF-α (P = 0.020) increased linearly with number of days fed an HG diet. The correlation analysis revealed significant correlation between the colonic mucosal mRNA expression of cytokines and mucosal bacterial composition. Generally, HG feeding increased colonic fermentation and altered colonic mucosal bacterial communities, which eventually caused colonic mucosal damage and led to colonic dysfunction, and these changes occurred gradually over at least 4 weeks. PMID:29123511

The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids

PubMed Central

Jaeger, Frederick; McGuire, Erin; Fouda, Genevieve; Amos, Joshua; Barbas, Kimberly; Ohashi, Tomoo; Alam, S. Munir; Erickson, Harold; Permar, Sallie R.

2016-01-01

Tenascin-C (TNC) is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment. As mucosal fluids are complex and contain a number of proteins known to interact with the HIV-1 envelope, we further studied the relationship between the concentration of TNC and neutralizing activity in breast milk. The amount of TNC correlated only weakly with the overall innate HIV-1-neutralizing activity of breast milk of uninfected women and negatively correlated with neutralizing activity in milk of HIV-1 infected women, indicating that the amount of TNC in mucosal fluids is not adequate to impede HIV-1 transmission. Moreover, the presence of polyclonal IgG from milk of HIV-1 infected women, but not other HIV-1 envelope-binding milk proteins or monoclonal antibodies, blocked the neutralizing activity of TNC. Finally, as exogenous administration of TNC would be necessary for it to mediate measurable HIV-1 neutralizing activity in mucosal compartments, we established that recombinantly produced TNC has neutralizing activity against transmitted/founder HIV-1 strains that mimic that of purified TNC. Thus, we conclude that endogenous TNC concentration in mucosal fluids is likely inadequate to block HIV-1 transmission to uninfected individuals. PMID:27182834

Nonerosive reflux disease: clinical concepts.

PubMed

Gyawali, C Prakash; Azagury, Dan E; Chan, Walter W; Chandramohan, Servarayan M; Clarke, John O; de Bortoli, Nicola; Figueredo, Edgar; Fox, Mark; Jodorkovsky, Daniela; Lazarescu, Adriana; Malfertheiner, Peter; Martinek, Jan; Murayama, Kenric M; Penagini, Roberto; Savarino, Edoardo; Shetler, Katerina P; Stein, Ellen; Tatum, Roger P; Wu, Justin

2018-05-15

Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosions are not seen on endoscopy (as for nonerosive reflux disease, NERD). Esophageal physiological tests (ambulatory pH or pH-impedance monitoring and manometry) can be of value in defining abnormal reflux burden and reflux-symptom association. NERD diagnosed on the basis of abnormal reflux burden on ambulatory reflux monitoring is associated with similar symptom response from antireflux therapy for erosive esophagitis. Acid suppression is the mainstay of therapy, and antireflux surgery has a definitive role in the management of persisting symptoms attributed to NERD, especially when the esophagogastric junction is compromised. Adjunctive approaches and complementary therapy may be of additional value in management. In this review, we describe the evaluation, diagnosis, differential diagnosis, and management of NERD. © 2018 New York Academy of Sciences.

Impact of dextran sulphate sodium-induced colitis on the intestinal transport of the colon carcinogen PhIP.

PubMed

Nicken, Petra; von Keutz, Anne; Willenberg, Ina; Ostermann, Annika I; Schebb, Nils Helge; Giovannini, Samoa; Kershaw, Olivia; Breves, Gerhard; Steinberg, Pablo

2016-05-01

Colorectal cancer is one of the most frequent cancers in Western countries. Chronic intestinal diseases such as Crohn's disease and ulcerative colitis, in which the intestinal barrier is massively disturbed, significantly raise the risk of developing a colorectal tumour. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a genotoxic heterocyclic aromatic amine that is formed after strongly heating fish and meat. In this study, the hypothesis that PhIP uptake in the gut is increased during chronic colitis was tested. Chronic colitis was induced by oral administration of dextran sulphate sodium (DSS) to Fischer 344 rats. The transport of PhIP in eight different rat intestinal segments was examined in Ussing chambers. The tissues were incubated with 10 µM PhIP for 90 min, and the concentration of PhIP was determined in the mucosal and serosal compartments of the Ussing chambers as well as in the clamped tissues by LC-MS. Although chronic colitis was clearly induced in the rats, no differences in the intestinal transport of PhIP were observed between control and DSS-treated animals. The hypothesis that in the course of chronic colitis more PhIP is taken up by the intestinal epithelium, thereby increasing the risk of developing colorectal cancer, could not be confirmed in the present report.

A combined oral contraceptive affects mucosal SHIV susceptibility factors in a pigtail macaque model

PubMed Central

Ostergaard, Sharon Dietz; Butler, Katherine; Ritter, Jana M.; Johnson, Ryan; Sanders, Jeanine; Powell, Nathaniel; Lathrop, George; Zaki, Sherif R.; McNicholl, Janet M.; Kersh, Ellen N.

2015-01-01

Background Injectable hormonal contraception may increase women’s risk of HIV acquisition, and can affect biological risk factors in animal models of HIV. We established, for the first time, a model to investigate whether combined oral contraceptives (COC) alter SHIV susceptibility in macaques. Methods Seven pigtail macaques were administered a monophasic levonorgestrel (LNG)/ethinyl estradiol (EE) COC at 33% or 66% of the human dose for 60 days. Menstrual cycling, vaginal epithelial thickness and other SHIV susceptibility factors were monitored for a mean of 18 weeks. Results Mean vaginal epithelial thicknesses was 290.8 μm at baseline and 186.2 μm during COC (p=0.0141, Mann Whitney test). Vaginal pH decreased from 8.5 during to 6.5 post- treatment (0.0176 two-tailed t-test). Measured microflora was unchanged. Conclusions COC caused thinning of the vaginal epithelium and vaginal pH changes, which may increase SHIV susceptibility. 0.033 mg LNG + 0.0066 mg EE appeared effective in suppressing ovulation. PMID:25536296

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

PubMed Central

Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

2016-01-01

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

ACE-like hydrolysis of gastrin analogs and CCK-8 by fundic mucosal cells of different species with release of the amidated C-terminal dipeptide.

PubMed

Dubreuil, P; Fulcrand, P; Rodriguez, M; Laur, J; Bali, J P; Martinez, J

1990-06-19

Various gastrin analogues and CCK-8 (Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) are hydrolyzed in vitro by angiotensin-converting enzyme (ACE), the main and initial cleavage occurring at the Met-Asp (or Leu-Asp) bond, releasing the C-terminal dipeptide amide Asp-Phe-NH2. Tetragastrin analogues (e.g., Boc-Trp-Leu-Asp-Phe-NH2) are degraded by a vesicular membrane fraction from rat gastric mucosa, yielding the C-terminal dipeptide Asp-Phe-NH2. We report here on the degradation of gastrin analogues and CCK-8 by a gastric mucosal cell preparation containing specific gastrin receptors. We have shown that gastrin analogues were specifically degraded by gastric mucosal cells from different species (e.g., rabbit and dog) at 37 degrees C (pH 7.4), releasing the C-terminal dipeptide Asp-Phe-NH2, similarly to ACE. This cleavage was found to be temperature and pH sensitive, and was inhibited by metalloproteinase inhibitors and by captopril, strongly suggesting that this enzymatic system closely resembles ACE. We have also demonstrated that a close correlation seems to exist between the apparent affinity of the gastrin analogues for gastrin receptors on gastric mucosal cells, and their ability of being hydrolyzed by this cell preparation. Moreover, all gastrin analogues which have been demonstrated to act as gastrin antagonists remained unaffected in the incubation conditions.

Esophageal Mucosal Impedance Pattern is Distinct in Patients With Extraesophageal Reflux Symptoms and Pathologic Acid Reflux.

PubMed

Kavitt, Robert T; Lal, Pooja; Yuksel, Elif Saritas; Ates, Fehmi; Slaughter, James C; Garrett, C Gaelyn; Higginbotham, Tina; Vaezi, Michael F

2017-05-01

Current diagnostic tests for gastroesophageal reflux disease (GERD) do not consistently measure chronicity of reflux. Mucosal impedance (MI) is a minimally invasive measurement to assess esophageal conductivity changes due to GERD. We aimed to investigate MI pattern in patients with symptoms of extraesophageal reflux (EER) in a prospective longitudinal cohort study. Patients with potential symptoms of EER undergoing esophagogastroduodenoscopy (EGD) with wireless pH monitoring were studied. Participants included those with erosive esophagitis (E+), normal EGD/abnormal pH (E-/pH+), and normal EGD/normal pH (E-/pH-). MI was measured from the site of injury in patients with E+, as well as at 2, 5, and 10 cm above the squamocolumnar junction (SCJ) in all participants. Forty-one patients with symptoms of EER were studied. MI measurements at 2 cm above the SCJ were significantly (P = 0.04) different among the three groups, with MI lowest for E+ and greatest for E-/pH- patients. Although not statistically significant, there is a graded increase in median (interquartile range) MI axially along the esophagus at 5 cm (P = 0.20) and at 10 cm (P = 0.27) above the SCJ, with those with reflux (E+ and E-/pH+) having a lower MI than those without. Patients with symptoms of EER and evidence of acid reflux have an MI lower than those without at 2 cm above the SCJ, with a trend at 5 cm and 10 cm as well. MI may be a tool to assess presence of GERD in patients presenting with EER symptoms. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

In vitro effects of hydrochloric acid and various concentrations of acetic, propionic, butyric, or valeric acids on bioelectric properties of equine gastric squamous mucosa.

PubMed

Andrews, Frank M; Buchanan, Benjamin R; Smith, Sionagh H; Elliott, Sarah B; Saxton, Arnold M

2006-11-01

To compare the effects of hydrochloric acid (HCl) and various concentrations of volatile fatty acids (VFAs) on tissue bioelectric properties of equine stomach nonglandular (NG) mucosa. Gastric tissues obtained from 48 adult horses. NG gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference (PD) were measured and electrical resistance (R) and conductance calculated for tissues after addition of HCl and VFAs (5, 10, 20, and 40 mM) in normal Ringer's solution (NRS). Mucosa exposed to HCl in NRS (pH of 1.5 and, to a lesser extent, 4.0) had a significant decrease in Isc, PD, and R, whereas tissues exposed to acetic acid at a pH of < 4.0, propionic and butyric acids at a pH of

Indications and interpretation of esophageal function testing.

PubMed

Gyawali, C Prakash; de Bortoli, Nicola; Clarke, John; Marinelli, Carla; Tolone, Salvatore; Roman, Sabine; Savarino, Edoardo

2018-05-12

Esophageal symptoms are common, and can arise from mucosal, motor, functional, and neoplastic processes, among others. Judicious use of diagnostic testing can help define the etiology of symptoms and can direct management. Endoscopy, esophageal high-resolution manometry (HRM), ambulatory pH or pH-impedance manometry, and barium radiography are commonly used for esophageal function testing; functional lumen imaging probe is an emerging option. Recent consensus guidelines have provided direction in using test findings toward defining mechanisms of esophageal symptoms. The Chicago Classification describes hierarchical steps in diagnosing esophageal motility disorders. The Lyon Consensus characterizes conclusive evidence on esophageal testing for a diagnosis of gastroesophageal reflux disease (GERD), and establishes a motor classification of GERD. Taking these recent advances into consideration, our discussion focuses primarily on the indications, technique, equipment, and interpretation of esophageal HRM and ambulatory reflux monitoring in the evaluation of esophageal symptoms, and describes indications for alternative esophageal tests. © 2018 New York Academy of Sciences.

Effectiveness of Indian Turmeric Powder with Honey as Complementary Therapy on Oral Mucositis : A Nursing Perspective among Cancer Patients in Mysore.

PubMed

Francis, Manjusha; Williams, Sheela

2014-01-01

Oral mucositis is a common, debilitating complication of cancer patients undergoing chemotherapy and radiotherapy, occurring in about 40 percent cases. Mucositis may limit the patient's ability to tolerate chemotherapy or radiation therapy, and nutrition status is compromised. The aim of the study was to assess the effect of Indian turmeric powder with honey as a complementary therapy on treatment induced oral mucositis. In the study, quasi experimental non-equivalent control group pre test post-test design was used and non-probability purposive sampling technique was adopted to select 60 cancer patients with treatment induced oral mucositis, 30 each in experimental and control group. The independent 't' value for post-test 2 and 3 (post-test 2: 2.86 for WHO OMAS and 4.58 for MPJ OMAS, post test 2: 5.42 for WHO OMAS and 7.2 for MPJ OMAS; p < 0.05) were significant between experimental and control group. It is inferred that the application of Indian turmeric and honey on treatment-induced oral mucositis is effective.

Isolation and characterization of a mucosal triacylglycerol pool undergoing hydrolysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tipton AD IV; Frase, S.; Mansbach, C.M. II

1989-12-01

Absorbed and processed mucosal neutral lipid has been shown to be composed of at least two pools of triacylglycerol. One is likely to subserve chylomicron formation, and the other appears to be transported from the intestine via a nonlymphatic route. In the present study, 50 +/- 5% of the mucosal lipid pellets was centrifuged at 75,000 g.min (low-speed pellet (LSP)). Discontinuous sucrose density gradient centrifugation of LSP showed that 61 +/- 7% of the lipid banded at the 0.25-0.86 M sucrose interface. Neutral lipid analysis showed that this subfraction was only 58% triacylglycerol, suggesting it was undergoing hydrolysis. Active lipolyticmore » activity in vitro was found on incubation. The lipase had an alkaline pH optimum (pH 8.5) and persisted despite pancreatic ductular diversion. Lipolysis in vivo in a LSP fraction was shown by infusing (14C)glyceryltrioleate for 3.5 h followed by (3H)glyceryltrioleate for 30 min. Discontinuous sucrose density centrifugation of the LSP followed by an analysis of the lipids at the 0.25-0.86 M sucrose interface showed that 14C-neutral lipids were only 70 +/- 6% triacylglycerol, whereas 3H-neutral lipids were 88 +/- 2% triacylglycerol. 3H entered LSP slowly compared with the floating lipid in the same centrifuge tube. These studies suggest both in vivo and in vitro mucosal lipolysis by a specific, alkaline-active lipase. The turnover rate of LSP is likely to be slow by comparison with neutral lipid floating to the top of the centrifuge tube.« less

Paul Carlson | Center for Cancer Research

Cancer.gov

Paul Carlson, Ph.D. March 28 Principal Investigator Laboratory of Mucosal Pathogens and Cellular Immunology Center for Biologics Evaluation and Research (CBER), FDA Topic:  "Research and Regulation of novel biologic products at the FDA's Center for Biologics Evaluation and Research"

The Effects of Switching to Vonoprazan, a Novel Potassium-Competitive Acid Blocker, on Gastric Acidity and Reflux Patterns in Patients with Erosive Esophagitis Refractory to Proton Pump Inhibitors.

PubMed

Yamashita, Hiroshi; Kanamori, Atsushi; Kano, Chise; Hashimura, Hiroki; Matsumoto, Kei; Tsujimae, Masahiro; Yoshizaki, Tetsuya; Momose, Kenji; Obata, Daisuke; Eguchi, Takaaki; Fujita, Mikio; Okada, Akihiko

2017-01-01

The effects of vonoprazan and proton pump inhibitors (PPIs) in patients with reflux esophagitis (RE) have not yet been compared using multichannel intraluminal impedance-pH (MII-pH). A total of 8 patients with persistent gastric mucosal injury, despite completing an 8-week standard PPI therapy, were enrolled in the study. While they were on standard PPI therapy, the baseline values of reflux parameters, holding time ratio (HTR) of gastric pH >4, and esophageal pH <4 were obtained by using 24 h MII-pH monitoring. They were re-evaluated after discontinuation of the therapy and 4 weeks of subsequent treatment with vonoprazan 20 mg/day. The patients were found to be CYP2C19 extensive metabolizers and negative for Helicobacter pylori infection. In 7 patients (87.5%), the mucosal lesions had healed completely after vonoprazan therapy. A significant increase in gastric pH >4 HTR was observed, from 26.5 to 78.0% (p = 0.029). A reduction in esophageal pH <4 HTR was also observed but it was not statistically significant. Furthermore, acid clearance time and the total number of reflux events, including acid and proximal reflux events, were significantly reduced. Vonoprazan may be a better therapy for the treatment of patients with PPI-refractory RE. © 2017 S. Karger AG, Basel.

Improvement of gastroesophageal reflux disease in Japanese patients with spinal kyphotic deformity who underwent surgical spinal correction.

PubMed

Sugimoto, Mitsushige; Hasegawa, Tomohiko; Nishino, Masafumi; Sahara, Shu; Uotani, Takahiro; Ichikawa, Hitomi; Kagami, Takuma; Sugimoto, Ken; Yamato, Yu; Togawa, Daisuke; Kobayashi, Sho; Hoshino, Hironobu; Matsuyama, Yukihiro; Furuta, Takahisa

2016-01-01

Spinal kyphotic deformity occasionally results in gastroesophageal reflux disease (GERD). The effects of acid reflux on the esophagus in kyphotic patients are unclear, however, and it is unknown whether acid reflux, endoscopic GERD, and reflux-related symptoms improve following surgical spinal correction in these patients. Herein, we investigated the characteristics of GERD in kyphotic patients and the improvement in GERD following surgical correction. In 48 patients with severe kyphotic deformity scheduled for surgical spinal correction, we conducted esophagogastroduodenoscopy, 24-h pH monitoring and three questionnaire surveys, including the frequency scale for the symptoms of GERD (FSSG). We repeated these measurements after surgical correction and compared pre- and post-surgery values. Of 48 patients, 70.8% [95% CI: 55.9-83.0%, 34/48] had endoscopically evaluated esophageal mucosal injury. Regarding pH before surgery, 64.9% (CI: 47.5-79.8%, 24/37) had abnormal acid reflux (intraesophageal pH < 4 more than 5% of the time). FSSG score was significantly associated with the severity of GERD, and the positive rate was 52.6% (CI: 35.8-69.0%, 20/38). Following surgical correction, esophageal mucosal injury improved endoscopically in 90% of patients, and median total FSSG score significantly decreased from 8 (0-30) to 5 (0-19) (P = 0.005). Regarding pH after surgery, prevalence of abnormal acid reflux decreased from 66.7% (95% CI: 41.0-86.7%) to 33.3% (95% CI: 13.3-59.0%) (P = 0.045). Surgical spinal correction in kyphosis patients improves not only kyphotic deformity-related disorders but also esophageal mucosal injury, abnormal acid reflux, and reflux-related symptoms. © 2015 Japan Gastroenterological Endoscopy Society.

Interactions of microbicide nanoparticles with a simulated vaginal fluid.

PubMed

das Neves, José; Rocha, Cristina M R; Gonçalves, Maria Pilar; Carrier, Rebecca L; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

2012-11-05

The interaction with cervicovaginal mucus presents the potential to impact the performance of drug nanocarriers. These systems must migrate through this biological fluid in order to deliver their drug payload to the underlying mucosal surface. We studied the ability of dapivirine-loaded polycaprolactone (PCL)-based nanoparticles (NPs) to interact with a simulated vaginal fluid (SVF) incorporating mucin. Different surface modifiers were used to produce NPs with either negative (poloxamer 338 NF and sodium lauryl sulfate) or positive (cetyltrimethylammonium bromide) surface charge. Studies were performed using the mucin particle method, rheological measurements, and real-time multiple particle tracking. Results showed that SVF presented rheological properties similar to those of human cervicovaginal mucus. Analysis of NP transport indicated mild interactions with mucin and low adhesive potential. In general, negatively charged NPs underwent subdiffusive transport in SVF, i.e., hindered as compared to their diffusion in water, but faster than for positively charged NPs. These differences were increased when the pH of SVF was changed from 4.2 to 7.0. Diffusivity was 50- and 172-fold lower in SVF at pH 4.2 than in water for negatively charged and positively charged NPs, respectively. At pH 7.0, this decrease was around 20- and 385-fold, respectively. The estimated times required to cross a layer of SVF were equal to or lower than 1.7 h for negatively charged NPs, while for positively charged NPs these values were equal to or higher than 7 h. Overall, our results suggest that negatively charged PCL NPs may be suitable to be used as carriers in order to deliver dapivirine and potentially other antiretroviral drugs to the cervicovaginal mucosal lining. Also, they further reinforce the importance in characterizing the interactions of nanosystems with mucus fluids or surrogates when considering mucosal drug delivery.

pH-sensitive Eudragit nanoparticles for mucosal drug delivery.

PubMed

Yoo, Jin-Wook; Giri, Namita; Lee, Chi H

2011-01-17

Drug delivery via vaginal epithelium has suffered from lack of stability due to acidic and enzymatic environments. The biocompatible pH-sensitive nanoparticles composed of Eudragit S-100 (ES) were developed to protect loaded compounds from being degraded under the rigorous vaginal conditions and achieve their therapeutically effective concentrations in the mucosal epithelium. ES nanoparticles containing a model compound (sodium fluorescein (FNa) or nile red (NR)) were prepared by the modified quasi-emulsion solvent diffusion method. Loading efficiencies were found to be 26% and 71% for a hydrophilic and a hydrophobic compound, respectively. Both hydrophilic and hydrophobic model drugs remained stable in nanoparticles at acidic pH, whereas they are quickly released from nanoparticles upon exposure at physiological pH. The confocal study revealed that ES nanoparticles were taken up by vaginal cells, followed by pH-responsive drug release, with no cytotoxic activities. The pH-sensitive nanoparticles would be a promising carrier for the vaginal-specific delivery of various therapeutic drugs including microbicides and peptides/proteins. Published by Elsevier B.V.

Detection of gastro-oesophageal reflux in the neonatal unit.

PubMed

Rossor, Thomas; Lingam, Ingran; Douiri, Abdel; Bhat, Ravindra; Greenough, Anne

2018-03-13

To determine whether a pH probe or multichannel intraluminal impedance (MII) more frequently detected gastro-oesophageal reflux and test the hypothesis that acid reflux was associated with lower baseline impedance. A prospective study of infants in whom reflux was suspected and evaluated using combined pH and multichannel impedance. Studies were considered abnormal if the acid index was >10% or there were >79MII reflux events in 24 hours. The acid index was the percentage of total study time with a pH

A Judgement Bias Test to Assess Affective State and Potential Therapeutics in a Rat Model of Chemotherapy-Induced Mucositis.

PubMed

George, Rebecca P; Barker, Timothy H; Lymn, Kerry A; Bigatton, Dylan A; Howarth, Gordon S; Whittaker, Alexandra L

2018-05-29

Chemotherapy-induced mucositis is an extremely painful condition that occurs in 40-60% of patients undergoing chemotherapy. As mucositis currently has no effective treatment, and due to the self-limiting nature of the condition, the major treatment aims are to manage symptoms and limit pain with significance placed on improving patient quality of life. Rodent models are frequently used in mucositis research. These investigations typically assess pathological outcomes, yet fail to include a measure of affective state; the key therapeutic goal. Assessment of cognitive biases is a novel approach to determining the affective state of animals. Consequently, this study aimed to validate a cognitive bias test through a judgement bias paradigm to measure affective state in a rat model of chemotherapy-induced intestinal mucositis. Rats with intestinal mucositis demonstrated a negative affective state, which was partially ameliorated by analgesic administration, whilst healthy rats showed an optimistic response. This study concluded that the judgement bias test was able to evaluate the emotional state of rats with chemotherapy-induced mucositis. These findings provide a foundation for future refinement to the experimental design associated with the animal model that will expedite successful transitioning of novel therapeutics to clinical practice, and also improve humane endpoint implementation.

Accuracy of diagnosing gastroesophageal reflux disease by GerdQ, esophageal impedance monitoring and histology.

PubMed

Zhou, Li Ya; Wang, Ye; Lu, Jing Jing; Lin, Lin; Cui, Rong Li; Zhang, He Jun; Xue, Yan; Ding, Shi Gang; Lin, San Ren

2014-05-01

To assess the performance of self-assessment gastroesophageal reflux disease questionnaire (GerdQ), 24-h impedance monitoring, proton pump inhibitor (PPI) test and intercellular space of esophageal mucosal epithelial cells in the diagnosis of gastroesophageal reflux disease (GERD). Patients with symptoms suspected of GERD were administered the GerdQ and underwent endoscopy (measurement of intercellular space in the biopsy specimen sampling at 2 cm above the Z-line) and 24-h impedance pH monitoring, together with a 2-week experimental treatment with esomeprazole. A total of 636 patients were included for the final analysis, including 352 with GERD. The sensitivity and specificity of GerdQ and 24-h impedance monitoring for diagnosing GERD were 57.7% and 48.9%, and 66.4% and 43.3%, respectively. The sensitivity of 24-h impedance pH monitoring increased to 93.7%. The sensitivity and specificity of dilated intercellular spaces (DIS) (≥0.9 μm) for diagnosing GERD were 61.2% and 56.1%, respectively, whereas those for PPI test were 70.5% and 44.4%. GerdQ score or PPI test alone cannot accurately diagnose GERD in a Chinese population suspected of GERD. A definitive diagnosis of GERD still depends on endoscopy or 24-h pH monitoring. 24-h impedance pH monitoring may increase the sensitivity for diagnosing GERD by 20%; however, when used alone, it results in poor specificity in patients without acid suppressive therapy. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

PubMed

Jug, Mario; Hafner, Anita; Lovrić, Jasmina; Kregar, Maja Lusina; Pepić, Ivan; Vanić, Željka; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena

2018-01-05

In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Update on Functional Heartburn

PubMed Central

Yamasaki, Takahisa; O’Neil, Jessica

2017-01-01

The definition of functional heartburn has been refined over the years. It is currently described, based upon Rome IV criteria, as typical heartburn symptoms in the presence of normal upper endoscopy findings (including normal biopsies), normal esophageal pH testing, and a negative association between symptoms and reflux events. Functional heartburn is very common, affecting women more than men, and with reflux hypersensitivity makes up the majority of heartburn patients who fail twice-daily proton pump inhibitor therapy. These disorders overlap with other functional gastrointestinal disorders and are often accompanied by psychological comorbidities. Diagnosis is made by using endoscopy with esophageal biopsies, wireless pH capsule, pH-impedance monitoring, and high-resolution esophageal manometry. Additional diagnostic tools that may be of value include magnification endoscopy, chromoendoscopy, narrow-band imaging, autofluorescence imaging, mucosal impedance, impedance baseline values, and histopathology scores. Functional heartburn is primarily treated with neuromodulators. Psychological intervention and complementary and alternative medicine may also play important roles in the treatment of these patients. PMID:29339948

Muco-inert nanoparticle probes and drug carriers

NASA Astrophysics Data System (ADS)

Wang, Ying-Ying

2011-12-01

Mucus coats the exposed surfaces of the eyes and respiratory, gastrointestinal (GI) and cervicovaginal (CV) tracts, and protects mucosal tissues against pathogens and other foreign particulates. Most foreign particles are effectively trapped in mucus through steric and adhesive interactions, and are rapidly eliminated by different mucus clearance mechanisms. Nevertheless, mucus also immobilizes conventional drug and gene carriers, thereby precluding sustained and targeted drug delivery to mucosal sites. Synthetic particles engineered with muco-inert surfaces, and some viruses, can readily penetrate mucus gel, and may serve as useful probes to understand the biophysical barrier properties of mucus. Improved understanding of the mucus barrier could provide insights into methods to enhance drug and gene delivery at mucosal surfaces, as well as understanding the occasional failure of mucus to protect against infection or injury. Recently, muco-inert nanoparticles were developed by conjugating a dense layer of low MW polyethylene glycol to particle surfaces. Since they are slowed only by steric obstruction from the mucus mesh, various sized muco-inert nanoparticles can be used to probe the microstructure and microrheology of mucus. I applied this technique to determine whether the mucus barrier may be altered by exogenous factors, including the presence of detergent, pH changes and synthetic nanoparticles. I first studied the microrheology of native human cervicovaginal mucus (CVM), and found that CVM behaves as a viscoelastic solid at length scales ≥ 1 microm (preventing large particles from diffusing through) but as a viscoelastic liquid at length scales up to at least 500 nm (allowing smaller particles to diffuse through low viscosity fluid-filled pores). Treating CVM with a nonionic detergent, N9, shifted the viscoelastic liquid-solid transition point to < 200 nm, suggesting hydrophobic interactions between mucin fibers play an important role in regulating the mucus microstructure and consequently the microrheology. Indeed, N9 caused the average mucus pore size to decrease from ˜340 nm to 130 nm. I then looked at the effect of pH on mucus and found that the microstructure of CVM is essentially pH-independent over a broad range of physiological pH. Between pH 4 (the native pH of CVM) and 6--7, the average pore size in the mucus mesh remained unchanged, and between pH 1--2 and 8--9, there was at most a 2-fold drop in the average pore size (likely due to changes in electrostatic vs. hydrophobic interactions between mucin fibers). Finally, I found that mucoadhesive synthetic nanoparticles, at sufficiently high concentrations, can bundle mucin fibers and create large openings in the mucus microstructure. Disruption of the mucus barrier in this manner allowed a greater fraction of large (1 microm) muco-inert particles to diffuse through the mucus mesh. Muco-inert nanoparticles---also referred to as "mucus-penetrating particles" (MPP)---offer the potential for sustained and targeted drug delivery to mucosal surfaces. By penetrating luminal mucus layers, MPP may be able to reach the slowly cleared adherent mucus layer or deep folds of the epithelium and thereby achieve prolonged retention. I first measured the long range penetration of MPP compared to conventional mucoadhesive particles (CP) into CVM. With minimal dilution of CVM, MPP could penetrate up to 200 microm over 1 hr with ˜530 particles/mm2 penetrating 100 microm or more, while CP remained immobilized (note that physiological mucus layer thicknesses are no more than ˜200 microm). Furthermore, with 30% v/v dilution, MPP could penetrate up to 1.5 mm over 1 hr with ˜74,000 particles/mm2 penetrating 100 microm or more, while CP continued to remain stuck. I then studied the distribution and retention of MPP vs. CP in the mouse vagina to determine whether improved mucus penetration leads to more uniform distribution and prolonged retention. I found that MPP were not only more uniformly distributed in the vaginal lumen, but also penetrated deep into epithelial folds. In contrast, CP were aggregated by luminal mucus and failed to reach the epithelium. Several-fold more MPP were retained on the vaginal epithelial surface than CP over at least ˜1 day. Drug and gene carriers that provide more uniform and longer-lasting coverage of mucosal surfaces may greatly improve the treatment or prevention of diseases at mucosal sites.

Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women.

PubMed

Thurman, Andrea Ries; Yousefieh, Nazita; Chandra, Neelima; Kimble, Thomas; Asin, Susana; Rollenhagen, Christiane; Anderson, Sharon M; Herold, Betsy C; Freiermuth, Jamie L; Starkman, Brian S; Mesquita, Pedro M M; Richardson-Harman, Nicola; Cunningham, Tina; Hillier, Sharon; Rabe, Lorna; Schwartz, Jill L; Doncel, Gustavo F

2017-08-01

The objective of this study was to characterize cervicovaginal (CV) mucosal factors modulating susceptibility to human immunodeficiency virus (HIV) acquisition in healthy premenopausal (PRE) and postmenopausal (POST) women before and after treatment with estradiol (E2). We compared CV mucosal epithelial histology and immune cells, vaginal microbiota, antimicrobial activity of and soluble mucosal protein concentrations in the CV fluid lavage (CVL), and p24 antigen production after ex vivo infection of ectocervical tissues with HIV-1 BaL among PRE women (n = 20) in the follicular and luteal phases of the menstrual cycle and POST women (n = 17) at baseline and after ∼1 month of treatment with 0.01% vaginal E2 cream. Compared to PRE women, we measured higher levels of p24 antigen after ex vivo infection in tissues from POST women. POST women had a significantly thinner vaginal epithelium with decreased tight junction proteins and a higher density of mucosal immune T cells and lower levels of CD1a antigen-presenting cells, antimicrobial peptides, and inflammatory cytokines in the CVL (p values <.05). POST women had higher vaginal pH and lower vaginal Lactobacilli (p values <.05) than PRE women. After vaginal E2 therapy, CV endpoints and ex vivo HIV replication in POST tissues were similar to those observed in PRE tissues. The CV mucosa in POST women is thinned and compromised, with increased HIV-target immune cells and decreased antimicrobial factors, being more susceptible to HIV infection. After POST women receive topical E2 treatment, mucosal endpoints are similar to PRE levels.

Gastroprotective potentials of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats.

PubMed

Gomathy, G; Venkatesan, D; Palani, S

2015-01-01

This study investigated the protective effects of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats. Gastric ulceration was induced by single intraperitoneal injection of indomethacin (30 mg/kg b.wt.). M. maderaspatana extract produced significant reduction in gastric mucosal lesions, malondialdehyde and serum tumour necrosis factor-α associated with a significant increase in gastric juice mucin content and gastric mucosal catalase, nitric oxide and prostaglandin E2 levels. The volume and acidity of the gastric juice decreased in pretreated rats. The plant extract was evaluated in the gastric juice of rats, untreated has showed near normal levels in pretreated rats. The M. maderaspatana was able to decrease acidity and increase the mucosal defence in the gastric area, therefore justifying its use as an antiulcerogenic agent. Ranitidine significantly increased pH value and decreased pepsin activity and gastric juice free and total acidity. The anti-ulcer effect was further confirmed histologically.

The effect of topical application of pure honey on radiation-induced mucositis: a randomized clinical trial.

PubMed

Motallebnejad, M; Akram, S; Moghadamnia, A; Moulana, Z; Omidi, S

2008-03-01

Radiation-induced mucositis is an early effect of head and neck radiotherapy. Mucositis can cause ulcers, and patients may experience pain and dysphasia which need treatment. The aim of this study is to evaluate the effect of pure natural honey on radiation induced mucositis. In this randomized single blind (examiner blind) clinical trial 40 patients with head and neck cancer requiring radiation to the oropharyngeal mucosa were randomly assigned to two groups. Twenty patients assigned to the study group received honey, while both the study and control groups received standard head and neck radiation therapy based on a standard protocol. In the study group patients were instructed to take 20 ml of honey 15 minutes before radiation therapy, then again at intervals of 15 minutes and six hours after radiation. In the control group patients were instructed to rinse with 20 ml of saline before and after radiation. Patients were evaluated weekly for progression of mucositis using the Oral Mucositis Assessing Scale (OMAS). Data were analyzed using the independent t-test, Mann-Whitney, and Friedman tests. A significant reduction in mucositis among honey-received patients compared with controls (p=0.000) occurred. Within the limits of this study the results showed the application of natural honey is effective in managing radiation induced mucositis. Natural honey is a product with rich nutritional qualities that could be a pleasant, simple, and economic modality for the management of radiation mucositis.

Effect of human papillomavirus and Chlamydia trachomatis co-infection on sperm quality in young heterosexual men with chronic prostatitis-related symptoms.

PubMed

Cai, Tommaso; Wagenlehner, Florian M E; Mondaini, Nicola; D'Elia, Carolina; Meacci, Francesca; Migno, Serena; Malossini, Gianni; Mazzoli, Sandra; Bartoletti, Riccardo

2014-02-01

To investigate the effect of human papillomavirus (HPV) and Chlamydia trachomatis (Ct) co-infection on sperm concentration, motility and morphology, in a large cohort of young heterosexual male patients with chronic prostatitis-related symptoms. Patients with chronic prostatitis-related symptoms, attending the same centre for sexually transmitted diseases from January 2005 and December 2010, were consecutively enrolled in this cross-sectional study. All patients underwent clinical and instrumental examination, microbiological cultures for common bacteria, DNA extraction, mucosal and serum antibodies evaluation for Ct, specific tests for HPV and semen analysis. The semen variables analysed were: volume; pH; sperm concentration; motility; and morphology. Subjects were subdivided in two groups: group A, patients with Ct infection alone and group B, patients with Ct and HPV co-infection. The main outcome measurement was the effect of Ct and HPV co-infection on the semen variables examined. Of 3050 screened patients, 1003 were enrolled (32.9%) in the study. A total of 716 (71.3%) patients were allocated to group A, and 287 (28.7%) to group B. Significant differences between the two groups were reported in terms of percentage of motile sperm (degrees of freedom [df] = 1001; t-test = 11.85; P < 0.001) and percentage of normal morphological forms (df = 1001; t-test = 7.18; P < 0.001), while no differences were reported in terms of semen volume or pH. According to World Health Organization thresholds for normal semen, 364 (50.8%) men in group A and 192 (66.8%) men in group B were subfertile (odds ratio = 1.95; 95% confidence interval 1.46-2.60; P < 0.001). No correlation between HPV genotype, mucosal IgA type and semen variables was found. In a population of prostatitis-related symptoms attributable to Ct infection, co-infection with HPV has a significant role in decreasing male fertility, in particular with regard to sperm motility and morphology. © 2013 The Authors. BJU International © 2013 BJU International.

Honey prevents oral mocositis in children undergoing chemotherapy: A quasi-experimental study with a control group.

PubMed

Kobya Bulut, Hacer; Güdücü Tüfekci, Fatma

2016-12-01

There are numerous pharmacological and non-pharmacological treatment options available in the treatment of oral mucositis. However, in spite of so many methods and products, medical professionals have not come to a consensus as to which of these offer the best results. This study was conducted to assess the effect of oral care with honey on children undergoing chemotherapy for the prevention and healing of oral mucositis. This quasi-experimental study was conducted on children undergoing chemotherapy. The study group consisted of 83 children who attended clinics and polyclinics for chemotherapy. All the children were included in the study period. The study was completed with a total of 76 children except for seven patients who were excluded from the study. The data were collected using a form and the World Health Organization Mucositis Assessment Index. The data were analyzed using percentage distributions, means, a chi-square test, a t-test, a variance analysis, and a Friedman test. Ethics approval of the study was obtained from the Institution Ethics Committee. It was found that the severity of oral mucositis in the children in the experimental group was significantly less than the control group. The mucositis recovery period in the experimental group was significantly shorter than the control group. Regular oral care with honey for children undergoing chemotherapy for hematological cancers prevents mucositis and also accelerates recovery of it when started after mucositis onset. Copyright © 2016. Published by Elsevier Ltd.

How to Diagnose and Treat Functional Chest Pain.

PubMed

Remes-Troche, Jose M

2016-12-01

Chest pain that is not explained by reflux disease or cardiac, musculoskeletal, mucosal, or motor esophageal abnormalities is classified as functional chest pain (FCP). Although several mechanisms are involved, esophageal hypersensitivity plays a major role and it could be considered a biomarker for FCP. Psychologic comorbidity such as anxiety, neuroticism, depression, and somatization is common. When the diagnosis of FCP is suspected, patients should undergo evaluation with esophageal motility testing, endoscopy, 24-h esophageal pH monitoring, and in some cases, sensory tests. Once the diagnosis of FCP has been established, treatment options rely on controlling patients' symptoms. Medical treatment has focused predominantly on medications that target pain, such as antidepressants and other pain neuromodulators. Non-pharmacologic interventions with complementary behavioral treatments, such as cognitive behavioral therapy, biofeedback, and hypnosis, have recently been recognized as useful in FCP patients. The latest findings on the evaluation and treatment of FCP are outlined herein.

Follow-up of pediatric celiac disease: value of antibodies in predicting mucosal healing, a prospective cohort study.

PubMed

Vécsei, Edith; Steinwendner, Stephanie; Kogler, Hubert; Innerhofer, Albina; Hammer, Karin; Haas, Oskar A; Amann, Gabriele; Chott, Andreas; Vogelsang, Harald; Schoenlechner, Regine; Huf, Wolfgang; Vécsei, Andreas

2014-02-13

In diagnosing celiac disease (CD), serological tests are highly valuable. However, their role in following up children with CD after prescription of a gluten-free diet is unclear. This study aimed to compare the performance of antibody tests in predicting small-intestinal mucosal status in diagnosis vs. follow-up of pediatric CD. We conducted a prospective cohort study at a tertiary-care center. 148 children underwent esophohagogastroduodenoscopy with biopsies either for symptoms ± positive CD antibodies (group A; n = 95) or following up CD diagnosed ≥ 1 year before study enrollment (group B; n = 53). Using biopsy (Marsh ≥ 2) as the criterion standard, areas under ROC curves (AUCs) and likelihood-ratios were calculated to estimate the performance of antibody tests against tissue transglutaminase (TG2), deamidated gliadin peptide (DGP) and endomysium (EMA). AUCs were higher when tests were used for CD diagnosis vs. follow-up: 1 vs. 0.86 (P = 0.100) for TG2-IgA, 0.85 vs. 0.74 (P = 0.421) for TG2-IgG, 0.97 vs. 0.61 (P = 0.004) for DPG-IgA, and 0.99 vs. 0.88 (P = 0.053) for DPG-IgG, respectively. Empirical power was 85% for the DPG-IgA comparison, and on average 33% (range 13-43) for the non-significant comparisons. Among group B children, 88.7% showed mucosal healing (median 2.2 years after primary diagnosis). Only the negative likelihood-ratio of EMA was low enough (0.097) to effectively rule out persistent mucosal injury. However, out of 12 EMA-positive children with mucosal healing, 9 subsequently turned EMA-negative. Among the CD antibodies examined, negative EMA most reliably predict mucosal healing. In general, however, antibody tests, especially DPG-IgA, are of limited value in predicting the mucosal status in the early years post-diagnosis but may be sufficient after a longer period of time.

Neuropeptide S reduces duodenal bicarbonate secretion and ethanol-induced increases in duodenal motility in rats

PubMed Central

Wan Saudi, Wan Salman

2017-01-01

Alcohol disrupts the intestinal mucosal barrier by inducing metabolic and functional changes in epithelial cells. Recently, we showed that neuropeptide S (NPS) decreases duodenal motility and increases mucosal paracellular permeability, suggesting a role of NPS in the pathogenesis of disorders and dysfunctions in the small intestine. The aim of the present study was to investigate the effects of NPS on ethanol- and HCl-induced changes of duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ. The effects on duodenal bicarbonate secretion, the blood-to-lumen clearance of 51Cr-EDTA, motility and transepithelial net fluid flux were investigated. Intravenous (i.v.) administration of NPS significantly reduced duodenal mucosal bicarbonate secretion and stimulated mucosal transepithelial fluid absorption, mechanisms dependent on nitrergic signaling. NPS dose-dependently reduced ethanol-induced increases in duodenal motility. NPS (83 pmol·kg-1·min-1, i.v.) reduced the bicarbonate and fluid secretory response to luminal ethanol, whereas a 10-fold higher dose stimulated fluid secretion but did not influence bicarbonate secretion. In NPS-treated animals, duodenal perfusion of acid (pH 3) induced greater bicarbonate secretory rates than in controls. Pre-treating animals with Nω-nitro-L-arginine methyl ester (L-NAME) inhibited the effect of NPS on bicarbonate secretion. In response to luminal acid, NPS-treated animals had significantly higher paracellular permeability compared to controls, an effect that was abolished by L-NAME. Our findings demonstrate that NPS reduces basal and ethanol-induced increases in duodenal motility. In addition, NPS increases luminal alkalinization and mucosal permeability in response to luminal acid via mechanisms that are dependent on nitric oxide signaling. The data support a role for NPS in neurohumoral regulation of duodenal mucosal barrier function and motility. PMID:28384243

Postconditioning of the small intestine: which is the most effective algorithm in a rat model?

PubMed

Rosero, Oliver; Onody, Peter; Stangl, Rita; Turoczi, Zsolt; Fulop, Andras; Garbaisz, David; Lotz, Gabor; Harsanyi, Laszlo; Szijarto, Attila

2014-04-01

Mesenteric ischemia is a serious clinical condition requiring immediate surgical intervention. The unavoidable ischemic-reperfusion (IR) injury may be ameliorated using the appropriate postconditioning protocol. The aim of the present study was to investigate the optimal postconditioning algorithm in a rat model of intestinal ischemic-reperfusion injury. Male Wistar rats were randomized into five groups (n = 10), one sham-operated, one IR, and three postconditioned groups, each with different protocols. The animals were subjected to 60 min of mesenteric ischemia, followed by 60 min of reperfusion. Postconditioning was applied at the onset of reperfusion using three different algorithms. Arterial pressure and mucosal microcirculation were monitored throughout the experiment. Mesenteric pH was determined at the early phase of reperfusion. Blood and tissue samples were taken at the end of reperfusion for histologic evaluation, serum lactate dehydrogenase, serum creatine kinase, serum tumor necrosis factor-α, serum interleukin-6, detailed mucosal antioxidant, and scavenger capacity assays. The shorter and intermediate length cycles of postconditioning enhanced mucosal microcirculation and redox state and significantly delayed the normalization of mesenteric pH. Furthermore, milder histopathologic lesions and lower concentrations of serum necroenzymes and proinflammatory cytokines were detected compared with the IR group. The protective effect of postconditioning using longer cycles could only be seen in a tendentious manner. In a rat model of intestinal ischemia-reperfusion, the shorter and intermediate length cycles of postconditioning proved to be more effective than the use of longer cycles. Copyright © 2014 Elsevier Inc. All rights reserved.

[Clinical and laboratory characteristics of patients with pathologic chronic gastroesophageal reflux].

PubMed

Csendes, A; Burdiles, P; Maluenda, F; Cortés, C; Korn, O; Rojas, J; Tepper, P; Huertas, C; Sagastume, H; Puente, G; Quezada, F; Csendes, P

1998-07-01

Sixty percent of adults has typical symptoms of gastroesophageal reflux in Chile. To report the clinical and laboratory features of patients with gastroesophageal reflux. Five hundred thirty-four patients (255 male) with gastroesophageal reflux were included in a prospective protocol that included clinical analysis, manometry and endoscopy in all patients, barium swallow in 427, scintigraphy in 195, acid reflux test in 359, 24 h pH in 175, and differential potential of gastroesophageal mucosa in 73 patients. There was no correlation between the severity of symptoms and the endoscopical severity. Patients with Barret esophagus were 12 years older, were male in a greater proportion and had a higher proportion of manometrically incompetent sphincters than patients with esophageal reflux but without esophagitis or with erosive esophagitis. Severity of acid reflux, measured with 24 h pH monitoring was proportional to the endoscopical damage of the mucosa. There was a close relationship between the mucosal change limit determined with differential potentials and with endoscopy. No short esophagi were found. Patients with symptoms of gastroesophageal reflux must be assessed using several objective measures to determine the severity of their pathological alterations.

Intragastric inulin as a measure of mucosal damage caused by aspirin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wittmers, L.E. Jr.; Anderson, L.A.; Fall, M.M.

In an attempt to find a method of gastric mucosal damage assessment that yields consistent results, the experiments presented here employed the measurement of the movement of inulin out of the gastric contents into the stomach wall and vascular compartment as an estimate of mucosal damage. Anesthetized male Sprague-Dawley rats were functionally nephrectomized and were administered a control or test solution containing 3H-inulin. The test solutions contained one of three doses of aspirin. Blood samples were taken at 15-min intervals over a 90-min exposure period. The stomach was removed from the animal and full-thickness tissue samples taken for measurement ofmore » 3H-inulin content. When the gastric mucosa was exposed to the test agents, there was a significantly greater accumulation of inulin in the body and antrum as well as in the plasma when compared to controls. We conclude that intragastric inulin can be employed to estimate gastric mucosal damage.« less

Transabdominal ultrasonography of the ruminal mucosa as a tool to diagnose subacute ruminal acidosis in adult dairy bulls: a pilot study.

PubMed

Mirmazhari-Anwar, Vahid; Sharifi, Kamran; Mirshahi, Ali; Mohri, Mehrdad; Grünberg, Walter

2013-01-01

Subacute rumen acidosis (SARA) is frequently encountered in ruminants on high-concentrate rations and characterized by mild to moderate rumen pH depression. Although the measurement of rumen pH is considered as a gold standard approach to diagnose SARA, rumen fluid collection is conceived as a cumbersome and invasive procedure. In the present study, the suitability of transabdominal ultrasonography to identify structural changes of the rumen mucosa associated with SARA was explored. Five adult rumen canulated bulls previously adjusted to a roughage-based ration were switched in 10-day intervals to rations with increasing concentrate content. Seven rations with a concentrate content ranging from 5% to 95% were fed. The rumen pH and rumen mucosal thickness were measured at the end of each 10-d feeding period. The left flank was divided into 12 acoustic windows and the mean rumen mucosal thickness for each acoustic window determined for each ration. Repeated measure ANOVA and stepwise regression analyses were conducted. Increasing the dietary concentrate content resulted in thickening of rumen mucosa which was most pronounced in the upper part of the ventral rumen sac and the least pronounced in the uppermost and lowermost parts of the rumen. The intersection of a horizontal line going through the costochondral junction and a vertical line coming from the third lumbar vertebra was found to be most suitable to identify animals with rumen pH < 5.5 at 4 h post feeding. We conclude that transabdominal ultrasonography of the rumen mucosa has the potential to be a suitable, non-invasive diagnostic tool to identify adult ruminants with SARA.

Transgene vaccination using Ulex europaeus agglutinin I (UEA-1) for targeted mucosal immunization against HIV-1 envelope.

PubMed

Wang, Xinhai; Kochetkova, Irina; Haddad, Asmahan; Hoyt, Teri; Hone, David M; Pascual, David W

2005-05-31

Receptor-mediated gene transfer using an M cell ligand has been shown to be an efficient method for mucosal DNA immunization. To investigate further into alternative M cell ligands, the plant lectin, Ulex europaeus agglutinin I (UEA-1), was tested. UEA-1 binds to human intestinal Caco-2 cells, and these cells can be transfected with poly-l-lysine (PL)-conjugated UEA-1 for expression of reporter cDNAs. When tested in vivo, mice nasally immunized with UEA-1-PL complexed to plasmid encoding HIV-1 envelope showed elevated systemic and mucosal antibody responses, and these were supported by tissue antibody-forming cells. Likewise, elevated envelope-specific CTLs were induced. Thus, UEA-1 mediated DNA delivery represents an alternative mucosal formulation for inducing humoral and cellular immunity against HIV-1.

24-h Multichannel Intraluminal Impedance PH-metry 1 Year After Laparocopic Sleeve Gastrectomy: an Objective Assessment of Gastroesophageal Reflux Disease.

PubMed

Georgia, Doulami; Stamatina, Triantafyllou; Maria, Natoudi; Konstantinos, Albanopoulos; Konstantinos, Filis; Emmanouil, Leandros; Georgios, Zografos; Dimitrios, Theodorou

2017-03-01

It is not yet clear if laparoscopic sleeve gastrectomy (LSG) causes newly onset gastroesophageal reflux (GERD) or worsens already existing GERD. This is due to the absence of prospective studies using objective assessment measures of GERD such as pH monitoring. Our study aims at assessing GERD 1-year post-LSG procedure for obesity. Twelve asymptomatic obese patients were studied prospectively by using 24-h multichannel intraluminal impedance-pHmetry (MIIpH) pre- and 12 months post-LSG. Of patients' 1-year post-LSG, 83.33 % of patients' suffer from GERD (either newly onset or worsening of already existing) as indicated by abnormal DeMeester score. Mean DeMeester score 1-year post LSG was 47, almost 2.5 times higher than the preoperative score (p = 0.072). The percentage of total time with pH lower than four was statistically significant higher postoperatively (13.27 % vs 3.87 %, p = 0.048). This study is one of the few assessing GERD post-LSG by using 24-h MIIpH. The majority of patients suffer from GERD 12 months postoperatively, implying that close postoperative monitor for GERD with the use of pH testing and upper gastrointestinal endoscopy in order to early diagnose GERD and identify possible mucosal injury and also a prophylactic proton pump inhibitor use may be of great importance.

Salicylate effects on proton gradient dissipation by isolated gastric mucosal surface cells.

PubMed

Olender, E J; Woods, D; Kozol, R; Fromm, D

1986-11-01

The effects of salicylate were examined on Na+/H+ exchange by isolated gastric mucosal surface cells loaded with H+ and resuspended in a buffered medium. Choline salicylate (pH 7.4) increases the dissipation of an intracellular proton gradient which was measured using acridine orange. The exchange of extracellular Na+ with intracellular H+ by surface cells not only remains intact but also is enhanced upon exposure to salicylate. This was confirmed by cellular uptake of 22Na and titration of cellular H+ efflux. Salicylate increases Na+/H+ exchange via a pathway predominantly sensitive to amiloride. However, the data also suggest that salicylate dissipates an intracellular proton gradient by an additional mechanism. The latter is independent of extracellular Na+ and not due to a generalized increase in cellular permeability.

Systemic and local effects of long-term exposure to alkaline drinking water in rats.

PubMed

Merne, M E; Syrjänen, K J; Syrjänen, S M

2001-08-01

Alkaline conditions in the oral cavity may be caused by a variety of stimuli, including tobacco products, antacids, alkaline drinking water or bicarbonate toothpaste. The effects of alkaline pH on oral mucosa have not been systematically studied. To assess the systemic (organ) and local (oral mucosal) effects of alkalinity, drinking water supplemented with Ca(OH)2 or NaOH, with pH 11.2 or 12 was administered to rats (n = 36) for 52 weeks. Tissues were subjected to histopathological examination; oral mucosal biopsy samples were also subjected to immunohistochemical (IHC) analyses for pankeratin, CK19, CK5, CK4, PCNA, ICAM-1, CD44, CD68, S-100, HSP 60, HSP70, and HSP90. At completion of the study, animals in the study groups had lower body weights (up to 29% less) than controls despite equal food and water intake, suggesting a systemic response to the alkaline treatment. The lowest body weight was found in rats exposed to water with the highest pH value and starting the experiment when young (6 weeks). No histological changes attributable to alkaline exposure occurred in the oral mucosa or other tissues studied. Alkaline exposure did not affect cell proliferation in the oral epithelium, as shown by the equal expression of PCNA in groups. The up-regulation of HSP70 protein expression in the oral mucosa of rats exposed to alkaline water, especially Ca(OH)2 treated rats, may indicate a protective response. Intercellular adhesion molecule-1 (ICAM-1) positivity was lost in 6/12 rats treated with Ca(OH)2 with pH 11.2, and loss of CD44 expression was seen in 3/6 rats in both study groups exposed to alkaline water with pH 12. The results suggest that the oral mucosa in rats is resistant to the effects of highly alkaline drinking water. However, high alkalinity may have some unknown systemic effects leading to growth retardation, the cause of which remains to be determined.

Pharmacodynamic Activity of Dapivirine and Maraviroc Single Entity and Combination Topical Gels for HIV-1 Prevention.

PubMed

Dezzutti, Charlene S; Yandura, Sarah; Wang, Lin; Moncla, Bernard; Teeple, Elizabeth A; Devlin, Brid; Nuttall, Jeremy; Brown, Elizabeth R; Rohan, Lisa C

2015-11-01

Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission. 0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety. The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm(2)/min(1/2)), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm(2)/min(1/2)). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe. The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention.

Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, M.J.; Adams, J.; Gu, X.A.

1990-10-01

We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of (51Cr)EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loopsmore » receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in (51Cr)EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress.« less

Lipopolysaccharide inhibits or accelerates biomedical titanium corrosion depending on environmental acidity

PubMed Central

Yu, Fei; Addison, Owen; Baker, Stephen J; Davenport, Alison J

2015-01-01

Titanium and its alloys are routinely used as biomedical implants and are usually considered to be corrosion resistant under physiological conditions. However, during inflammation, chemical modifications of the peri-implant environment including acidification occur. In addition certain biomolecules including lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls and driver of inflammation have been shown to interact strongly with Ti and modify its corrosion resistance. Gram-negative microbes are abundant in biofilms which form on dental implants. The objective was to investigate the influence of LPS on the corrosion properties of relevant biomedical Ti substrates as a function of environmental acidity. Inductively coupled plasma mass spectrometry was used to quantify Ti dissolution following immersion testing in physiological saline for three common biomedical grades of Ti (ASTM Grade 2, Grade 4 and Grade 5). Complementary electrochemical tests including anodic and cathodic polarisation experiments and potentiostatic measurements were also conducted. All three Ti alloys were observed to behave similarly and ion release was sensitive to pH of the immersion solution. However, LPS significantly inhibited Ti release under the most acidic conditions (pH 2), which may develop in localized corrosion sites, but promoted dissolution at pH 4–7, which would be more commonly encountered physiologically. The observed pattern of sensitivity to environmental acidity of the effect of LPS on Ti corrosion has not previously been reported. LPS is found extensively on the surfaces of skin and mucosal penetrating Ti implants and the findings are therefore relevant when considering the chemical stability of Ti implant surfaces in vivo. PMID:25634122

A randomized, double-blind, placebo-controlled study of rebamipide for gastric mucosal injury taking aspirin with or without clopidogrel.

PubMed

Tozawa, Katsuyuki; Oshima, Tadayuki; Okugawa, Takuya; Ogawa, Tomohiro; Ohda, Yoshio; Tomita, Toshihiko; Hida, Nobuyuki; Fukui, Hirokazu; Hori, Kazutoshi; Watari, Jiro; Nakamura, Shiro; Miwa, Hiroto

2014-08-01

Antithrombotic drugs, such as low-dose aspirin (LDA) and clopidogrel, can cause upper gastrointestinal complications. The goal of the present study was to investigate whether a mucosal-protective agent, rebamipide, could prevent gastric mucosal injuries induced by LDA with or without clopidogrel in healthy subjects. A randomized, double-blind, placebo-controlled trial was performed with 32 healthy male volunteers. Subjects were randomly assigned to a 14-day course of one of the following regimens: group A, placebo (tid) + LDA; group B, rebamipide (100 mg tid) + LDA (100 mg once-daily); group C, placebo + LDA + clopidogrel (75 mg once-daily); or group D, rebamipide + LDA + clopidogrel. The grade of gastric mucosal injuries was evaluated by esophagogastroduodenoscopy before and after dosing (on day 0 and day 14), and the grade of gastric mucosal injury was assessed according to the modified Lanza score. Subjective symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS). A rapid urease test was performed on day 0, and blood tests were performed on day 0 and day 14. Rebamipide significantly inhibited gastric mucosal injury induced by LDA alone or by LDA plus clopidogrel when compared with placebo in healthy subjects. GSRS score and hemoglobin level were not significantly different among the four groups. Rebamipide is useful for the primary prevention of gastric mucosal injury induced by LDA alone or by LDA plus clopidogrel in healthy subjects.

Rectal mucosal electrosensitivity - what is being tested?

PubMed

Meagher, A P; Kennedy, M L; Lubowski, D Z

1996-01-01

The results of rectal mucosal electrosensitivity (RME) testing have been used to support theories regarding the aetiology of both idiopathic constipation and bowel dysfunction following rectopexy. The aim of this study was to assess the validity of tests of RME. Sixty-eight patients, comprising three groups (group 1: 50 patients undergoing assessment in the Anorectal Physiology Unit, group 2: 10 patients with coloanal or ileoanal anastomosis, group 3: 8 patients with a stoma) underwent mucosal electrosensitivity testing, with the threshold stimulus required to elicit sensation being recorded. In addition the RME was measured in groups 1 and 2 when placing the electrode, mounted on a catheter with a central wire, against the anterior, posterior, right and left rectal or neorectal walls. To asses the influence on this test of loss of mucosal contact due to faeces, a further 8 cases with a normal rectum had RME performed with and without a layer of water soaked gauze around the electrode to stimulate faeces and prevent the electrode from making contact with the rectal mucosa. There was marked variance in the sensitivity of the different regions of rectal wall tested (P < 0.001). In group 1 patients the mean sensitivities were: central 36.6 mA, anterior 27.4 mA, posterior 37.9 mA, right 22.3 mA and left 25.6 mA. This circumferential variation suggests that the pelvic floor rather than rectal mucosa was being stimulated. All patients in group 2 had recordable sensitivities, and the mean sensitivity threshold was significantly higher than group 1 patients in the central (P = 0.03), right (P = 0.03) and left (P = 0.007) positions. In group 3 the sensitivity was greater within the stoma at the level of the abdominal wall muscle than intra-abdominally or subcutaneously, again suggesting an extra-colonic origin of the sensation. The sensitivity threshold was significantly greater with the electrode wrapped in gauze (P < 0.01), and loss of mucosal contact was not detected by the EMG machine. Therefore RME testing would seem not to measure mucosal sensitivity, and is probably influenced by the presence of faeces.

Microcirculatory perfusion shift in the gut wall layers induced by extracorporeal circulation.

PubMed

Kalder, Johannes; Ajah, Dieudonne; Keschenau, Paula; Kennes, Lieven N; Tolba, Rene; Kokozidou, Maria; Jacobs, Michael J; Koeppel, Thomas A

2015-02-01

Extracorporeal circulation (ECC) is regularly applied to maintain organ perfusion during major aortic and cardiovascular surgery. During thoracoabdominal aortic repair, ECC-driven selective visceral arterial perfusion (SVP) results in changed microcirculatory perfusion (shift from the muscularis toward the mucosal small intestinal layer) in conjunction with macrohemodynamic hypoperfusion. The underlying mechanism, however, is unclear. Therefore, the aim of this study was to assess in a porcine model whether ECC itself or the hypoperfusion induced by SVP is responsible for the mucosal/muscular shift in the small intestinal wall. A thoracoabdominal aortic approach was performed in 15 healthy pigs divided equally into three groups: group I, control; group II, thoracic aortic cross-clamping with distal aortic perfusion; and group III, thoracic aortic cross-clamping with distal aortic perfusion and SVP. Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurement and fluorescent microspheres. In addition, markers for metabolism and intestinal ischemia-reperfusion injury were determined. ECC with a roller pump induced a significant switch from the muscularis and mucosal layer of the small intestine, even with adequate macrocirculation (mucosal/muscular perfusion ratio: group I vs II, P = .005; group I vs III, P = .0018). Furthermore, the oxygen extraction ratio increased significantly in groups II (>30%) and III (>40%) in the beginning of the ECC compared with the control (group I vs II, P = .0037; group I vs III, P = .0062). Lactate concentrations and pH values did not differ between groups I and II; but group III demonstrated a significant shifting toward a lactate-associated acidosis (lactate: group I vs III, P = .0031; pH: group I vs III, P = .0001). We demonstrated a significant shifting between the small intestinal gut wall layers induced by roller pump-driven ECC. The shift occurs independently of macrohemodynamics, with a significant effect on aerobic metabolism in the gut wall. Consequently, an optimal intestinal perfusion cannot be guaranteed by a roller pump; therefore, perfusion techniques need to be optimized. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Effect of topical honey on limitation of radiation-induced oral mucositis: an intervention study.

PubMed

Khanal, B; Baliga, M; Uppal, N

2010-12-01

Radiation therapy for oral carcinoma is therapeutically useful in dose of at least 6000 cGy but causes mucositis that severely interferes with oral function. The literature indicates that honey appears to promote wound healing, so the authors investigated whether its anti-inflammatory properties might limit the severity of radiation-induced oral mucositis. A single-blinded, randomized, controlled clinical trial was carried out to compare the mucositis-limiting qualities of honey with lignocaine. A visual assessment scale permitted scoring of degrees of mucositis and statistical evaluation of the results was performed using the χ(2) test. Only 1 of 20 patients in the honey group developed intolerable oral mucositis compared with the lignocaine group, indicating that honey is strongly protective (RR=0.067) against the development of mucositis. The proportion of patients with intolerable oral mucositis was lower in the honey group and this was statistically significant (p=0.000). Honey applied topically to the oral mucosa of patients undergoing radiation therapy appears to provide a distinct benefit by limiting the severity of mucositis. Honey is readily available, affordable and well accepted by patients making it useful for improving the quality of life in irradiated patients. Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Rabeprazole test for the diagnosis of gastro-oesophageal reflux disease: Results of a study in a primary care setting

PubMed Central

des Varannes, Stanislas Bruley; Sacher-Huvelin, Sylvie; Vavasseur, Fabienne; Masliah, Claude; Rhun, Marc Le; Aygalenq, Philippe; Bonnot-Marlier, Sylvie; Lequeux, Yves; Galmiche, Jean Paul

2006-01-01

AIM: To determine the diagnostic value of the rabeprazole test in patients seen by general practitioners. METHODS: Eighty-three patients with symptoms suggestive of GERD were enrolled by general practitioners in this multi-centre, randomized and double-blind study. All patients received either rabeprazole (20 mg bid) or a placebo for one week. The diagnosis of GERD was established on the presence of mucosal breaks at endoscopy and/or an abnormal esophageal 24-h pH test. The test was considered to be positive if patients reported at least a “clear improvement” of symptoms on a 7-point Likert scale. RESULTS: The sensitivities of the test for rabeprazole and the placebo were 83% and 40%, respectively. The corresponding specificity, positive and negative predictive values were 45% and 67%, 71% and 71%, and 62% and 35%, respectively. A receiver operating characteristics (ROC) analysis confirmed that the best discriminatory cut-off corresponded to description of “clear improvement”. CONCLUSION: The poor specificity of the proton-pump inhibitor (PPI) test does not support such an approach to establish a diagnosis of GERD in a primary care setting. PMID:16688803

Pharmacokinetic and pharmacodynamic effects of two omeprazole formulations on stomach pH and gastric ulcer scores.

PubMed

Raidal, S L; Andrews, F M; Nielsen, S G; Trope, G

2017-11-01

Limited data are available on the relative pharmacokinetics and pharmacodynamics of different omeprazole formulations. To compare pharmacokinetic and pharmacodynamic effects of a novel omeprazole formulation against a currently registered product. Masked 2 period, 2 treatment crossover. Twelve clinically healthy horses were studied over two 6-day treatment periods. Horses were randomly assigned to receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h on the day prior to commencing treatment (Day -1) and after 6 days of oral treatment (Day 5) using in situ antimony pH probes within an indwelling nasogastric tube. Plasma pharmacokinetics were determined on Days 0 and 6. Treatment significantly (P<0.005) increased gastric pH on Day 5, compared to results obtained prior to treatment (Day -1) and there was no significant difference between products (P = 0.773). Similarly, comparison of median hourly gastric pH (P = 0.593), mean gastric pH (P = 0.154), percentage time pH<4 (P = 0.259) and area under the time-gastric pH response curve (P = 0.734) did not discriminate between products. Both treatments resulted in significantly lower gastric ulcer severity scores (both P = 0.004), with no difference between treatments (P = 0.688). Comparison of mean log area under time-plasma concentration curves demonstrated that, although the lower limit of the 90% confidence interval was within the -20% limit for bioequivalence, the upper limit was exceeded, suggesting that the test product could have greater bioavailability than the reference product. The small sample size, large interhorse plasma omeprazole concentrations, and low bioavailability of omeprazole impacted the sensitivity of the bioequivalence analysis. ULS matched or slightly exceeded OMO plasma concentrations. Both products resulted in equivalent increases in gastric pH, gastric pH profiles and decrease in gastric ulcer scores. Thus, ULS was pharmacodynamically equivalent to OMO and was associated with an equivalent beneficial effect on gastric squamous mucosal ulceration. © 2017 EVJ Ltd.

Nanoparticle mucoadhesive system as a new tool for fish immune system modulation.

PubMed

Charlie-Silva, Ives; de Melo, Nathalie Ferreira Silva; Gomes, Juliana M M; Fraceto, Leonardo Fernandes; de Melo, Daniela Chemim; de Oliveira Silva, Juliana; de Barros, André Luis Branco; Corrêa Junior, Jose Dias

2018-05-30

Recently, chitosan-based nanoparticles with mucoadhesive properties emerged as a strategy for mucosal drug release. This study aimed to characterize the interaction of mucoadhesive system chitosancoated PLGA nanoparticles (NPMA) with fish external mucus. NP suspensions with fluorescent probe were prepared and characterized by size, polydispersity, zeta potential and pH measures. In post-exposure fish were observed an increase in fluorescence imaging over time and it was significantly influenced by NPMA concentration. We also observed the main predominance the fluorescence in the spleen, followed by liver, gill and other tissues. The use of mucoadhesive nanocarriers becomes an alternative for administration of drugs and immunomodulators in immersion systems since the nanosystem can adhere to the mucosal surface of the fish with little residual effect in the water. Copyright © 2018. Published by Elsevier Ltd.

Impact of gastro-esophageal reflux on mucin mRNA expression in the esophageal mucosa.

PubMed

van Roon, Aafke H C; Mayne, George C; Wijnhoven, Bas P L; Watson, David I; Leong, Mary P; Neijman, Gabriëlle E; Michael, Michael Z; McKay, Andrew R; Astill, David; Hussey, Damian J

2008-08-01

Changes in the expression of mucin genes in the esophageal mucosa associated with uncomplicated gastro-esophageal reflux disease have not been evaluated even though such changes could be associated with reflux-induced mucosal damage. We therefore sought to identify reflux-induced changes in mucin gene expression using a cell line and biopsies from the esophageal mucosa in patients with and without reflux. MUC-1, MUC-3, MUC-4, and MUC-5AC gene expressions were investigated in the HET-1A cell line following exposure to acid (pH 4) and/or bile (120 muM of a bile salt milieu), and in esophageal mucosal biopsies from controls, subjects with non-erosive gastro-esophageal reflux, and subjects with reflux associated with ulcerative esophagitis (erosive). The mucosal biopsies were also evaluated for IL-6 mRNA expression (inflammatory marker) and CK-14 mRNA expression (mucosal basal cell layer marker). Gene expression was determined using real-time reverse transcriptase-polymerase chain reaction analysis. In the cell line studies, there were differences in mRNA levels for all of the evaluated mucins following treatment with either acid or the acid and bile combination. In the studies which evaluated tissue specimens, IL-6 and CK-14 mRNA levels increased according to degree of reflux pathology. The expression of MUC-1 and MUC-4 in mucosa from patients with erosive reflux was lower than in subjects without reflux and in patients with non-erosive reflux, whereas the expression of MUC-3 and MUC-5AC was increased (although these differences did not reach significance at p < 0.05). When mRNA expression data for tissue samples from all groups were combined, significant correlations were identified between IL-6 vs. CK-14 and IL-6 vs. MUC-3, MUC-3 vs. CK-14 and MUC-3 vs. MUC-5AC, and for MUC-1 vs. MUC-5AC. The correlation between IL-6 and CK-14 was also significant within the control and non-erosive reflux groups. The correlation between IL-6 and MUC-3 was significant within the control and erosive reflux groups, and the correlation between MUC-1 and MUC-5AC was significant within the erosive reflux group. The results of this study suggest that the profile of mucin expression in the esophageal mucosa is influenced by the pH and composition of the gastro-esophageal reflux. Further work should explore the response of these genes to acid and bile reflux, and their role in the etiology of mucosal damage in gastro-esophageal reflux.

[Specific features of gastroesophageal reflux disease associated with obesity and overweight].

PubMed

Livzan, M A; Lapteva, I V; Krolevets, T S; Kiselev, I E

2016-01-01

To reveal the specific features of gastroesophageal reflux disease (GERD) associated with obesity and overweight, by investigating the clinical and endoscopic manifestations of the disease, 24-hour pH-metry scores, and leptin levels. A total of 131 patients with GERD were examined. The data about complaints and those from life and medical histories were collected; anthropometric measurements and the results of blood biochemical tests, esophagoduodenoscopy (EPDS), and pH-metry were assessed; and the serum levels of leptin and its receptor were estimated. The patients were allocated into a study group (104 obese and/or overweight patients) and a comparison one (27 normal weight people). Waist circumference, hip circumference, and blood glucose levels proved to be statistically significantly higher in the study group (p<0.00000, p<0.00002, and p<0.02, respectively). The obese patients were found to have a statistically significantly higher level of leptin and a lower level of its soluble receptors: the median leptin levels were 30.42 (13.42-45.62) ng/ml in the study group and 5.47 (3.35-7.68) ng/ml in the comparison group; the median levels of the receptors were 18.83 (14.98-25.11) ng/ml and 30.93 (24.68-33.53) ng/ml, respectively). This group showed a moderate negative correlation between these indicators (rs=-0.451; p<0.0004). The study group displayed higher pH values in the gastric cardia and body (p<0.05 and p<0.04, respectively). The mucosal contact time with the refluxate having with a low pH value (<4) in the above segments turned out to be longer in the comparison group (p<0.05). There were weight-independent relationships of the leptin level to its spread, aggressiveness quotient, to the highest pH value in the gastric cardia and body, and to the mucosal contact time with the refluxate having a pH below 4.0 (rs=0.543; p<0.006; rs=0.432; p<0.04; rs=0.431; p<0.04; rs=-0.450; p<0.03, respectively), leptin receptors with a pH ratio in the gastric cardia and body, to the number of reflux episodes longer than 5 minutes in the esophagus, and to the De Meester index for this indicator (rs=0.471; p<0.04; rs=-0.455; p<0.04; rs=-0,454; p<0.04, respectively). Obese and overweight patients develop GERD in the presence of leptin resistance and biliary tract disease, which determines the specific features of the disease (alkaline or mixed refluxate) and the need for individualized therapy.

Ba-Wei-Die-Huang-Wan (Hachimi-jio-gan) can ameliorate cyclophosphamide-induced ongoing bladder overactivity and acidic adenosine triphosphate solution-induced hyperactivity on rats prestimulated bladder.

PubMed

Lee, Wei-Chia; Wu, Chia-Ching; Chuang, Yao-Chi; Tain, You-Lin; Chiang, Po-Hui

2016-05-26

Ba-Wei-Die-Huang-Wan (BWDHW) is the traditional Chinese medicine formula containing eight ingredients, namely Rehmannia glutinosa (Gaetn.) DC., root, steamed & dried; Cornus officinalis Siebold & Zucc., fructus, dried; Dioscorea oppositifolia L., root, dried; Alisma plantago-aquatica, subsp. orientale (Sam.) Sam., tuber, dried; Poria cocos (Fr.) Wolf., sclerotium, dried; Paeonia×suffruticosa Andrews, bark, dried; Cinnamomum cassia (Nees & T.Nees) J. Presl, bark, dried; Aconitum carmichaeli Debeaux, lateral root, dried & processed. It has been used for diabetes and urinary frequency treatments. We investigate effects of BWDHW on cyclophosphamide (CYP)-induced ongoing bladder overactivity and acidic adenosine triphosphate (ATP) solution-induced hyperactivity on rat's prestimulated bladder. Female Wistar rats were injected with intraperitoneal CYP (100mg/kg) or saline respectively. Rats were treated with BWDHW (90mg/kg/day) or vehicle for the next five days. After treatments animals were evaluated both in metabolic cage model and then by cystometry. Acidic ATP solution (5mM, pH 3.3) was instilled to provoke bladder hyperactivity. Bladder mucosa and muscle proteins were assessed by Western blotting. As compared to the controls, the CYP group showed significantly decreased mean cystometric intercontractile interval and increased micturition frequency, whereas the CYP/BWDWH group did not. The CYP group had significant protein overexpression in mucosal M2, M3, P2X2, and P2X3 receptors as well as detrusor M2 and M3 receptors. However, the CYP/BWDWH group had insignificant changes from controls. In the provoking test, the control/BWDHW and CYP/BWDHW groups were less affected by acidic ATP stimulation of intercontractile interval changes than the control group. Compared to the control group, the control/BWDHW group showed significantly lower mucosal P2X3 protein expression and the CYP group showed significant mucosal TRPV1 protein upregulation after the provoking test. BWDHW treatment can ameliorate CYP-induced ongoing bladder overactivity and suppress mucosal P2X2, P2X3, M2, and M3 receptor protein overexpression, as well as detrusor M2 and M3 receptor protein overexpression. BWDHW pretreatment can reduce acidic ATP solution-provoked hyperactivity by preventing TRPV1 receptor overexpression in CYP-treated bladder mucosa and inhibiting P2X3 receptor overexpression in naïve bladder mucosa. Copyright © 2016. Published by Elsevier Ireland Ltd.

Influence of reaction medium during synthesis of Gantrez AN 119 nanoparticles for oral vaccination.

PubMed

Vandamme, Katrien; Melkebeek, Vesna; Cox, Eric; Deforce, Dieter; Lenoir, Joke; Adriaens, Els; Vervaet, Chris; Remon, Jean Paul

2010-02-01

Two synthesis methods of poly(methyl vinyl ether-co-maleic anhydride) (Gantrez AN 119) nanoparticles (NP) (used for oral vaccination) were compared. Wheat germ agglutinin (WGA) was used as ligand to enhance the bioadhesive properties of NP and beta-galactosidase as antigen. The first method encapsulated beta-galactosidase in NP by co-precipitation in an acetone/water mixture containing 44% acetone. In the second method, antigen addition occurred in 100% acetone. To improve stability, NP were crosslinked with 1,3-diaminopropane. The stability of WGA-conjugated NP with encapsulated antigen diminished at lower pH and when decreasing the amount of crosslinker. The binding type between WGA and polymer depended on the synthesis method: predominantly ionic bonds were formed using the 44% acetone method, whereas synthesis via the 100% acetone method resulted in covalent bonds. The biological activity of the WGA coating, evaluated via a pig gastric mucin binding test, was lower in NP prepared via the 100% acetone method. No release of native antigen was detected after hydrolysis of NP, due to the covalent antigen binding during antigen encapsulation and the high reactivity of the polymer. Moreover, the mucosal irritation capacity was evaluated upon nanoparticle hydrolysis using a slug mucosal irritation assay. Herein, hydrolysed NP of the 44% acetone method were classified as mild irritative. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Colonoscopic allergen provocation test with rBet v 1 in patients with pollen-associated food allergy.

PubMed

Pickert, C N; Lorentz, A; Manns, M P; Bischoff, S C

2012-10-01

After consumption of fruits, nuts, and vegetables, several patients with pollen allergy experience gastrointestinal (GI) tract symptoms that are possibly caused by pollen-associated food allergy. The aim of this study was to evaluate the colonoscopic allergen provocation (COLAP) test using the recombinant birch pollen allergen Bet v 1 (rBet v 1) for in vivo diagnosis of pollen-associated food allergy manifesting in the GI tract. Thirty-four patients with a history of adverse reactions to food, GI tract symptoms, and birch pollen pollinosis and five healthy controls underwent COLAP test. Twenty minutes after endoscopic challenge of the cecal mucosa with rBet v 1, the mucosal wheal and flare reaction was registered semiquantitatively, and tissue biopsy specimens were examined for eosinophil mucosal activation. The mucosal reaction to rBet v 1 was correlated with the presence of pollinosis (P = 0.004), history of adverse reaction to Bet v 1-associated food allergens (P = 0.001), and tissue eosinophils' activation (P < 0.001). A wheal and flare reaction in the COLAP test was observed in 13 of 16 patients (81%) with a history of GI tract symptoms associated with the ingestion of Bet v 1-related foods and in four of 18 (22%) patients with a negative history (P < 0.001). The control group did not develop visible mucosal reactions to rBet v 1. Systemic anaphylactic reactions did not occur. The mucosal administration of rBet v 1 by COLAP test provides a new diagnostic tool that might support the diagnosis of Bet v 1-associated food allergy manifesting in the GI tract. © 2012 John Wiley & Sons A/S.

Helicobacter pylori coinfection is a confounder, modulating mucosal inflammation in oral submucous fibrosis.

PubMed

Rajendran, R; Rajeev, R; Anil, S; Alasqah, Mohammed; Rabi, Abdul Gafoor

2009-01-01

The oral cavity has been considered a potential reservoir for Helicobacter pylori (H pylori) , from where the organism causes recurrent gastric infections. With this case-control study we tried to evaluate the role of H pylori in the etiology of mucosal inflammation, a condition that compounds the morbid state associated with oral submucous fibrosis (OSF). Subjects ( n = 150) were selected following institutional regulations on sample collection and grouped into test cases and positive and negative controls based on the presence of mucosal fibrosis and inflammation. The negative controls had none of the clinical signs. All patients underwent an oral examination as well as tests to assess oral hygiene/periodontal disease status; a rapid urease test (RUT) of plaque samples was also done to estimate the H pylori bacterial load. We used univariate and mutivariate logistic regression for statistical analysis of the data and calculated the odds ratios to assess the risk posed by the different variables. The RUT results differed significantly between the groups, reflecting the variations in the bacterial loads in each category. The test was positive in 52% in the positive controls (where nonspecific inflammation of oral mucosa was seen unassociated with fibrosis), in 46% of the test cases, and in 18% of the negative controls (healthy volunteers) (chi2 = 13.887; P < 0.01). A positive correlation was seen between the oral hygiene/periodontal disease indices and RUT reactivity in all the three groups. The contribution of the H pylori in dental plaque to mucosal inflammation and periodontal disease was significant. Logistic regression analysis showed gastrointestinal disease and poor oral hygiene as being the greatest risk factors for bacterial colonization, irrespective of the subject groups. A positive correlation exists between RUT reactivity and the frequency of mucosal inflammation.

Smart Polymers in Nasal Drug Delivery

PubMed Central

Chonkar, Ankita; Nayak, Usha; Udupa, N.

2015-01-01

Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones. PMID:26664051

Pharmacodynamic activity of Dapivirine and Maraviroc single entity and combination topical gels for HIV-1 prevention

PubMed Central

Dezzutti, Charlene S.; Yandura, Sarah; Wang, Lin; Moncla, Bernard; Teeple, Elizabeth A.; Devlin, Brid; Nuttall, Jeremy; Brown, Elizabeth R.; Rohan, Lisa C.

2015-01-01

Purpose Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission. Methods 0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety. Results The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm2/min1/2), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm2/min1/2). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe. Conclusions The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention. PMID:26078001

Oral mucosal conditions in preschool children of low socioeconomic status: prevalence and determinant factors.

PubMed

Vieira-Andrade, Raquel Gonçalves; Martins-Júnior, Paulo Antônio; Corrêa-Faria, Patrícia; Stella, Paulo Eduardo Melo; Marinho, Sandra Aparecida; Marques, Leandro Silva; Ramos-Jorge, Maria Letícia

2013-05-01

The aim of the present study was to determine the prevalence of oral mucosal conditions and associated factors among 541 preschoolers of low socioeconomic status. A cross-sectional study was carried out. Sociodemographic data and information on harmful oral habits were gathered with the use of a questionnaire. A clinical exam was performed for the determination of oral mucosal conditions, dental caries and level of oral hygiene. Data analysis involved statistical analysis, the Kruskal-Wallis test, Mann-Whitney test, chi-square test, Fisher's exact test and multivariate regression (p < 0.05, 95 % CI). The prevalence of oral mucosal conditions was 40.7 %. The most prevalent oral mucosal conditions were coated tongue (23.4 %), melanotic macules (14.4 %), oral ulcers (11.8 %), Fordyce's spots (8.1 %), angular cheilitis (3.0 %), geographic tongue (2.8 %), linea alba (1.5 %) and fistula (1.3 %). Children between 3 and 5 years of age had a greater chance of exhibiting coated tongue (OR, 2.55; 95 % CI, 1.6-4.1), melanotic macules (OR, 4.07; 95 % CI, 2.3-7.2) and Fordyce's spots (OR, 12.70; 95 % CI, 7.2-28.6). The female gender had a greater chance of exhibiting melanotic macules (OR, 2.23; 95 % CI, 1.3-1.8). Coated tongue was more prevalent among children from low-income families (OR, 2.35; 95 % CI, 1.3-4.3) and those with inadequate oral hygiene (OR, 4.65; 95 % CI, 2.9-7.4). Caries constituted a predictive factor for oral ulcers (OR, 2.15; 95 % CI, 1.2-3.9) and fistula (OR, 12.00; 95 % CI, 1.4-11.3). Bruxism (teeth clenching/grinding) was a predictive factor for angular cheilitis (OR, 5.55; 95 % CI, 1.9-16.3). The determinant factors for oral mucosal conditions were the female gender, age between 3 and 5 years, inadequate oral hygiene, low household income, residence in rural areas and presence of dental caries and bruxism.

Mandibular pseudocarcinomatous hyperplasia.

PubMed

Warter, A; Walter, P; Meyer, C; Barrière, P; Galatir, L; Wilk, A

2000-08-01

Three unusual cases of pseudocarcinomatous (pseudoepitheliomatous) hyperplasia (PH) affecting chronic osteomyelitic mandibular sequestra are reported to highlight the differences with the various squamous neoplasms which occur in that site. In two patients carrying a mandibular graft following the excision of an ameloblastoma, mucosal ulcers resulted in chronic osteomyelitis. In a third patient, an apical dental infection was associated with fistulated osteomyelitis. Histology of the three sequestra showed an intraosseous squamous proliferation. It was characterized by a peripheral involvement of medullary spaces, the more mature epithelial layer covering the bone trabeculae without intervening stroma, and the basal type epithelial layer surrounding a central fibrovascular core. There were no histological or cytological signs of malignancy. PH shows an inverted pattern when compared with the centro-medullary tumoural islands seen in the various oral or odontogenic squamous neoplasms which occur in the jaws. The lack of signs of malignancy distinguish PH from common squamous cell carcinomas. A short clinical course is an important feature in the distinction of PH from the well differentiated squamous cell carcinomas which may develop in fistulated chronic osteomyelitis.

Analyzing the value of monitoring duodenal mucosal perfusion using photoplethysmography.

PubMed

Fink, Mitchell P

2014-10-13

Photoplethysmography (PPG) is a technique that permits noninvasive measurement of changes in the volume of tissues. A novel device uses PPG to assess changes in duodenal mucosal perfusion. When tested in septic piglets, data obtained using this device correlate with the blood lactate concentration and duodenal serosal microvascular blood flow as measured with a laser Doppler flowmeter. This new PPG-based approach for continuously monitoring gut mucosal perfusion warrants further development, leading to prospective clinical trials in patients.

Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis.

PubMed

Weijenborg, Pim W; Smout, André J P M; Verseijden, Caroline; van Veen, Henk A; Verheij, Joanne; de Jonge, Wouter J; Bredenoord, Albert J

2014-08-01

Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus is associated with the expression of filaggrin. Copyright © 2014 the American Physiological Society.

Gastric exocrine “failure” in critically ill patients: incidence and associated features

PubMed Central

Stannard, V A; Hutchinson, A; Morris, D L; Byrne, A

1988-01-01

Following the observation that many critically ill patients cannot maintain their gastric juice pH below 4 without treatment a study was performed to measure the gastric juice pH in such patients and relate it to other clinical data. The case notes of 64 patients who had been admitted to the intensive care unit and taken part in two trials of ranitidine treatment were reviewed. During those trials gastric juice was aspirated hourly and the pH and volume measured. In this study the values recorded during a six hour untreated control phase were used. Data on age, diagnosis, treatment, outcome, episodes of hypoxia, episodes of hypotension, and use of inotropic drugs were also reviewed. Full data were available for 61 patients: 27 had a mean baseline pH of >5 during the control phase and 34 a mean baseline pH of <5. Significantly more of those with a high pH suffered hypotension (21/27 v 13/34) and received inotropic drugs (16/27 v 8/34). These findings suggest that hypotension in critically ill patients adversely affects gastric exocrine function; prophylaxis with drugs that can improve gastric mucosal blood flow may be more effective than with antacids. PMID:3122979

Use of Curcumin Mouthrinse in Radio-Chemotherapy Induced Oral Mucositis Patients: A Pilot Study.

PubMed

Patil, Karthikeya; Guledgud, Mahima V; Kulkarni, P K; Keshari, Deepika; Tayal, Srishti

2015-08-01

Oral Mucositis is a complex and distinct pathobiologic entity resulting in injuries in mucosa that is a common complication in cancer patients undergoing chemotherapy (CT) and radiation therapy (RT). Phytochemicals, such as Curcumin, turmeric extract, has attracted great attention for its therapeutic benefits in clinical oncology due to its chemopreventive, antitumoral, chemosensibilizing and radiosensibilizing activities against various types of cancers and the complications associated with their management. To evaluate the efficacy and safety of curcumin mouthwash in the management of Oral Mucositis in cancer patients undergoing radio-chemotherapy. The research group consisted of 20 adult cancer patients undergoing radio-chemotherapy at the Regional Oncology Centre, who were evaluated for signs and symptoms of oral mucositis and then randomly divided into two groups. Standard preventive oral care i.e. chlorhexidine mouthwash 0.2% was given to one group while the other group was provided with freshly prepared curcumin mouthwash; each to be used thrice daily. Oral mucositis was assessed at days 0, 10 and 20. The World Health Organization (WHO) scale, the Oral Mucositis Assessment Scale (OMAS), and a Numerical Rating Scale (NRS; patient reporting scale of 0-10) were used. Adverse events were tracked. Descriptive statistics, Independent sample t-test and repeated measure ANOVA test were performed. Statistically significant difference was found in the NRS (p=0.000), Erythema (p=0.050), ulceration (p=0.000) and WHO scores (p=0.003) between the two groups. Curcumin was found to be better than chlorhexidine mouth wash in terms of rapid wound healing and better patient compliance in management of radio-chemotherapy induced oral mucositis. No oral or systemic complications were reported.

Anthrax Vaccine Powder Formulations for Nasal Mucosal Delivery

DTIC Science & Technology

2005-08-04

inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and...fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7–8 using trehalose as stabilizer and a CpG...gas- trointestinal, and pulmonary routes. The inhaled form is of particular concern considering its de- monstrated use as a bioweapon.1–4 Inhalational

Oral manifestations in gastroesophageal reflux disease.

PubMed

Preetha, A; Sujatha, D; Patil, Bharathi A; Hegde, Sushmini

2015-01-01

Many systemic diseases exert their influence on oral health. Among these, gastroesophageal reflux disease (GERD) is the most common. In this study, 100 patients who were previously diagnosed with GERD were examined following a 12-hour fast and evaluated in terms of the severity (grade) of the disease as well as any oral, dental, and/or salivary pH changes. Results found 11 patients with tooth erosion. These patients were older, and their average mean duration of GERD was longer in comparison to those without erosion. There was an inverse relationship between salivary pH and the GERD duration and grade of severity. As the GERD grade increased, the severity of tooth erosion increased. Patients with erosion also exhibited oral mucosal changes. Thus severe, long-term GERD was found to be potentially detrimental to oral soft tissues, dental structures, and salivary pH, whereas milder forms of the disease did not necessarily cause dental side effects.

Systemic and local effects of long-term exposure to alkaline drinking water in rats

PubMed Central

Merne, Marina ET; Syrjänen, Kari J; Syrjänen, Stina M

2001-01-01

Alkaline conditions in the oral cavity may be caused by a variety of stimuli, including tobacco products, antacids, alkaline drinking water or bicarbonate toothpaste. The effects of alkaline pH on oral mucosa have not been systematically studied. To assess the systemic (organ) and local (oral mucosal) effects of alkalinity, drinking water supplemented with Ca(OH)2 or NaOH, with pH 11.2 or 12 was administered to rats (n = 36) for 52 weeks. Tissues were subjected to histopathological examination; oral mucosal biopsy samples were also subjected to immunohistochemical (IHC) analyses for pankeratin, CK19, CK5, CK4, PCNA, ICAM-1, CD44, CD68, S-100, HSP 60, HSP70, and HSP90. At completion of the study, animals in the study groups had lower body weights (up to 29% less) than controls despite equal food and water intake, suggesting a systemic response to the alkaline treatment. The lowest body weight was found in rats exposed to water with the highest pH value and starting the experiment when young (6 weeks). No histological changes attributable to alkaline exposure occurred in the oral mucosa or other tissues studied. Alkaline exposure did not affect cell proliferation in the oral epithelium, as shown by the equal expression of PCNA in groups. The up-regulation of HSP70 protein expression in the oral mucosa of rats exposed to alkaline water, especially Ca(OH)2 treated rats, may indicate a protective response. Intercellular adhesion molecule-1 (ICAM-1) positivity was lost in 6/12 rats treated with Ca(OH)2 with pH 11.2, and loss of CD44 expression was seen in 3/6 rats in both study groups exposed to alkaline water with pH 12. The results suggest that the oral mucosa in rats is resistant to the effects of highly alkaline drinking water. However, high alkalinity may have some unknown systemic effects leading to growth retardation, the cause of which remains to be determined. PMID:11493345

Chemotherapy-induced oral mucositis and associated infections in a novel organotypic model.

PubMed

Sobue, T; Bertolini, M; Thompson, A; Peterson, D E; Diaz, P I; Dongari-Bagtzoglou, A

2018-06-01

Oral mucositis is a common side effect of cancer chemotherapy, with significant adverse impact on the delivery of anti-neoplastic treatment. There is a lack of consensus regarding the role of oral commensal microorganisms in the initiation or progression of mucositis because relevant experimental models are non-existent. The goal of this study was to develop an in vitro mucosal injury model that mimics chemotherapy-induced mucositis, where the effect of oral commensals can be studied. A novel organotypic model of chemotherapy-induced mucositis was developed based on a human oral epithelial cell line and a fibroblast-embedded collagen matrix. Treatment of organotypic constructs with 5-fluorouracil (5-FU) reproduced major histopathologic characteristics of oral mucositis, such as DNA synthesis inhibition, apoptosis and cytoplasmic vacuolation, without compromising the three-dimensional structure of the multilayer organotypic mucosa. Although structural integrity of the model was preserved, 5-FU treatment resulted in a widening of epithelial intercellular spaces, characterized by E-cadherin dissolution from adherens junctions. In a neutrophil transmigration assay we discovered that this treatment facilitated transport of neutrophils through epithelial layers. Moreover, 5-FU treatment stimulated key proinflammatory cytokines that are associated with the pathogenesis of oral mucositis. 5-FU treatment of mucosal constructs did not significantly affect fungal or bacterial biofilm growth under the conditions tested in this study; however, it exacerbated the inflammatory response to certain bacterial and fungal commensals. These findings suggest that commensals may play a role in the pathogenesis of oral mucositis by amplifying the proinflammatory signals to mucosa that is injured by cytotoxic chemotherapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Macroscopic and microscopic effects of GaAIAs diode laser and dexamethasone therapies on oral mucositis induced by fluorouracil in rats.

PubMed

Lara, Renata Nemetala; da Guerra, Eliete Neves Silva; de Melo, Nilce Santos

2007-01-01

To present an animal model for mucositis induced by fluorouracil in rats, and test two therapeutic options, the GaAIAs laser and topical dexamethasone, analysing them with regard to the quality and quantity of tissue alterations and comparing them with the phases of mucositis. Forty-five Wistar rats (250 g) were treated with fluorouracil (60 mg/kg) and, in order to mimic the clinical effect of chronic irritation, the palatal mucosa was irritated by superficial scratching with an 18-gauge needle. When all of the rats presented oral ulcers of mucositis, they were randomly allocated to one of three groups: group I was treated with laser (GaAIAs), group II was treated with topical dexamethasone, and group III was not treated. Excisional biopsies of the palatal mucosa were then performed, and the rats were killed. Tissue sections were stained with haematoxylin and eosin for morphological analyses, and with toluidine blue for mast-cell counts. Group I specimens showed higher prevalence of ulcers, bacterial biofilm, necrosis and vascularisation, while group II specimens showed higher prevalance of granulation tissue formation. There were no significant statistical differences in the numbers of mast cells and epithelial thickness between groups. For the present model of mucositis, rats with palatal mucositis treated with laser (GaAIAs) showed characteristics compatible with the ulcerative phase of oral mucositis, and rats treated with topical dexamethasone showed characteristics compatible with the healing phase of mucositis. Topical dexamethasone was more efficient in the treatment of rats' oral mucositis than the laser.

Changes in microflora in dental plaque from cancer patients undergoing chemotherapy and the relationship of these changes with mucositis: A pilot study.

PubMed

Vozza, Iole; Caldarazzo, Vito; Ottolenghi, Livia

2015-05-01

To assess changes in oral microflora in dental plaque from cancer patients within 7 days of the first course of chemotherapy, and the relationship of the changes with mucositis. Thirty cancer patients, divided into a test group undergoing chemotherapy and a control group no undergoing chemotherapy, were enrolled in this pilot study. Oral microflora were cultured from three samples of dental plaque at t0 (before chemotherapy), t1 (1 day after chemotherapy) and t2 (7 days after chemotherapy). Single and crossed descriptive analyses were used to establish prevalence, and the χ² test was used to establish the statistical significance of the differences observed in distributions (significance level: P<0.05). In most patients (57%), oral microflora consisted mainly of Gram-positive cocci, while the remaining 43% of the bacterial flora also had periodontal-pathogenic species. No Porphyromonas gingivalis appeared in the test group. Actinobacillus was the least frequently found bacterium among periodontal pathogens in the test group, while Fusobacterium nucleatum was the most frequently found. No significant differences were found in quantitative bacterial changes between t0, t1 and t2 in either the test or control groups, or between the two groups. According to World Health Organization scores, oral mucositis developed in 10 patients (66.6%) in the test group. The results of this pilot study indicate that there were no changes in microflora in dental plaque in cancer patients within 7 days of the first course of chemotherapy. No correlations between oral mucositis and specific microorganisms were assessed.

The evaluation of the local tolerance of vaginal formulations containing dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal irritation test.

PubMed

Dhondt, Marijke M M; Adriaens, Els; Roey, Jens Van; Remon, Jean Paul

2005-08-01

The purpose of this study was to evaluate the local tolerance of vaginal gels (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug Mucosal Irritation test and to compare the results with those of the rabbit vaginal irritation test. The irritation potential on the slug mucosa was assessed by the mucus production caused by a repeated treatment for 5 successive days. Additionally, membrane damage was estimated by the protein and enzyme release. By means of a classification prediction model the formulations were classified into four irritation classes. The effect of a 10-day intravaginal application of the gels on the rabbit vaginal and cervical mucosa was evaluated by means of macroscopic and microscopic examination. The placebo and dapivirine gels induced no irritation of the slug mucosa (low mucus production and protein release, no enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol caused severe irritation of the slug mucosa (increased mucus production, protein release, and enzyme release) and irritation of the rabbit vagina and cervix. The results obtained with the Slug Mucosal Irritation test were comparable to those of the rabbit vaginal irritation test.

Colorectal Carcinogenesis: A Cellular Response to Sustained Risk Environment

PubMed Central

Fung, Kim Y. C.; Ooi, Cheng Cheng; Zucker, Michelle H.; Lockett, Trevor; Williams, Desmond B.; Cosgrove, Leah J.; Topping, David L.

2013-01-01

The current models for colorectal cancer (CRC) are essentially linear in nature with a sequential progression from adenoma through to carcinoma. However, these views of CRC development do not explain the full body of published knowledge and tend to discount environmental influences. This paper proposes that CRC is a cellular response to prolonged exposure to cytotoxic agents (e.g., free ammonia) as key events within a sustained high-risk colonic luminal environment. This environment is low in substrate for the colonocytes (short chain fatty acids, SCFA) and consequently of higher pH with higher levels of free ammonia and decreased mucosal oxygen supply as a result of lower visceral blood flow. All of these lead to greater and prolonged exposure of the colonic epithelium to a cytotoxic agent with diminished aerobic energy availability. Normal colonocytes faced with this unfavourable environment can transform into CRC cells for survival through epigenetic reprogramming to express genes which increase mobility to allow migration and proliferation. Recent data with high protein diets confirm that genetic damage can be increased, consistent with greater CRC risk. However, this damage can be reversed by increasing SCFA supply by feeding fermentable fibre as resistant starch or arabinoxylan. High protein, low carbohydrate diets have been shown to alter the colonic environment with lower butyrate levels and apparently greater mucosal exposure to ammonia, consistent with our hypothesis. Evidence is drawn from in vivo and in vitro genomic and biochemical studies to frame experiments to test this proposition. PMID:23807509

An infrared spectroscopy method to detect ammonia in gastric juice.

PubMed

Giovannozzi, Andrea M; Pennecchi, Francesca; Muller, Paul; Balma Tivola, Paolo; Roncari, Silvia; Rossi, Andrea M

2015-11-01

Ammonia in gastric juice is considered a potential biomarker for Helicobacter pylori infection and as a factor contributing to gastric mucosal injury. High ammonia concentrations are also found in patients with chronic renal failure, peptic ulcer disease, and chronic gastritis. Rapid and specific methods for ammonia detection are urgently required by the medical community. Here we present a method to detect ammonia directly in gastric juice based on Fourier transform infrared spectroscopy. The ammonia dissolved in biological liquid samples as ammonium ion was released in air as a gas by the shifting of the pH equilibrium of the ammonium/ammonia reaction and was detected in line by a Fourier transform infrared spectroscopy system equipped with a gas cell for the quantification. The method developed provided high sensitivity and selectivity in ammonia detection both in pure standard solutions and in a simulated gastric juice matrix over the range of diagnostic concentrations tested. Preliminary analyses were also performed on real gastric juice samples from patients with gastric mucosal injury and with symptoms of H. pylori infection, and the results were in agreement with the clinicopathology information. The whole analysis, performed in less than 10 min, can be directly applied on the sample without extraction procedures and it ensures high specificity of detection because of the ammonia fingerprint absorption bands in the infrared spectrum. This method could be easily used with endoscopy instrumentation to provide information in real time and would enable the endoscopist to improve and integrate gastroscopic examinations.

Effect of 5-hydroxytryptamine on duodenal mucosal bicarbonate secretion in mice.

PubMed

Tuo, Bi-Guang; Isenberg, Jon I

2003-09-01

5-hydroxytryptamine (5-HT) is an important neurotransmitter and intercellular messenger that modulates many gastrointestinal functions. Because little is known about the role of 5-HT in the regulation of duodenal bicarbonate secretion, we examined the role of 5-HT on duodenal bicarbonate secretion and define neural pathways involved in the actions of 5-HT. Duodenal mucosa from National Institutes of Health Swiss mice was stripped of seromuscular layers and mounted in Ussing chambers. The effect of 5-HT on duodenal bicarbonate secretion was determined by the pH stat technique. Acetylcholine (ACh) release from duodenal mucosa was assessed by preincubating the tissue with [(3)H] choline and measuring 5-HT-evoked release of tritium. 5-HT added to the serosal bath markedly stimulated duodenal bicarbonate secretion and short circuit current (Isc) in a dose-dependent manner (10(-7) mol/L to 10(-3) mol/L; P < 0.0001), whereas mucosally added 5-HT was without effect. 5-HT-stimulated bicarbonate secretion was independent of luminal Cl(-). Pretreatment with tetrodotoxin (TTX) (10(-6) mol/L) or atropine (10(-5) mol/L) markedly reduced 5-HT-stimulated duodenal bicarbonate secretion (by 60% and 65%, respectively; P < 0.001) and Isc (by 45% and 27%, respectively; P < 0.001 and P < 0.05). Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME) (10(-3) mol/L), propranolol (10(-5) mol/L), or phentolamine (10(-5) mol/L) did not significantly alter 5-HT-stimulated duodenal mucosal bicarbonate secretion or Isc. 5-HT concentration-dependently evoked ACh release from duodenal mucosal preparations (P < 0.0001). TTX markedly inhibited 5-HT-evoked ACh release (P < 0.001). 5-HT is a potent activator of duodenal mucosal bicarbonate secretion in mice. Duodenal bicarbonate secretion induced by 5-HT in vitro occurs principally via a cholinergic neural pathway.

Preventive Effect of Glycyrrhiza Glabra Extract on Oral Mucositis in Patients Under Head and Neck Radiotherapy: A Randomized Clinical Trial

PubMed Central

Najafi, Shamsolmolok; Koujan, Soraiya Ebrahimpour; Manifar, Soheila; Kharazifard, Mohammad Javad; Kidi, Saba

2017-01-01

Objectives: About two-thirds of cancer patients undergo radiotherapy. Oral mucositis represents a major complication of radiotherapy, causing morbidity and mortality and decreasing the quality of life of patients. This study aimed to assess the preventive effect of Glycyrrhiza aqueous extract on oral mucositis in cancer patients under head and neck radiotherapy. Materials and Methods: In this double-blind clinical trial, 37 head and neck cancer patients were divided into intervention (n=19) group receiving Glycyrrhiza aqueous extract and control (n=18) group receiving placebo. Patients in the test group used Glycyrrhiza aqueous extract topically twice a day from the first day of starting radiotherapy until the end of the second week. Patients were examined in the first day of radiotherapy for any type of wound before treatment and those with oral ulcers before radiotherapy were excluded from the study. The grade of mucositis was determined using the classification by the World Health Organization. ANCOVA was performed to assess any difference between the two groups with regard to oral mucosal irritation and wound size after the intervention while controlling for the covariates such as sex and age. Results: Significant differences were found in the maximum grade of mucositis and oral mucosal irritation between the intervention and control groups (P<0.001). Conclusions: This study showed that aqueous extract of Glycyrrhiza can be effective for decreasing the severity of oral mucositis in head and neck cancer patients undergoing radiotherapy. PMID:29296112

Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage.

PubMed

Green, F W; Kaplan, M M; Curtis, L E; Levine, P H

1978-01-01

In a series of in vitro studies, both the soluble (plasmatic) coagulation system and the cellular (platelet-mediated) aspect of coagulation were shown to be extremely sensitive to relatively minor increases in hydrogen ion concentration. All studies became abnormal at pH 6.8. At pH 6.4, assays of the intrinsic and extrinsic coaglution systems, the polymerization of fibrinogen, and assay of the availability of platelet phospholipid (platelet factor 3) were twice prolonged over control values. Platelet aggregation was reduced by more than 50%. At pH 5.4 in vitro, platelet aggregation and plasma coagulation were both virtually abolished. Furthermore, previously formed platelet aggregates disaggregated at a slightly acid pH. Pepsin further enhanced platelet disaggregation. Because gastric acidity is normally two to four orders of magnitude greater than that which abolishes platelet aggregation and plasma clotting in vitro, and pepsin is present in abundance, we call attention to the probable antihemostatic effect of hydrocloric acid and pepsin in the upper gastrointestinal tract. This in vitro study may provide a rationale for meticulous regulation of intragastric pH in an effort to control upper gastrointestinal hemorrhage.

Vinegar decreases allergenic response in lentil and egg food allergy.

PubMed

Armentia, A; Dueñas-Laita, A; Pineda, F; Herrero, M; Martín, B

2010-01-01

Food allergy results from an atypical response of the mucosal immune system to orally consumed allergens. Antacid medication inhibits the digestion of dietary proteins and causes food allergy. A decrease of the gastric pH might enhance the function of digestion and reduce the risk of food allergy. To test a possible decrease in the allergenicity of powerful food allergens (egg, chicken, lentils) with the addition of vinegar during the cooking process. We included seven patients who suffered from anaphylaxis due to egg, chicken and lentils. We added vinegar to egg, chicken and lentil processed extracts used for skin prick tests (SPT) and compared the wheal areas obtained with the same extracts sources and the same way but without vinegar addition. Immunodetection was performed with the different processed extracts and patients' sera. Only one patient consented food challenge with vinegar-marinated-chicken. Wheal areas were significantly minor with the food extract with vinegar. Immunodetection showed a decrease of the response with vinegar processed extracts. Vinegar addition during the cooking process may decrease lentil and chicken allergenicity. Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Investigation of Helicobacter pylori in tonsillary tissue with Pronto Dry test and pathologic examination.

PubMed

Aslan, Sundus; Yilmaz, Ismail; Bal, Nebil; Sener, Mesut; Butros, Reha; Demirhan, Beyhan; Ozluoglu, Levent N

2007-09-01

The objectives of this clinical study were to identify, by means of the Pronto Dry test and pathologic examination, Helicobacter pylori (HP) in tonsillary tissue and to establish the role of HP in tonsillary microbiology by identifying that bacterium in the tonsillary mucosa or within the tonsil core. The subjects consisted of 52 patients (25 men and 27 women; age range, 3-65 years; mean age, 15.1+/-14.5 years) who were scheduled to undergo tonsillectomy for the treatment of chronic tonsillitis and who had not been treated with an antibiotic or a bismuth-containing compound for 6 months before the initiation of the study. In each patient, two specimens (one 4 mm x 4 mm tissue sample from the nonmucosal tonsil core and one 4 mm x 4 mm sample of mucosal tissue) were excised from both tonsils immediately after tonsillectomy. The specimens were placed in the Pronto Dry test kit, and the test results were obtained 1 h later. The remaining tonsillary tissues were submitted for pathologic analysis via hematoxylin-eosin stain, Giemsa stain, Warthin-Starry silver stain, and staining for inducible nitric oxide synthase (iNOS). The results of the Pronto Dry test were positive for HP in 42% (n=22) of the excised mucosal tissue and in 47% (n=24) of the excised core tissue. In 27% (n=14) of the patients, both the core and the mucosal tissues tested positive for HP. There was no significant difference between the positive Pronto Dry test ratios of the biopsies obtained from the mucosa and those obtained from the core (P=0.693). iNOS staining showed that macrophage iNOS activity was significantly higher (P=0.025) in biopsied mucosal tissues with a positive Pronto Dry test result than in those with a negative result. Light microscopy revealed no HP in samples stained with hematoxylin-eosin stain, Giemsa stain, or Warthin-Starry silver stain. Positive Pronto Dry test results and the results of iNOS staining showed that HP contributes to chronic tonsillitis, especially at the mucosal layer. Although HP does not colonize, it contributes to the chronic tonsillary inflammatory process as a triggering agent by affecting macrophages in the tonsil and thus increasing iNOS expression.

Mucosal Impedance: a New Approach to Diagnosing Gastroesophageal Reflux Disease and Eosinophilic Esophagitis.

PubMed

Barrett, Caroline; Choksi, Yash; Vaezi, Michael F

2018-06-09

In this review, we discuss current diagnostic testing modalities for both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) and then introduce mucosal impedance (MI), a novel technology that measures epithelial integrity in real time during endoscopy. We describe the advantages and disadvantages of MI as compared with traditional diagnostic testing. We review studies that demonstrate that GERD and EoE have distinct MI patterns, and that physicians can accurately diagnose and distinguish the two during endoscopy with minimal time added to the procedure. We also review studies showing that MI has the capability to assess treatment response in both GERD and EoE and that it can be used to diagnose GERD in patients with extraesophageal reflux symptoms. Mucosal impedance testing is a major advancement in the diagnosis of GERD and EoE. Future studies are planned to assess whether MI can be used as a treatment endpoint in EoE and whether it can be used to predict response to anti-reflux surgery.

KIT amplification and gene mutations in acral/mucosal melanoma in Korea.

PubMed

Yun, Jina; Lee, Jeeyun; Jang, Jiryeon; Lee, Eui Jin; Jang, Kee Taek; Kim, Jung Han; Kim, Kyoung-Mee

2011-06-01

Mucosal and acral melanomas have demonstrated different genetic alterations and biological behavior compared with more common cutaneous melanomas. It was recently reported that gain-of-function KIT mutations and/or copy number increases are more common in mucosal and acral melanomas. Thus, we studied the frequency and pattern of KIT aberrations in mucosal and acral melanomas in Korea. We analyzed 97 patients who were pathologically confirmed with mucosal or acral melanoma between 1997 and 2010 at Samsung Medical Center. Of the 97 melanoma patients, 92 were screened for mutations in KIT exons 11, 13, 17, and 18, BRAF and NRAS genes. KIT copy number was assessed by quantitative, real-time PCR. Of the 97 patients, 55 (56.7%) were mucosal, 40 (41.2%) were acral melanoma, and two were of unknown primary origin. Among seven cases with KIT mutation, five (60.0%) occurred in exon 11, one (20.0%) in exon 17, and one (20.0%) in exon 13. Point mutations were the most common, resulting in substitutions in exon 11 (K558R, T574A, L576P, and V559A), exon 13 (N655K), and exon 17 (N822K). A novel Thr574Ala (c.1720A>G) KIT mutation, which has not been reported in melanoma or other tumor types, was identified in one genital melanoma case. Of the 97 mucosal or acral melanoma specimens, 49 were tested for KIT gene copy number changes using quantitative PCR. Increased KIT copy number was identified in 15 patients: seven (40%) of 20 acral melanomas and eight (31%) of 26 mucosal melanomas. Our study implicates that a significant proportion of acral and mucosal melanomas have KIT mutations in Asian population. © 2011 The Authors. APMIS © 2011 APMIS.

Leptin accelerates enterocyte turnover during methotrexate-induced intestinal mucositis in a rat.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Shteinberg, Dan; Karry, Rahel; Lurie, Michael; Ure, Benno M; Shaoul, Ron; Coran, Arnold G

2009-05-01

Gastrointestinal mucositis occurs as a consequence of cytotoxic treatment. In the present study, we tested whether leptin can protect gut epithelial cells from methotrexate (MTX)-induced intestinal damage. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of leptin for 24 h. Cell proliferation and apoptosis were assessed using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-rats were treated with a single dose of MTX, and MTX-LEP rats were also treated with leptin for 3 d. Intestinal mucosal damage (Park score), mucosal structural changes (bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth), enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. RT-PCR was used to determine the level of bax and bcl-2 mRNA expression. In the vitro experiment, treatment with leptin of Caco-2 cells pre-treated with MTX resulted in a significant stimulation of cell proliferation and inhibition of cell apoptosis in a dose-dependent manner. In the vivo experiment, MTX-LEP rats demonstrated a greater jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, as well as a greater enterocyte proliferation index compared to MTX-animals. MTX-LEP rats also showed a trend toward an increase in enterocyte apoptosis that was accompanied by an increase in bax mRNA and decrease in bcl-2 mRNA expression. In conclusion, leptin enhances proliferation and decreases apoptosis in Caco-2 cells pretreated with MTX. In a rat model of MTX-induced mucositis, treatment with leptin improves intestinal recovery and enhances enterocyte turnover.

Binding of Helocobacter pyori to Human Gastric Mucose: Identification and Characterization of a Lewis b Bingind Protein.

DTIC Science & Technology

1995-06-01

putative virulence factors of H. pylori have been identified to date. These factors include a urease , flagella, a mucinase, a cytotoxin, and two adhesins...The urease is believed to aid in bacterial survival of the harsh gastric environment by generating ammonia from urea to neutralize the low pH (Segal...A Laboratory Manual. Cold Spring Harbor, New York. Cold Spring Harbor Laboratory Press. Hazell, S., A. Lee. 1986. Campylobacter pyloridis urease

Cone-Beam Computed Tomography Analysis of Mucosal Thickening in Unilateral Cleft Lip and Palate Maxillary Sinuses.

PubMed

Kula, Katherine; Hale, Lindsay N; Ghoneima, Ahmed; Tholpady, Sunil; Starbuck, John M

2016-11-01

  To compare maxillary mucosal thickening and sinus volumes of unilateral cleft lip and palate subjects (UCLP) with noncleft (nonCLP) controls.   Randomized, retrospective study of cone-beam computed tomographs (CBCT).   University.   Fifteen UCLP subjects and 15 sex- and age-matched non-CLP controls, aged 8 to 14 years.   Following institutional review board approval and reliability tests, Dolphin three-dimensional imaging software was used to segment and slice maxillary sinuses on randomly selected CBCTs. The surface area (SA) of bony sinus and airspace on all sinus slices was determined using Dolphin and multiplied by slice thickness (0.4 mm) to calculate volume. Mucosal thickening was the difference between bony sinus and airspace volumes. The number of slices with bony sinus and airspace outlines was totaled. Right and left sinus values for each group were pooled (t tests, P > .05; n = 30 each group). All measures were compared (principal components analysis, multivariate analysis of variance, analysis of variance) by group and age (P ≤ .016 was considered significant).   Principal components analysis axis 1 and 2 explained 89.6% of sample variance. Principal components analysis showed complete separation based on the sample on axis 1 only. Age groups showed some separation on axis 2. Unilateral cleft lip and palate subjects had significantly smaller bony sinus and airspace volumes, fewer bony and airspace slices, and greater mucosal thickening and percentage mucosal thickening when compared with controls. Older subjects had significantly greater bony sinus and airspace volumes than younger subjects.   Children with UCLP have significantly more maxillary sinus mucosal thickening and smaller sinuses than controls.

Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines

PubMed Central

2011-01-01

Food-grade Lactic Acid Bacteria (LAB) have been safely consumed for centuries by humans in fermented foods. Thus, they are good candidates to develop novel oral vectors, constituting attractive alternatives to attenuated pathogens, for mucosal delivery strategies. Herein, this review summarizes our research, up until now, on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of our work has been based on the model LAB Lactococcus lactis, for which we have developed efficient genetic tools, including expression signals and host strains, for the heterologous expression of therapeutic proteins such as antigens, cytokines and enzymes. Resulting recombinant lactococci strains have been tested successfully for their prophylactic and therapeutic effects in different animal models: i) against human papillomavirus type 16 (HPV-16)-induced tumors in mice, ii) to partially prevent a bovine β-lactoglobulin (BLG)-allergic reaction in mice and iii) to regulate body weight and food consumption in obese mice. Strikingly, all of these tools have been successfully transposed to the Lactobacillus genus, in recent years, within our laboratory. Notably, anti-oxidative Lactobacillus casei strains were constructed and tested in two chemically-induced colitis models. In parallel, we also developed a strategy based on the use of L. lactis to deliver DNA at the mucosal level, and were able to show that L. lactis is able to modulate the host response through DNA delivery. Today, we consider that all of our consistent data, together with those obtained by other groups, demonstrate and reinforce the interest of using LAB, particularly lactococci and lactobacilli strains, to develop novel therapeutic protein mucosal delivery vectors which should be tested now in human clinical trials. PMID:21995317

How Helicobacter pylori urease may affect external pH and influence growth and motility in the mucus environment: evidence from in-vitro studies.

PubMed

Sidebotham, Ramon L; Worku, Mulugeta L; Karim, Q Najma; Dhir, Nirmal K; Baron, J Hugh

2003-04-01

Survival of Helicobacter pylori is dependent upon urease in the cytoplasm and at the bacterial surface. We have sought to clarify how alkaline ammonium salts, released from urea by this enzyme, might alter mucus pH and so affect growth and motility of the bacterium in the gastric mucus environment. Experiments were conducted in vitro to determine how the growth and motility of H. pylori are affected by changes in external pH, and how the bacterium, by hydrolysing urea, alters the pH of the bicarbonate buffer that occurs at the gastric mucosal surface. These data were fitted into experimental models that describe how pH varies within the mucus layer in the acid-secreting stomach. H. pylori was motile between pH 5 and 8, with optimal motility at pH 5. It grew between pH 6 and 8, with optimal growth at pH 6. The bacterium had urease activity between pH 2.7 and 7.4, as evidenced by pH rises in bicarbonate-buffered solutions of urea. Changes in buffer pH were dependent upon initial pH and urea concentration, with the greatest rate of pH change occurring at pH 3. Modelling experiments utilizing these data indicated that (1) in the absence of urease, H. pylori growth and motility in the mucus layer would be restricted severely by low mucus pH in the acid-secreting stomach, and (2) urease will sometimes inhibit H. pylori growth and motility in the mucus layer by elevating the pH of the mucus environment above pH 8. Urease is essential to the growth and motility of H. pylori in the mucus layer in the acid-secreting stomach, but, paradoxically, sometimes it might suppress colonization by raising the mucus pH above 8. This latter effect may protect the bacteria from the adverse consequences of overpopulation.

Evaluation of the effect of cryotherapy in preventing oral mucositis associated with chemotherapy - a randomized controlled trial.

PubMed

Katrancı, Nilgün; Ovayolu, Nimet; Ovayolu, Ozlem; Sevinc, Alper

2012-09-01

The goal of this study was to assess the effect of oral cryotherapy on the development of oral mucositis related to infusion of 5-fluorouracil (5-FU) with leucovorin. This study, a randomized controlled trial with random assignments to the experimental and control groups, was conducted with cancer patients. The study included 60 patients; 30 patients in the study group were instructed to hold ice cubes in their mouth shortly before, during, and shortly after infusion of 5-FU with leucovorin, the 30 patients in the control group received routine care. Oral mucositis in the patients was evaluated at 7, 14, and 21 days after chemotherapy. For analysis of data, chi-square, Fisher's tests were used; p < 0.05 was accepted as statistically significant. In the majority of patients receiving cryotherapy, oral mucositis was not observed (Grade 0) at 7 and 14 days. Similarly, incidence of Grades 1, 2, and 3 oral mucositis in the experimental group was quite a bit lower when compared to the control group (p < 0.05). On day 21, no statistically significant difference between the experimental and control groups was determined based on the development of oral mucositis (p > 0.05). We found that oral cryotherapy has a significant contribution to the protection of oral health by reducing mucositis score according to the WHO mucositis scale, especially on the 7th and 14th days. Nurses' awareness of how cryotherapy can affect patients and options for resolving problems will enable them to provide a higher standard of individualized care. Copyright © 2011 Elsevier Ltd. All rights reserved.

Discounting the duration of bolus exposure in impedance testing underestimates acid reflux.

PubMed

Vikneswaran, Namasivayam; Murray, Joseph A

2016-06-08

Combined impedance-pH testing (MII) allows for detection of reflux episodes regardless of pH. However impedance-based diagnosis of reflux may not routinely account for duration of the reflux episode. We hypothesize that impedance testing may be less sensitive than pH-testing in detecting acid reflux off therapy as a result of discounting duration of exposure. Baseline characteristics and reflux parameters of MII studies performed off-anti-secretory medications were analyzed. Studies on acid suppressive medication and those with recording times less than 20 h or low baseline impedance were excluded. A total of 73 consecutive MII studies were analyzed of which 31 MII studies had elevated acid exposure while 16 were abnormal by impedance criteria. MII testing off-therapy was more likely to be abnormal by pH criteria (percent time pH < 4) than impedance criteria (total reflux):[42 vs 22 % (p =0.02)]. Acid exposure (percent time pH < 4) identified more studies as abnormal than MII-detected acid reflux episodes [42 vs 34 % (p < 0.01)]. Mean acid clearance time (pH-detected) was significantly longer than median bolus clearance time (impedance-detected) in the total [98.7 s vs 12.6 s (p < 0.01)], upright [58.6 s vs 13.1 s (p < 0.01)], and recumbent positions [136.7 s vs 14.2 s (p < 0.01)] with the greatest difference seen in the recumbent position. The mean ratio of mean acid clearance time (pH-detected) and the median bolus clearance time (impedance-detected) was significantly higher in the recumbent position compared to the upright position [11. vs 5.3 (p = 0.01)]. Ambulatory impedance testing underestimates acid reflux compared to esophageal acid exposure by discounting the prolonged period of mucosal contact with each acid reflux episode, particularly in the recumbent position.

Duodenal prostaglandin synthesis and acid load in health and in duodenal ulcer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahlquist, D.A.; Dozois, R.R.; Zinsmeister, A.R.

1983-09-01

We sought to test the hypothesis that duodenal ulcer disease results from an imbalance between duodenal acid load, an injurious force, and mucosal prostaglandin generation, a protective factor. Ten patients with duodenal ulcer and 8 healthy controls were studied. The duodenal acid load after an amino acid soup was quantified by a double-marker technique. Mucosal biopsy specimens were taken endoscopically from the duodenal bulb before and after the test meal. Prostaglandin synthesis activity was measured by incubating biopsy homogenates in excess (/sup 14/C)arachidonic acid. Although mean duodenal acid load was higher in duodenal ulcer, ranges overlapped. Neither the qualitative normore » quantitative profile of mucosal prostaglandin synthesis activities differed significantly between test groups. Prostaglandin synthesis activities, however, tended to increase post cibum in controls, but change little or decrease in duodenal ulcer. Only by comparing the responses with a meal of both parameters together (duodenal acid load and the change in prostaglandin synthesis activities) was there complete or nearly complete separation of duodenal ulcer from controls. Greatest discrimination was observed with prostacyclin (6-keto-PGF1 alpha). We conclude that in health, mucosal prostaglandin generation in the duodenum is induced post cibum in relation to duodenal acid load; this may be a physiologic example of adaptive cytoprotection. In duodenal ulcer there may be a defect in such a mechanism.« less

Esophageal mucosal integrity improves after laparoscopic antireflux surgery in children with gastroesophageal reflux disease.

PubMed

Mauritz, Femke A; Rinsma, Nicolaas F; van Heurn, Ernest L W; Sloots, Cornelius E J; Siersema, Peter D; Houwen, Roderick H J; van der Zee, David C; Masclee, Ad A M; Conchillo, José M; Van Herwaarden-Lindeboom, Maud Y A

2017-07-01

Esophageal intraluminal baseline impedance reflects the conductivity of the esophageal mucosa and may be an instrument for in vivo evaluation of mucosal integrity in children with gastroesophageal reflux disease (GERD). Laparoscopic antireflux surgery (LARS) is a well-established treatment option for children with proton pump inhibitory (PPI) therapy resistant GERD. The effect of LARS in children on baseline impedance has not been studied in detail. The aim of this study was to evaluate the effect of LARS on baseline impedance in children with GERD. This is a prospective, multicenter, nationwide cohort study (Dutch national trial registry: NTR2934) including 25 patients [12 males, median age 6 (range 2-18) years] with PPI-resistant GERD scheduled to undergo LARS. Twenty-four hour multichannel intraluminal impedance pH monitoring (MII-pH monitoring) was performed before and 3 months after LARS. Baseline impedance was evaluated during consecutive 2-h intervals in the 24-h tracings. LARS reduced acid exposure time from 8.5 % (6.0-16.2 %) to 0.8 % (0.2-2.8 %), p < 0.001. Distal baseline impedance increased after LARS from 2445 Ω (1147-3277 Ω) to 3792 Ω (3087-4700 Ω), p < 0.001. Preoperative baseline impedance strongly correlated with acid exposure time (r -0.76, p < 0.001); however, no association between symptomatic outcome and baseline impedance was identified. LARS significantly increased baseline impedance likely reflecting recovery of mucosal integrity. As the change in baseline impedance was not associated with the clinical outcome of LARS, other factors besides mucosal integrity may contribute to symptom perception in children with GERD.

Li-Fraumeni syndrome presenting as mucosal melanoma: Case report and treatment considerations.

PubMed

Klein, Jonah D; Kupferman, Michael E

2017-02-01

Li-Fraumeni syndrome (LFS) is a familial cancer predisposition associated with a germline mutation in TP53. Patients with LFS are at risk of developing malignancies and require comprehensive screening. We describe an index case of LFS presenting with mucosal melanoma. A 21-year-old woman presented with a left maxillary mucosal lesion and a left neck mass. Biopsies revealed metastatic mucosal melanoma, which is a pathology previously unreported in LFS families. Genetic testing revealed LFS, with a germline TP53 mutation, and pedigree analysis identified 9 first-degree and second-degree relatives with hematologic malignancies. The patient underwent a maxillectomy and left neck dissection, followed by adjuvant radiotherapy. At 30-month follow-up, there was no evidence of local, regional, or distant failure, nor did she develop a second primary tumor. This represents the first reported case of LFS associated with mucosal melanoma. Treatment considerations, specifically the risks of adjuvant therapy in LFS, are discussed. © 2016 Wiley Periodicals, Inc. Head Neck 39: E20-E22, 2017. © 2016 Wiley Periodicals, Inc.

Development of standard operating procedures to obtain longitudinal vaginal specimens from nulliparous rabbits as part of HIV vaccine mucosal immunogenicity studies.

PubMed

Gómez Román, Victor Raúl; Vinner, Lasse; Grevstad, Berit; Hansen, Jesper Juhl; Wegmann, Frank; Spetz, Anna-Lena; Fomsgaard, Anders

2010-12-15

The New Zealand white rabbit model (Oryctolagus cuniculus) is widely used to test whether HIV vaccine candidates elicit systemic antibody responses; however, its use in mucosal immunology has not been fully exploited due to the difficulty in collecting mucosal specimens longitudinally and reproducibly. Here we describe feasible and non-feasible methods to collect vaginal and nasal specimens from nulliparous rabbits. Non-feasible methods were those resulting in poor reproducibility and considerable animal twitching during sampling, whereas feasible methods resulted in no animal twitching and potential for sampling reproducibility. Standard operating procedures (SOPs) were implemented to collect vaginal swabs yielding total IgA titres ranging from 12,500 to 312,500. Intranasal immunisation with a naked DNA vaccine encoding HIV gp140 elicited HIV envelope-specific IgA detectable in nasal but not in vaginal secretions. Our methods provide an alternative to reliably assess pre- and post-vaccination mucosal antibody titres longitudinally in rabbits as part of mucosal HIV vaccine immunogenicity studies. Copyright © 2010 Elsevier B.V. All rights reserved.

Dynamic electrophoretic fingerprinting of the HIV-1 envelope glycoprotein

PubMed Central

2013-01-01

Background Interactions between the HIV-1 envelope glycoprotein (Env) and its primary receptor CD4 are influenced by the physiological setting in which these events take place. In this study, we explored the surface chemistry of HIV-1 Env constructs at a range of pH and salinities relevant to mucosal and systemic compartments through electrophoretic mobility (EM) measurements. Sexual transmission events provide a more acidic environment for HIV-1 compared to dissemination and spread of infection occurring in blood or lymph node. We hypothesize functional, trimeric Env behaves differently than monomeric forms. Results The dynamic electrophoretic fingerprint of trimeric gp140 revealed a change in EM from strongly negative to strongly positive as pH increased from that of the lower female genital tract (pHx) to that of the blood (pHy). Similar findings were observed using a trimeric influenza Haemagglutinin (HA) glycoprotein, indicating that this may be a general attribute of trimeric viral envelope glycoproteins. These findings were supported by computationally modeling the surface charge of various gp120 and HA crystal structures. To identify the behavior of the infectious agent and its target cells, EM measurements were made on purified whole HIV-1 virions and primary T-lymphocytes. Viral particles had a largely negative surface charge, and lacked the regions of positivity near neutral pH that were observed with trimeric Env. T cells changed their surface chemistry as a function of activation state, becoming more negative over a wider range of pH after activation. Soluble recombinant CD4 (sCD4) was found to be positively charged under a wide range of conditions. Binding studies between sCD4 and gp140 show that the affinity of CD4-gp140 interactions depends on pH. Conclusions Taken together, these findings allow a more complete model of the electrochemical forces involved in HIV-1 Env functionality. These results indicate that the influence of the localized environment on the interactions of HIV with target cells are more pronounced than previously appreciated. There is differential chemistry of trimeric, but not monomeric, Env under conditions which mimic the mucosa compared to those found systemically. This should be taken into consideration during design of immunogens which targets virus at mucosal portals of entry. PMID:23514633

Younger age at diagnosis predisposes to mucosal recovery in celiac disease on a gluten-free diet: A meta-analysis

PubMed Central

Mátrai, Péter; Hegyi, Péter; Szabó, Imre; Vincze, Áron; Balaskó, Márta; Mosdósi, Bernadett; Sarlós, Patrícia; Simon, Mária; Márta, Katalin; Mikó, Alexandra; Pécsi, Dániel; Demcsák, Alexandra; Bajor, Judit

2017-01-01

Background and aims Persistent intestinal damage is associated with higher complication rates in celiac disease. We aimed to assess the potential modifiers of mucosal recovery. Materials and methods We screened databases (PubMed, Embase, Cochrane Trials, and Web of Science) for papers on celiac disease. Papers discussing (1) celiac patients (2) follow-up biopsy and (3) mucosal recovery after commencement of a gluten-free diet were included. The primary outcome was to produce a comprehensive analysis of complete mucosal recovery (i.e., Marsh 0 on follow-up). We compared children’s recovery ratios to those of adults. Patients following a strict gluten-free dietary regimen were included in a subgroup. Summary point estimates, 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated. Heterogeneity was tested with I2-statistic. The PROSPERO registration number is CRD42016053482. Results The overall complete mucosal recovery ratio, calculated from 37 observational studies, was 0.36 (CI: 0.28–0.44, PI: -0.12–0.84; I2: 98.4%, p<0.01). Children showed higher complete mucosal recovery ratio than adults (p<0.01): 0.65 (CI: 0.44–0.85, PI: -0.10–1.39; I2: 96.5%, p<0.01) as opposed to 0.24 (CI: 0.15–0.33, PI: -0.19–1.08; I2: 96.3%, p<0.01). In the strict dietary adherence subgroup, complete mucosal recovery ratio was 0.47 (CI: 0.24–0.70, PI: -0.47–1.41; I2: 98.8%, p<0.001). On meta-regression, diagnostic villous atrophy (Marsh 3) ratio (-8.97, p<0.01) and male ratio (+6.04, p<0.01) proved to be a significant determinant of complete mucosal recovery, unlike duration of gluten-free diet (+0.01, p = 0.62). The correlation between complete mucosal recovery ratio and age on diagnosis is of borderline significance (-0.03, p = 0.05). Conclusions There is considerable heterogeneity across studies concerning complete mucosal recovery ratios achieved by a gluten-free diet in celiac disease. Several celiac patients fail to achieve complete mucosal recovery even if a strict dietary regimen is followed. Younger age on diagnosis, less severe initial histologic damage and male gender predispose for achieving mucosal recovery. PMID:29095937

Younger age at diagnosis predisposes to mucosal recovery in celiac disease on a gluten-free diet: A meta-analysis.

PubMed

Szakács, Zsolt; Mátrai, Péter; Hegyi, Péter; Szabó, Imre; Vincze, Áron; Balaskó, Márta; Mosdósi, Bernadett; Sarlós, Patrícia; Simon, Mária; Márta, Katalin; Mikó, Alexandra; Pécsi, Dániel; Demcsák, Alexandra; Bajor, Judit

2017-01-01

Persistent intestinal damage is associated with higher complication rates in celiac disease. We aimed to assess the potential modifiers of mucosal recovery. We screened databases (PubMed, Embase, Cochrane Trials, and Web of Science) for papers on celiac disease. Papers discussing (1) celiac patients (2) follow-up biopsy and (3) mucosal recovery after commencement of a gluten-free diet were included. The primary outcome was to produce a comprehensive analysis of complete mucosal recovery (i.e., Marsh 0 on follow-up). We compared children's recovery ratios to those of adults. Patients following a strict gluten-free dietary regimen were included in a subgroup. Summary point estimates, 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated. Heterogeneity was tested with I2-statistic. The PROSPERO registration number is CRD42016053482. The overall complete mucosal recovery ratio, calculated from 37 observational studies, was 0.36 (CI: 0.28-0.44, PI: -0.12-0.84; I2: 98.4%, p<0.01). Children showed higher complete mucosal recovery ratio than adults (p<0.01): 0.65 (CI: 0.44-0.85, PI: -0.10-1.39; I2: 96.5%, p<0.01) as opposed to 0.24 (CI: 0.15-0.33, PI: -0.19-1.08; I2: 96.3%, p<0.01). In the strict dietary adherence subgroup, complete mucosal recovery ratio was 0.47 (CI: 0.24-0.70, PI: -0.47-1.41; I2: 98.8%, p<0.001). On meta-regression, diagnostic villous atrophy (Marsh 3) ratio (-8.97, p<0.01) and male ratio (+6.04, p<0.01) proved to be a significant determinant of complete mucosal recovery, unlike duration of gluten-free diet (+0.01, p = 0.62). The correlation between complete mucosal recovery ratio and age on diagnosis is of borderline significance (-0.03, p = 0.05). There is considerable heterogeneity across studies concerning complete mucosal recovery ratios achieved by a gluten-free diet in celiac disease. Several celiac patients fail to achieve complete mucosal recovery even if a strict dietary regimen is followed. Younger age on diagnosis, less severe initial histologic damage and male gender predispose for achieving mucosal recovery.

Highly Human Immunodeficiency Virus-Exposed Seronegative Men Have Lower Mucosal Innate Immune Reactivity.

PubMed

Fulcher, Jennifer A; Romas, Laura; Hoffman, Jennifer C; Elliott, Julie; Saunders, Terry; Burgener, Adam D; Anton, Peter A; Yang, Otto O

2017-08-01

Risk of HIV acquisition varies, and some individuals are highly HIV-1-exposed, yet, persistently seronegative (HESN). The immunologic mechanisms contributing to this phenomenon are an area of intense interest. As immune activation and inflammation facilitate disease progression in HIV-1-infected persons and gastrointestinal-associated lymphoid tissue is a highly susceptible site for transmission, we hypothesized that reduced gut mucosal immune reactivity may contribute to reduced HIV-1 susceptibility in HESN men with a history of numerous rectal sexual exposures. To test this, we used ex vivo mucosal explants from freshly acquired colorectal biopsies from healthy control and HESN subjects who were stimulated with specific innate immune ligands and inactivated whole pathogens. Immune reactivity was then assessed via cytokine arrays and proteomic analysis. Mucosal immune cell compositions were quantified via immunohistochemistry. We found that explants from HESN subjects produced less proinflammatory cytokines compared with controls following innate immune stimulation; while noninflammatory cytokines were similar between groups. Proteomic analysis identified several immune response proteins to be differentially expressed between HIV-1-stimulated HESN and control explants. Immunohistochemical examination of colorectal mucosa showed similar amounts of T cells, macrophages, and dendritic cells between groups. The results of this pilot study suggest that mucosal innate immune reactivity is dampened in HESN versus control groups, despite presence of similar densities of immune cells in the colorectal mucosa. This observed modulation of the rectal mucosal immune response may contribute to lower risk of mucosal HIV-1 transmission in these individuals.

Phenytoin mouthwash to treat cancer therapy-induced oral mucositis: A pilot studyPrimary neuroendocrine carcinoma of breast: A rare tumor.

PubMed

Baharvand, M; Hamian, M; Moosavizadeh, M A; Mortazavi, A; Ameri, A

2015-01-01

Oral mucositis is one of the most common side effects of cancer therapy with no definite treatment. Phenytoin has positive effects on healing of mucosal and dermal wounds. In this study efficacy of 1% phenytoin mouthwash on severity of mucositis (on the basis of WHO scale), pain relief (based on Visual Analogue Scale), and improvement of patients' quality of life (on the basis of EORTC-QLQ-H and N35 questionnaire) was evaluated. In a pilot -double-blind randomized clinical trial, eight patients in study group were given 1% phenytoin mouthwash while eight patients in control group used normal saline. Data analysis was performed by Mann-Whitney and Repeated Measured ANOVA tests. Reduction of mucositis severity was observed, but the difference was not significant. On the other hand, patients on phenytoin therapy had better pain relief (VAS# 6.75 ± 1.58 at the beginning of the study reached to # 3.75 ± 1.16 after 3 weeks in phenytoin group) and improvement in quality of life (score of QOL was 70.63 ± 5.5 that reached to 63.61 ± 6.39 in phenytoin group) than normal saline group significantly (P < 0.05). One percent phenytoin mouthwash caused pain relief and improvement of life quality significantly in patients with mucositis due to cancer therapy, but it did not reduce the severity of mucositis in a statistically significant scale.

The effect of cola consumption on oral mucosa in rats.

PubMed

Kapicloğlu, S; Baki, A H; Tekelioğlu, Y; Araz, K

2000-01-01

Drinks that contain phosphoric acid have been shown to have erosive effects and cola drinks are strongly acidic (pH 2.5). Gingivitis may be caused by dietary acids. Therefore, this study analyses the interaction of Coca Cola consumption and oral mucosal damage. Thirty rats were divided into three groups of 10. The animals received saline (pH 7.0) or HCl acid buffered to pH 2.6 or Coca Cola (pH 2.6) per os with 24-h free access to these solutions. A biopsy was taken from the front of the gingiva and the tongue. Histopathological analysis showed no specific lesion and there were no differences among saline, Coca Cola and HCl groups. Flow cytometric analysis was used to assess proliferative activity. In the HCl acid and Coca Cola groups, cell cycle analysis showed that the effects of Coca Cola and HCl acid in inducing oral mucosal damage are similar. In both Coca Cola [G0/G1, 70.38+/-7.9; S, 28.06+/-10.13; G2/M, 1.62+/-2.80; proliferative index (PI), 28.68+/-7.981 and HCI (G0/G1, 67.7+/-18.9; S, 27.8+/-17.5; G2/M, 4.4+/-3.8; PI, 30.9+/-20.98), the rat cell population G0/G1 and G2/M phases were found to be low (p < 0.05) and the cell population S and PI phases were found to be significantly elevated compared with the control group (p < 0.05) (G0/G1, 86.92+/-8.69; S, 9.8+/-1.21; G2/M, 3.25+/-2.87; P1, 13.2+/-8.7). This result was reflected in the proliferative index, which is used as a measure of the regeneration index. The data show that Coca Cola and HCl acid have similar proliferative and regenerative effects on oral mucosa, and it is possible that their regenerative effects are caused as a result of an irritant effect.

Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage

PubMed Central

Demitrack, Elise S; Aihara, Eitaro; Kenny, Susan; Varro, Andrea; Montrose, Marshall H

2012-01-01

Background and aims The authors’ goal was to measure pH at the gastric surface (pHo) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium. Methods Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pHo. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion. Results Similar rates of epithelial repair and resting pHo values (~pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pHo was lower (2.5±0.2, P <0.05 vs pH 3). Epithelial repair was slower at luminal pH 7 and pHo was higher (6.4±0.1, P<0.001). In all conditions, pHo increased adjacent to damage. At luminal pH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments. Conclusions Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH. PMID:21997560

Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity

PubMed Central

Vinderola, Gabriel; Matar, Chantal; Perdigón, Gabriela

2007-01-01

Background Fermented milks containing probiotic bacteria are a way of delivering bioactive constituents to targets in the gastrointestinal tract. We reported previously that the fermentation of milk at constant pH 6 by L. helveticus R389 increased its content of peptide fractions, and the oral administration of the non-bacterial fraction (FMSpH6) to mice increased total secretory IgA in the intestinal lumen and enhanced the number of IgA and various cytokines producing cells as well as the secretion of IL-6 by small intestine epithelial cells. We also demonstrated that this FMSpH6 was effective for the prevention of Salmonella typhimurium infection in mice. In this work, we studied in mice the impact of the oral administration of the supernatant of milk fermented by L. helveticus R389 on the gut physiology by measuring parameters such as calcium channels and E-cadherin expression, the activation of the biological signal calcineurin and mast and goblet cells, as a way to determine some mechanisms involved in the immunomodulating effects of the milk fermentation products, observed in previous studies. We analyzed the impact of the supernatant of milk fermented by L. helveticus R389 at pH6-controlled on the expression of calcineurin and on the reinforcement of the ephitelial barrier, measuring parameters such as calcium channels and E-cadherin expression and in the reinforcement of the non-specific immunity determining mast cells and goblet cells associated to the gut. Results We observed an enhanced expression of TRPV6 channels in the duodenum, indicating an improved capacity for dietary Ca2+ uptake. We demonstrated an enhanced expression of calcineurin in the small intestine, able to upregulate immune parameters such as IL-2 and TNF production, with an increase in the number of these cytokines secreting cells. We determined an increase in the number of mucosal mast cells and goblet cells, which would mean an improved state of mucosal surveillance at sites of infection. Conclusion The oral administration of the supernatant of milk fermented by L. helveticus R389 enhanced the gut mucosal immunity by improving the mechanisms that reinforce the epithelial and non-specific barriers and the gut functioning at sites of infection, with an improvement in the expression of the enzyme calcineurin, an important signal in the network that activates the gut immune system. The results of this work contribute to revealing the mechanisms underlying the immunomodulation of the gut immune function by fermented milks with probiotic bacteria. PMID:17825099

Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity.

PubMed

Vinderola, Gabriel; Matar, Chantal; Perdigón, Gabriela

2007-09-07

Fermented milks containing probiotic bacteria are a way of delivering bioactive constituents to targets in the gastrointestinal tract. We reported previously that the fermentation of milk at constant pH 6 by L. helveticus R389 increased its content of peptide fractions, and the oral administration of the non-bacterial fraction (FMSpH6) to mice increased total secretory IgA in the intestinal lumen and enhanced the number of IgA and various cytokines producing cells as well as the secretion of IL-6 by small intestine epithelial cells. We also demonstrated that this FMSpH6 was effective for the prevention of Salmonella typhimurium infection in mice. In this work, we studied in mice the impact of the oral administration of the supernatant of milk fermented by L. helveticus R389 on the gut physiology by measuring parameters such as calcium channels and E-cadherin expression, the activation of the biological signal calcineurin and mast and goblet cells, as a way to determine some mechanisms involved in the immunomodulating effects of the milk fermentation products, observed in previous studies. We analyzed the impact of the supernatant of milk fermented by L. helveticus R389 at pH6-controlled on the expression of calcineurin and on the reinforcement of the ephitelial barrier, measuring parameters such as calcium channels and E-cadherin expression and in the reinforcement of the non-specific immunity determining mast cells and goblet cells associated to the gut. We observed an enhanced expression of TRPV6 channels in the duodenum, indicating an improved capacity for dietary Ca2+ uptake. We demonstrated an enhanced expression of calcineurin in the small intestine, able to upregulate immune parameters such as IL-2 and TNF production, with an increase in the number of these cytokines secreting cells. We determined an increase in the number of mucosal mast cells and goblet cells, which would mean an improved state of mucosal surveillance at sites of infection. The oral administration of the supernatant of milk fermented by L. helveticus R389 enhanced the gut mucosal immunity by improving the mechanisms that reinforce the epithelial and non-specific barriers and the gut functioning at sites of infection, with an improvement in the expression of the enzyme calcineurin, an important signal in the network that activates the gut immune system. The results of this work contribute to revealing the mechanisms underlying the immunomodulation of the gut immune function by fermented milks with probiotic bacteria.

Important role of mucosal serotonin in colonic propulsion and peristaltic reflexes: in vitro analyses in mice lacking tryptophan hydroxylase 1.

PubMed

Heredia, Dante J; Gershon, Michael D; Koh, Sang Don; Corrigan, Robert D; Okamoto, Takanubu; Smith, Terence K

2013-12-01

Although there is general agreement that mucosal 5-hydroxytryptamine (5-HT) can initiate peristaltic reflexes in the colon, recent studies have differed as to whether or not the role of mucosal 5-HT is critical. We therefore tested the hypothesis that the secretion of 5-HT from mucosal enterochromaffin (EC) cells is essential for the manifestation of murine colonic peristaltic reflexes. To do so, we analysed the mechanisms underlying faecal pellet propulsion in isolated colons of mice lacking tryptophan hydroxylase 1 (Tph1(-/-) mice), which is the rate-limiting enzyme in the biosynthesis of mucosal but not neuronal 5-HT. We used video analysis of faecal pellet propulsion, tension transducers to record colonic migrating motor complexes (CMMCs) and intracellular microelectrodes to record circular muscle activity occurring spontaneously or following intraluminal distension. When compared with control (Tph1(+/+)) mice, Tph1(-/-) animals exhibited: (1) an elongated colon; (2) larger faecal pellets; (3) orthograde propulsion followed by retropulsion (not observed in Tph1(+/+) colon); (4) slower in vitro propulsion of larger faecal pellets (28% of Tph1(+/+)); (5) CMMCs that infrequently propagated in an oral to anal direction because of impaired descending inhibition; (6) reduced CMMCs and inhibitory responses to intraluminal balloon distension; (7) an absence of reflex activity in response to mucosal stimulation. In addition, (8) thin pellets that propagated along the control colon failed to do so in Tph1(-/-) colon; and (9) the 5-HT3 receptor antagonist ondansetron, which reduced CMMCs and blocked their propagation in Tph1(+/+) mice, failed to alter CMMCs in Tph1(-/-) animals. Our observations suggest that mucosal 5-HT is essential for reflexes driven by mucosal stimulation and is also important for normal propagation of CMMCs and propulsion of pellets in the isolated colon.

Thiolated alkyl-modified carbomers: Novel excipients for mucoadhesive emulsions.

PubMed

Bonengel, Sonja; Hauptstein, Sabine; Leonaviciute, Gintare; Griessinger, Julia; Bernkop-Schnürch, Andreas

2015-07-30

The aim of this study was the design and evaluation of mucoadhesive emulsifying polymeric excipients. Three thiol bearing ligands with increasing pKa values of their sulfhydryl group, namely 4-aminothiophenol (pKa=6.86), l-cysteine (pKa=8.4) and d/l-homocysteine (pKa=10.0) were coupled to the polymeric backbone of alkyl-modified carbomer (PA1030). Resulting conjugates displayed 818.5μmol 4-aminothiophenol, 698.5μmol cysteine and 651.5μmol homocysteine per gram polymer and were evaluated regarding the reactivity of thiol groups, emulsifying and mucoadhesive properties. In general, the synthesized conjugates showed a pH dependent reactivity, whereby the fastest oxidation occurred in PA1030-cysteine, as almost no free thiol groups could be detected after 120min. Emulsification of medium chain triglycerides was feasible with all synthesized conjugates leading to oil-in-water-emulsions. Emulsions with PA1030-cysteine displayed the highest stability and the smallest droplet size among the tested formulations. Oxidation and consequently cross-linking of the thiomers prior to the emulsification process led to an overall decreased emulsion stability. Evaluating mucosal residence time of thiomer emulsions on porcine buccal mucosa, a 9.2-fold higher amount of formulation based on PA1030-cysteine remained on the mucosal tissue within 3h compared to the unmodified polymer. According to these results, the highest reactive ligand l-cysteine seems to be most promising in order to obtain thiolated polymers for the preparation of mucoadhesive o/w-emulsions. Copyright © 2015 Elsevier B.V. All rights reserved.

Intranasal and sublingual delivery of inactivated polio vaccine.

PubMed

Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

2017-05-09

Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after complete OPV cessation and post-polio eradication. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Recurrent conjunctivitis as a presentation of munchausen syndrome by proxy.

PubMed

Baskin, Darrell E; Stein, Fernando; Coats, David K; Paysse, Evelyn A

2003-08-01

To report a case of Munchausen syndrome by proxy, which manifested as recurrent bilateral keratoconjunctivitis in an infant. Interventional case report. The patient underwent numerous diagnostic studies, including two endoscopies, skin biopsy, conjunctival pH measurement, and a skeletal survey. She underwent daily eye examinations until the corneal and conjunctival epithelial defects resolved. Resolution of cutaneous, mucosal, corneal, and conjunctival epithelial defects. A punch biopsy of the right postauricular area was performed, and pathology subsequently determined that the findings seemed to be the result of an exogenous injury. The conjunctival pH was 8.0, consistent with exposure to an exogenous, caustic agent. The acute ocular lesions resolved. Munchausen syndrome by proxy can be seen with ophthalmic manifestations and should be considered in the differential diagnosis when ocular abnormalities cannot be explained after a thorough and methodical evaluation.

Tonometry revisited: perfusion-related, metabolic, and respiratory components of gastric mucosal acidosis in acute cardiorespiratory failure.

PubMed

Jakob, Stephan M; Parviainen, Ilkka; Ruokonen, Esko; Kogan, Alexander; Takala, Jukka

2008-05-01

Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial pCO2 gradient, DeltapCO2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial pCO2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63+/-2 [mean+/-SEM]; Acute Physiology and Chronic Health Evaluation II score, 20+/-1; Sequential Organ Failure Assessment score, 8+/-0). pHi, and the effects of bicarbonate and arterial and mucosal pCO2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27+/-0.01) due to low arterial bicarbonate and increased DeltapCO2. Low pHi (<7.32) at admission (n=58; mortality, 29% vs. 13% in those with pHi>or=7.32 at admission; P=0.061) was associated with an increased DeltapCO2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltapCO2; P=0.0003). An increased versus normal DeltapCO2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P<0.0001; n=39) and at 6 h (34% vs. 13%; P=0.016; n=45). A delayed normalization or persistently low pHi (n=47) or high DeltapCO2 (n=25) was associated with high mortality (low pHi [34%] vs. high DeltapCO2 [60%]; P=0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all P

The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs.

PubMed

Adriaens, E; Dierckens, K; Bauters, T G; Nelis, H J; van Goethem, F; Vanparys, P; Remon, J P

2001-07-01

The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism. The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs were measured. The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay. The antimicrobial activity of the different BAC analogues was also assessed. All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 < BAC-C14 < BAC-C12 approximately BAC-mix. A similar ranking was obtained with the BCOP assay for eye irritation. The relative order of activities among the three BAC analogues was the same, i.e., BAC-C14 > or = BAC-C16 > BAC-C12. The BAC-C14 exhibited higher activity than the BAC-mix. The toxicity and activity of BAC analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered.

Esophageal acid sensitivity and mucosal integrity in patients with functional heartburn.

PubMed

Weijenborg, P W; Smout, A J P M; Bredenoord, A J

2016-11-01

Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity. We aimed to determine esophageal sensitivity and mucosal integrity in FH and non-erosive reflux disease (NERD) patients. In this prospective experimental study, we performed an acid perfusion test and upper endoscopy with biopsies in 12 patients with NERD and nine patients with FH. Mucosal integrity was measured during endoscopy using electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance and transepithelial permeability. Lag time to heartburn perception was significantly longer in FH patients (median 12 min) than in NERD patients (median 3 min). Once perceived, intensity of heartburn was scored equal with median visual analog scale 6.5 and 7.1 respectively. Esophageal mucosal integrity was also comparable between FH and NERD patients, both in vivo extracellular impedance and ex vivo transepithelial resistance and permeability were similar. Patients with FH did not show acid hypersensitivity as seen in patients with NERD. However, once perceived, intensity of heartburn is similar. Esophageal mucosal integrity is similar between NERD and FH patients, and is therefore unlikely to be the underlying cause of the observed difference in esophageal acid perception. © 2016 John Wiley & Sons Ltd.

Molecular profiling of mucosal tissue associated microbiota in patients manifesting acute exacerbations and remission stage of ulcerative colitis.

PubMed

Walujkar, Sandeep A; Kumbhare, Shreyas V; Marathe, Nachiket P; Patangia, Dhrati V; Lawate, Parimal S; Bharadwaj, Renu S; Shouche, Yogesh S

2018-05-23

Dysbiosis of intestinal microflora has been postulated in ulcerative colitis (UC), which is characterized by imbalance of mucosal tissue associated bacterial communities. However, the specific changes in mucosal microflora during different stages of UC are still unknown. The aim of the current study was to investigate the changes in mucosal tissue associated microbiota during acute exacerbations and remission stages of UC. The mucosal microbiota associated with colon biopsy of 12 patients suffering from UC (exacerbated stage) and the follow-up samples from the same patients (remission stage) as well as non-IBD subjects was studied using 16S rRNA gene-based sequencing and quantitative PCR. The total bacterial count in patients suffering from exacerbated phase of UC was observed to be two fold lower compared to that of the non-IBD subjects (p = 0.0049, Wilcox on matched-pairs signed rank tests). Bacterial genera including Stenotrophomonas, Parabacteroides, Elizabethkingia, Pseudomonas, Micrococcus, Ochrobactrum and Achromobacter were significantly higher in abundance during exacerbated phase of UC as compared to remission phase. The alterations in bacterial diversity with an increase in the abnormal microbial communities signify the extent of dysbiosis in mucosal microbiota in patients suffering from UC. Our study helps in identifying the specific genera dominating the microbiota during the disease and thus lays a basis for further investigation of the possible role of these bacteria in pathogenesis of UC.

Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

PubMed

Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

2016-02-01

Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

The Effect of Honey on Radiation-induced Oral Mucositis in Head and Neck Cancer Patients

PubMed Central

Amanat, Amna; Ahmed, Asrar; Kazmi, Abbas; Aziz, Bushra

2017-01-01

Aim: The aim of this study is to evaluate the effect of honey on clinically scoring grades of oral mucositis. Materials and Methods: This interventional study was carried out in Radiation Oncology Department of Mayo Hospital, Lahore. In this study, 82 patients of both genders, of head and neck cancer, planned for radiotherapy, were divided into two groups by random sampling numbers. Patients in both groups were treated with a total dose of 60–78 Grays in 4–6 weeks. In treatment group, patients were instructed to take 20 mL of honey. In control group, they were advised to rinse with 0.9% of saline. Patients were evaluated every week to assess the grades of oral mucositis up to 6 weeks. The assessment tool was Radiation Therapy Oncology Group Grading System. The statistical analysis was done by Chi-square test. Results: In honey-treated group, the proportion of mucositis (Grades 3 and 4) was lower and statistically significant as compared to control group at the end of 6 weeks of radiation. Conclusion: This study showed that oral intake of honey during radiotherapy is valuable in the reduction of severity of oral mucositis. PMID:28827938

Clinics, prognosis and new therapeutic options in patients with mucosal melanoma: A retrospective analysis of 75 patients.

PubMed

Schaefer, Tim; Satzger, Imke; Gutzmer, Ralf

2017-01-01

Mucosal melanomas represent a rare entity with different risk factors and molecular features compared to cutaneous melanomas. They arise most commonly from mucosal surfaces in the head/neck region, the female genital tract (FGT) and the anorectal region. The aim of this study was to evaluate clinics, prognosis, and treatment options of patients with mucosal melanoma, in particular with regard to different primary sites.We retrospectively analyzed 75 patients with mucosal melanomas diagnosed in the years 1993 to 2015 in our department. The primary melanomas were located in the head/neck region (n = 32), the FGT (n = 24), and the anorectal region (n = 19).The median age of the patients was 66 years. At initial diagnosis the primary melanoma was not completely resectable in 11 (15%) patients, 18 (24%) patients had regional lymph node metastases, and 7 (9%) patients distant metastases. During follow-up, 22 (29%) patients suffered from a local recurrence, in particular patients with primary melanoma in the head/neck region without postoperative radiotherapy. By multivariate analysis location of the primary melanoma in the head/neck area or anorectal region and presence of metastases at time of diagnosis represented poor prognostic factors for recurrence-free survival. In 62 tested individuals 7 KIT mutations were found, 2 BRAF mutations in 57 tested patients. Four patients received targeted therapies, 14 checkpoint inhibitors, 4 (1/1 on vemurafenib, 1/7 on ipilimumab, and 2/7 on PD-1 inhibitors) patients showed responses of more than 100 days duration.Mucosal melanomas are often locally advanced or metastatic at initial diagnosis, thus they require extensive staging procedures. The high rate of local recurrences in the head/neck region can be significantly reduced by postoperative radiotherapy. For the potential use of medical treatment a mutation analysis for KIT and BRAF genes should be performed. The use of new immunologic and targeted therapies has to be further evaluated.

Physical and Chemical Stability of Budesonide Mucoadhesive Oral Suspensions (MucoLox).

PubMed

Ip, Kendice; Carvalho, Maria; Shan, Ashley; Banov, Daniel

2017-01-01

Budesonide is a corticosteroid that has been shown effective in the treatment of eosinophilic esophagitis, but there are currently no commercial medicines to treat this chronic allergic/immune condition, despite its prevalence in the U.S. Therefore, pharmaceutical compounding is the alternative choice to meet the therapeutic need of eosinophilic esophagitis patients. Two budesonide mucoadhesive oral suspensions (1 mg/10 mL and 2 mg/10 mL) were developed using the compounding vehicle MucoLox, a proprietary mucoadhesive polymer blend that promotes mucosal adhesion. The physical and chemical stability of the oral suspensions was tested over a period of 182 days, at room temperature and refrigerated conditions, in order to determine the corresponding beyond-use date. The physical characterization consisted in observing all samples for color/appearance and odor, and testing for pH and density, whereas the chemical characterization consisted in ultra-performance liquid chromatography assay testing. Both oral suspensions were proven physically and chemically stable, and the ultra-performance liquid chromatography method was proven stability indicating. As a result, the beyond-use date of the budesonide 1-mg/10-mL and 2-mg/10-mL mucoadhesive oral suspensions (MucoLox), in amber plastic bottles, is six months at both room temperature and refrigerated conditions. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

[Values of the micronucleus test on animal epithelial cells exposed to titanium dioxide].

PubMed

Iurchenko, V V; Krivtsova, E K; Iuretseva, N A; Tul'skaia, E A; Mamonov, R A; Zholdakova, Z I; Sinitsyna, O O; Mal'tseva, M M; Pankratova, G P; Sycheva, L P

2011-01-01

The genetic safety of titanium dioxide (TD)-containing foods and cosmetic products has been little investigated. The study evaluated the mutagenic activity of TD in the micronucleus test with animal visceral mucosal epithelial cells. Two simethicone-coated anatase samples (mean size 160 and 33.2 nm) were inserted into the mouse stomach in doses of 40-200-1000 mg/kg seven times and applied as an ingredient of 10 and 25% cream (doses 250 and 625 mg/kg, respectively) to the hair-sheared rat skin once for 4 hours. Analysis of cytogenetic disorders (micronuclei, protrusions, and the atypical form of the nucleus) revealed no mutagenic properties of TD on the mucosal epithelium of the mouse and rat intestine, mouse prostomach, and rat uterine bladder. Enhanced mitotic activity was observed in all the study tissues after exposure of both samples to TD given in some or in all (in the rat urinary bladder mucosal epithelium) doses.

Biologic assessment of antiseptic mouthwashes using a three-dimensional human oral mucosal model.

PubMed

Moharamzadeh, Keyvan; Franklin, Kirsty L; Brook, Ian M; van Noort, Richard

2009-05-01

The biologic safety profile of oral health care products is often assumed on the basis of simplistic test models such as monolayer cell culture systems. We developed and characterized a tissue-engineered human oral mucosal model, which was proven to represent a potentially more informative and more clinically relevant alternative for the biologic assessment of mouthwashes. The aim of this study was to evaluate the biologic effects of alcohol-containing mouthwashes on an engineered human oral mucosal model. Three-dimensional (3D) models were engineered by the air/liquid interface culture technique using human oral fibroblasts and keratinocytes. The models were exposed to phosphate buffered saline (negative control), triethylene glycol dimethacrylate (positive control), cola, and three types of alcohol-containing mouthwashes. The biologic response was recorded using basic histology; a cell proliferation assay; 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tissue-viability assay; transmission electron microscopy (TEM) analysis; and the measurement of release of interleukin (IL)-1beta by enzyme-linked immunosorbent assay. Statistical analysis showed that there was no significant difference in tissue viability among the mouthwashes, cola, and negative control groups. However, exposure to the positive control significantly reduced the tissue viability and caused severe cytotoxic epithelial damage as confirmed by histology and TEM analysis. A significant increase of IL-1beta release was observed with the positive control and, to a lesser extent, with two of the tested mouthrinses. The 3D human oral mucosal model can be a suitable model for the biologic testing of mouthwashes. The alcohol-containing mouthwashes tested in this study do not cause significant cytotoxic damage and may slightly stimulate IL-1beta release.

Effects of acute chemotherapy-induced mucositis on spontaneous behaviour and the grimace scale in laboratory rats.

PubMed

Whittaker, A L; Leach, M C; Preston, F L; Lymn, K A; Howarth, G S

2016-04-01

Intestinal mucositis is a frequent side-effect of chemotherapy treatment. Many oncological research programs aim to identify novel treatments for this distressing condition, and these programs frequently use rat models. Little is known about the presence and progression of pain in these models and how this can best be treated by analgesic therapy. We used a number of behaviour-based methods of pain assessment to determine which tools were best suited for pain identification. Baseline measures for behavioural assessment, rat grimace score and sociability were determined through analysis of continuously recorded video data and an applied social interaction test (n = 16). Mucositis was then induced by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and further behavioural analyses undertaken. An assessment of enrichment interaction was also made by determining the mass of a plastic chew toy gnawed both pre- and post-chemotherapy injection. Behavioural scoring was performed 1, 6, 12, 24 and 48 h after injection, with facial expression being scored at the 12, 24 and 48 h time-points. Sociability testing was performed once during the post-injection period. No significant differences were found in grimace scores between baseline and later daily measures. Behaviours similar to those previously reported post-laparotomy were observed. Writhing, twitching and back-arching behaviours were most evident in rats affected by mucositis and were increased in frequency (respective P values: 0.002, 0.004 and 0.008) 48 h after chemotherapy injection compared with baseline, implying that pain onset occurred around this time-point. Social investigatory behaviour was also increased (P = 0.002) following disease onset. Each day, rats post-5FU injection gnawed a greater percentage of their Nylabone enrichment by weight than the saline-injected control rats (P = 0.046). These data suggest that, of the tools tested, behavioural assessment scoring may find greatest utility in rodent models of intestinal mucositis and should be investigated further. © The Author(s) 2015.

Recent advances in diagnostic testing for gastroesophageal reflux disease.

PubMed

Naik, Rishi D; Vaezi, Michael F

2017-06-01

Gastroesophageal reflux disease (GERD) has a large economic burden with important complications that include esophagitis, Barrett's esophagus, and adenocarcinoma. Despite endoscopy, validated patient questionnaires, and traditional ambulatory pH monitoring, the diagnosis of GERD continues to be challenging. Areas covered: This review will explore the difficulties in diagnosing GERD with a focus on new developments, ranging from basic fundamental changes (histology and immunohistochemistry) to direct patient care (narrow-band imaging, impedance, and response to anti-reflux surgery). We searched PubMed using the noted keywords. We included data from full-text articles published in English. Further relevant articles were identified from the reference lists of review articles. Expert commentary: Important advances in novel parameters in intraluminal impedance monitoring such as baseline impedance monitoring has created some insight into alternative diagnostic strategies in GERD. Recent advances in endoscopic assessment of esophageal epithelial integrity via mucosal impedance measurement is questioning the paradigm of prolonged ambulatory testing for GERD. The future of reflux diagnosis may very well be without the need for currently employed technologies and could be as simple as assessing changes in epithelia integrity as a surrogate marker for GERD. However, future studies must validate such an approach.

Aspirin can elicit the recurrence of gastric ulcer induced with acetic acid in rats.

PubMed

Wang, Guo-Zhong; Huang, Guo-Ping; Yin, Guo-Li; Zhou, Gang; Guo, Chun-Juan; Xie, Chun-Gang; Jia, Bing-Bing; Wang, Jin-Fu

2007-01-01

This study was supported by grants of New Ideas Capability for Backbone Teachers in Universities of Heilongjiang and of Scientific Research foundation in Qiqihar Medical College. Ulcer recurrence and poor healing may be critically important to the development of serious gastrointestinal complications in patients with long-term non-steroid anti-inflammatory drugs (NSAIDs). The present study is to investigate the effects of aspirin on ulcer recurrence and healing quality and to explore the mechanism. Gastric ulcers were induced with acetic acid in rats; aspirin was administrated by gavage from day 25 to day 54 after ulcer induction. The gastric juice volume, pH, gastric mucus, gastric mucosal blood flow (GMBF) and prostaglandin E(2) (PGE(2)) were measured. The mRNA transcription of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were analyzed with RT-PCR and protein expression with Western blot. The gastric juice volume was significantly increased in aspirin group compared with those of fasting or saline control groups (P<0.01); while the pH, mucus, GMBF and PGE(2) were significantly decreased in aspirin treated rats compared with those of other two groups (P<0.01). COX-2, evaluated with mRNA and protein expression, was significantly augmented in aspirin group compared with others. The quality of ulcer healing (QOUH) in Aspirin group was poorer than that of fasting or saline control groups. Aspirin enhance the recurrence of gastric ulcer. The inhibition of cycloxygenase, mucus secretion and mucosal blood flow may be involved. Aspirin also impair the quality of ulcer healing.

Nystatin and lidocaine pastilles for the local treatment of oral mucositis.

PubMed

Silva, Filipa Cosme; Marto, Joana M; Salgado, Ana; Machado, Paula; Silva, Alexandra N; Almeida, António J

2017-03-01

Oral mucositis (OM) is a common adverse reaction to radiotherapy and chemotherapy in oncology. Its treatment requires oral formulations that enhance therapy compliance, improve administration and ensure drug effectiveness. Solid dosage forms that act by slow dissolution, such as pastilles, are an effective alternative to mouthwashes, for their versatility, ease of administration and extended residence time in the oral cavity. The present work describes the development and stability studies of an innovative formulation of nystatin and lidocaine pastilles for the treatment of oral mucositis. Full pharmaceutical quality testing was carried out, including disintegration and dissolution testing, texture profile analysis, grittiness and an antifungal activity testing. A soft pastille formulation containing 0.25% lidocaine and 78,000 IU nystatin was obtained, presenting suitable pharmaceutical characteristics, as a disintegration time of 17 ± 2 min, dissolution rate and microbiological and physicochemical for 30 days when stored at 2-8 °C under light protection. Palatability was also evaluated, being well accepted by a panel of 38 healthy volunteers. This formulation allows an accurate drug dosing by the prescriber, while enabling the patients to control the retention time of the drugs in the oral cavity and consequently manage their pain treatment.

Dietary gluten alters the balance of pro-inflammatory and anti-inflammatory cytokines in T cells of BALB/c mice

PubMed Central

Antvorskov, Julie C; Fundova, Petra; Buschard, Karsten; Funda, David P

2013-01-01

Several studies have documented that dietary modifications influence the development of type 1 diabetes. However, little is known about the interplay of dietary components and the penetration of diabetes incidence. In this study we tested if wheat gluten is able to induce differences in the cytokine pattern of Foxp3+ regulatory T cells, as well as Foxp3− T cells, isolated from intestinal mucosal lymphoid tissue and non-mucosal lymphoid compartments in BALB/c mice. The gluten-containing standard diet markedly changed the cytokine expression within Foxp3− T cells, in all lymphoid organs tested, towards a higher expression of pro-inflammatory interferon-γ (IFN-γ), interleukin-17 (IL-17) and IL-2. In Foxp3+ regulatory T cells, gluten ingestion resulted in a mucosal increase in IL-17 and IL-2 and an overall increase in IFN-γ and IL-4. The gluten-free diet induced an anti-inflammatory cytokine profile with higher proportion of transforming growth factor-β (TGF-β)+ Foxp3− T cells in all tested lymphoid tissues and higher IL-10 expression within non-T cells in spleen, and a tendency towards a mucosal increase in TGF-β+ Foxp3+ regulatory T cells. Our data shows that the gluten-containing standard diet modifies the cytokine pattern of both Foxp3− T cells and Foxp3+ regulatory T cells towards a more inflammatory cytokine profile. This immune profile may contribute to the higher type 1 diabetes incidence associated with gluten intake. PMID:22913724

Esophageal Epithelial Resistance and Lower Esophageal Sphincter Muscle Contraction Increase in a Chronic Diabetic Rabbit Model.

PubMed

Capanoglu, Doga; Coskunsever, Deniz; Olukman, Murat; Ülker, Sibel; Bor, Serhat

2016-07-01

Esophageal motility disorders and possibly gastroesophageal reflux disease are common in patients with diabetes mellitus. We aimed to investigate both the electrophysiological characteristics of the esophageal epithelium and the contractility of the lower esophageal sphincter (LES) muscle in alloxane-induced diabetic rabbits. Electrophysiological properties were measured using an Ussing chamber method. An acid-pepsin model was employed with pH 1.7 or weakly acidic (pH 4) Ringer and/or pepsin. Smooth muscle strips of the LES were mounted in an isolated organ bath. Contractile responses to an electrical field stimulation and cumulative concentrations of acetylcholine were recorded. Contractility of the muscle strips were tested in the presence of Rho-kinase inhibitor (Y-27632) and nonspecific nitric oxide inhibitor (L-NAME). The resistance of diabetic tissue perfused in the pH 1.7 Ringer decreased 17 %; pepsin addition decreased it by 49 %. The same concentrations caused a more distinct loss of resistance in the control tissues (22 and 76 %, p < 0.05). The perfusion of tissues in increased concentrations of luminal and serosal glucose did not change the tissue resistance and voltage. Diabetes significantly increased both the electrical field stimulation and acetylcholine-induced contractions in the LES muscle strips (p < 0.01). Incubation with Y-27632 significantly decreased the acetylcholine-induced contractions in a concentration-dependent manner (p < 0.01). The acid-pepsin model in the diabetic rabbit esophageal tissue had less injury compared with the control. The diabetic rabbit LES muscle had higher contractility, possibly because of the activation of the Rho-Rhokinase pathway. Our results show that in a chronic diabetic rabbit model the esophagus resists reflux by activating mechanisms of mucosal defense and increasing the contractility of the LES.

Gram stain of skin lesion

MedlinePlus

... during the procedure. Considerations A skin or mucosal culture may be done along with this test. Other ... are examined by other tests or a viral culture. Alternative Names Skin lesion gram stain Images Viral ...

Roles of calcitonin gene-related peptide in maintenance of gastric mucosal integrity and in enhancement of ulcer healing and angiogenesis.

PubMed

Ohno, Takashi; Hattori, Youichiro; Komine, Rie; Ae, Takako; Mizuguchi, Sumito; Arai, Katsuharu; Saeki, Takeo; Suzuki, Tatsunori; Hosono, Kanako; Hayashi, Izumi; Oh-Hashi, Yoshio; Kurihara, Yukiko; Kurihara, Hiroki; Amagase, Kikuko; Okabe, Susumu; Saigenji, Katsunori; Majima, Masataka

2008-01-01

The gastrointestinal tract is known to be rich in neural systems, among which afferent neurons are reported to exhibit protective actions. We tested whether an endogenous neuropeptide, calcitonin gene-related peptide (CGRP), can prevent gastric mucosal injury elicited by ethanol and enhance healing of acetic acid-induced ulcer using CGRP knockout mice (CGRP(-/-)). The stomach was perfused with 1.6 mmol/L capsaicin or 1 mol/L NaCl, and gastric mucosal injury elicited by 50% ethanol was estimated. Levels of CGRP in the perfusate were determined by enzyme immunoassay. Gastric ulcers were induced by serosal application of absolute acetic acid. Capsaicin inhibited injured area dose-dependently. Fifty percent ethanol containing capsaicin immediately increased intragastric levels of CGRP in wild-type (WT) mice, although 50% ethanol alone did not. The protective action of capsaicin against ethanol was completely abolished in CGRP(-/-). Preperfusion with 1 mol/L NaCl increased CGRP release and reduced mucosal damage during ethanol perfusion. However, 1 mol/L NaCl was not effective in CGRP(-/-). Healing of ulcer elicited by acetic acid in CGRP(-/-) mice was markedly delayed, compared with that in WT. In WT, granulation tissues were formed at the base of ulcers, and substantial neovascularization was induced, whereas those were poor in CGRP(-/-). Expression of vascular endothelial growth factor was more markedly reduced in CGRP(-/-) than in WT. CGRP has a preventive action on gastric mucosal injury and a proangiogenic activity to enhance ulcer healing. These results indicate that the CGRP-dependent pathway is a good target for regulating gastric mucosal protection and maintaining gastric mucosal integrity.

Effects of corn oil administered orally on conspicuity of ultrasonographic small intestinal lesions in dogs with lymphangiectasia.

PubMed

Pollard, Rachel E; Johnson, Eric G; Pesavento, Patricia A; Baker, Tomas W; Cannon, Allison B; Kass, Philip H; Marks, Stanley L

2013-01-01

Lymphangiectasia is one of the causes of protein-losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full-thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P < 0.05) and were best identified in dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal. © 2013 Veterinary Radiology & Ultrasound.

Important role of mucosal serotonin in colonic propulsion and peristaltic reflexes: in vitro analyses in mice lacking tryptophan hydroxylase 1

PubMed Central

Heredia, Dante J; Gershon, Michael D; Koh, Sang Don; Corrigan, Robert D; Okamoto, Takanubu; Smith, Terence K

2013-01-01

Although there is general agreement that mucosal 5-hydroxytryptamine (5-HT) can initiate peristaltic reflexes in the colon, recent studies have differed as to whether or not the role of mucosal 5-HT is critical. We therefore tested the hypothesis that the secretion of 5-HT from mucosal enterochromaffin (EC) cells is essential for the manifestation of murine colonic peristaltic reflexes. To do so, we analysed the mechanisms underlying faecal pellet propulsion in isolated colons of mice lacking tryptophan hydroxylase 1 (Tph1−/− mice), which is the rate-limiting enzyme in the biosynthesis of mucosal but not neuronal 5-HT. We used video analysis of faecal pellet propulsion, tension transducers to record colonic migrating motor complexes (CMMCs) and intracellular microelectrodes to record circular muscle activity occurring spontaneously or following intraluminal distension. When compared with control (Tph1+/+) mice, Tph1−/− animals exhibited: (1) an elongated colon; (2) larger faecal pellets; (3) orthograde propulsion followed by retropulsion (not observed in Tph1+/+ colon); (4) slower in vitro propulsion of larger faecal pellets (28% of Tph1+/+); (5) CMMCs that infrequently propagated in an oral to anal direction because of impaired descending inhibition; (6) reduced CMMCs and inhibitory responses to intraluminal balloon distension; (7) an absence of reflex activity in response to mucosal stimulation. In addition, (8) thin pellets that propagated along the control colon failed to do so in Tph1−/− colon; and (9) the 5-HT3 receptor antagonist ondansetron, which reduced CMMCs and blocked their propagation in Tph1+/+ mice, failed to alter CMMCs in Tph1−/− animals. Our observations suggest that mucosal 5-HT is essential for reflexes driven by mucosal stimulation and is also important for normal propagation of CMMCs and propulsion of pellets in the isolated colon. PMID:24127620

Effects of dexpanthenol with or without Aloe vera extract on radiation-induced oral mucositis: preclinical studies.

PubMed

Dörr, W; Schlichting, S; Bray, M A; Flockhart, I R; Hopewell, J W

2005-03-01

To define the effect of dexpanthenol with or without Aloe vera extract on radiation-induced oral mucositis. Mouse tongue mucosal ulceration was analysed as the clinically relevant endpoint. Graded single or fractionated dose irradiation (10 x 3 Gy/2 weeks, graded test doses on day 14) were combined with topical administration of dexpanthenol or a base, with or without Aloe vera extract. The formulations were applied for 14 days (single dose) or 24 days after the first fraction. Single dose irradiation resulted in an ED50 (dose at which a positive mucosal response was expected in 50% of the animals irradiated) of 11.9+/-1.2 Gy. None of the formulations yielded a significant change in incidence or time course of ulceration. Test irradiation after 10 x 3 Gy gave an ED50 of 9.0+/-0.1 Gy. Base treatment increased the ED50-values to 10.5+/-0.8 Gy (p = 0.0095) and 9.9+/-0.7 Gy (p = 0.0445) without or with Aloe vera. Dexpanthenol resulted in ED50 values of 9.5+/-0.1 Gy without Aloe vera (p > 0.05), and of 10.9+/-0.9 Gy (p = 0.0035) with Aloe vera. The latent time to ulceration was prolonged, compared to the control (6.3 days) without Aloe vera (8.0-8.2 days, p < 0.001) and with dexpanthenol and Aloe vera (7.3 days, p = 0.0239). With single dose irradiation, neither dexpanthenol nor Aloe vera extract significantly changed the oral mucosal radiation response. With fractionated irradiation, drug administration significantly increased the isoeffective radiation doses, independent of dexpanthenol or Aloe vera content. Neither dexpanthenol nor Aloe vera display a prophylactic potential.

Effect of topical chamomile on immunohistochemical levels of IL-1β and TNF-α in 5-fluorouracil-induced oral mucositis in hamsters.

PubMed

Curra, Marina; Martins, Marco Antonio T; Lauxen, Isabel S; Pellicioli, Ana Carolina A; Sant'Ana Filho, Manoel; Pavesi, Vanessa Christina S; Carrard, Vinicius C; Martins, Manoela D

2013-02-01

The aim of the present study was to evaluate the effect of topical chamomile and corticosteroid treatment on the profile of tissue cytokines (IL-1β and TNF-α) in 5-fluorouracil-induced oral mucositis in hamsters. Thirty-six hamsters were randomly separated into three groups (12 animals each): Group I--without treatment (control); Group II-treatment with chamomile (Ad-Muc(®)); and Group III--treatment with corticosteroid (betamethasone elixir- Celestone(®)). The animals received an intraperitoneal injection of 5--fluorouracil on Days 0 and 2. On Days 3 and 4, the buccal mucosa was scratched and therapy was initiated on Day 5. Three animals from each group were killed on Days 0, 5, 10, and 14 and the buccal mucosa was removed. The streptavidin-biotin complex method was used to delineate the in situ distribution, localization, and semiquantitative analysis of IL-1β and TNF-α. Data from the semiquantitative analysis of immunohistochemical staining were comparatively analyzed using the Kruskal-Wallis test, followed by Dunn's multiple comparisons test. The distribution and localization of IL-1β and TNF-α immunolabeling were similar. These proteins exhibited a diffuse pattern distributed throughout the connective tissue. The epithelium and adipose tissue were negative for both proteins. The semiquantitative analysis revealed that immunolabeling of IL-1β and TNF-α increased in all groups with the development of mucositis. On Day 10 (period of peak mucositis), the group treated with chamomile had lower scores for both pro-inflammatory cytokines. Treatment with topical chamomile reduced the tissue levels of IL-1β and TNF-α, thereby demonstrating anti-inflammatory action in oral mucositis in hamsters.

Effects of internal and external pH on amiloride-blockable Na transport across toad urinary bladder vesicles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garty, H.; Civan, E.D.; Civan, M.M.

1985-01-01

The authors have examined the effect of internal and external pH on Na+ transport across toad bladder membrane vesicles. Of the total SSNa uptake measured 0.5-2.0 min after introducing tracer, 80 +/- 4% (mean +/- SE, n = 9) is blocked by the diuretic with a KI of 2 X 10(-8) M. Thus, this amiloride-sensitive flux is mediated by the apical sodium-selective channels. Varying the internal (cytosolic) pH over the physiologic range 7.0-8.0 had no effect on sodium transport; this result suggests that variation of intracellular pH in vivo has no direct apical effect on modulating sodium uptake. On themore » other hand, SSNa was directly and monotonically dependent on external pH. External acidification also reduced the amiloride-sensitive efflux across the walls of the vesicles. This inhibition of 22Na efflux was noted at external Na concentrations of both 0.2 microM and 53 mM. These results are different from those reported with whole toad bladder. A number of possible bases for these differences are considered and discussed. They suggest that the natriferic response induced by mucosal acidification of whole toad urinary bladder appears to operate indirectly through one or more factors, presumably cytosolic, present in whole cells and absent from the vesicles.« less

Molecular Characteristics of High-Dose Melphalan Associated Oral Mucositis in Patients with Multiple Myeloma: A Gene Expression Study on Human Mucosa

PubMed Central

Bødker, Julie Støve; Christensen, Heidi Søgaard; Johansen, Preben; Nielsen, Søren; Christiansen, Ilse; Bergmann, Olav Jonas; Bøgsted, Martin; Dybkær, Karen; Vyberg, Mogens; Johnsen, Hans Erik

2017-01-01

Background Toxicity of the oral and gastrointestinal mucosa induced by high-dose melphalan is a clinical challenge with no documented prophylactic interventions or predictive tests. The aim of this study was to describe molecular changes in human oral mucosa and to identify biomarkers correlated with the grade of clinical mucositis. Methods and Findings Ten patients with multiple myeloma (MM) were included. For each patient, we acquired three buccal biopsies, one before, one at 2 days, and one at 20 days after high-dose melphalan administration. We also acquired buccal biopsies from 10 healthy individuals that served as controls. We analyzed the biopsies for global gene expression and performed an immunohistochemical analysis to determine HLA-DRB5 expression. We evaluated associations between clinical mucositis and gene expression profiles. Compared to gene expression levels before and 20 days after therapy, at two days after melphalan treatment, we found gene regulation in the p53 and TNF pathways (MDM2, INPPD5, TIGAR), which favored anti-apoptotic defense, and upregulation of immunoregulatory genes (TREM2, LAMP3) in mucosal dendritic cells. This upregulation was independent of clinical mucositis. HLA-DRB1 and HLA-DRB5 (surface receptors on dendritic cells) were expressed at low levels in all patients with MM, in the subgroup of patients with ulcerative mucositis (UM), and in controls; in contrast, the subgroup with low-grade mucositis (NM) displayed 5–6 fold increases in HLA-DRB1 and HLA-DRB5 expression in the first two biopsies, independent of melphalan treatment. Moreover, different splice variants of HLA-DRB1 were expressed in the UM and NM subgroups. Conclusions Our results revealed that, among patients with MM, immunoregulatory genes and genes involved in defense against apoptosis were affected immediately after melphalan administration, independent of the presence of clinical mucositis. Furthermore, our results suggested that the expression levels of HLA-DRB1 and HLA-DRB5 may serve as potential predictive biomarkers for mucositis severity. PMID:28052121

Cryopreservation of Human Mucosal Leukocytes.

PubMed

Hughes, Sean M; Shu, Zhiquan; Levy, Claire N; Ferre, April L; Hartig, Heather; Fang, Cifeng; Lentz, Gretchen; Fialkow, Michael; Kirby, Anna C; Adams Waldorf, Kristina M; Veazey, Ronald S; Germann, Anja; von Briesen, Hagen; McElrath, M Juliana; Dezzutti, Charlene S; Sinclair, Elizabeth; Baker, Chris A R; Shacklett, Barbara L; Gao, Dayong; Hladik, Florian

2016-01-01

Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible. To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10-15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension. Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes.

Increased proximal reflux in a hypersensitive esophagus might explain symptoms resistant to proton pump inhibitors in patients with gastroesophageal reflux disease.

PubMed

Rohof, Wout O; Bennink, Roelof J; de Jonge, Hugo; Boeckxstaens, Guy E

2014-10-01

Approximately 30% of patients with gastroesophageal reflux disease have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability, and possibly the position of the gastric acid pocket might underlie a partial response to PPIs. To what extent these mechanisms interact and contribute to PPI-resistant symptoms, however, has not been investigated previously. In 18 gastroesophageal reflux disease patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability, and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the lower esophageal sphincter. The mucosal permeability of 4 esophageal biopsy specimens per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH impedance after a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs PPI partial responders 4.2 ± 0.4; P = .54), or in the position of the acid pocket was observed in PPI partial responders compared with PPI responders. In addition, the permeability of the esophageal mucosa was similar in both groups, as shown by a similar transepithelial electrical resistance and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent, compared with PPI responders, and were more sensitive to balloon distension, both in the upper and lower esophagus. PPI-resistant symptoms most likely are explained by increased proximal reflux in a hypersensitive esophagus and less likely by increased mucosal permeability or the position of the acid pocket. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Artemisia supplementation differentially affects the mucosal and luminal ileal microbiota of diet-induced obese mice

PubMed Central

Shawna, Wicks; M., Taylor Christopher; Meng, Luo; Eugene, Blanchard IV; David, Ribnicky; T., Cefalu William; L., Mynatt Randall; A., Welsh David

2014-01-01

Objective The gut microbiome has been implicated in obesity and metabolic syndrome; however, most studies have focused on fecal or colonic samples. Several species of Artemisia have been reported to ameliorate insulin signaling both in vitro and in vivo. The aim of this study was to characterize the mucosal and luminal bacterial populations in the terminal ileum with or without supplementation with Artemisia extracts. Materials/Methods Following 4 weeks of supplementation with different Artemisia extracts (PMI 5011, Santa or Scopa), diet-induced obese mice were sacrificed and luminal and mucosal samples of terminal ileum were used to evaluate microbial community composition by pyrosequencing of 16S rDNA hypervariable regions. Results Significant differences in community structure and membership were observed between luminal and mucosal samples, irrespective of diet group. All Artemisia extracts increased the Bacteroidetes:Firmicutes ratio in mucosal samples. This effect was not observed in the luminal compartment. There was high inter-individual variability in the phylogenetic assessments of the ileal microbiota, limiting the statistical power of this pilot investigation. Conclusions Marked differences in bacterial communities exist dependent upon the biogeographic compartment in the terminal ileum. Future studies testing the effects of Artemisia or other botanical supplements require larger sample sizes for adequate statistical power. PMID:24985102

Treatment-induced mucositis: an old problem with new remedies.

PubMed

Symonds, R P

1998-05-01

Mucositis may be a painful, debilitating, dose-limiting side-effect of both chemotherapy and radiotherapy for which there is no widely accepted prophylaxis or effective treatment. The basis of management is pain relief, prevention of dehydration and adequate nutrition. When tested vigorously, most antiseptic mouthwashes and anti-ulcer agents are ineffective. Simple mechanical cleansing by saline is the most effective traditional measure. A variety of new agents are effective. Granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) act outwith the haemopoeitic system and can reduce mucositis, but the best schedule, dosage and method of administration is not known or which is the best growth factor to prevent this side-effect. A placebo-controlled randomized trial of antibiotic pastilles has shown a significant reduction in mucositis and weight loss during radiotherapy for head and neck cancer. Another method to reduce radiation effects in normal tissue is to stimulate cells to divide before radiotherapy by silver nitrate or interleukin 1. These methods may be particularly effective when given along with hyperfractionated radiation treatment such as CHART.

Gastrointestinal cell lines form polarized epithelia with an adherent mucus layer when cultured in semi-wet interfaces with mechanical stimulation.

PubMed

Navabi, Nazanin; McGuckin, Michael A; Lindén, Sara K

2013-01-01

Mucin glycoproteins are secreted in large quantities by mucosal epithelia and cell surface mucins are a prominent feature of the glycocalyx of all mucosal epithelia. Currently, studies investigating the gastrointestinal mucosal barrier use either animal experiments or non-in vivo like cell cultures. Many pathogens cause different pathology in mice compared to humans and the in vitro cell cultures used are suboptimal because they are very different from an in vivo mucosal surface, are often not polarized, lack important components of the glycocalyx, and often lack the mucus layer. Although gastrointestinal cell lines exist that produce mucins or polarize, human cell line models that reproducibly create the combination of a polarized epithelial cell layer, functional tight junctions and an adherent mucus layer have been missing until now. We trialed a range of treatments to induce polarization, 3D-organization, tight junctions, mucin production, mucus secretion, and formation of an adherent mucus layer that can be carried out using standard equipment. These treatments were tested on cell lines of intestinal (Caco-2, LS513, HT29, T84, LS174T, HT29 MTX-P8 and HT29 MTX-E12) and gastric (MKN7, MKN45, AGS, NCI-N87 and its hTERT Clone5 and Clone6) origins using Ussing chamber methodology and (immuno)histology. Semi-wet interface culture in combination with mechanical stimulation and DAPT caused HT29 MTX-P8, HT29 MTX-E12 and LS513 cells to polarize, form functional tight junctions, a three-dimensional architecture resembling colonic crypts, and produce an adherent mucus layer. Caco-2 and T84 cells also polarized, formed functional tight junctions and produced a thin adherent mucus layer after this treatment, but with less consistency. In conclusion, culture methods affect cell lines differently, and testing a matrix of methods vs. cell lines may be important to develop better in vitro models. The methods developed herein create in vitro mucosal surfaces suitable for studies of host-pathogen interactions at the mucosal surface.

Gastrointestinal Cell Lines Form Polarized Epithelia with an Adherent Mucus Layer when Cultured in Semi-Wet Interfaces with Mechanical Stimulation

PubMed Central

Navabi, Nazanin; McGuckin, Michael A.; Lindén, Sara K.

2013-01-01

Mucin glycoproteins are secreted in large quantities by mucosal epithelia and cell surface mucins are a prominent feature of the glycocalyx of all mucosal epithelia. Currently, studies investigating the gastrointestinal mucosal barrier use either animal experiments or non-in vivo like cell cultures. Many pathogens cause different pathology in mice compared to humans and the in vitro cell cultures used are suboptimal because they are very different from an in vivo mucosal surface, are often not polarized, lack important components of the glycocalyx, and often lack the mucus layer. Although gastrointestinal cell lines exist that produce mucins or polarize, human cell line models that reproducibly create the combination of a polarized epithelial cell layer, functional tight junctions and an adherent mucus layer have been missing until now. We trialed a range of treatments to induce polarization, 3D-organization, tight junctions, mucin production, mucus secretion, and formation of an adherent mucus layer that can be carried out using standard equipment. These treatments were tested on cell lines of intestinal (Caco-2, LS513, HT29, T84, LS174T, HT29 MTX-P8 and HT29 MTX-E12) and gastric (MKN7, MKN45, AGS, NCI-N87 and its hTERT Clone5 and Clone6) origins using Ussing chamber methodology and (immuno)histology. Semi-wet interface culture in combination with mechanical stimulation and DAPT caused HT29 MTX-P8, HT29 MTX-E12 and LS513 cells to polarize, form functional tight junctions, a three-dimensional architecture resembling colonic crypts, and produce an adherent mucus layer. Caco-2 and T84 cells also polarized, formed functional tight junctions and produced a thin adherent mucus layer after this treatment, but with less consistency. In conclusion, culture methods affect cell lines differently, and testing a matrix of methods vs. cell lines may be important to develop better in vitro models. The methods developed herein create in vitro mucosal surfaces suitable for studies of host-pathogen interactions at the mucosal surface. PMID:23869232

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome

PubMed Central

Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong

2015-01-01

Aim: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. Methods: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g·kg−1·d−1, ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4+ and CD8+ cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. Results: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4+/CD8+ cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4+/CD8+ cell ratio and expression of IL-1β and IL-4. Conclusion: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects. PMID:25960135

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome.

PubMed

Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong

2015-06-01

The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1β and IL-4. Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

Evaluation of formalin-inactivated Clostridium difficile vaccines administered by parenteral and mucosal routes of immunization in hamsters.

PubMed Central

Torres, J F; Lyerly, D M; Hill, J E; Monath, T P

1995-01-01

Clostridium difficile produces toxins that cause inflammation, necrosis, and fluid in the intestine and is the most important cause of nosocomial antibiotic-associated diarrhea and colitis. We evaluated C. difficile antigens as vaccines to protect against systemic and intestinal disease in a hamster model of clindamycin colitis. Formalin-inactivated culture filtrates from a highly toxigenic strain were administered by mucosal routes (intranasal, intragastric, and rectal) with cholera toxin as a mucosal adjuvant. A preparation of culture filtrate and killed whole cells was also tested rectally. The toxoid was also tested parenterally (subcutaneously and intraperitoneally) and by a combination of three intranasal immunizations followed by a combined intranasal-intraperitoneal boost. Serum antibodies against toxins A and B and whole-cell antigen were measured by enzyme-linked immunosorbent assay, neutralization of cytotoxic activity, and bacterial agglutination. The two rectal immunization regimens induced low antibody responses and protected only 20% of hamsters against death and 0% against diarrhea. The intragastric regimen induced high antibody responses but low protection, 40% against death and 0% against diarrhea. Hamsters immunized by the intranasal, intraperitoneal, and subcutaneous routes were 100% protected against death and partially protected (40, 40, and 20%, respectively) against diarrhea. Among the latter groups, intraperitoneally immunized animals had the highest serum anticytotoxic activity and the highest agglutinating antibody responses. Hamsters immunized intranasally and revaccinated intraperitoneally were 100% protected against both death and diarrhea. Protection against death and diarrhea correlated with antibody responses to all antigens tested. The results indicate that optimal protection against C. difficile disease can be achieved with combined parenteral and mucosal immunization. PMID:7591115

GC-MS Analysis and Gastroprotective Evaluations of Crude Extracts, Isolated Saponins, and Essential Oil from Polygonum hydropiper L.

PubMed Central

Ayaz, Muhammad; Junaid, Muhammad; Ullah, Farhat; Sadiq, Abdul; Shahid, Muhammad; Ahmad, Waqar; Ullah, Ihsan; Ahmad, Ashfaq; Syed, Nawazish-i-Husain

2017-01-01

Peptic ulceration is among the most prevalent gastrointestinal disorders characterized by pepsin and gastric acid mediated mucosal damage, as result of imbalance between defensive and offensive processes. The main objective of the current study was to investigate the antiulcer potentials of Polygonum hydropiper crude methanolic ectract (Ph.Cr) in aspirin induced ulcerogenesis using pylorus ligated rat model. In-vitro urease and Proteus mirabilis inhibitory potentials were evaluated using standard protocols. All fractions were analyzed using GC-MS to identify major components. The aspirin induced ulcerogenesis in pylorus ligated rat model was associated with significant changes in the mean ulcer score [F(5, 30) = 7.141, P = 0.0002], gastric juice volume [F(5, 30) = 8.245, P < 0.0001], gastric juice pH [F(5, 30) = 5.715, P = 0.0008], free acidity [F(5, 30) = 4.544, P = 0.0033], total acidity [F(5, 30) = 2.740, P = 0.0373], and pepsin concentration [F(5, 30) = 2.335, P = 0.0664]. Pre-treatment with Ph.Cr at 100, 200, and 400 mg/kg dose exhibited marked gastroprotective and anti-ulcerogenic effect in the aspirin induced pyloric ligation ulcerogenesis model at 100, 200, and 400 mg/kg as indicated by ulcerative biochemical parameters. In urease inhibition assay, leaves essential oil (Ph.Lo), saponins (Ph.Sp), and chloroform extract (Ph.Chf) exhibited highest activities with IC50 of 90, 98, and 520 μg/ml, respectively. Ph.Sp, Ph.Chf, ethyl acetate (Ph.EtAc), and Ph.Cr showed MICs of 25, 30, 32.25, and 40.50 μg/ml, respectively against P. mirabilis. Several compounds were identified in GC-MS analysis of samples. Significant in-vivo antiulcer, urease inhibitory as well as anti-proteus potentials of P. hydropiper solvent extracts, signify its potential use for the management of peptic ulcers and may provide scientific bases for the traditional uses of the plant. PMID:28824906

GC-MS analysis and gastroprotective evaluations of crude extracts, isolated saponins and essential oil from Polygonum hydropiper L.

NASA Astrophysics Data System (ADS)

Ayaz, Muhammad; Junaid, Muhammad; Ullah, Farhat; Sadiq, Abdul; Shahid, Muhammad; Ahmad, Waqar; Ullah, Ihsan; Ahmad, Ashfaq; Syed, Nawazish-i.-Husain

2017-08-01

Peptic ulceration is among the most prevalent gastrointestinal disorders characterized by pepsin and gastric acid mediated mucosal damage, as result of imbalance between defensive and offensive processes. The main objective of the current study was to investigate the antiulcer potentials of Polygonum hydropiper crude methanolic ectract (Ph.Cr) in aspirin induced ulcerogenesis using pylorus ligated rat model. In-vitro urease and Proteus mirabilis inhibitory potentials were evaluated using standard protocols. All fractions were analyzed using GC-MS to identify major components. The aspirin induced ulcerogenesis in pylorus ligated rat model was associated with significant changes in the mean ulcer score (F5,30 = 7.141, P = 0.0002), gastric juice volume (F5,30 = 8.245, P < 0.0001), gastric juice pH (F5,30 = 5.715, P = 0.0008), free acidity (F5,30 = 4.544, P = 0.0033), total acidity (F5,30 = 2.740, P = 0.0373) and pepsin concentration (F5,30 = 2.335, P = 0.0664). Pre treatment with Ph.Cr at 100, 200 and 400 mg/kg dose exhibited marked gastroprotective and anti-ulcerogenic effect in the aspirin induced pyloric ligation ulcerogenesis model at 100, 200 and 400 mg/kg as indicated by ulcerative biochemical parameters. In urease inhibition assay, leaves essential oil (Ph.Lo), saponins (Ph.Sp) and chloroform extract (Ph.Chf) exhibited highest activities with IC50 of 90, 98 and 520 µg/ml respectively. Ph.Sp, Ph.Chf, ethyl acetate (Ph.EtAc) and Ph.Cr showed MICs of 25, 30, 32.25 and 40.50 µg/ml respectively against Proteus mirabilis. Several compounds were identified in GC-MS analysis of samples. Significant in-vivo antiulcer, urease inhibitory as well as anti-proteus potentials of P. hydropiper solvent extracts, signify its potential use for the management of peptic ulcers and may provide scientific bases for the traditional uses of the plant.

Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis.

PubMed

Battaglia, Alex; Nguyen, Thanh

2017-12-01

The aim of this study was to test the hypothesis that tincture of benzoin (TOB) facilitates immediate transmucosal nicotine absorption while simultaneously promoting a safe and sustained delivery of the nicotine. In combination with TOB, nicotine toxicity and diffusion across human mucosal cells were measured using a 3-D human mucosal tissue model. Nicotine was delivered 2.1 times more quickly in combination with TOB than in combination with saline (p < 0.05). Despite the increased diffusion, nicotine in combination with TOB significantly increased mucosal cell survival (p < 0.05) by reducing the release of mitochondrial cytochrome c into the cytoplasm when compared with nicotine without TOB. The average percentage distribution of cytochrome c in the cytosolic fraction over time of nicotine + 79% ethyl alcohol (ETOH) versus nicotine plus TOB (79% ETOH) was significantly different over 120 min (60.0 ± 29.9% cytosol, 16.1 ± 9.4% cytosol, p = 0.03). Related to the reduction of cytochrome c release into the cytoplasm, TOB suppressed caspase-3 and -9 activity, thereby preventing intrinsic apoptosis and providing cytoprotection of the mucosal cells (ETOH + nicotine vs ETOH + nicotine + TOB: p = 0.008 for caspase 3, p < 0.001 for caspase 9). Two hours of TOB (17-24% benzoin, 79% ETOH) plus nicotine promotes diffusion of nicotine across human mucosal cells and simultaneously prevents human mucosal cell toxicity by inhibiting cytochrome c release into the cytosol, thereby preventing caspase 3 and 9 activity and subsequent intrinsic apoptosis.

Ambulatory 24-hour multichannel intraluminal impedance-pH monitoring and high resolution endoscopy distinguish patients with non-erosive reflux disease from those with functional heartburn

PubMed Central

Chu, Chuanlian; Du, Quanlin; Li, Changqing; Zhang, Linlu; Zhou, Xiaoyan; Zuo, Fang; Zhang, Yanmin; Li, Fang; Xie, Guofeng; Li, Yanqing

2017-01-01

Aims To assess the contribution of 24-h esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring and high resolution endoscopy (HRE) with i-scan imaging in differentiating non erosive reflux disease (NERD) from functional heartburn (FH). Methods This is a retrospective cohort study of patients with heartburn from the Endoscopy Unit. NERD patients and FH patients were defined by 24-h MII-pH monitoring and white light endoscopy. Minimal mucosal changes were assessed by HRE with i-scan imaging. Results Total of 156 consecutive patients with heartburn but without esophageal mucosal erosions were studied. Forty-eight of these subjects had NERD, with increased acid exposure time (AET) and positive SAP and/or SI. Eighteen had FH with normal AET and negative SAP and SI. When compared to FH patients and healthy controls, NERD patients had significantly increased number of total acid reflux episodes, as well as increased number of weakly acidic reflux episodes (p<0.01). The rate of proximal reflux episodes in NERD patients was higher than that of FH patients and healthy controls (p<0.01). Irregular or blurring of the Z-line (58.3%) and white mucosal turbidity (47.9%) were the most common endoscopic findings of minimal mucosal changes observed in this study. NERD patients had more prevalent minimal changes than FH patients and the controls (87.5%vs. 66.6%vs. 61.9%; p = 0.004) with sensitivity of 87.5%. Histopathological evaluation showed that NERD patients had significantly higher average scores of intercellular spaces dilation (2.82±0.9 vs. 1.2±0.6, p = 0.005) and papillae elongation (2.65±1.0 vs. 1.5±0.8, p = 0.014), but not for basal cell proliferation (1.6±1.3 vs. 1.0±0.9, p = 0.070). The histological scores of the NERD patients were 7.1±1.2, which were higher than those of FH patients (3.4±1.0, p = 0.004). Conclusions Minimal mucosal changes could be useful markers to support clinical diagnosis of NERD. Combination of 24-h MII-pH monitoring and i-scan high resolution endoscopy can distinguish patients with NERD from those with FH. PMID:28384225

Ambulatory 24-hour multichannel intraluminal impedance-pH monitoring and high resolution endoscopy distinguish patients with non-erosive reflux disease from those with functional heartburn.

PubMed

Chu, Chuanlian; Du, Quanlin; Li, Changqing; Zhang, Linlu; Zhou, Xiaoyan; Zuo, Fang; Zhang, Yanmin; Li, Fang; Xie, Guofeng; Li, Yanqing

2017-01-01

To assess the contribution of 24-h esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring and high resolution endoscopy (HRE) with i-scan imaging in differentiating non erosive reflux disease (NERD) from functional heartburn (FH). This is a retrospective cohort study of patients with heartburn from the Endoscopy Unit. NERD patients and FH patients were defined by 24-h MII-pH monitoring and white light endoscopy. Minimal mucosal changes were assessed by HRE with i-scan imaging. Total of 156 consecutive patients with heartburn but without esophageal mucosal erosions were studied. Forty-eight of these subjects had NERD, with increased acid exposure time (AET) and positive SAP and/or SI. Eighteen had FH with normal AET and negative SAP and SI. When compared to FH patients and healthy controls, NERD patients had significantly increased number of total acid reflux episodes, as well as increased number of weakly acidic reflux episodes (p<0.01). The rate of proximal reflux episodes in NERD patients was higher than that of FH patients and healthy controls (p<0.01). Irregular or blurring of the Z-line (58.3%) and white mucosal turbidity (47.9%) were the most common endoscopic findings of minimal mucosal changes observed in this study. NERD patients had more prevalent minimal changes than FH patients and the controls (87.5%vs. 66.6%vs. 61.9%; p = 0.004) with sensitivity of 87.5%. Histopathological evaluation showed that NERD patients had significantly higher average scores of intercellular spaces dilation (2.82±0.9 vs. 1.2±0.6, p = 0.005) and papillae elongation (2.65±1.0 vs. 1.5±0.8, p = 0.014), but not for basal cell proliferation (1.6±1.3 vs. 1.0±0.9, p = 0.070). The histological scores of the NERD patients were 7.1±1.2, which were higher than those of FH patients (3.4±1.0, p = 0.004). Minimal mucosal changes could be useful markers to support clinical diagnosis of NERD. Combination of 24-h MII-pH monitoring and i-scan high resolution endoscopy can distinguish patients with NERD from those with FH.

Novel vaccine development strategies for inducing mucosal immunity

PubMed Central

Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro

2012-01-01

To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed. PMID:22380827

Spectrophotometric and visual evaluation of peri-implant soft tissue color.

PubMed

Benic, Goran I; Scherrer, Daniela; Sancho-Puchades, Manuel; Thoma, Daniel S; Hämmerle, Christoph H F

2017-02-01

To spectrophotometrically and visually test whether the peri-implant mucosal color differs from the color of the natural gingiva. Forty single implants in the incisor and premolar region of 40 patients were assessed 3-7 years after implant placement. The differences of the color components lightness, chroma along red-green axis, chroma along yellow-blue axis, and the total color difference ΔE between peri-implant mucosa and natural gingiva were measured with a spectrophotometer. The color difference between peri-implant mucosa and natural gingiva was visually evaluated by clinicians and rated as "clinically visible" or "clinically invisible" from speaking distance. The dimensions of peri-implant mucosa and gingiva at the mid-buccal aspect were evaluated by using cone-beam CT. Spearman analysis was performed to detect correlations between different variables. Two-sided t-test, ANOVA, Mann-Whitney, and Kruskal-Wallis tests were applied to detect differences between the groups. The spectrophotometrically assessed color difference ΔE between peri-implant mucosa and natural gingiva amounted to 7.0 ± 3.9. The peri-implant mucosa presented a significant dark, greenish and bluish discoloration in comparison with gingiva at control teeth. Clinical investigation revealed that in 60% of sites the color difference between peri-implant mucosa and natural gingiva was clinically visible from speaking distance. The threshold value ΔE for the extraoral clinical distinction of mucosal color differences measured 7.5. When comparing the groups with visible and invisible color differences with respect to the three color components, a significant difference was found only for chroma along yellow-blue axis. In the group with visible color difference, mucosa presented a bluish discoloration. Correlation analysis indicated that with an increase in mucosal thickness, a trend for smaller ΔE was found. The spectrophotometrically assessed color of the peri-implant mucosa revealed more dark, green and blue components compared to the natural gingiva. At 60% of the implants, peri-implant mucosal discoloration was visible from speaking distance. The sites with visible and those with invisible mucosal discolorations differed significantly only regarding the chroma along yellow-blue axis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mechanisms of Gastroprotective Effects of Ethanolic Leaf Extract of Jasminum sambac against HCl/Ethanol-Induced Gastric Mucosal Injury in Rats

PubMed Central

AlRashdi, Ahmed S.; Salama, Suzy M.; Alkiyumi, Salim S.; Abdulla, Mahmood A.; Hadi, A. Hamid A.; Abdelwahab, Siddig I.; Taha, Manal M.; Hussiani, Jamal; Asykin, Nur

2012-01-01

Jasminum sambac is used in folk medicine as the treatment of many diseases. The aim of the present investigation is to evaluate the gastroprotective effects of ethanolic extracts of J. sambac leaves against acidified ethanol-induced gastric ulcers in rats. Seven groups of rats were orally pre-treated with carboxymethylcellulose (CMC) as normal group, CMC as ulcer group, 20 mg/kg of omeprazole as positive group, 62.5, 125, 250, and 500 mg/kg of extract as the experimental groups, respectively. An hour later, CMC was given orally to normal group and acidified ethanol solution was given orally to the ulcer control, positive control, and the experimental groups. The rats were sacrificed after an hour later. Acidity of gastric content, the gastric wall mucus, ulcer areas, and histology and immunohistochemistry of the gastric wall were assessed. Gastric homogenates were determined for prostaglandin E2 (PGE2), superoxide dismutase (SOD), andmalondialdehyde (MDA) content. Ulcer group exhibited significantly severe mucosal injury as compared with omeprazole or extract which shows significant protection towards gastric mucosal injury the plant promotes ulcer protection as it shows significant reduction of ulcer area grossly, and histology showed marked reduction of edema and leucocytes infiltration of submucosal layer compared with ulcer group. Immunohistochemistry showed overexpression of Hsp70 protein and downexpression of Bax protein in rats pretreated with extract. Significant increased in the pH, mucus of gastric content and high levels of PGE2, SOD and reduced amount of MDA was observed. PMID:22550543

Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

PubMed Central

Kataoka, Kosuke; Fujihashi, Kohtaro

2009-01-01

In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens. PMID:19722892

An Innovative Field-Applicable Molecular Test to Diagnose Cutaneous Leishmania Viannia spp. Infections

PubMed Central

Saldarriaga, Omar A.; Castellanos-Gonzalez, Alejandro; Porrozzi, Renato; Baldeviano, Gerald C.; Lescano, Andrés G.; de Los Santos, Maxy B.; Fernandez, Olga L.; Saravia, Nancy G.; Costa, Erika; Melby, Peter C.; Travi, Bruno L.

2016-01-01

Cutaneous and mucosal leishmaniasis is widely distributed in Central and South America. Leishmania of the Viannia subgenus are the most frequent species infecting humans. L. (V.) braziliensis, L. (V.) panamensis are also responsible for metastatic mucosal leishmaniasis. Conventional or real time PCR is a more sensitive diagnostic test than microscopy, but the cost and requirement for infrastructure and trained personnel makes it impractical in most endemic regions. Primary health systems need a sensitive and specific point of care (POC) diagnostic tool. We developed a novel POC molecular diagnostic test for cutaneous leishmaniasis caused by Leishmania (Viannia) spp. Parasite DNA was amplified using isothermal Recombinase Polymerase Amplification (RPA) with primers and probes that targeted the kinetoplast DNA. The amplification product was detected by naked eye with a lateral flow (LF) immunochromatographic strip. The RPA-LF had an analytical sensitivity equivalent to 0.1 parasites per reaction. The test amplified the principal L. Viannia species from multiple countries: L. (V.) braziliensis (n = 33), L. (V.) guyanensis (n = 17), L. (V.) panamensis (n = 9). The less common L. (V.) lainsoni, L. (V.) shawi, and L. (V.) naiffi were also amplified. No amplification was observed in parasites of the L. (Leishmania) subgenus. In a small number of clinical samples (n = 13) we found 100% agreement between PCR and RPA-LF. The high analytical sensitivity and clinical validation indicate the test could improve the efficiency of diagnosis, especially in chronic lesions with submicroscopic parasite burdens. Field implementation of the RPA-LF test could contribute to management and control of cutaneous and mucosal leishmaniasis. PMID:27115155

Comparison of subcutaneous versus intranasal immunization of male koalas (Phascolarctos cinereus) for induction of mucosal and systemic immunity against Chlamydia pecorum.

PubMed

Waugh, Courtney A; Timms, Peter; Andrew, Dean; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Beagley, Kenneth W

2015-02-11

Chlamydia pecorum infections are debilitating in the koala, contributing significantly to morbidity and mortality, with current antibiotic treatments having minimal success and adversely affecting gut microflora. This, combined with the sometimes-asymptomatic nature of the infection, suggests that an efficacious anti-chlamydial vaccine is required to control chlamydial infections in the koala. To date vaccination studies have focused primarily on female koalas, however, given the physiological differences between male and female reproductive tracts, we tested the efficacy of a vaccine in 12 captive male koalas. We evaluated the potential of both subcutaneous and intranasal vaccine delivery to elicit mucosal immunity in male koalas. Our results showed that both intranasal and subcutaneous delivery of a vaccine consisting of C. pecorum major outer membrane protein (MOMP) and the adjuvant immunostimulating complex (ISC) induced significant immune responses in male koalas. Subcutaneous immunization elicited stronger cell-mediated responses in peripheral blood lymphocytes (PBL), and greater plasma antibody levels whereas the intranasal immunization elicited stronger humoral responses in urogenital tract (UGT) secretions. This is the first time a Chlamydia vaccine has been tested in the male koala and the first assessment of a mucosal vaccination route in this species. Our results suggest that vaccination of male koalas can elicit mucosal immunity and could contribute to the long-term survivability of wild populations of the koala. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cryopreservation of Human Mucosal Leukocytes

PubMed Central

Shu, Zhiquan; Levy, Claire N.; Ferre, April L.; Hartig, Heather; Fang, Cifeng; Lentz, Gretchen; Fialkow, Michael; Kirby, Anna C.; Adams Waldorf, Kristina M.; Veazey, Ronald S.; Germann, Anja; von Briesen, Hagen; McElrath, M. Juliana; Dezzutti, Charlene S.; Sinclair, Elizabeth; Baker, Chris A. R.; Shacklett, Barbara L.; Gao, Dayong; Hladik, Florian

2016-01-01

Background Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible. Methods and Findings To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10–15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension. Conclusions Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes. PMID:27232996

Acute effects of carprofen and meloxicam on canine gastrointestinal permeability and mucosal absorptive capacity.

PubMed

Craven, Melanie; Chandler, Marge L; Steiner, Jörg M; Farhadi, Ashkan; Welsh, Elizabeth; Pratschke, Kathryn; Shaw, Darren J; Williams, David A

2007-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to dogs for their analgesic, antipyretic, and anti-inflammatory properties. Their beneficial actions can be offset by gastrointestinal (GI) toxicosis. Endoscopy has traditionally been employed to detect GI lesions, but alterations in GI permeability precede the development of mucosal damage. Carprofen and meloxicam alter GI permeability and mucosal absorptive capacity of dogs. Twenty adult dogs treated with an NSAID for >7 days were evaluated by permeability tests while receiving either carprofen (10 dogs) or meloxicam (10 dogs). Prospective, longitudinal observational study. A 6-sugar permeability test (sucrose, lactulose, rhamnose, 3-O-methyl-D-glucose, D-xylose, and sucralose) was performed on the day before NSAID treatment, and after 3 and 8 days of treatment. There were no significant differences in the urinary recovery ratios of lactulose: rhamnose, D-xylose: 3-O-methyl-D-glucose, or sucralose recovery within either group at any time during the study. Sucrose permeability in the meloxicam group did not alter significantly over time. However, sucrose permeability in the carprofen group decreased significantly by day 3 (P = .049) and increased again by day 8 (P = .049), to a level that was not significantly different to permeability before treatment (P = .695). The absence of increased GI permeability and diminished mucosal absorptive capacity in this group of dogs does not support the development of acute GI toxicosis during treatment with either meloxicam or carprofen.

Effect of a chlorhexidine-containing brush-on gel on peri-implant mucositis.

PubMed

Hallström, H; Lindgren, S; Twetman, S

2017-05-01

The aim was to evaluate the effect of a chlorhexidine-containing brush-on gel when used as supplement to oral hygiene instructions and mechanical debridement, on peri-implant mucositis in adults. The study group consisted of 38 adults (48-87 years.) with peri-implant mucositis that were consecutively enrolled in three private clinics after informed consent. The study employed a double-blind controlled design with two parallel arms. After baseline registrations, oral hygiene reinforcement and mechanical debridement, the patients were randomly allocated to either a test group with once daily tooth brushing with an oral care brush-on gel containing 0.2% chlorhexidine digluconate (Cervitec Gel) or a control gel group. The duration of the intervention was 12 weeks. The primary outcome was bleeding on probing (BOP) and secondary endpoints were local plaque score (LPS) and pocket probing depth (PPD). The groups were balanced at baseline. The daily use of the chlorhexidine-containing gel resulted in reduced BOP after 4 and 12 weeks compared with the control group (P < 0.05). The PPD was significantly reduced (P < 0.05) after 12 weeks compared to baseline in the test group, but not in the control group. No side effects or adverse events were reported. The present findings indicated moderate but significant improvements of clinical parameters when mechanical debridement was combined with a self-applied oral care brush-on gel for the management of peri-implant mucositis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence of and risk factors for oral human papillomavirus among young women in Costa Rica.

PubMed

Lang Kuhs, Krystle A; Gonzalez, Paula; Struijk, Linda; Castro, Felipe; Hildesheim, Allan; van Doorn, Leen-Jan; Rodriguez, Ana Cecilia; Schiffman, Mark; Quint, Wim; Lowy, Douglas R; Porras, Carolina; Delvecchio, Corey; Katki, Hormuzd A; Jimenez, Silvia; Safaeian, Mahboobeh; Schiller, John; Solomon, Diane; Wacholder, Sholom; Herrero, Rolando; Kreimer, Aimée R

2013-11-15

Little is known about the epidemiology of oral human papillomavirus (HPV) in Latin America. Women (N = 5838) aged 22-29 in the control and vaccine arms of an HPV-16/18 vaccine trial in Costa Rica had oral, cervical, and anal specimens collected. Samples were tested for alpha mucosal HPV types (SPF10/LiPA25 version 1); a subset of oral samples (n = 500) was tested for cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu. In the control arm (n = 2926), 1.9% of women had an oral alpha mucosal HPV detected, 1.3% had carcinogenic HPV, and 0.4% had HPV-16; similar patterns for non-16/18 HPV types were observed in the vaccine arm. Independent risk factors for any oral alpha mucosal HPV among women in the control arm included marital status (adjusted odds ratio [AOR], 3.2; 95% confidence interval [CI], 1.8-5.7 for single compared to married/living as married), number of sexual partners (AOR, 2.4; 95% CI, 1.0-6.1 for ≥4 partners compared to 0-1 partners), chronic sinusitis (AOR, 3.1; 95% CI, 1.5-6.7), and cervical HPV infection (AOR, 2.6; 95% CI, 1.4-4.6). Detection of beta HPV was common (18.6%) and not associated with sexual activity. Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in the oral region and were predominately associated with sexual behavior. Clinical Trials Registration. NCT00128661.

Influence of plant-originated gastroproteciive and antiulcer substances on gastric mucosal repair.

PubMed

Zayachkivska, O S; Konturek, S J; Drozdowicz, D; Brzozowski, T; Gzhegotsky, M R

2004-01-01

Fundamental basis of cellular and molecular mechanisms involved in mucosal injury and repair in gastrointestinal tract helps to develop new therapeutic approaches to various gut mucosal injury- related diseases. The study was aimed to assess the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulceric activities and to deteminate if these effects are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically. The following plant-originated substances were considered: Solon, capsaicin, grapefruit-seed extract and amaranth. The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). male Wistar rats, weighing 180-220 g fasted for 24 h before the study, 100% ethanol was applied ig to induced gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by an increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment-with L-NNA. Plant-originated substances are highly gastroprotective probably due to enhancement of the expression of NOS I, NO release and an increase in gastric microcirculation.

Prevalence of oral lesions and measurement of salivary pH in the different trimesters of pregnancy.

PubMed

Jain, Kanu; Kaur, Harshaminder

2015-01-01

Oral changes observed during pregnancy have been studied for many years, but their magnitude and frequency have not been stressed upon. This study was undertaken to assess the prevalence of oral lesions during different trimesters of pregnancy and their correlation with salivary pH change. The gingival, simplified oral hygiene, community periodontal and decayed-missing-filled teeth indices were used to assess a total of 120 pregnant women (40 in each trimester group) and 40 nonpregnant women (control group). Salivary pH was measured using a digital pH meter. Presence of any oral lesions was determined via oral examination. Scores for all indices increased while salivary pH decreased from the control group to the first trimester group, through to the third. Oral lesions were seen in 44.2% of pregnant women. Lesions were seen in 27.5%, 52.5% and 52.5% of women in the first, second and third trimesters, respectively. The percentage of pregnant women with one oral lesion was highest in the second trimester (47.5%), whereas the third trimester had the highest prevalence (17.5%) of two concurrent oral lesions. The incidence of fissured tongue was highest in the first trimester group, and that of gingival enlargement was highest in the third trimester group. In the second trimester group, there was an almost equal incidence of fissured tongue and gingival/mucosal enlargement. Most changes in oral tissues during pregnancy can be avoided with good oral hygiene. Salivary pH could be used to assess the prevalence of oral lesions in the different trimesters of pregnancy.

The comparison of extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous pantoprazole on the gastric pH of critically ill-patients.

PubMed

Dabiri, Yasamin; Fahimi, Fanak; Jamaati, Hamidreza; Hashemian, Seyed Mohammad Reza

2015-01-01

Stress-related mucosal disease occurs in many critically ill-patients within 24 h of admission. Proton pump inhibitor therapy has been documented to produce more potent inhibition of gastric acid secretion than histamine 2 receptor antagonists. This study aimed to compare extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous (IV) pantoprazole on the gastric pH in intensive care unit patients. This was a randomized single-blind-study. Patients of ≥ 16 years of age with a nasogastric tube, who required mechanical ventilation for ≥ 48 h, were eligible for inclusion. The excluded patients were those with active gastrointestinal bleeding, known allergy to omeprazole and pantoprazole and those intolerant to the nasogastric tube. Fifty-six patients were randomized to treatment with omeprazole suspension 2 mg/ml (40 mg every day), pantoprazole suspension 2 mg/ml (40 mg every day) and IV pantoprazole (40 mg every day) for up to 14 days. Gastric aspirates were sampled before and 1-2.5 h after the drug administration for the pH measurement using an external pH meter. Data were analyzed using SPSS (version 21.0). In this study, 56 critically ill-patients (39 male, 17 female, mean age: 61.5 ± 15.65 years) were followed for the control of the gastric pH. On each of the 14 trial days the mean of the gastric pH alteration was significantly higher in omeprazole and pantoprazole suspension-treated patients than in IV pantoprazole-treated patients (P < 0.001). Omeprazole and pantoprazole oral suspension are more effective than IV pantoprazole in increasing the gastric pH.

The comparison of extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous pantoprazole on the gastric pH of critically ill-patients

PubMed Central

Dabiri, Yasamin; Fahimi, Fanak; Jamaati, Hamidreza; Hashemian, Seyed Mohammad Reza

2015-01-01

Background: Stress-related mucosal disease occurs in many critically ill-patients within 24 h of admission. Proton pump inhibitor therapy has been documented to produce more potent inhibition of gastric acid secretion than histamine 2 receptor antagonists. This study aimed to compare extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous (IV) pantoprazole on the gastric pH in intensive care unit patients. Materials and Methods: This was a randomized single-blind-study. Patients of ≥ 16 years of age with a nasogastric tube, who required mechanical ventilation for ≥ 48 h, were eligible for inclusion. The excluded patients were those with active gastrointestinal bleeding, known allergy to omeprazole and pantoprazole and those intolerant to the nasogastric tube. Fifty-six patients were randomized to treatment with omeprazole suspension 2 mg/ml (40 mg every day), pantoprazole suspension 2 mg/ml (40 mg every day) and IV pantoprazole (40 mg every day) for up to 14 days. Gastric aspirates were sampled before and 1-2.5 h after the drug administration for the pH measurement using an external pH meter. Data were analyzed using SPSS (version 21.0). Results: In this study, 56 critically ill-patients (39 male, 17 female, mean age: 61.5 ± 15.65 years) were followed for the control of the gastric pH. On each of the 14 trial days the mean of the gastric pH alteration was significantly higher in omeprazole and pantoprazole suspension-treated patients than in IV pantoprazole-treated patients (P < 0.001). Conclusion: Omeprazole and pantoprazole oral suspension are more effective than IV pantoprazole in increasing the gastric pH. PMID:25624646

High-grain feeding alters caecal bacterial microbiota composition and fermentation and results in caecal mucosal injury in goats.

PubMed

Liu, Junhua; Xu, Tingting; Zhu, Weiyun; Mao, Shengyong

2014-08-14

The effect of high-grain (HG) feeding on caecal bacterial microbiota composition and fermentation and mucosa health is largely unknown. In the present study, ten male goats were randomly assigned to either a group fed a hay diet (0 % grain; n 5) or a group fed a HG diet (65 % grain; n 5) to characterise the changes in the composition of the bacterial community and mucosal morphology in the caecum. After 7 weeks of feeding, the HG diet decreased the caecal pH (P< 0·001) and increased (P< 0·001 to P< 0·004) the caecal digesta concentrations of total volatile fatty acids and lipopolysaccharide (LPS). Pyrosequencing of the 16S ribosomal RNA gene revealed that HG feeding increased (P= 0·001 to P= 0·009) the abundance of predominant genera Turicibacter and Clostridium in the caecal lumen and in the caecal mucosa and decreased (P< 0·001 to P< 0·009) the proportion of Bacteroides in the lumen and Mucispirillum in the mucosa compared with the hay diet. Furthermore, the HG diet-fed goats exhibited intense epithelial damage and up-regulation (P< 0·001 to P< 0·025) of the relative mRNA expression of IL-1β, IL-6, IL-12 and interferon-γ (IFN-γ) in the caecal mucosa. The correlation analysis revealed that alterations in caecal pH, LPS concentration and mucosa-associated microbiota abundance during HG feeding might partly contribute to local inflammation. Collectively, these results provide insight into the adaptive response of caecal bacterial populations to HG feeding in goats and reveal that the fermentable substrates that flow into the caecum may cause dramatic alterations in microbial compositions and play a significant role in caecal dysfunction.

Development of HIV-1 Rectal-Specific Microbicides and Colonic Tissue Evaluation

PubMed Central

Dezzutti, Charlene S.; Russo, Julie; Wang, Lin; Abebe, Kaleab Z.; Li, Jie; Friend, David R.; McGowan, Ian M.; Rohan, Lisa C.

2014-01-01

The gastrointestinal tract is structurally and functionally different from the vagina. Thus, the paradigm of topical microbicide development and evaluation has evolved to include rectal microbicides (RMs). Our interest was to create unique RM formulations to safely and effectively deliver antiretroviral drugs to mucosal tissue. RMs were designed to include those that spread and coat all surfaces of the rectum and distal colon rapidly (liquid) and those that create a deformable, erodible barrier and remain localized at the administration site (gel). Tenofovir (TFV) (1%) was formulated as an aqueous thermoreversible fluid and a carbopol-based aqueous hydrogel. Lipid-based liquid and gel formulations were prepared for UC781 (0.1%) using isopropyl myristate and GTCC (Caprylic/Capric Triglycerides), respectively. Formulations were characterized for pH, viscosity, osmolality, and drug content. Pre-clinical testing incorporated ex vivo colonic tissue obtained through surgical resections and flexible sigmoidoscopy (flex sig). As this was the first time using tissue from both sources side-by-side, the ability to replicate HIV-1 was compared. Efficacy of the RM formulations was tested by applying the products with HIV-1 directly to polarized colonic tissue and following viral replication. Safety of the formulations was determined by MTT assay and histology. All products had a neutral pH and were isoosmolar. While HIV-1BaL and HIV-1JR-CSF alone and in the presence of semen had similar replication trends between surgically resected and flex sig tissues, the magnitude of viral replication was significantly better in flex sig tissues. Both TFV and UC781 formulations protected the colonic tissue, regardless of tissue source, from HIV-1 and retained tissue viability and architecture. Our in vitro and ex vivo results show successful formulation of unique RMs. Moreover, the results of flex sig and surgically resected tissues were comparable suggesting the incorporation of both in pre-clinical testing algorithms. PMID:25025306

Development of HIV-1 rectal-specific microbicides and colonic tissue evaluation.

PubMed

Dezzutti, Charlene S; Russo, Julie; Wang, Lin; Abebe, Kaleab Z; Li, Jie; Friend, David R; McGowan, Ian M; Rohan, Lisa C

2014-01-01

The gastrointestinal tract is structurally and functionally different from the vagina. Thus, the paradigm of topical microbicide development and evaluation has evolved to include rectal microbicides (RMs). Our interest was to create unique RM formulations to safely and effectively deliver antiretroviral drugs to mucosal tissue. RMs were designed to include those that spread and coat all surfaces of the rectum and distal colon rapidly (liquid) and those that create a deformable, erodible barrier and remain localized at the administration site (gel). Tenofovir (TFV) (1%) was formulated as an aqueous thermoreversible fluid and a carbopol-based aqueous hydrogel. Lipid-based liquid and gel formulations were prepared for UC781 (0.1%) using isopropyl myristate and GTCC (Caprylic/Capric Triglycerides), respectively. Formulations were characterized for pH, viscosity, osmolality, and drug content. Pre-clinical testing incorporated ex vivo colonic tissue obtained through surgical resections and flexible sigmoidoscopy (flex sig). As this was the first time using tissue from both sources side-by-side, the ability to replicate HIV-1 was compared. Efficacy of the RM formulations was tested by applying the products with HIV-1 directly to polarized colonic tissue and following viral replication. Safety of the formulations was determined by MTT assay and histology. All products had a neutral pH and were isoosmolar. While HIV-1BaL and HIV-1JR-CSF alone and in the presence of semen had similar replication trends between surgically resected and flex sig tissues, the magnitude of viral replication was significantly better in flex sig tissues. Both TFV and UC781 formulations protected the colonic tissue, regardless of tissue source, from HIV-1 and retained tissue viability and architecture. Our in vitro and ex vivo results show successful formulation of unique RMs. Moreover, the results of flex sig and surgically resected tissues were comparable suggesting the incorporation of both in pre-clinical testing algorithms.

Hypoadrenocorticism (Addison's disease) in a Hoffmann's two-toed sloth (Choloepus hoffmanni).

PubMed

Kline, Sarah; Rooker, Leah; Nobrega-Lee, Michelle; Guthrie, Amanda

2015-03-01

A 22-yr-old, captive-born, presumed female Hoffmann's two-toed sloth (Choloepus hoffmanni) presented in respiratory distress with severe dehydration and symptoms of hypotension. During treatment, dysphagia was noted and oral examination revealed enlarged palatine tonsils and mucosal plaques. Bloodwork showed a decreased sodium:potassium ratio, a low baseline cortisol, a decreased adrenocorticotropin response test, and a blunted aldosterone stimulation test. All values were compared to a healthy male Hoffmann's two-toed sloth at the same facility. Despite aggressive medical management and treatment for hypoadrenocorticism, the sloth was found deceased. Necropsy revealed abdominal effusion, multifocal plaques throughout the upper gastrointestinal tract, and testes. Histopathology showed marked adrenal cortical atrophy and intranuclear mucosal inclusions in the gastrointestinal tract; advanced molecular techniques did not uncover any viral etiologies. This is the first reported case of hypoadrenocorticism in a sloth.

Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa.

PubMed

Williams, R; Rankin, N; Smith, T; Galler, D; Seakins, P

1996-11-01

To review the available literature on the relationship between the humidity and temperature of inspired gas and airway mucosal function. International computerized databases and published indices, experts in the field, conference proceedings, bibliographies. Two hundred articles/texts on respiratory tract physiology and humidification were reviewed. Seventeen articles were selected from 40 articles for inclusion in the published data verification of the model. Selection was by independent reviewers. Extraction was by consensus, and was based on finding sufficient data. A relationship exists between inspired gas humidity and temperature, exposure time to a given humidity level, and mucosal function. This relationship can be modeled and represented as an inspired humidity magnitude vs. exposure time map. The model is predictive of mucosal function and can be partially verified by the available literature. It predicts that if inspired humidity deviates from an optimal level, a progressive mucosal dysfunction begins. The greater the humidity deviation, the faster the mucosal dysfunction progresses. A model for the relationship between airway mucosal dysfunction and the combination of the humidity of inspired gas and the duration over which the airway mucosa is exposed to that humidity is proposed. This model suggests that there is an optimal temperature and humidity above which, and below which, there is impaired mucosal function. This optimal level of temperature and humidity is core temperature and 100% relative humidity. However, existing data are only sufficient to test this model for gas conditions below core temperature and 100% relative humidity. These data concur with the model in that region. No studies have yet looked at this relationship beyond 24 hrs. Longer exposure times to any given level of inspired humidity and inspired gas temperatures and humidities above core temperature and 100% relative humidity need to be studied to fully verify the proposed model.

The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells

PubMed Central

Gupta, Sandeep; Gach, Johannes S.; Becerra, Juan C.; Phan, Tran B.; Pudney, Jeffrey; Moldoveanu, Zina; Joseph, Sarah B.; Landucci, Gary; Supnet, Medalyn Jude; Ping, Li-Hua; Corti, Davide; Moldt, Brian; Hel, Zdenek; Lanzavecchia, Antonio; Ruprecht, Ruth M.; Burton, Dennis R.; Mestecky, Jiri; Anderson, Deborah J.; Forthal, Donald N.

2013-01-01

The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure. PMID:24278022

The acid pocket: a target for treatment in reflux disease?

PubMed

Kahrilas, Peter J; McColl, Kenneth; Fox, Mark; O'Rourke, Lisa; Sifrim, Daniel; Smout, Andre J P M; Boeckxstaens, Guy

2013-07-01

The nadir esophageal pH of reflux observed during pH monitoring in the postprandial period is often more acidic than the concomitant intragastric pH. This paradox prompted the discovery of the "acid pocket", an area of unbuffered gastric acid that accumulates in the proximal stomach after meals and serves as the reservoir for acid reflux in healthy individuals and gastroesophageal reflux disease (GERD) patients. However, there are differentiating features between these populations in the size and position of the acid pocket, with GERD patients predisposed to upward migration of the proximal margin onto the esophageal mucosa, particularly when supine. This upward migration of acid, sometimes referred to as an "acid film", likely contributes to mucosal pathology in the region of the squamocolumnar junction. Furthermore, movement of the acid pocket itself to a supradiaphragmatic location with hiatus hernia increases the propensity for acid reflux by all conventional mechanisms. Consequently, the acid pocket is an attractive target for GERD therapy. It may be targeted in a global way with proton pump inhibitors that attenuate acid pocket development, or with alginate/antacid combinations that colocalize with the acid pocket and displace it distally, thereby demonstrating the potential for selective targeting of the acid pocket in GERD.

Seasonal changes in gastric mucosal factors associated with peptic ulcer bleeding.

PubMed

Yuan, Xiao-Gang; Xie, Chuan; Chen, Jiang; Xie, Yong; Zhang, Kun-He; Lu, Nong-Hua

2015-01-01

A close association has been established between climate and peptic ulcer bleeding (PUB). The incidence of PUB in cold climates is significantly higher than that in hot climates. In this study, gastric mucosal damage and its barrier function (through associated barrier factors) in extreme climate conditions were examined to investigate the pathogenesis of PUB in extreme cold climates. Gastric juice and biopsy specimens were collected from 176 patients with peptic ulcer. Conventional hematoxylin and eosin staining was used to exclude malignant ulcers. Helicobacter pylori infections were detected by modified Giemsa staining. pH values of the gastric juice samples were obtained on-site by precise pH dipstick readings. The protein expression levels of heat shock protein (HSP) 70, occludin, nitric oxide synthase (NOS), epidermal growth factor (EGF) and EGF receptor (EGFR) in the gastric mucosa were detected by immunohistochemistry. No significant differences were identified between the high and low bleeding risk groups in the rates of H. pylori infection and the pH values of the gastric juices in the extreme hot or cold climates. Furthermore, no statistically significant differences were identified in the protein expression levels of occludin, NOS, EGF and EGFR between the high and low bleeding risk groups. In the extreme cold climate, the expression of HSP70 and the mucus thickness of the gastric antrum in the high bleeding risk group were significantly lower than those in the low bleeding risk group. The protein expression levels of occludin, HSP70, NOS and EGFR in the extreme cold climate were significantly lower than those in the extreme hot climate, whereas the gastric acid secretion was significantly higher in the extreme cold climate than that in the extreme hot climate. In conclusion, low expression of HSP70 in the gastric mucosa and reduced gastric mucus thickness may play key roles in the mechanism of PUB in extreme cold climates. The significant decrease in barrier factors and increase in damage in extreme cold climates may be associated with the seasonal pattern of peptic ulcers.

Seasonal changes in gastric mucosal factors associated with peptic ulcer bleeding

PubMed Central

YUAN, XIAO-GANG; XIE, CHUAN; CHEN, JIANG; XIE, YONG; ZHANG, KUN-HE; LU, NONG-HUA

2015-01-01

A close association has been established between climate and peptic ulcer bleeding (PUB). The incidence of PUB in cold climates is significantly higher than that in hot climates. In this study, gastric mucosal damage and its barrier function (through associated barrier factors) in extreme climate conditions were examined to investigate the pathogenesis of PUB in extreme cold climates. Gastric juice and biopsy specimens were collected from 176 patients with peptic ulcer. Conventional hematoxylin and eosin staining was used to exclude malignant ulcers. Helicobacter pylori infections were detected by modified Giemsa staining. pH values of the gastric juice samples were obtained on-site by precise pH dipstick readings. The protein expression levels of heat shock protein (HSP) 70, occludin, nitric oxide synthase (NOS), epidermal growth factor (EGF) and EGF receptor (EGFR) in the gastric mucosa were detected by immunohistochemistry. No significant differences were identified between the high and low bleeding risk groups in the rates of H. pylori infection and the pH values of the gastric juices in the extreme hot or cold climates. Furthermore, no statistically significant differences were identified in the protein expression levels of occludin, NOS, EGF and EGFR between the high and low bleeding risk groups. In the extreme cold climate, the expression of HSP70 and the mucus thickness of the gastric antrum in the high bleeding risk group were significantly lower than those in the low bleeding risk group. The protein expression levels of occludin, HSP70, NOS and EGFR in the extreme cold climate were significantly lower than those in the extreme hot climate, whereas the gastric acid secretion was significantly higher in the extreme cold climate than that in the extreme hot climate. In conclusion, low expression of HSP70 in the gastric mucosa and reduced gastric mucus thickness may play key roles in the mechanism of PUB in extreme cold climates. The significant decrease in barrier factors and increase in damage in extreme cold climates may be associated with the seasonal pattern of peptic ulcers. PMID:25452787

Mucosal immunization: a review of strategies and challenges.

PubMed

Patel, Hinal; Yewale, Chetan; Rathi, Mohan N; Misra, Ambikanandan

2014-01-01

The vast majority of pathogens enter the human body via the mucosal surfaces of the gastrointestinal, respiratory, and urogenital tracts, where they initiate mucosal infections that lead to systemic infections. Despite strong evidence that a good mucosal immune response can effectively prevent systemic infection too, only a few mucosal vaccines are available due to their low efficiency. Most current immunization techniques involve systemic injection, but they are ineffective to induce immunization at a mucosal site. It is a great challenge to target a mucosal compartment that can induce protective immunity at mucosal sites as well as systemic sites. A better understanding of cellular and molecular factors involved in the regulation of mucosal immunity will aid in the design of safer mucosal vaccines that elicit the desired protective immunity against infectious diseases such as HIV. The development of mucosal vaccines, whether for prevention of infectious diseases or for immunotherapy, requires antigen delivery and adjuvant systems that can effectively present vaccine or immunotherapeutic antigens to the mucosal sites. In this review, we examine the mechanism of mucosal protection, induction of mucosal immune response, types of vaccines, current status of marketed vaccines, and novel strategies for protection against infections and for treatment of inflammatory disorders. Additionally, we offer perspectives on future challenges and research directions.

Shigella sonnei Vaccine Candidates WRSs2 and WRSs3 Are as Immunogenic as WRSS1, a Clinically Tested Vaccine Candidate, in a Primate Model of Infection

DTIC Science & Technology

2011-01-01

Experiments in rabbit ileal loops and in rhesus monkeys have shown that shigellae are initially taken up by antigen sampling microfold (M) cells that are...2011) – Table 1 Shigella antigen-specific immune responses and colonization in rhesus monkeys after nasogastric administration of WRSS1, WRSs2...the respective antigens. 3.3. Mucosal responses in rhesus monkeys The mucosal immune response to Shigella LPS, and Invaplex- 50 antigens are summarized

Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract

PubMed Central

Arnold, Kelly; Romas, Laura; Westmacott, Garrett; McCorrister, Stuart; McKinnon, Lyle R.; Cohen, Craig R.; Mackelprang, Romel; Lingappa, Jairam; Lauffenburger, Doug A.; Klatt, Nichole R.; Burgener, Adam D.

2016-01-01

The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity. PMID:27656899

A Novel Peptide to Treat Oral Mucositis Blocks Endothelial and Epithelial Cell Apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu Xiaoyan; Chen Peili; Sonis, Stephen T.

2012-07-01

Purpose: No effective agents currently exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head-and-neck cancer. We identified a novel 21-amino acid peptide derived from antrum mucosal protein-18 that is cytoprotective, mitogenic, and motogenic in tissue culture and animal models of gastrointestinal epithelial cell injury. We examined whether administration of antrum mucosal protein peptide (AMP-p) could protect against and/or speed recovery from OM. Methods and Materials: OM was induced in established hamster models by a single dose of radiation, fractionated radiation, or fractionated radiation together with cisplatin to simulate conventional treatments of head-and-neck cancer. Results:more » Daily subcutaneous administration of AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in all three models. A delay in the onset of erythema after irradiation was observed, suggesting that a protective effect exists even before injury to mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on tumor necrosis factor-{alpha}-induced apoptosis were studied in an endothelial cell line (human dermal microvascular endothelial cells) as well as an epithelial cell line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to model the oral mucosa. AMP-p treatment, either before or after cell monolayers were exposed to tumor necrosis factor-{alpha}, protected against development of apoptosis in both cell types when assessed by annexin V and propidium iodide staining followed by flow cytometry or ligase-mediated polymerase chain reaction. Conclusions: These observations suggest that the ability of AMP-p to attenuate radiation-induced OM could be attributable, at least in part, to its antiapoptotic activity.« less

Wild eel microbiome reveals that skin mucus of fish could be a natural niche for aquatic mucosal pathogen evolution.

PubMed

Carda-Diéguez, Miguel; Ghai, Rohit; Rodríguez-Valera, Francisco; Amaro, Carmen

2017-12-21

Fish skin mucosal surfaces (SMS) are quite similar in composition and function to some mammalian MS and, in consequence, could constitute an adequate niche for the evolution of mucosal aquatic pathogens in natural environments. We aimed to test this hypothesis by searching for metagenomic and genomic evidences in the SMS-microbiome of a model fish species (Anguilla Anguilla or eel), from different ecosystems (four natural environments of different water salinity and one eel farm) as well as the water microbiome (W-microbiome) surrounding the host. Remarkably, potentially pathogenic Vibrio monopolized wild eel SMS-microbiome from natural ecosystems, Vibrio anguillarum/Vibrio vulnificus and Vibrio cholerae/Vibrio metoecus being the most abundant ones in SMS from estuary and lake, respectively. Functions encoded in the SMS-microbiome differed significantly from those in the W-microbiome and allowed us to predict that successful mucus colonizers should have specific genes for (i) attachment (mainly by forming biofilms), (ii) bacterial competence and communication, and (iii) resistance to mucosal innate immunity, predators (amoeba), and heavy metals/drugs. In addition, we found several mobile genetic elements (mainly integrative conjugative elements) as well as a series of evidences suggesting that bacteria exchange DNA in SMS. Further, we isolated and sequenced a V. metoecus strain from SMS. This isolate shares pathogenicity islands with V. cholerae O1 from intestinal infections that are absent in the rest of sequenced V. metoecus strains, all of them from water and extra-intestinal infections. We have obtained metagenomic and genomic evidence in favor of the hypothesis on the role of fish mucosal surfaces as a specialized habitat selecting microbes capable of colonizing and persisting on other comparable mucosal surfaces, e.g., the human intestine.

Regulatory role of Lactobacillus acidophilus on inflammation and gastric dysmotility in intestinal mucositis induced by 5-fluorouracil in mice.

PubMed

Justino, Priscilla F C; Melo, Luis F M; Nogueira, Andre F; Morais, Cecila M; Mendes, Walber O; Franco, Alvaro X; Souza, Emmanuel P; Ribeiro, Ronaldo A; Souza, Marcellus H L P; Soares, Pedro Marcos Gomes

2015-03-01

Lactobacillus acidophilus is widely used for gastrointestinal disorders, but its role in inflammatory conditions like in chemotherapy-induced mucositis is unclear. Here, we report the effect of L. acidophilus on 5-fluorouracil-induced (5-FU) intestinal mucositis in mice. Mice weighing 25-30 g (n = 8) were separated into three groups, saline, 5-FU, and 5-FU + L. acidophilus (5-FU-La) (16 × 10(9) CFU/kg). In the 5-FU-La group, L. acidophilus was administered concomitantly with 5-FU on the first day and alone for two additional days. Three days after the last administration of L. acidophilus, the animals were euthanized and the jejunum and ileum were removed for histopathological assessment and for evaluation of levels of myeloperoxidase activity, sulfhydryl groups, nitrite, and cytokines (TNF-α, IL-1β, CXCL-1, and IL-10). In addition, we investigated gastric emptying using spectrophotometry after feeding a 1.5-ml test meal by gavage and euthanasia. Data were submitted to ANOVA and Bonferroni's test, with the level of significance at p < 0.05. Intestinal mucositis induced by 5-FU significantly (p < 0.05) reduced the villus height-crypt depth ratio and GSH concentration and increased myeloperoxidase activity and the nitrite concentrations compared with the control group. Furthermore, 5-FU significantly (p < 0.05) increased cytokine (TNF-α, IL-1β, and CXCL-1) concentrations and decreased IL-10 concentrations compared with the control group. 5-FU also significantly (p < 0.05) delayed gastric emptying and gastrointestinal transit compared with the control group. All of these changes were significantly (p < 0.05) reversed by treatment with L. acidophilus. Lactobacillus acidophilus improves the inflammatory and functional aspects of intestinal mucositis induced by 5-FU.

Effectiveness of honey on radiation-induced oral mucositis, time to mucositis, weight loss, and treatment interruptions among patients with head and neck malignancies: A meta-analysis and systematic review of literature.

PubMed

Co, Jayson L; Mejia, Michael Benedict A; Que, Jocelyn C; Dizon, Janine Margarita R

2016-07-01

Mucositis is a disabling effect of radiotherapy in head and neck cancers. There is no current standard on management of radiation-induced mucositis. Honey has been shown to reduce radiation-induced mucositis. A systematic review and meta-analysis were undertaken to assess the ability of honey in reducing the severity of oral mucositis, time to mucositis, weight loss, and treatment interruptions. Eight studies were included and showed that honey was significantly better in lowering the risk for treatment interruptions, weight loss, and delaying time to mucositis, but not severity of mucositis. There is current evidence that honey is beneficial for patients with head and neck cancers by decreasing treatment interruptions, weight loss, and delaying the onset of oral mucositis, but not in decreasing peak mucositis score. In light of the results, honey is a reasonable treatment for radiation-induced mucositis, but more randomized clinical trials (RCTs) should be done. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1119-1128, 2016. © 2016 Wiley Periodicals, Inc.

Effect of chloroquine on intestinal lipid metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mansbach, C.M. 2d.; Arnold, A.; Garrett, M.

1987-11-01

Most studies that have quantitated recovery of infused lipid in the intestinal mucosa and mesenteric lymph have only been able to recapture 50-75%. One possibility is that the missing lipid enters a triacylglycerol (TG) storage pool in the enterocyte and is hydrolyzed by lysosomal lipase, and the free fatty acid released is transported by the portal vein. This postulate was tested by comparing glyceryl trioleate (TO)-infused rats pretreated with the lysosomotropic drug, chloroquine (6.3 mg.kg-1.h-1) with saline controls. Chloroquine increased mucosal TG from 94 +/- 6 to 128 +/- 8 mumol. Additionally, the specific activity of the mucosal TG relativemore » to the infused (/sup 3/H)TO was reduced in the treated rats. The mucosal TG increase was not due to impaired TG output, which remained the same as controls. We conclude that the TG in the acid lipase-sensitive pool derives most of its glyceride-glycerol from endogenous sources. Furthermore, the increment in mucosal TG caused by chloroquine is not enough to explain the majority of the acyl groups unaccounted for in the mucosa and lymph after a TG infusion. For these a direct passage of acyl groups through the enterocyte is postulated.« less

[Comparative pathology of early stress-induced changes in the duodenal mucosa in laboratory rats and in humans].

PubMed

Peychl, L; Brejcha, A

2003-01-01

Our presentation comprises results of two studies: The first was an experimental investigation of 60 Wistar-strain rats used in a toxicological study. The other part analysed stress changes in the duodenal mucosa in the human autopsy material. Both humans and rats had been exposed to stress and showed similar histological changes. In the rats the same duodenal lesions were present both in the test group and the control animals in the toxicological study. Lesions consisted of oedema of the duodenal villi and erosions in the tips of the villi. We believe that in the experimental group the stress was caused by restraining the animals by daily introduction of the gastric metallic tube, by taking blood from the retrobulbar plexus, and by anaesthesia. The autopsy study comprised 35 cases displaying congestion and macroscopically recognizable multifocal bleeding into the duodenal mucosal folds. The microscopic investigation revealed bleeding into the mucosal villi and small erosions. In some cases there were cuneiform mucosal infarcts extending into the submucosa. In the humans, severe cardiovascular diseases and circulatory disturbances represented the main causes of the stress. Local hypoxia and gastric juice acidity were involved in the pathogenesis of the duodenal mucosal changes.

Pantoprazole for the treatment of peptic ulcer bleeding and prevention of rebleeding.

PubMed

van Rensburg, Christo J; Cheer, Susan

2012-01-01

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers.

Pantoprazole for the Treatment of Peptic Ulcer Bleeding and Prevention of Rebleeding

PubMed Central

van Rensburg, Christo J.; Cheer, Susan

2012-01-01

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers. PMID:24833934

Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

PubMed Central

Bateman, Emma; Bowen, Joanne; Stringer, Andrea; Mayo, Bronwen; Plews, Erin; Wignall, Anthony; Greenberg, Norman; Schiffrin, Eduardo; Keefe, Dorothy

2013-01-01

Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo), and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets) for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA) was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis. PMID:24084053

Rebamipide, a novel antiulcer agent, attenuates Helicobacter pylori induced gastric mucosal cell injury associated with neutrophil derived oxidants.

PubMed Central

Suzuki, M; Miura, S; Mori, M; Kai, A; Suzuki, H; Fukumura, D; Suematsu, M; Tsuchiya, M

1994-01-01

The effect of rebamipide, a novel antiulcer compound, on Helicobacter pylori activated neutrophil dependent in vitro gastric epithelial cell injury was investigated. Luminol dependent chemiluminescence (ChL), which detects toxic oxidants from neutrophils exhibited a 12-fold increase when the bacterial suspension of H pylori was added to the isolated human neutrophils. This change was significantly attenuated by rebamipide at a concentration less than 1 mM, showing that rebamipide may inhibit oxidant production from H pylori elicited neutrophils. To assess whether rebamipide attenuates gastric mucosal injury, we tested its inhibitory action on H pylori induced gastric mucosal damage associated with neutrophils in vitro. Rabbit gastric mucosal cells were monolayered in culture wells and coincubated with human neutrophils and H pylori, and the cytotoxicity index was then calculated. Cultured gastric cells were significantly damaged when they were incubated with human neutrophils activated by H pylori. This cellular damage was attenuated by rebamipide in a dose-dependent manner. Furthermore, spectrophotometrical measurement showed that rebamipide (1 mM) inhibits urease activity by 21.7%. As monochloramine (an oxidant yielded by reaction of neutrophil derived chlorinated oxidant and ammonia) is proposed as an important toxic molecule in this model, the current findings suggest that the preventive effect of rebamipide on H pylori elicited neutrophil induced gastric mucosal injury may result from its inhibitory actions on the neutrophilic oxidative burst as well as H pylori derived urease activity. PMID:7959190

A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.

PubMed

Eliasson, Dubravka Grdic; Helgeby, Anja; Schön, Karin; Nygren, Caroline; El-Bakkouri, Karim; Fiers, Walter; Saelens, Xavier; Lövgren, Karin Bengtsson; Nyström, Ida; Lycke, Nils Y

2011-05-23

Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4°C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Aggregate complexes of HIV-1 induced by multimeric antibodies.

PubMed

Stieh, Daniel J; King, Deborah F; Klein, Katja; Liu, Pinghuang; Shen, Xiaoying; Hwang, Kwan Ki; Ferrari, Guido; Montefiori, David C; Haynes, Barton; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Michael, Nelson L; Robb, Merlin L; Kim, Jerome H; Denny, Thomas N; Tomaras, Georgia D; Shattock, Robin J

2014-10-02

Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells. These functions may work together to provide effective immune exclusion of virus from mucosal tissue; however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical to the design of successful immunization strategies to facilitate viral immune exclusion at the mucosal portals of entry. The potential of neutralizing and non-neutralizing IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable viral aggregate populations that could be separated from uncomplexed virions. Epitope specificity influenced both the degree of aggregation and formation of higher order complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders were able to efficiently opsonize viral particles in the absence of significant aggregation, reflective of monomeric IgA. These results collectively demonstrate that dIgA is capable of forming stable viral aggregates providing a plausible basis for testing the effectiveness of aggregation as a potential protection mechanism at the mucosal portals of viral entry.

Normal Tissue Complication Probability (NTCP) Modelling of Severe Acute Mucositis using a Novel Oral Mucosal Surface Organ at Risk.

PubMed

Dean, J A; Welsh, L C; Wong, K H; Aleksic, A; Dunne, E; Islam, M R; Patel, A; Patel, P; Petkar, I; Phillips, I; Sham, J; Schick, U; Newbold, K L; Bhide, S A; Harrington, K J; Nutting, C M; Gulliford, S L

2017-04-01

A normal tissue complication probability (NTCP) model of severe acute mucositis would be highly useful to guide clinical decision making and inform radiotherapy planning. We aimed to improve upon our previous model by using a novel oral mucosal surface organ at risk (OAR) in place of an oral cavity OAR. Predictive models of severe acute mucositis were generated using radiotherapy dose to the oral cavity OAR or mucosal surface OAR and clinical data. Penalised logistic regression and random forest classification (RFC) models were generated for both OARs and compared. Internal validation was carried out with 100-iteration stratified shuffle split cross-validation, using multiple metrics to assess different aspects of model performance. Associations between treatment covariates and severe mucositis were explored using RFC feature importance. Penalised logistic regression and RFC models using the oral cavity OAR performed at least as well as the models using mucosal surface OAR. Associations between dose metrics and severe mucositis were similar between the mucosal surface and oral cavity models. The volumes of oral cavity or mucosal surface receiving intermediate and high doses were most strongly associated with severe mucositis. The simpler oral cavity OAR should be preferred over the mucosal surface OAR for NTCP modelling of severe mucositis. We recommend minimising the volume of mucosa receiving intermediate and high doses, where possible. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Prevalence of oral lesions and measurement of salivary pH in the different trimesters of pregnancy

PubMed Central

Jain, Kanu; Kaur, Harshaminder

2015-01-01

INTRODUCTION Oral changes observed during pregnancy have been studied for many years, but their magnitude and frequency have not been stressed upon. This study was undertaken to assess the prevalence of oral lesions during different trimesters of pregnancy and their correlation with salivary pH change. METHODS The gingival, simplified oral hygiene, community periodontal and decayed-missing-filled teeth indices were used to assess a total of 120 pregnant women (40 in each trimester group) and 40 nonpregnant women (control group). Salivary pH was measured using a digital pH meter. Presence of any oral lesions was determined via oral examination. RESULTS Scores for all indices increased while salivary pH decreased from the control group to the first trimester group, through to the third. Oral lesions were seen in 44.2% of pregnant women. Lesions were seen in 27.5%, 52.5% and 52.5% of women in the first, second and third trimesters, respectively. The percentage of pregnant women with one oral lesion was highest in the second trimester (47.5%), whereas the third trimester had the highest prevalence (17.5%) of two concurrent oral lesions. The incidence of fissured tongue was highest in the first trimester group, and that of gingival enlargement was highest in the third trimester group. In the second trimester group, there was an almost equal incidence of fissured tongue and gingival/mucosal enlargement. CONCLUSION Most changes in oral tissues during pregnancy can be avoided with good oral hygiene. Salivary pH could be used to assess the prevalence of oral lesions in the different trimesters of pregnancy. PMID:25640100

Relation between gastric histology and gastric juice pH and nitrite and N-nitroso compound concentrations in the stomach after surgery for duodenal ulcer.

PubMed Central

Watt, P C; Sloan, J M; Donaldson, J; Campbell, G; Kennedy, T L

1984-01-01

Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes. PMID:6725597

Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

PubMed

Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi

2015-04-01

Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Transforming growth factor-alpha stimulates enterocyte proliferation and accelerates intestinal recovery following methotrexate-induced intestinal mucositis in a rat and a cell culture model.

PubMed

Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Shamian, Benhoor; Coran, Arnold G

2008-12-01

Recent evidence suggests that transforming growth factor-alpha (TGF-alpha) enhances enterocyte proliferation and exerts a gut trophic effect. The purpose of the present study was to evaluate the effect of TGF-alpha on enterocyte proliferation and intestinal recovery following methotrexate (MTX)-induced intestinal mucositis in rats and in Caco-2 cells. Nonpretreated Caco-2 cells and those pretreated with MTX were incubated with increasing concentrations of TGF-alpha. Cell proliferation was determined by FACS cytometry. Adult rats were divided into three groups: control rats treated with vehicle, MTX rats treated with one dose (20 microg/kg) of MTX given intraperitoneally, and MTX-TGF-alpha rats treated with one dose of MTX followed by two doses of TGF-alpha (75 microg/kg a day). Three days after MTX injection, rats were sacrificed. Intestinal mucosal damage (Park's score), mucosal structural changes, and enterocyte proliferation were measured at sacrifice. Western blotting was used to determine the level of extracellular signal-related kinase (ERK) protein, a marker of cell proliferation. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with P value less than 0.05 considered statistically significant. The in vitro experiment demonstrated that treatment with TGF-alpha of Caco-2 cells resulted in a significant stimulation of cell proliferation in a dose-dependent manner. The in vivo experiment showed that treatment with TGF-alpha resulted in a significant increase in bowel and mucosal weight, DNA and protein content in jejunum and ileum, villus height in jejunum and ileum, crypt depth in ileum, and increased cell proliferation in jejunum and ileum compared to the MTX group. MTX-TGF-alpha rats also had a significantly lower intestinal injury score in ileum when compared to MTX animals. The increase in levels of cell proliferation in MTX-TGF-alpha rats corresponded with the increase in ERK protein levels in intestinal mucosa. Treatment with TGF-alpha prevents mucosal injury, enhances ERK-induced enterocyte proliferation, and improves intestinal recovery following MTX-induced intestinal mucositis in rats. These findings correlated with the observation that TGF-alpha also caused a significant stimulation of cell proliferation in a Caco-2 cell culture model treated with MTX. These observations may have significant implications for the treatment of patients on chemotherapy who develop severe mucositis.

Primary mucosal melanomas: a comprehensive review

PubMed Central

Mihajlovic, Marija; Vlajkovic, Slobodan; Jovanovic, Predrag; Stefanovic, Vladisav

2012-01-01

Primary mucosal melanomas arise from melanocytes located in mucosal membranes lining respiratory, gastrointestinal and urogenital tract. Although a majority of mucosal melanomas originate from the mucosa of the nasal cavity and accessory sinuses, oral cavity, anorectum, vulva and vagina, they can arise in almost any part of mucosal membranes. Most of mucosal melanomas occur in occult sites, which together with the lack of early and specific signs contribute to late diagnosis, and poor prognosis. Because of their rareness the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well established protocols for staging and treatment of mucosal melanomas. Surgery is the mainstay of treatment, with trends toward more conservative treatment since radical surgery did not show an advantage for survival. Radiotherapy can provide better local control in some locations, but did not show improvement in survival. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have lowest percent of five-year survival. Recently revealed molecular changes underlying mucosal melanomas offer new hope for development of more effective systemic therapy for mucosal melanomas. Herein we presented a comprehensive review of various locations of primary melanoma along mucosal membranes, their epidemiological and clinical features, and treatment options. We also gave a short comparison of some characteristics of cutaneous and mucosal melanomas. PMID:23071856

Primary mucosal melanomas: a comprehensive review.

PubMed

Mihajlovic, Marija; Vlajkovic, Slobodan; Jovanovic, Predrag; Stefanovic, Vladisav

2012-01-01

Primary mucosal melanomas arise from melanocytes located in mucosal membranes lining respiratory, gastrointestinal and urogenital tract. Although a majority of mucosal melanomas originate from the mucosa of the nasal cavity and accessory sinuses, oral cavity, anorectum, vulva and vagina, they can arise in almost any part of mucosal membranes. Most of mucosal melanomas occur in occult sites, which together with the lack of early and specific signs contribute to late diagnosis, and poor prognosis. Because of their rareness the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well established protocols for staging and treatment of mucosal melanomas. Surgery is the mainstay of treatment, with trends toward more conservative treatment since radical surgery did not show an advantage for survival. Radiotherapy can provide better local control in some locations, but did not show improvement in survival. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have lowest percent of five-year survival. Recently revealed molecular changes underlying mucosal melanomas offer new hope for development of more effective systemic therapy for mucosal melanomas. Herein we presented a comprehensive review of various locations of primary melanoma along mucosal membranes, their epidemiological and clinical features, and treatment options. We also gave a short comparison of some characteristics of cutaneous and mucosal melanomas.

Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for development of protective HIV-1 vaccines.

PubMed

Belyakov, I M; Ahlers, J D

2011-01-01

Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection.

The pH-sensing receptor OGR1 improves barrier function of epithelial cells and inhibits migration in an acidic environment.

PubMed

de Vallière, Cheryl; Vidal, Solange; Clay, Ieuan; Jurisic, Giorgia; Tcymbarevich, Irina; Lang, Silvia; Ludwig, Marie-Gabrielle; Okoniewski, Michal; Eloranta, Jyrki J; Kullak-Ublick, Gerd A; Wagner, Carsten A; Rogler, Gerhard; Seuwen, Klaus

2015-09-15

The pH-sensing receptor ovarian cancer G protein-coupled receptor 1 (OGR1; GPR68) is expressed in the gut. Inflammatory bowel disease is typically associated with a decrease in local pH, which may lead to altered epithelial barrier function and subsequent gastrointestinal repair involving epithelial cell adhesion and migration. As the mechanisms underlying the response to pH changes are not well understood, we have investigated OGR1-mediated, pH-dependent signaling pathways in intestinal epithelial cells. Caco-2 cells stably overexpressing OGR1 were created and validated as tools to study OGR1 signaling. Barrier function, migration, and proliferation were measured using electric cell-substrate impedance-sensing technology. Localization of the tight junction proteins zonula occludens protein 1 and occludin and the rearrangement of cytoskeletal actin were examined by confocal microscopy. Paracellular permeability and protein and gene expression analysis using DNA microarrays were performed on filter-grown Caco-2 monolayers. We report that an acidic pH shift from pH 7.8 to 6.6 improved barrier function and stimulated reorganization of filamentous actin with prominent basal stress fiber formation. Cell migration and proliferation during in vitro wound healing were inhibited. Gene expression analysis revealed significant upregulation of genes related to cytoskeleton remodeling, cell adhesion, and growth factor signaling. We conclude that acidic extracellular pH can have a signaling function and impact the physiology of intestinal epithelial cells. The deconstruction of OGR1-dependent signaling may aid our understanding of mucosal inflammation mechanisms. Copyright © 2015 the American Physiological Society.

Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine

PubMed Central

Jakab, Robert L.; Collaco, Anne M.

2012-01-01

Changes in intestinal luminal pH affect mucosal ion transport. The aim of this study was to compare how luminal pH and specific second messengers modulate the membrane traffic of four major ion transporters (CFTR, NHE3, NKCC1, and NBCe1) in rat small intestine. Ligated duodenal, jejunal, and ileal segments were infused with acidic or alkaline saline, 8-Br-cAMP, or the calcium agonist carbachol in vivo for 20 min. Compared with untreated intestine, lumen pH was reduced after cAMP or carbachol and increased following HCO3−-saline. Following HCl-saline, lumen pH was restored to control pH levels. All four secretory stimuli resulted in brush-border membrane (BBM) recruitment of CFTR in crypts and villi. In villus enterocytes, CFTR recruitment was coincident with internalization of BBM NHE3 and basolateral membrane recruitment of the bicarbonate transporter NBCe1. Both cAMP and carbachol recruited NKCC1 to the basolateral membrane of enterocytes, while luminal acid or HCO3− retained NKCC1 in intracellular vesicles. Luminal acid resulted in robust recruitment of CFTR and NBCe1 to their respective enterocyte membrane domains in the upper third of the villi; luminal HCO3− induced similar membrane changes lower in the villi. These findings indicate that each stimulus promotes a specific transporter trafficking response along the crypt-villus axis. This is the first demonstration that physiologically relevant secretory stimuli exert their actions in villus enterocytes by membrane recruitment of CFTR and NBCe1 in tandem with NHE3 internalization. PMID:22936272

Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine.

PubMed

Jakab, Robert L; Collaco, Anne M; Ameen, Nadia A

2012-10-15

Changes in intestinal luminal pH affect mucosal ion transport. The aim of this study was to compare how luminal pH and specific second messengers modulate the membrane traffic of four major ion transporters (CFTR, NHE3, NKCC1, and NBCe1) in rat small intestine. Ligated duodenal, jejunal, and ileal segments were infused with acidic or alkaline saline, 8-Br-cAMP, or the calcium agonist carbachol in vivo for 20 min. Compared with untreated intestine, lumen pH was reduced after cAMP or carbachol and increased following HCO(3)(-)-saline. Following HCl-saline, lumen pH was restored to control pH levels. All four secretory stimuli resulted in brush-border membrane (BBM) recruitment of CFTR in crypts and villi. In villus enterocytes, CFTR recruitment was coincident with internalization of BBM NHE3 and basolateral membrane recruitment of the bicarbonate transporter NBCe1. Both cAMP and carbachol recruited NKCC1 to the basolateral membrane of enterocytes, while luminal acid or HCO(3)(-) retained NKCC1 in intracellular vesicles. Luminal acid resulted in robust recruitment of CFTR and NBCe1 to their respective enterocyte membrane domains in the upper third of the villi; luminal HCO(3)(-) induced similar membrane changes lower in the villi. These findings indicate that each stimulus promotes a specific transporter trafficking response along the crypt-villus axis. This is the first demonstration that physiologically relevant secretory stimuli exert their actions in villus enterocytes by membrane recruitment of CFTR and NBCe1 in tandem with NHE3 internalization.

Pretreatment with Saccharomyces boulardii does not prevent the experimental mucositis in Swiss mice.

PubMed

Maioli, Tatiani Uceli; de Melo Silva, Brenda; Dias, Michelle Nobre; Paiva, Nivea Carolina; Cardoso, Valbert Nascimento; Fernandes, Simone Odilia; Carneiro, Cláudia Martins; Dos Santos Martins, Flaviano; de Vasconcelos Generoso, Simone

2014-04-11

The antimetabolite chemotherapy 5-Fluorouracil is one of the most commonly prescribed drugs in clinical cancer treatment. Although this drug is not specific for cancer cells and also acts on healthy cells, it can cause mucositis, a common collateral effect. Dysbiosis has also been described in 5-fluorouracil-induced mucositis and is likely to contribute to the overall development of mucositis. In light of this theory, the use of probiotics could be a helpful strategy to alleviate mucositis. So the aim of this study was evaluate the impact of the probiotic Saccharomyces boulardii in a model of mucositis. After induced of mucositis, mice from the Mucositis groups showed a decrease in food consumption (p < 0.05) and therefore had a greater weight loss (p < 0.05). The treatment with Saccharomyces boulardii did not reverse this effect (p > 0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p < 0.05). There were no differences in mucosal lesions, intestinal permeability and sIgA secretion (p > 0.05) in mice pretreated with S. boulardii. S. boulardii was not able to prevent the effects of experimental mucositis induced by 5- Fluorouracil.

Pretreatment with Saccharomyces boulardii does not prevent the experimental mucositis in Swiss mice

PubMed Central

2014-01-01

Background The antimetabolite chemotherapy 5-Fluorouracil is one of the most commonly prescribed drugs in clinical cancer treatment. Although this drug is not specific for cancer cells and also acts on healthy cells, it can cause mucositis, a common collateral effect. Dysbiosis has also been described in 5-fluorouracil-induced mucositis and is likely to contribute to the overall development of mucositis. In light of this theory, the use of probiotics could be a helpful strategy to alleviate mucositis. So the aim of this study was evaluate the impact of the probiotic Saccharomyces boulardii in a model of mucositis. Results After induced of mucositis, mice from the Mucositis groups showed a decrease in food consumption (p < 0.05) and therefore had a greater weight loss (p < 0.05). The treatment with Saccharomyces boulardii did not reverse this effect (p > 0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (p < 0.05). There were no differences in mucosal lesions, intestinal permeability and sIgA secretion (p > 0.05) in mice pretreated with S. boulardii. Conclusions S. boulardii was not able to prevent the effects of experimental mucositis induced by 5- Fluorouracil. PMID:24721659

Mucositis care in acute leukemia and non-Hodgkin lymphoma patients undergoing high-dose chemotherapy.

PubMed

Martinez, José Manuel; Pereira, Dulcineia; Chacim, Sérgio; Mesquita, Edgar; Sousa, Inês; Martins, Ângelo; Azevedo, Teresa; Mariz, José Mário

2014-09-01

This study intends to provide new insights into the incidence and care of mucositis by the epidemiological characterization of patients with hematological malignancy treated at our institution. It also aims to understand the effectiveness of several treatments used. This is a longitudinal observational single-center study-convenience sample-which includes malignant hematologic inpatients submitted to high-dose CT from February to August 2012. We registered epidemiological data, diagnosis, oral mucositis daily questionnaire (OMDQ), World Health Organization (WHO) oral toxicity scale, and supportive medications used for mucositis. We evaluated 30 patients who had 73 episodes of hospitalization, having recorded the development of mucositis in 21.9 % (n = 16) episodes (22 patients with acute leukemia (AL) and 8 patients with non-Hodgkin lymphoma (NHL)). Grades 3-4 mucositis was reported in 4.1 % of the total episodes. The results of OMDQ showed some limitations in the quality of life, of patients with mucositis, related with the ability to eat and drink due to mouth pain (p < 0.001). In patients with NHL and AL, neutropenia entails an increased risk of mucositis (p < 0.001). Patients who did not initiate early prophylaxis with conservative measures developed mucositis earlier (p < 0.05). The incidence of mucositis is high, being reported mainly in AL patients, with limitations in quality of life. Grade 4 neutropenia increases mucositis risk. Early prophylaxis with basic oral care may delay mucositis. Further studies are crucial to characterize mucositis epidemiology, physiopathology, and its management.

Velopharyngeal mucosal surface topography in healthy subjects and subjects with obstructive sleep apnea.

PubMed

Lambeth, Christopher; Amatoury, Jason; Wang, Ziyu; Foster, Sheryl; Amis, Terence; Kairaitis, Kristina

2017-03-01

Macroscopic pharyngeal anatomical abnormalities are thought to contribute to the pathogenesis of upper airway (UA) obstruction in obstructive sleep apnea (OSA). Microscopic changes in the UA mucosal lining of OSA subjects are reported; however, the impact of these changes on UA mucosal surface topography is unknown. This study aimed to 1 ) develop methodology to measure UA mucosal surface topography, and 2 ) compare findings from healthy and OSA subjects. Ten healthy and eleven OSA subjects were studied. Awake, gated (end expiration), head and neck position controlled magnetic resonance images (MRIs) of the velopharynx (VP) were obtained. VP mucosal surfaces were segmented from axial images, and three-dimensional VP mucosal surface models were constructed. Curvature analysis of the models was used to study the VP mucosal surface topography. Principal, mean, and Gaussian curvatures were used to define surface shape composition and surface roughness of the VP mucosal surface models. Significant differences were found in the surface shape composition, with more saddle/spherical and less flat/cylindrical shapes in OSA than healthy VP mucosal surface models ( P < 0.01). OSA VP mucosal surface models were also found to have more mucosal surface roughness ( P < 0.0001) than healthy VP mucosal surface models. Our novel methodology was utilized to model the VP mucosal surface of OSA and healthy subjects. OSA subjects were found to have different VP mucosal surface topography, composed of increased irregular shapes and increased roughness. We speculate increased irregularity in VP mucosal surface may increase pharyngeal collapsibility as a consequence of friction-related pressure loss. NEW & NOTEWORTHY A new methodology was used to model the upper airway mucosal surface topography from magnetic resonance images of patients with obstructive sleep apnea and healthy adults. Curvature analysis was used to analyze the topography of the models, and a new metric was derived to describe the mucosal surface roughness. Increased roughness was found in the obstructive sleep apnea vs. healthy group, but further research is required to determine the functional effects of the measured difference on upper airway airflow mechanics. Copyright © 2017 the American Physiological Society.

Oral mucositis - self-care

MedlinePlus

Cancer treatment - mucositis; Cancer treatment - mouth pain; Cancer treatment - mouth sores; Chemotherapy - mucositis; Chemotherapy - mouth pain; Chemotherapy - mouth sores; Radiation therapy - mucositis; Radiation therapy - mouth pain; Radiation therapy - mouth ...

An oral vaccine based on U-Omp19 induces protection against B. abortus mucosal challenge by inducing an adaptive IL-17 immune response in mice.

PubMed

Pasquevich, Karina A; Ibañez, Andrés E; Coria, Lorena M; García Samartino, Clara; Estein, Silvia M; Zwerdling, Astrid; Barrionuevo, Paula; Oliveira, Fernanda S; Seither, Christine; Warzecha, Heribert; Oliveira, Sergio C; Giambartolomei, Guillermo H; Cassataro, Juliana

2011-01-14

As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could be radical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune response elicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; or with plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucella when orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challenge when parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explained at least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneally administered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response was induced. Depletion of CD4(+) T cells in mice orally vaccinated with U-Omp19 resulted in a loss of the elicited protection, indicating that this cell type mediates immune protection. The role of IL-17 against Brucella infection has never been explored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal U-Omp19 vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did not influence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate that an oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus by inducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does not contribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays a central role in vaccine mediated anti-Brucella mucosal immunity.

Dual-focus Magnification, High-Definition Endoscopy Improves Pathology Detection in Direct-to-Test Diagnostic Upper Gastrointestinal Endoscopy.

PubMed

Bond, Ashley; Burkitt, Michael D; Cox, Trevor; Smart, Howard L; Probert, Chris; Haslam, Neil; Sarkar, Sanchoy

2017-03-01

In the UK, the majority of diagnostic upper gastrointestinal (UGI) endoscopies are a result of direct-to-test referral from the primary care physician. The diagnostic yield of these tests is relatively low, and the burden high on endoscopy services. Dual-focus magnification, high-definition endoscopy is expected to improve detection and classification of UGI mucosal lesions and also help minimize biopsies by allowing better targeting. This is a retrospective study of patients attending for direct-to-test UGI endoscopy from January 2015 to June 2015. The primary outcome of interest was the identification of significant pathology. Detection of significant pathology was modelled using logistic regression. 500 procedures were included. The mean age of patients was 61.5 (±15.6) years; 60.8% of patients were female. Ninety-four gastroscopies were performed using dual-focus magnification high-definition endoscopy. Increasing age, male gender, type of endoscope, and type of operator were all identified as significant factors influencing the odds of detecting significant mucosal pathology. Use of dual-focus magnification, high-definition endoscopy was associated with an odds ratio of 1.87 (95%CI 1.11-3.12) favouring the detection of significant pathology. Subsequent analysis suggested that the increased detection of pathology during dual-focus magnification, high-definition endoscopy also influenced patient follow-up and led to a 3.0 fold (p=0.04) increase in the proportion of patients entered into an UGI endoscopic surveillance program. Dual-focus magnification, high-definition endoscopy improved the diagnostic yield for significant mucosal pathology in patients referred for direct-to-test endoscopy. If this finding is recapitulated elsewhere it will have substantial impact on the provision of UGI endoscopic services.

Ammonia Movement in the Small Intestine: Preferential Transport by the Ileum *

PubMed Central

Mossberg, Sanford M.; Ross, George

1967-01-01

Isolated, surviving sacs of everted small intestine were used to characterize ammonia transport in the golden hamster. Jejunal and ileal sacs incubated aerobically in ammonia-free test solution liberated the same quantity of ammonia as did sacs that were filled and immediately emptied of their contents, indicating no significant evolution of metabolic ammonia. Under aerobic conditions, ileal sacs transferred a solution of high ammonia content from the mucosal surface to the serosal surface against a concentration gradient. This transport was not glucose dependent and exhibited first-order Michaelis-Menten kinetics. Inhibition of absorption occurred with anaerobiosis, 2,4-dinitrophenol, and sodium cyanide. In jejunal segments ammonia was not transported against an adverse chemical gradient. Ileal ammonia absorption was accompanied by bicarbonate secretion and acidification of the serosal solution. Both bicarbonate movement and pH gradients were abolished by inhibitors of ammonia transport. In the jejunum, the absence of ammonia movement occurred in association with minimal bicarbonate secretion and no appreciable change in serosal pH. Despite the creation of hydrogen ion gradients tending to augment or to retard ammonia absorption by nonionic diffusion, ammonia movement was unaffected, i.e., relative acidification of serosal contents did not augment ammonia absorption, and relative alkalinization of serosal fluid caused no inhibition of ammonia transport. In the absence of bicarbonate ion, ammonia transport did not occur. The significance of these findings is discussed with consideration of both ionic and nonionic mechanisms of ammonia movement. It is suggested that ammonia is absorbed in the ileum by active ionic transport. PMID:6021202

Dependences of mucosal dose on photon beams in head-and-neck intensity-modulated radiation therapy: a Monte Carlo study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, James C.L., E-mail: james.chow@rmp.uhn.on.ca; Department of Radiation Oncology, University of Toronto, Toronto, Ontario; Department of Physics, Ryerson University, Toronto, Ontario

2012-07-01

Dependences of mucosal dose in the oral or nasal cavity on the beam energy, beam angle, multibeam configuration, and mucosal thickness were studied for small photon fields using Monte Carlo simulations (EGSnrc-based code), which were validated by measurements. Cylindrical mucosa phantoms (mucosal thickness = 1, 2, and 3 mm) with and without the bone and air inhomogeneities were irradiated by the 6- and 18-MV photon beams (field size = 1 Multiplication-Sign 1 cm{sup 2}) with gantry angles equal to 0 Degree-Sign , 90 Degree-Sign , and 180 Degree-Sign , and multibeam configurations using 2, 4, and 8 photon beams inmore » different orientations around the phantom. Doses along the central beam axis in the mucosal tissue were calculated. The mucosal surface doses were found to decrease slightly (1% for the 6-MV photon beam and 3% for the 18-MV beam) with an increase of mucosal thickness from 1-3 mm, when the beam angle is 0 Degree-Sign . The variation of mucosal surface dose with its thickness became insignificant when the beam angle was changed to 180 Degree-Sign , but the dose at the bone-mucosa interface was found to increase (28% for the 6-MV photon beam and 20% for the 18-MV beam) with the mucosal thickness. For different multibeam configurations, the dependence of mucosal dose on its thickness became insignificant when the number of photon beams around the mucosal tissue was increased. The mucosal dose with bone was varied with the beam energy, beam angle, multibeam configuration and mucosal thickness for a small segmental photon field. These dosimetric variations are important to consider improving the treatment strategy, so the mucosal complications in head-and-neck intensity-modulated radiation therapy can be minimized.« less

13C-breath tests for sucrose digestion in congenital sucrase isomaltase-deficient and sacrosidase-supplemented patients

USDA-ARS?s Scientific Manuscript database

Congenital sucrase-isomaltase deficiency (CSID) is characterized by absence or deficiency of the mucosal sucrase-isomaltase enzyme. Specific diagnosis requires upper gastrointestinal biopsy with evidence of low to absent sucrase enzyme activity and normal histology. The hydrogen breath test (BT) is ...

New generation of oral mucosal vaccines targeting dendritic cells

PubMed Central

Owen, Jennifer L.; Sahay, Bikash; Mohamadzadeh, Mansour

2013-01-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including B. anthracis in experimental models of disease. PMID:23835515

Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury.

PubMed

Ota, Kazuhiro; Takeuchi, Toshihisa; Nouda, Sadaharu; Ozaki, Haruhiko; Kawaguchi, Shinpei; Takahashi, Yoshiaki; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Kuramoto, Takanori; Higuchi, Kazuhide

2016-11-01

Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20-65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group). Esophagogastroduodenoscopy and video capsule endoscopy were performed, and the fecal occult blood reaction and fecal calprotectin levels were measured before and two weeks after drug administration. Although the fecal calprotectin levels increased significantly in Group A, they did not increase in Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among the three groups. In conclusion, standard-dose rebamipide is sufficient for preventing mucosal injury of the small intestine induced by low-dose aspirin, indicating that high-dose rebamipide is not necessary.

Mucosal and systemic adjuvant effects of cholera toxin and Cry1Ac protoxin on the specific antibody response to HIV-1 C4/V3 peptides are different and depend on the antigen co-administered.

PubMed

Esquivel-Pérez, Rita; Moreno-Fierros, Leticia

2005-01-01

Evidence from several sources support the assertion that cholera toxin (CT) is a potent immunogen and mucosal adjuvant; however there are also reports showing its lack of adjuvanticity against some antigens. Cry1Ac protoxin also exerts adjuvant effects in the antibody responses to proteins and polysaccharides but its adjuvanticity with regard to peptide vaccines had not been tested. To probe whether the adjuvant effects of these proteins varied depending on the antigen co-administered, we evaluated antipeptide antibody responses in serum and mucosal samples (vaginal, intestinal, and pulmonary) of mice that were immunized by intranasal or intraperitoneal routes with one of two distinct hybrid C4/V3 HIV peptides, either alone or with CT or Cry1Ac. The tested HIV 1 peptides differed in two aminoacids, T1SP10MN(A) was modified at the SP10 region by the substitution of the isoleucines 12 and 14 for cysteines and was called modified (m)T1SP10MN(A). Our data indicate that the adjuvant effects of CT and Cry1Ac are different. In addition they vary depending on the antigen co-administered and the number of antigen doses, because after three doses moderate adjuvant effects of CT and Cry1Ac on anti-peptide serum and mucosal antibody responses were observed only against the mT1SP10MN(A). In contrast, to attain significant adjuvant effects against the T1SP10MN, four doses were required. Interestingly we found that modification of the HIV peptide increases its immunogenicity without altering the principal neutralizing determinant (SP10).

Prevalence of and Risk Factors for Oral Human Papillomavirus Among Young Women in Costa Rica

PubMed Central

Lang Kuhs, Krystle A.; Gonzalez, Paula; Struijk, Linda; Castro, Felipe; Hildesheim, Allan; van Doorn, Leen-Jan; Rodriguez, Ana Cecilia; Schiffman, Mark; Quint, Wim; Lowy, Douglas R.; Porras, Carolina; DelVecchio, Corey; Katki, Hormuzd A.; Jimenez, Silvia; Safaeian, Mahboobeh; Schiller, John; Solomon, Diane; Wacholder, Sholom; Herrero, Rolando; Kreimer, Aimée R.; Herrero, Rolando; Alfaro, Mario; Bratti, M. Concepción; Cortés, Bernal; Espinoza, Albert; Estrada, Yenory; Guillén, Diego; Jiménez, Silvia E.; Morales, Jorge; Villegas, Luis; Morera, Lidia Ana; Porras, Carolina; Rodríguez, Ana Cecilia; Hildesheim, Allan; Kreimer, Aimée R.; Lowy, Douglas R.; Macklin, Nora; Schiffman, Mark; Schiller, John T.; Sherman, Mark; Solomon, Diane; Wacholder, Sholom; Freer, Enrique; Bonilla, José; García-Piñeres, Alfonso; Silva, Sandra; Atmella, Ivannia; Ramírez, Margarita; Pinto, Ligia; Kemp, Troy; Eklund, Claire; Hutchinson, Martha; Sidawy, Mary; Quint, Wim; van Doorn, Leen-Jan; Struijk, Linda

2013-01-01

Background. Little is known about the epidemiology of oral human papillomavirus (HPV) in Latin America. Methods. Women (N = 5838) aged 22–29 in the control and vaccine arms of an HPV-16/18 vaccine trial in Costa Rica had oral, cervical, and anal specimens collected. Samples were tested for alpha mucosal HPV types (SPF10/LiPA25 version 1); a subset of oral samples (n = 500) was tested for cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu. Results. In the control arm (n = 2926), 1.9% of women had an oral alpha mucosal HPV detected, 1.3% had carcinogenic HPV, and 0.4% had HPV-16; similar patterns for non-16/18 HPV types were observed in the vaccine arm. Independent risk factors for any oral alpha mucosal HPV among women in the control arm included marital status (adjusted odds ratio [AOR], 3.2; 95% confidence interval [CI], 1.8–5.7 for single compared to married/living as married), number of sexual partners (AOR, 2.4; 95% CI, 1.0–6.1 for ≥4 partners compared to 0–1 partners), chronic sinusitis (AOR, 3.1; 95% CI, 1.5–6.7), and cervical HPV infection (AOR, 2.6; 95% CI, 1.4–4.6). Detection of beta HPV was common (18.6%) and not associated with sexual activity. Conclusions. Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in the oral region and were predominately associated with sexual behavior. Clinical Trials Registration. NCT00128661. PMID:24014882

Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters.

PubMed

Barr, Jeremy J; Auro, Rita; Sam-Soon, Nicholas; Kassegne, Sam; Peters, Gregory; Bonilla, Natasha; Hatay, Mark; Mourtada, Sarah; Bailey, Barbara; Youle, Merry; Felts, Ben; Baljon, Arlette; Nulton, Jim; Salamon, Peter; Rohwer, Forest

2015-11-03

Bacteriophages (phages) defend mucosal surfaces against bacterial infections. However, their complex interactions with their bacterial hosts and with the mucus-covered epithelium remain mostly unexplored. Our previous work demonstrated that T4 phage with Hoc proteins exposed on their capsid adhered to mucin glycoproteins and protected mucus-producing tissue culture cells in vitro. On this basis, we proposed our bacteriophage adherence to mucus (BAM) model of immunity. Here, to test this model, we developed a microfluidic device (chip) that emulates a mucosal surface experiencing constant fluid flow and mucin secretion dynamics. Using mucus-producing human cells and Escherichia coli in the chip, we observed similar accumulation and persistence of mucus-adherent T4 phage and nonadherent T4∆hoc phage in the mucus. Nevertheless, T4 phage reduced bacterial colonization of the epithelium >4,000-fold compared with T4∆hoc phage. This suggests that phage adherence to mucus increases encounters with bacterial hosts by some other mechanism. Phages are traditionally thought to be completely dependent on normal diffusion, driven by random Brownian motion, for host contact. We demonstrated that T4 phage particles displayed subdiffusive motion in mucus, whereas T4∆hoc particles displayed normal diffusion. Experiments and modeling indicate that subdiffusive motion increases phage-host encounters when bacterial concentration is low. By concentrating phages in an optimal mucus zone, subdiffusion increases their host encounters and antimicrobial action. Our revised BAM model proposes that the fundamental mechanism of mucosal immunity is subdiffusion resulting from adherence to mucus. These findings suggest intriguing possibilities for engineering phages to manipulate and personalize the mucosal microbiome.

Mucosal excision and suturing for obesity and GERD.

PubMed

Légner, András; Tsuboi, Kazuto; Stadlhuber, Rudolf; Yano, Fumiaki; Halvax, Peter; Hunt, Brandon; Penka, Wayne; Filipi, Charles J

2013-12-01

Suture and staple-based endoluminal devices for gastroesophageal reflux disease (GERD) and obesity have failed to demonstrate long-term efficacy. To demonstrate the feasibility of mucosal excision and full-thickness suture apposition of the excision beds to create sufficient scar tissue formation at the gastroesophageal junction for the intraluminal treatment of GERD or obesity. Survival animal experiments. Seven mongrel dogs. Interventions. Under general endotracheal anesthesia, a Barostat test was performed on 4 dogs. A mucosal excision device was introduced through the esophagus into the proximal stomach. Two to 4 mucosal excisions were performed on all dogs at or just below the gastroesophageal junction and the mucosal pieces were removed. After hemostasis, an intraluminal suturing instrument was introduced and either 2 or 4 sutures were placed through the excision beds to bring them into apposition. These were tied and the suture strands cut. All dogs were survived for 2 months. End-term endoscopies were performed, and a repeat Barostat procedure was performed on the animals undergoing an antireflux procedure. After euthanasia the stomachs were explanted, examined, photographed, and sectioned for histologic examination. All dogs survived without complication. In the 4 GERD dogs, the Barostat studies demonstrated a significant decrease in gastroesophageal junction compliance. In the 3 dogs undergoing the obesity procedure, the gastric outlet apposition to a 6-mm endoscope was satisfactory with full insufflation and the desired scarring was seen on histologic examination. It is possible to create adequate gastroesophageal junction scarring for the treatment of GERD and obesity. A clinical pilot study will be initiated.

Mechanisms of gastroprotection.

PubMed

Konturek, S J

1990-01-01

Gastric mucosa is constantly exposed to various irritants, but it usually maintains its integrity owing to several lines of defense, including mucus-alkaline secretion, mucosal hydrophobicity, rich mucosal blood flow, stabilization of tissue lysosomes, maintenance of mucosal sulfhydryls, and rapid proliferation and renewal of mucosal cells. Prostaglandins (PG) inhibit experimental gastric mucosal damage and ulcerations induced by a wide variety of agents, hence PG have been proposed to contribute to the overall protective process by activation of various mucosal defence lines--particularly by prevention of vasocongestion, ischemia, and deep hemorrhagic necrosis. The relation between tissue PG generation and mucosal protection does not appear to be closely related, and probably only minute amounts of PG are required to maintain mucosal integrity. In contrast to PG, other products of arachidonate metabolism, such as TxA2, LTC4 or LTD4, and the related lipid, platelet-activating factor, appear to mediate mucosal damage mainly by the disturbance in mucosal microcirculation and tissue ischemia. Gastroprotection can be achieved by stimulation of mucosal biosynthesis of protective PG or by the inhibition of the release or action of the proulcerogenic arachidonate metabolites. Certain natural substances, such as sulfhydryls, epidermal growth factor, or polyamines, protect the mucosa via a PG-independent mechanism, probably by enhancing the tissue repair processes.(ABSTRACT TRUNCATED AT 250 WORDS)

A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T cell mucosal response characterized by high levels of α4β7 integrin and an effector memory phenotype

PubMed Central

Neeson, Paul; Boyer, Jean; Kumar, Sanjeev; Lewis, Mark G.; Veazey, Lennox MattiasRon; Weiner, David; Paterson, Yvonne

2006-01-01

In this study in Rhesus macaques, we tested whether IL-12 or IL-15 in a DNA prime-oral Listeria boost amplifies the SIV-Gag specific CD8 mucosal response. SIV-specific CD8 T cells were demonstrated in the peripheral blood (PB) in all test vaccine groups, but not the control group. SIV Gag-specific CD8 T cells in the PB expressed α4β7 integrin, the gut-homing receptor; a minor subset co-express αEβ7 integrin. SIV Gag-specific CD8 T cells were also detected in the gut tissue, intraepithelial (IEL) and lamina propria lymphocytes (LPL) of the duodenum and ileum. These cells were characterized by high levels of β7 integrin expression and a predominance of the effector memory phenotype. Neither Il-12 nor IL-15 amplified the frequency of SIV-specific CD8 T cells in the gut. Thus, the DNA prime oral Listeria boost strategy induced a mucosal SIV-Gag specific CD8 T cell response characterized by expression of the α4β7 integrin gut-homing receptor. PMID:16904153

Fluorescein transport properties across artificial lipid membranes, Caco-2 cell monolayers and rat jejunum.

PubMed

Berginc, Katja; Zakelj, Simon; Levstik, Lea; Ursic, Darko; Kristl, Albin

2007-05-01

Membrane transport characteristics of a paracellular permeability marker fluorescein were evaluated using artificial membrane, Caco-2 cell monolayers and rat jejunum, all mounted in side-by-side diffusion cells. Modified Ringer buffers with varied pH values were applied as incubation salines on both sides of artificial membrane, cell culture monolayers or rat jejunum. Passive transport according to pH partition theory was determined using all three permeability models. In addition to that, active transport of fluorescein in the M-S (mucosal-to-serosal) direction through rat jejunum was observed. The highest M-S P(app) values regarding the active transport through the rat jejunum were observed in incubation saline with pH 6.5. Fluorescein transport through the rat jejunum was inhibited by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) and alpha-CHC (alpha-cyano-4-hydroxycinnamic acid). Thus, we assume that two pH-dependent influx transporters could be involved in the fluorescein membrane transport through the intestinal (jejunal) epithelium. One is very likely an MCT (monocarboxylic acid cotransporter) isoform, inhibited by specific MCT inhibitor alpha-CHC, while the involvement of the second one with overlapping substrate/inhibitor specificities (most probably a member of the organic anion-transporting polypeptide family, inhibited at least partially by DIDS) could not be excluded.

Anthrax vaccine powder formulations for nasal mucosal delivery.

PubMed

Jiang, Ge; Joshi, Sangeeta B; Peek, Laura J; Brandau, Duane T; Huang, Juan; Ferriter, Matthew S; Woodley, Wendy D; Ford, Brandi M; Mar, Kevin D; Mikszta, John A; Hwang, C Robin; Ulrich, Robert; Harvey, Noel G; Middaugh, C Russell; Sullivan, Vincent J

2006-01-01

Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6-8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7-8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization.

Salivary biomarker levels and oral health status of children with autistic spectrum disorders: a comparative study.

PubMed

Bhandary, S; Hari, N

2017-04-01

To evaluate the oral health status, salivary flow rate, pH and buffering capacity in children with autistic spectrum disorders (ASD) in comparison to their healthy siblings. A total of 30 subjects with ASD and 30 normal healthy siblings between the ages of 6-12 years of both genders attending various special schools and hospitals of Mangalore, India were recruited. Estimation of salivary pH, flow rate and buffering capacity were performed and oral health status was assessed using the WHO oral assessment form for children (World Health Organization in Oral health surveys: basic methods, World Health Organization, Geneva, 2013). The oral hygiene of the subjects was assessed using the oral hygiene index-simplified. Dental erosive lesions, presence of mucosal lesions and dental trauma were recorded for both the study and the control groups. It was observed that salivary pH and buffering capacity were lower in children with ASD than their healthy siblings, the dental caries incidence was higher in ASD children when compared to their healthy siblings and oral hygiene was fair with gingival bleeding in children with ASD. This study clearly indicates a need for better home care measures, parent, caregiver and institutional education on the importance of oral well-being among children with ASD.

21 CFR 884.1100 - Endometrial brush.

Code of Federal Regulations, 2010 CFR

2010-04-01

... endometrium (the mucosal lining of the uterus) by brushing its surface. This device is used to study... perforation, or a recent cesarean section, and (3) Design and testing: (i) The sampling component is covered...

21 CFR 884.1100 - Endometrial brush.

Code of Federal Regulations, 2011 CFR

2011-04-01

... endometrium (the mucosal lining of the uterus) by brushing its surface. This device is used to study... perforation, or a recent cesarean section, and (3) Design and testing: (i) The sampling component is covered...

New generation of oral mucosal vaccines targeting dendritic cells.

PubMed

Owen, Jennifer L; Sahay, Bikash; Mohamadzadeh, Mansour

2013-12-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including Bacillus anthracis in experimental models of disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation

PubMed Central

Parthasarathy, Gopanandan; Chen, Jun; Chen, Xianfeng; Chia, Nicholas; O'Connor, Helen M.; Wolf, Patricia G.; Gaskins, H. Rex; Bharucha, Adil E.

2015-01-01

Background & Aims In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Methods Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average of 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Results Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P<.05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P<.05) and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. Conclusions After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation. PMID:26460205

Oral Disease Profiles in Chronic Graft versus Host Disease

PubMed Central

Fassil, H.; Mays, J.W.; Edwards, D.; Baird, K.; Steinberg, S.M.; Cowen, E.W.; Naik, H.; Datiles, M.; Stratton, P.; Gress, R.E.; Pavletic, S.Z.

2015-01-01

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer’s tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials. PMID:25740857

Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease.

PubMed

van Hoeij, Froukje B; Weijenborg, Pim W; van den Bergh Weerman, Marius A; van den Wijngaard, René M J G J; Verheij, J; Smout, André J P M; Bredenoord, Albert J

2016-07-01

Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) (P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) (P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm(-2)·h(-1)) than in the proximal segment (368 nmol·cm(-2)·h(-1)) (P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability. Copyright © 2016 the American Physiological Society.

The Role of Wnt/β-Catenin Signaling in Enterocyte Turnover during Methotrexate-Induced Intestinal Mucositis in a Rat

PubMed Central

Sukhotnik, Igor; Geyer, Tatiana; Pollak, Yulia; Mogilner, Jorge G.; Coran, Arnold G.; Berkowitz, Drora

2014-01-01

Background/Aims Intestinal mucositis is a common side-effect in patients who receive aggressive chemotherapy. The Wnt signaling pathway is critical for establishing and maintaining the proliferative compartment of the intestine. In the present study, we tested whether Wnt/β-catenin signaling is involved in methotrexate (MTX)-induced intestinal damage in a rat model. Methods Non-pretreated and pretreated with MTX Caco-2 cells were evaluated for cell proliferation and apoptosis using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-2 animals were treated with a single dose of MTX given IP and were sacrificed on day 2, and MTX-4 rats were treated with MTX similar to group B and were sacrificed on day 4. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. Real Time PCR and Western blot was used to determine the level of Wnt/β-catenin related genes and protein expression. Results In the vitro experiment, treatment with MTX resulted in marked decrease in early cell proliferation rates following by a 17-fold increase in late cell proliferation rates compared to early proliferation. Treatment with MTX resulted in a significant increase in early and late apoptosis compared to Caco-2 untreated cells. In the vivo experiment, MTX-2 and MTX-4 rats demonstrated intestinal mucosal hypoplasia. MTX-2 rats demonstrated a significant decrease in FRZ-2, Wnt 3A Wnt 5A, β-catenin, c-myc mRNA expression and a significant decrease in β-catenin and Akt protein levels compared to control animals. Four days following MTX administration, rats demonstrated a trend toward a restoration of Wnt/β-catenin signaling especially in ileum. Conclusions Wnt/β-catenin signaling is involved in enterocyte turnover during MTX-induced intestinal mucositis in a rat. PMID:25375224

Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation.

PubMed

Parthasarathy, Gopanandan; Chen, Jun; Chen, Xianfeng; Chia, Nicholas; O'Connor, Helen M; Wolf, Patricia G; Gaskins, H Rex; Bharucha, Adil E

2016-02-01

In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average, 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P < .05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P < .05), and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Acemetacin-phosphatidylcholine interactions are determined by the drug ionization state.

PubMed

Pereira-Leite, Catarina; Nunes, Cláudia; Grahl, Débora; Bozelli, José C; Schreier, Shirley; Kamma-Lorger, Christina S; Cuccovia, Iolanda M; Reis, Salette

2018-05-17

Gastrointestinal (GI) toxicity is a major drawback of the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). The NSAIDs topical actions on the protective phospholipid layers of the GI mucosa seem to be a central toxicity mechanism of these pharmaceuticals. This work describes the interactions of acemetacin, a commercialized NSAID, with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers at pH 3.0, 5.0, and 7.4. This pH range was chosen to mimic the pH gradient found in the gastric mucosa, and to ultimately gain insights into the mechanisms underlying the acemetacin-induced gastric toxicity. Various experimental techniques were combined to characterize the partitioning of acemetacin in DMPC bilayers, and its effects on the phase transition behavior, as well as the structure and dynamics of DMPC bilayers. The acemetacin-DMPC interactions were clearly pH-dependent. The neutral (protonated) form of acemetacin had more affinity for the DMPC bilayer than the negatively charged form. Due to the higher affinity of neutral acemetacin, the drug effects on the phase transition and the structure and dynamics of the DMPC bilayer were more pronounced at lower pH values. In general, acemetacin decreased the temperature and the cooperativity of the lipid phase transition and induced changes in the packing and dynamics of the DMPC bilayer. These results support the hypothesis that acemetacin-induced gastric toxicity may be related to its effects on the protective phospholipid layers of the mucosal barrier.

[Regulation of moxibustion for expression of gastric mucosa cell-related marker protein in rats with acute gastric ulcer].

PubMed

Yang, Zong-Bao; Wang, Chen-Guang; Gong, An; Xie, Yu-feng; Liu, Qiong; Yang, Qing

2013-11-01

To explore relevant material basis of moxibustion for recovering gastric mucosal lesion. METHODL Forty-five SD rats were randomly divided into a normal goup, a model group, an acupoint group and a control group, 15 rats in the model group and 10 rats in the rest three groups. Except the normal group, binding and cold stress method were used to establish gastric mucosa injury model. The suspended moxibustion was applied in the acupoint group and control group at acupoints of the stomach meridian ("Liangmen" (ST 21) and "Zusanli" (ST36) and control acupoints (Laterally 1cm next to the "Liangmen" (ST 21) and Zusanli" (ST36), once a day, consectutively for 12 days. After 12 days, morphology of gastric mucosal was observed under optical microscope; protein fingerprints of gastric mucosa cell in rats were detected by protein fingerprint technology, weak cation chip and weak anion chip. Also mass to charge ratio of differential proteins in groups were compared and analyzed. Compared with the model group, index of gastric mucosal lesion in the acupoint group was reduced and its morphology was obviously improved (P<0.05). Campared with control group, index and morphology of gastric mucosal lesion were significantly improved in the acupoint group (P<0.05). According to test of weak cation chip, there was four marker proteins that had expression differences, indicating moxibustion at acupoints of stomach meridian could inrease expression of three marker protein whose molecular weight was 1354Da, 5692Da and 8432Da (all P<0.05) while reduce expression of marker protein with molecular weight of 3287Da (_<0.05). According to test of weak anion chip, moxibustion at acupoints of stomach meridian could increase expression of three marker proteins whose molecular weight was 2412 Da, 3026Da and 6475 Da (allP<0.05). Moxibustion at acupoints of the stomach meridian could regulate differential expression of gastric mucosa cell-related marker protein in rats with acute gastric ulcer and recover gastric mucosal lesion, it's effect is better than that of the points of laterally 1 cm next to acupoint.

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011

PubMed Central

2012-01-01

Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These – necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data. PMID:22784600

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011.

PubMed

Ruffin, Nicolas; Borggren, Marie; Euler, Zelda; Fiorino, Fabio; Grupping, Katrijn; Hallengärd, David; Javed, Aneele; Mendonca, Kevin; Pollard, Charlotte; Reinhart, David; Saba, Elisa; Sheik-Khalil, Enas; Sköld, Annette; Ziglio, Serena; Scarlatti, Gabriella; Gotch, Frances; Wahren, Britta; Shattock, Robin J

2012-07-11

Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These - necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data.

Structural and Antimicrobial Features of Peptides Related to Myticin C, a Special Defense Molecule from the Mediterranean Mussel Mytilus galloprovincialis.

PubMed

Domeneghetti, Stefania; Franzoi, Marco; Damiano, Nunzio; Norante, Rosa; El Halfawy, Nancy M; Mammi, Stefano; Marin, Oriano; Bellanda, Massimo; Venier, Paola

2015-10-28

Mussels (Mytilus spp.) have a large repertoire of cysteine-stabilized α,β peptides, and myticin C (MytC) was identified in some hundreds of transcript variants after in vivo immunostimulation. Using a sequence expressed in Italian mussels, we computed the MytC structure and synthesized the mature MytC and related peptide fragments (some of them also prepared in oxidized form) to accurately assess their antibacterial and antifungal activity. Only when tested at pH 5 was the reduced MytC as well as reduced and oxidized fragments including structural β-elements able to inhibit Gram-positive and -negative bacteria (MIC ranges of 4-32 and 8-32 μM, respectively). Such fragments caused selective Escherichia coli killing (MBC of 8-32 μM) but scarcely inhibited two fungal strains. In detail, the antimicrobial β-hairpin MytC[19-40]SOX caused membrane-disrupting effects in E. coli despite its partially ordered conformation in membrane-mimetic environments. In perspective, MytC-derived peptides could be employed to protect acidic mucosal tissues, in cosmetic and food products, and, possibly, as adjuvants in aquaculture.

Mucosal melanomas in the racially diverse population of California.

PubMed

Altieri, Lisa; Wong, Michael K; Peng, David H; Cockburn, Myles

2017-02-01

Mucosal melanomas are rare, poorly understood neoplasms without a consensus standard of care. We sought to define mucosal melanoma tumor characteristics and the racial/ethnic attributes of patients with mucosal melanomas. We analyzed 130,920 cutaneous melanomas and 1919 mucosal melanomas recorded in the population-based California Cancer Registry from 1988 to 2013. Although only 1% of melanomas occurring in nonHispanic whites were mucosal, other racial/ethnic groups had a higher proportion of mucosal melanomas (15% for Asian/Pacific Islanders, 9% for nonHispanic blacks, and 4% for Hispanics). Anorectal mucosal melanomas were most common in female Asian/Pacific Islanders, whereas genitourinary mucosal melanomas were highest in nonHispanic whites, and head and neck tumors were most common among Hispanics. Stage at presentation was not uniform among racial/ethnic groups, with Asian/Pacific Islanders having the highest rates of metastasis. The lack of a standardized staging system for mucosal melanomas confounds classification and knowledge regarding metastasis. Small sample size limits comparative analysis across race, stage, site, and depth. Mucosal melanomas differ by race/ethnicity with regard to anatomic site, stage, and depth. Because early detection offers the best chance of increased survival, greater awareness will aid clinicians who care for patients at risk for these aggressive tumors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Recombinant poxviruses as mucosal vaccine vectors.

PubMed

Gherardi, M Magdalena; Esteban, Mariano

2005-11-01

The majority of infections initiate their departure from a mucosal surface, such as Human immunodeficiency virus (HIV), a sexually transmitted virus. Therefore, the induction of mucosal immunity is a high priority in the development of vaccines against mucosal pathogens. The selection of an appropriate antigen delivery system is necessary to induce an efficient mucosal immune response. Poxvirus vectors have been the most intensively studied live recombinant vector, and numerous studies have demonstrated their ability to induce mucosal immune responses against foreign expressed antigens. Previous studies have demonstrated that recombinants based on the attenuated modified vaccinia virus Ankara (MVA) vector were effective in inducing protective responses against different respiratory viruses, such as influenza and respiratory syncytial virus, following immunization via mucosal routes. Recent studies performed in the murine and macaque models have shown that recombinant MVA (rMVA) does not only stimulate HIV-specific immunity in the genital and rectal tracts following mucosal delivery, but can also control simian/human immunodeficiency viraemia and disease progression. In addition, a prime-boost vaccination approach against tuberculosis emphasized the importance of the intranasal rMVA antigen delivery to induce protective immunity against Mycobacterium tuberculosis. The aim of this review is to summarize the studies employing recombinant poxviruses, specifically rMVA as a mucosal delivery vector. The results demonstrate that rMVAs can activate specific immune responses at mucosal surfaces, and encourage further studies to characterize and improve the MVA mucosal immunogenicity of poxvirus vectors.

Oral mucositis in head and neck cancer: risk, biology, and management.

PubMed

Sonis, Stephen T

2013-01-01

Of the toxicities associated with conventional forms of treatment for head and neck cancers, probably none has such a consistent legacy as oral mucositis.1 Despite the fact that mucosal injury was noted as far back as Marie Curie's first forays into therapeutic radiation, an effective intervention has yet to be developed. In addition to its historic link to radiation, new therapeutic strategies including induction chemotherapy often produce mucositis, and targeted therapies appear to alter mucositis risk and its severity and course.2 The symptomatic effect of oral mucositis is profound. Disabling oral and oropharyngeal pain prevents patients from eating normally, requires opiate analgesics, and in some cases results in alteration or discontinuation of anticancer therapy.3 Furthermore, the health and economic consequences of oral mucositis are far from trivial. The incremental cost of oral mucositis in patients with head and neck cancer exceeds $17,000 (USD).4.

Dark Agouti rat model of chemotherapy-induced mucositis: establishment and current state of the art.

PubMed

Vanhoecke, Barbara; Bateman, Emma; Mayo, Bronwen; Vanlancker, Eline; Stringer, Andrea; Thorpe, Daniel; Keefe, Dorothy

2015-06-01

Mucositis is a major oncological problem. The entire gastrointestinal and genitourinary tract and also other mucosal surfaces can be affected in recipients of radiotherapy, and/or chemotherapy. Major progress has been made in recent years in understanding the mechanisms of oral and small intestinal mucositis, which appears to be more prominent than colonic damage. This progress is largely due to the development of representative laboratory animal models of mucositis. This review focuses on the development and establishment of the Dark Agouti rat mammary adenocarcinoma model by the Mucositis Research Group of the University of Adelaide over the past 20 years to characterize the mechanisms underlying methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to summarize the results from studies using different animal model systems to identify new molecular and cellular markers of mucositis. © 2015 by the Society for Experimental Biology and Medicine.

DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations.

PubMed Central

Fynan, E F; Webster, R G; Fuller, D H; Haynes, J R; Santoro, J C; Robinson, H L

1993-01-01

Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been tested for their ability to raise protective immunity against lethal influenza challenges of the same subtype. In trials using two inoculations of from 50 to 300 micrograms of purified DNA in saline, 67-95% of test mice and 25-63% of test chickens have been protected against a lethal influenza challenge. Parenteral routes of inoculation that achieved good protection included intramuscular and intravenous injections. Successful mucosal routes of vaccination included DNA drops administered to the nares or trachea. By far the most efficient DNA immunizations were achieved by using a gene gun to deliver DNA-coated gold beads to the epidermis. In mice, 95% protection was achieved by two immunizations with beads loaded with as little as 0.4 micrograms of DNA. The breadth of routes supporting successful DNA immunizations, coupled with the very small amounts of DNA required for gene-gun immunizations, highlight the potential of this remarkably simple technique for the development of subunit vaccines. Images Fig. 1 PMID:8265577

Assessment of ocular discomfort caused by 5 shampoos using the Slug Mucosal Irritation test.

PubMed

Petit, Jean-Yanique; Doré, Vanessa; Marignac, Geneviève; Perrot, Sébastien

2017-04-01

Assessment of ocular discomfort caused by veterinary care products is less legitimately regulated than that caused by human care products. The Slug Mucosal Irritation (SMI) assay was adapted to evaluate canine hygiene shampoos to predict ocular discomfort. Experiments were performed using four commercial canine shampoos, a baby care product, and two controls (ArtTear® and BAC1%). Groups of 3 slugs were tested with 5% dilution of the 7 test substances. The negative control (ArtTear®) was the best tolerated. The baby care product Mixa bébé as well as Douxo Entretien Démêlant and Phlox Shampooing Entretien were classified to cause mild ocular discomfort. Together with the positive control (BAC 1%), Shampooing Physiologique Virbac and Physiovet Shampooing were considered to cause severe ocular discomfort. Different intensities of ocular discomfort were measured for veterinary care products. The SMI model was considered as a reproducible and adaptable evaluation method for screening veterinary care products causing ocular discomfort. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interobserver variability and feasibility of polymerase chain reaction-based assay in distinguishing ischemic colitis from Clostridium difficile colitis in endoscopic mucosal biopsies.

PubMed

Wiland, Homer O; Procop, Gary W; Goldblum, John R; Tuohy, Marion; Rybicki, Lisa; Patil, Deepa T

2013-06-01

Polymerase chain reaction (PCR)-based assays using stool samples are currently the most effective method of detecting Clostridium difficile. This study examines the feasibility of this assay using mucosal biopsy samples and evaluates the interobserver reproducibility in diagnosing and distinguishing ischemic colitis from C difficile colitis. Thirty-eight biopsy specimens were reviewed and classified by 3 observers into C difficile and ischemic colitis. The findings were correlated with clinical data. PCR was performed on 34 cases using BD GeneOhm C difficile assay. The histologic interobserver agreement was excellent (κ= 0.86) and the agreement between histologic and clinical diagnosis was good (κ = 0.84). All 19 ischemic colitis cases tested negative (100% specificity) and 3 of 15 cases of C difficile colitis tested positive (20% sensitivity). C difficile colitis can be reliably distinguished from ischemic colitis using histologic criteria. The C difficile PCR test on endoscopic biopsy specimens has excellent specificity but limited sensitivity.

Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

PubMed

de Bortoli, Nicola; Martinucci, Irene; Savarino, Edoardo; Tutuian, Radu; Frazzoni, Marzio; Piaggi, Paolo; Bertani, Lorenzo; Furnari, Manuele; Franchi, Riccardo; Russo, Salvatore; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino

2015-06-01

Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Antibodies and Their Receptors: Different Potential Roles in Mucosal Defense

PubMed Central

Horton, Rachel E.; Vidarsson, Gestur

2013-01-01

Over recent years it has become increasingly apparent that mucosal antibodies are not only restricted to the IgM and IgA isotypes, but that also other isotypes and particularly IgG can be found in significant quantities at some mucosal surfaces, such as in the genital tract. Their role is more complex than traditionally believed with, among other things, the discovery of novel function of mucosal immunoglobulin receptors. A thorough knowledge in the source and function and mucosal immunoglobulins is particularly important in development of vaccines providing mucosal immunity, and also in the current climate of microbicide development, to combat major world health issues such as HIV. We present here a comprehensive review of human antibody mediated mucosal immunity. PMID:23882268

Mucosal and systemic adjuvant activity of alphavirus replicon particles

NASA Astrophysics Data System (ADS)

Thompson, Joseph M.; Whitmore, Alan C.; Konopka, Jennifer L.; Collier, Martha L.; Richmond, Erin M. B.; Davis, Nancy L.; Staats, Herman F.; Johnston, Robert E.

2006-03-01

Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines. vaccine vector | Venezuelan equine encephalitis virus | viral immunology | RNA virus

Attenuated portal hypertension in germ-free mice: Function of bacterial flora on the development of mesenteric lymphatic and blood vessels.

PubMed

Moghadamrad, Sheida; McCoy, Kathy D; Geuking, Markus B; Sägesser, Hans; Kirundi, Jorum; Macpherson, Andrew J; De Gottardi, Andrea

2015-05-01

Intestinal bacterial flora may induce splanchnic hemodynamic and histological alterations that are associated with portal hypertension (PH). We hypothesized that experimental PH would be attenuated in the complete absence of intestinal bacteria. We induced prehepatic PH by partial portal vein ligation (PPVL) in germ-free (GF) or mice colonized with altered Schaedler's flora (ASF). After 2 or 7 days, we performed hemodynamic measurements, including portal pressure (PP) and portosystemic shunts (PSS), and collected tissues for histomorphology, microbiology, and gene expression studies. Mice colonized with intestinal microbiota presented significantly higher PP levels after PPVL, compared to GF, mice. Presence of bacterial flora was also associated with significantly increased PSS and spleen weight. However, there were no hemodynamic differences between sham-operated mice in the presence or absence of intestinal flora. Bacterial translocation to the spleen was demonstrated 2 days, but not 7 days, after PPVL. Intestinal lymphatic and blood vessels were more abundant in colonized and in portal hypertensive mice, as compared to GF and sham-operated mice. Expression of the intestinal antimicrobial peptide, angiogenin-4, was suppressed in GF mice, but increased significantly after PPVL, whereas other angiogenic factors remained unchanged. Moreover, colonization of GF mice with ASF 2 days after PPVL led to a significant increase in intestinal blood vessels, compared to controls. The relative increase in PP after PPVL in ASF and specific pathogen-free mice was not significantly different. In the complete absence of gut microbial flora PP is normal, but experimental PH is significantly attenuated. Intestinal mucosal lymphatic and blood vessels induced by bacterial colonization may contribute to development of PH. © 2015 by the American Association for the Study of Liver Diseases.

Correlation between hypersensitivity induced by esophageal acid infusion and the baseline impedance level in patients with suspected gastroesophageal reflux.

PubMed

Seo, A Young; Shin, Cheol Min; Kim, Nayoung; Yoon, Hyuk; Park, Young Soo; Lee, Dong Ho

2015-07-01

To evaluate the relevance between the pH parameters and baseline impedance level or esophageal hypomotility in patients with suspected gastroesophageal reflux. The recordings of 51 patients with heartburn, acid regurgitation, globus or noncardiac chest pain were analyzed. Evaluation included a 24-h multichannel intraluminal impedance-pH test while on off-proton pump inhibitor therapy over 1 week, high-resolution manometry and Bernstein test. Mean baseline impedance level at the most distal portion of the impedance channel was assessed manually. Esophageal hypomotility was evaluated using transitional zone defect (TZD) and distal break (DB) length measurement. In the study subjects (n = 51), 6 had a DeMeester score of more than 14.7 and 14 had a positive symptom index. The Bernstein test was positive in ten patients. The baseline impedance level was inversely correlated with the acid exposure time % (r = -0.660, P < 0.001). Also, all reflux and weakly acid reflux time % measured by impedance monitoring showed a weak correlation with TZD + DB length (r = 0.327 and 0.324, P = 0.019 and 0.020, respectively). Although a positive Bernstein test has no relevance for the acid exposure time or acid-related symptoms as represented by the DeMeester score or symptom index, the baseline impedance level was significantly lower in patients with a positive Bernstein test than in those with a negative one (2,628.4 ± 862.7 vs. 1,752.2 ± 611.1 Ω, P = 0.004). A lower baseline impedance level is closely related to increased esophageal acid exposure. Hypersensitivity induced by esophageal acid infusion might be attributed to acid-induced mucosal changes of the esophagus.

Mucosal secretion changes during radiotherapy in the oral cavity.

PubMed

Aziz, Luaay; Ebenfelt, Anders

2007-09-01

Mucositis in the oral cavity is a serious complication during radiation therapy for head and neck cancer, causing local discomfort and pain. In severe cases, hospitalization and interruption of radiotherapy may be necessary. The pathogenesis of this mucositis is not clear. With the purpose of getting more understanding of the pathogenesis of the mucositis, we examined the mucosal secretion from ten patients during radiotherapy with an imprint technique. In the secretion we studied the cellular composition and cellular function. In eight of ten treated patients the numbers of granulocytes increased in the secretion after 2 weeks of radiation therapy. The granulocytes, however, did not show any signs of phagocytosis. The patients all developed mucositis. We propose that the granulocytes in the secretion might play an important role in the development of mucositis during radiotherapy.

Malignancy, weight loss, and the small intestinal mucosa

PubMed Central

Barry, R. E.

1974-01-01

The mucosal architecture and mucosal dynamics of the small bowel have been studied in patients with malignant disease not of the gastrointestinal tract but associated with severe weight loss. Mucosal changes in malignant disease are demonstrated by stereomicroscopy, mucosal architectural measurement, and decreased lactose utilization. Measurement of the epithelial DNA loss rate indicates, in association with mucosal measurement, that the architectural changes are caused by a hypoplasia of the epithelium. Similar findings are demonstrated in patients with profound weight loss due to other non-malignant wasting diseases. Although mucosal changes undoubtedly occur in malignant disease, the changes are not specific for malignancy and the concept of `cancer enteropathy' is not tenable. It is suggested that mucosal changes are the effect of and not the cause of cachexia. ImagesFig 1 PMID:4430474

Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma.

PubMed

Hintzsche, Jennifer D; Gorden, Nicholas T; Amato, Carol M; Kim, Jihye; Wuensch, Kelsey E; Robinson, Steven E; Applegate, Allison J; Couts, Kasey L; Medina, Theresa M; Wells, Keith R; Wisell, Joshua A; McCarter, Martin D; Box, Neil F; Shellman, Yiqun G; Gonzalez, Rene C; Lewis, Karl D; Tentler, John J; Tan, Aik Choon; Robinson, William A

2017-06-01

Mucosal melanomas are a rare subtype of melanoma, arising in mucosal tissues, which have a very poor prognosis due to the lack of effective targeted therapies. This study aimed to better understand the molecular landscape of these cancers and find potential new therapeutic targets. Whole-exome sequencing was performed on mucosal melanomas from 19 patients and 135 sun-exposed cutaneous melanomas, with matched peripheral blood samples when available. Mutational profiles were compared between mucosal subgroups and sun-exposed cutaneous melanomas. Comparisons of molecular profiles identified 161 genes enriched in mucosal melanoma (P<0.05). KIT and NF1 were frequently comutated (32%) in the mucosal subgroup, with a significantly higher incidence than that in cutaneous melanoma (4%). Recurrent SF3B1 R625H/S/C mutations were identified and validated in 7 of 19 (37%) mucosal melanoma patients. Mutations in the spliceosome pathway were found to be enriched in mucosal melanomas when compared with cutaneous melanomas. Alternative splicing in four genes were observed in SF3B1-mutant samples compared with the wild-type samples. This study identified potential new therapeutic targets for mucosal melanoma, including comutation of NF1 and KIT, and recurrent R625 mutations in SF3B1. This is the first report of SF3B1 R625 mutations in vulvovaginal mucosal melanoma, with the largest whole-exome sequencing project of mucosal melanomas to date. The results here also indicated that the mutations in SF3B1 lead to alternative splicing in multiple genes. These findings expand our knowledge of this rare disease.

Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma

PubMed Central

Hintzsche, Jennifer D.; Gorden, Nicholas T.; Amato, Carol M.; Kim, Jihye; Wuensch, Kelsey E.; Robinson, Steven E.; Applegate, Allison J.; Couts, Kasey L.; Medina, Theresa M.; Wells, Keith R.; Wisell, Joshua A.; McCarter, Martin D.; Box, Neil F.; Shellman, Yiqun G.; Gonzalez, Rene C.; Lewis, Karl D.; Tentler, John J.

2017-01-01

Mucosal melanomas are a rare subtype of melanoma, arising in mucosal tissues, which have a very poor prognosis due to the lack of effective targeted therapies. This study aimed to better understand the molecular landscape of these cancers and find potential new therapeutic targets. Whole-exome sequencing was performed on mucosal melanomas from 19 patients and 135 sun-exposed cutaneous melanomas, with matched peripheral blood samples when available. Mutational profiles were compared between mucosal subgroups and sun-exposed cutaneous melanomas. Comparisons of molecular profiles identified 161 genes enriched in mucosal melanoma (P<0.05). KIT and NF1 were frequently comutated (32%) in the mucosal subgroup, with a significantly higher incidence than that in cutaneous melanoma (4%). Recurrent SF3B1 R625H/S/C mutations were identified and validated in 7 of 19 (37%) mucosal melanoma patients. Mutations in the spliceosome pathway were found to be enriched in mucosal melanomas when compared with cutaneous melanomas. Alternative splicing in four genes were observed in SF3B1-mutant samples compared with the wild-type samples. This study identified potential new therapeutic targets for mucosal melanoma, including comutation of NF1 and KIT, and recurrent R625 mutations in SF3B1. This is the first report of SF3B1 R625 mutations in vulvovaginal mucosal melanoma, with the largest whole-exome sequencing project of mucosal melanomas to date. The results here also indicated that the mutations in SF3B1 lead to alternative splicing in multiple genes. These findings expand our knowledge of this rare disease. PMID:28296713

Mucosal immunity and probiotics in fish.

PubMed

Lazado, Carlo C; Caipang, Christopher Marlowe A

2014-07-01

Teleost mucosal immunity has become the subject of unprecedented research studies in recent years because of its diversity and defining characteristics. Its immune repertoire is governed by the mucosa-associated lymphoid tissues (MALT) which are divided into gut-associated lymphoid tissues (GALT), skin-associated lymphoid tissues (SALT), and gill-associated lymphoid tissues (GIALT). The direct contact with its immediate environment makes the mucosal surfaces of fish susceptible to a wide variety of pathogens. The inherent immunocompetent cells and factors in the mucosal surfaces together with the commensal microbiota have pivotal role against pathogens. Immunomodulation is a popular prophylactic strategy in teleost and probiotics possess this beneficial feature. Most of the studies on the immunomodulatory properties of probiotics in fish mainly discussed their impacts on systemic immunity. In contrast, few of these studies discussed the immunomodulatory features of probiotics in mucosal surfaces and are concentrated on the influences in the gut. Significant attention should be devoted in understanding the relationship of mucosal immunity and probiotics as the present knowledge is limited and are mostly based on extrapolations of studies in humans and terrestrial vertebrates. In the course of the advancement of mucosal immunity and probiotics, new perspectives in probiotics research, e.g., probiogenomics have emerged. This review affirms the relevance of probiotics in the mucosal immunity of fish by revisiting and bridging the current knowledge on teleost mucosal immunity, mucosal microbiota and immunomodulation of mucosal surfaces by probiotics. Expanding the knowledge of immunomodulatory properties of probiotics especially on mucosal immunity is essential in advancing the use of probiotics as a sustainable and viable strategy for successful fish husbandry. Copyright © 2014 Elsevier Ltd. All rights reserved.

Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus

PubMed Central

Verma, Harish; Sharma, Prashant; Yang, Jae Seung; Saletti, Giulietta; Ahmad, Mohammad; Bahl, Sunil K.; Wierzba, Thomas F.; Nandy, Ranjan K.; Deshpande, Jagadish M.; Sutter, Roland W.; Czerkinsky, Cecil

2016-01-01

Background The “gold standard” for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. Methods 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. Results An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4β7+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4β7+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus. Discussion Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program. PMID:26730586

Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus.

PubMed

Dey, Ayan; Molodecky, Natalie A; Verma, Harish; Sharma, Prashant; Yang, Jae Seung; Saletti, Giulietta; Ahmad, Mohammad; Bahl, Sunil K; Wierzba, Thomas F; Nandy, Ranjan K; Deshpande, Jagadish M; Sutter, Roland W; Czerkinsky, Cecil

2016-01-01

The "gold standard" for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4β7+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4β7+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus. Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program.

Primary Localization and Tumor Thickness as Prognostic Factors of Survival in Patients with Mucosal Melanoma

PubMed Central

Mehra, Tarun; Grözinger, Gerd; Mann, Steven; Guenova, Emmanuella; Moos, Rudolf; Röcken, Martin; Claussen, Claus Detlef; Dummer, Reinhard; Clasen, Stephan

2014-01-01

Background Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations. Methodology 116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages. Principal Findings We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas. Conclusion Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006). It also depends on T-stage at the time of diagnosis (p<0.0001). PMID:25383553

Primary localization and tumor thickness as prognostic factors of survival in patients with mucosal melanoma.

PubMed

Mehra, Tarun; Grözinger, Gerd; Mann, Steven; Guenova, Emmanuella; Moos, Rudolf; Röcken, Martin; Claussen, Claus Detlef; Dummer, Reinhard; Clasen, Stephan; Naumann, Aline; Garbe, Claus

2014-01-01

Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations. 116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages. We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas. Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006). It also depends on T-stage at the time of diagnosis (p < 0.0001).

Quantitative Study for the Surface Dehydration of Vocal Folds Based on High-Speed Imaging.

PubMed

Li, Lin; Zhang, Yu; Maytag, Allison L; Jiang, Jack J

2015-07-01

From the perspective of the glottal area and mucosal wave, quantitatively estimate the differences of vocal fold on laryngeal activity during phonation at three different dehydration levels. Controlled three sets of tests. A dehydration experiment for 10 excised canine larynges was conducted at 16 cm H2O. According to the dehydration cycle time (H), dehydration levels were divided into three degrees (0% H, 50% H, 75% H). The glottal area and mucosal wave under three dehydration levels were extracted from high-speed images and digital videokymography (DKG) image sequences. Direct and non-direct amplitude components were derived from glottal areas. The amplitude and frequency of mucosal wave were calculated from DKG image sequences. These parameters in condition of three dehydration levels were compared for statistical analysis. The results showed a significant difference in direct (P = 0.001; P = 0.005) and non-direct (P = 0.005; P = 0.016) components of glottal areas between every two different dehydration levels. Considering the right-upper, right-lower, left-upper, and left-lower of vocal fold, the amplitudes of mucosal waves consistently decreased with increasing of dehydration levels. But, there was no significant difference in frequency. Surface dehydration could give rise to complex variation of vocal fold on tissues and vibratory mechanism, which should need analyzing from multiple perspectives. The results suggested that the combination of glottal area and mucosal wave could be better to research the change of vocal fold at different dehydrations. It would become a better crucial research tool for the clinical treatment of dehydration-induced laryngeal pathologies. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines

PubMed Central

Hjelm, Brooke E; Kilbourne, Jacquelyn; Herbst-Kralovetz, Melissa M

2014-01-01

Virus-like particles (VLPs) are an active area of vaccine research, development and commercialization. Mucosal administration of VLPs provides an attractive avenue for delivery of vaccines with the potential to produce robust immune responses. Nasal and oral delivery routes are particularly intriguing due to differential activation of mucosa-associated lymphoid tissues. We compared both intranasal and oral administration of VLPs with a panel of toll-like receptor (TLR) agonists (TLR3, 5, 7, 7/8, and 9) to determine the mucosal adjuvant activity of these immunomodulators. We selected Norwalk virus (NV) VLPs because it is an effective model antigen and an active area of research and commercialization. To prioritize these adjuvants, VLP-specific antibody production in serum (IgG, IgG1, IgG2a), vaginal lavages (IgG, IgA), and fecal pellets (IgA) were measured across a longitudinal timeseries in vaccinated mice. Additional distal mucosal sites (nasal, brochoalveolar, salivary, and gastrointestinal) were evaluated for VLP-specific responses (IgA). Intranasal co-delivery of VLPs with TLR7 or TLR9 agonists produced the most robust and broad-spectrum immune responses, systemically and at distal mucosal sites inducing VLP-specific antibodies at all sites evaluated. In addition, these VLP-specific antibodies blocked binding of NV VLPs to histo-blood group antigen (H type 1), supporting their functionality. Oral administration and/or other TLR agonists tested in the panel did not consistently enhance VLP-specific immune responses. This study demonstrates that intranasal co-delivery of VLPs with TLR7 or TLR9 agonists provides dose-sparing advantages for induction of specific and functional antibody responses against VLPs (i.e., non-replicating antigens) in the respiratory, gastrointestinal, and reproductive tract. PMID:24280723

Testing stem cell therapy in a rat model of inflammatory bowel disease: role of bone marrow stem cells and stem cell factor in mucosal regeneration.

PubMed

Qu, Bo; Xin, Guo-Rong; Zhao, Li-Xia; Xing, Hui; Lian, Li-Ying; Jiang, Hai-Yan; Tong, Jia-Zhao; Wang, Bei-Bei; Jin, Shi-Zhu

2014-01-01

The gastrointestinal (GI) mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs) and soluble stem cell factor (SCF) in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD). BMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls. PKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA), Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group. BMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD.

What interactions drive the salivary mucosal pellicle formation?

PubMed Central

Gibbins, Hannah L.; Yakubov, Gleb E.; Proctor, Gordon B.; Wilson, Stephen; Carpenter, Guy H.

2014-01-01

The bound salivary pellicle is essential for protection of both the enamel and mucosa in the oral cavity. The enamel pellicle formation is well characterised, however the mucosal pellicle proteins have only recently been clarified and what drives their formation is still unclear. The aim of this study was to examine the salivary pellicle on particles with different surface properties (hydrophobic or hydrophilic with a positive or negative charge), to determine a suitable model to mimic the mucosal pellicle. A secondary aim was to use the model to test how transglutaminase may alter pellicle formation. Particles were incubated with resting whole mouth saliva, parotid saliva and submandibular/sublingual saliva. Following incubation and two PBS and water washes bound salivary proteins were eluted with two concentrations of SDS, which were later analysed using SDS-PAGE and Western blotting. Experiments were repeated with purified transglutaminase to determine how this epithelial-derived enzyme may alter the bound pellicle. Protein pellicles varied according to the starting salivary composition and the particle chemistry. Amylase, the single most abundant protein in saliva, did not bind to any particle indicating specific protein binding. Most proteins bound through hydrophobic interactions and a few according to their charges. The hydrophobic surface most closely matched the known salivary mucosal pellicle by containing mucins, cystatin and statherin but an absence of amylase and proline-rich proteins. This surface was further used to examine the effect of added transglutaminase. At the concentrations used only statherin showed any evidence of crosslinking with itself or another saliva protein. In conclusion, the formation of the salivary mucosal pellicle is probably mediated, at least in part, by hydrophobic interactions to the epithelial cell surface. PMID:24921197

Different risk factors between reflux symptoms and mucosal injury in gastroesophageal reflux disease.

PubMed

Li, Chung-Hsien; Hsieh, Tsung-Cheng; Hsiao, Tsung-Hsien; Wang, Pin-Chao; Tseng, Tai-Chung; Lin, Hans Hsienhong; Wang, Chia-Chi

2015-06-01

Gastroesophageal reflux disease (GERD) is diagnosed based on typical symptoms in clinical practice. It can be divided into two groups using endoscopy: erosive and nonerosive reflux disease (NERD). This study aims to determine the risk factors of reflux symptoms and mucosal injury. This was a two-step case-control study derived from a cohort of 998 individuals having the data of reflux disease questionnaire (RDQ) and endoscopic findings. Those with minor reflux symptoms were excluded. The first step compared symptomatic GERD patients with healthy controls. The 2(nd) step compared patients with erosive esophagitis with healthy controls. In this study, the prevalence of symptomatic GERD and erosive esophagitis were 163 (16.3%) and 166 (16.6%), respectively. A total of 507 asymptomatic individuals without mucosal injury of the esophagus on endoscopy were selected as healthy controls. Compared with healthy controls, multivariate analyses showed that symptomatic GERD patients had a higher prevalence of hypertriglyceridemia [odds ratio (OR), 1.83; 95% confidence interval (CI) 1.13-2.96] and obesity (OR, 1.85; 95% CI 1.08-3.02). By contrast, male sex (OR, 2.24; 95% CI 1.42-3.52), positive Campylo-like organism (CLO) test (OR, 0.56; 95% CI 0.37-0.84), and hiatus hernia (OR, 14.36; 95% CI 3.05-67.6) were associated with erosive esophagitis. In conclusion, obesity and hypertriglyceridemia were associated with reflux symptoms. By contrast, male sex, negative infection of Helicobacter pylori, and hiatus hernia were associated with mucosal injury. Our results suggested that risk factors of reflux symptoms or mucosal injury might be different in GERD patients. The underlying mechanism awaits further studies to clarify. Copyright © 2015. Published by Elsevier Taiwan.

Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis.

PubMed

Woodland, Philip; Lee, Chung; Duraisamy, Yasotha; Duraysami, Yasotha; Farré, Ricard; Dettmar, Peter; Sifrim, Daniel

2013-04-01

Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection. Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions. Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05). Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.

Macroscopic findings in collagenous colitis: a multi-center, retrospective, observational cohort study

PubMed Central

Koulaouzidis, Anastasios; Yung, Diana E.; Nemeth, Artur; Sjöberg, Klas; Giannakou, Andry; Qureshi, Raheel; Bartzis, Leonidas; McNeill, Morna; Johansson, Gabriele Wurm; Lucendo, Alfredo J.; Fineron, Paul; Trimble, Ken C.; Saeed, Athar; Plevris, John N.; Toth, Ervin

2017-01-01

Background Collagenous colitis (CC) is by definition a histological diagnosis. However, colonoscopy often reveals characteristic endoscopic findings. The aim of this study was to evaluate the frequency and type of endoscopic findings in patients diagnosed with CC in 4 participating centers. Methods This was a retrospective study; the databases of 2 university hospitals in Edinburgh (Scotland) and Malmö (Sweden), and 2 district general hospitals in Tomelloso (Spain) and Gateshead (England) were interrogated for patients diagnosed with CC between May 2008 and August 2013. Endoscopy reports and images were retrieved and reviewed; data on lesions, sedation, bowel preparation and endoscopist experience were abstracted. Categorical data are reported as mean±SD. Fischer’s exact, chi-square and t (unpaired) tests were used to compare datasets. A two-tailed P-value of <0.05 was considered statistically significant. Results 607 patients (149 male, mean age 66.9±12.25 years) were diagnosed with CC. A total of 108/607 (17.8%) patients had one or more suggestive endoscopy findings: i.e., mucosal erythema/edema, 91/607 (15%); linear colonic mucosal defects, 12/607 (2%); or mucosal scarring, 5/607 (0.82%). For colonic mucosa erythema, there was no difference in the odds of finding erythema with the use of different bowel preparation methods (P=0.997). For colonic mucosal defects there was some evidence (P=0.005) that patients colonoscoped by experienced endoscopists had 87% less odds of developing such defects. Moreover, there was evidence that analgesia reduced the odds of developing mucosal defects by 84%. Conclusion A significant minority of patients with CC have endoscopic findings in colonoscopy. The description of such findings appears to be related to the endoscopist’s experience. PMID:28469361

[The influence of corvitin on secretory processes and blood flow in the rat gastric mucosa].

PubMed

Vovkun, T V; Ianchuk, P I; Shtanova, L Ia; Vesel'skyĭ, S P; Baranovs'kyĭ, V A

2013-01-01

We studied parameters of gastric secretion in pylorus-ligated rat and blood flow in the rat gastric mucosa under the influence of drug corvitin used intragastrically in doses of 2.5 and 5 mg/kg. Biochemical analysis of gastric juice was based on the determination of pH, total hydrochloric acid production and total protein, hexosamine and cysteine concentration. Gastric juice analysis in control rats found the presence of hexosamines-- a gastric mucus indicators and cysteine--free amino acid whith properties of a strong antioxidant. Concentration of these compounds in the gastric juice increased as a consequence of corvitin action. However, corvitin did not affect at these parameters of gastric secretion as the volume of gastric juice, pH, hydrochloric acid output rate, protein concentration. Additionally it was shown that corvitin in dose-dependent manner increased blood flow in the gastric mucosa. This results give reason to believe that corvitin can be considered as a tool that amplifies gastric mucosal defense mechanisms without affecting the secretion of gastric hydrochloric acid and total protein.

Guided bone regeneration and abutment connection augment the buccal soft tissue contour: 3-year results of a prospective comparative clinical study.

PubMed

Benic, Goran I; Ge, Yanjun; Gallucci, German O; Jung, Ronald E; Schneider, David; Hämmerle, Christoph H F

2017-02-01

To test whether implant placement with simultaneous guided bone regeneration (GBR) differs from implant placement without GBR regarding the change in marginal mucosal contour. In 28 patients, single implants were placed >4 months after tooth extraction. Eighteen implants were completely surrounded by native bone, and no bone augmentation was performed. At 10 implant sites, bone defects and thin bone plates were grafted with deproteinized bovine-derived bone mineral and covered with collagen membrane. Impressions were taken prior to implant placement (baseline), at 3 months before abutment connection, at 6 months immediately after crown insertion, at 1 year, and at 3 years. Models were optically scanned and 3D images were superimposed for the evaluation of mucosal contour changes at the mid-buccal aspect. The nonparametric Mann-Whitney U-test was applied to detect differences. From baseline to 6 months, horizontal contour change at the level 1 and 2 mm apical to the mucosal margin measured 0.65 ± 0.74 mm and 0.55 ± 0.56 mm at sites without GBR, and 1.92 ± 0.87 mm and 1.76 ± 0.70 mm at sites with GBR (P < 0.05). In the period from baseline to 1 year, the corresponding values amounted to 0.81 ± 0.67 mm and 0.60 ± 0.55 mm in the group without GBR, and to 1.81 ± 0.86 mm and 1.37 ± 0.62 mm in the group with GBR (P < 0.05). From baseline to 6 months, mucosal margin moved 0.16 ± 0.49 mm in the coronal direction in the group without GBR and 0.82 ± 0.65 mm in the group with GBR (P < 0.05). In the period from baseline to 1 year, vertical change of mucosal margin amounted to 0.64 ± 0.54 mm in the group without GBR and to 1.17 ± 0.53 mm in the GBR group (P < 0.05). From 1 to 3 years, the mucosal contours remained stable. Implant placement with simultaneous GBR resulted in more gain of buccal soft tissue contour in comparison with implant placement without GBR. Abutment connection increased the contour of the marginal mucosa at the augmented and the nonaugmented sites. GBR procedure contributed more to the contour gain than did the abutment connection. The augmented and the nonaugmented ridges exhibited stable peri-implant mucosal contour over a 3-year period. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The oesophageal zero-stress state and mucosal folding from a GIOME perspective

PubMed Central

Liao, Donghua; Zhao, Jingbo; Yang, Jian; Gregersen, Hans

2007-01-01

The oesophagus is a cylindrical organ with a collapsed lumen and mucosal folds. The mucosal folding may serve to advance the function of the oesophagus, i.e. the folds have a major influence on the flow of air and bolus through the oesophagus. Experimental studies have demonstrated oesophageal mucosal folds in the no-load state. This indicates that mucosal buckling must be considered in the analysis of the mechanical reference state since the material stiffness drops dramatically after tissue collapse. Most previous work on the oesophageal zero-stress state and mucosal folding has been experimental. However, numerical analysis offers a promising alternative approach, with the additional ability to predict the mucosal buckling behaviour and to calculate the regional stress and strain in complex structures. A numerical model used for describing the mechanical behaviour of the mucosal-folded, three-layered, two-dimensional oesophageal model is reviewed. GIOME models can be used in the future to predict the tissue function physiologically and pathologically. PMID:17457964

Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

PubMed

Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

2006-12-01

We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

Determining the activity of mucosal adjuvants.

PubMed

Baudner, Barbara C; Giudice, Giuseppe Del

2010-01-01

Mucosal vaccination offers the advantage of blocking pathogens at the portal of entry, improving patient's compliance, facilitating vaccine delivery, and decreasing the risk of unwanted spread of infectious agents via contaminated syringes.Recent advances in vaccinology have created an array of vaccine constructs that can be delivered to mucosal surfaces of the respiratory, gastrointestinal, and genitourinary tracts using intranasal, oral, and vaginal routes. Due to the different characteristics of mucosal immune response, as compared with systemic response, mucosal immunization requires particular methods of antigen presentation. Well-tolerated adjuvants that enhance the efficacy of such vaccines will play an important role in mucosal immunization. Among promising mucosal adjuvants, mutants of cholera toxin and the closely related heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli present powerful tools, augmenting the local and systemic serum antibody response to co-administered antigens.In this chapter, we describe the formulation and application of vaccines using the genetically modified LTK63 mutant as a prototype of the family of these mucosal adjuvants and the tools to determine its activity in the mouse model.

DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques.

PubMed

Jalah, Rashmi; Kulkarni, Viraj; Patel, Vainav; Rosati, Margherita; Alicea, Candido; Bear, Jenifer; Yu, Lei; Guan, Yongjun; Shen, Xiaoying; Tomaras, Georgia D; LaBranche, Celia; Montefiori, David C; Prattipati, Rajasekhar; Pinter, Abraham; Bess, Julian; Lifson, Jeffrey D; Reed, Steven G; Sardesai, Niranjan Y; Venzon, David J; Valentin, Antonio; Pavlakis, George N; Felber, Barbara K

2014-01-01

We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques.

Analysis of a Cholera Toxin B Subunit (CTB) and Human Mucin 1 (MUC1) Conjugate Protein in a MUC1 Tolerant Mouse Model

PubMed Central

Pinkhasov, Julia; Alvarez, M. Lucrecia; Pathangey, Latha B.; Tinder, Teresa L.; Mason, Hugh S.; Walmsley, Amanda M.; Gendler, Sandra J.; Mukherjee, Pinku

2011-01-01

Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1 tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12), did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1. PMID:20824430

Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model.

PubMed

Pinkhasov, Julia; Alvarez, M Lucrecia; Pathangey, Latha B; Tinder, Teresa L; Mason, Hugh S; Walmsley, Amanda M; Gendler, Sandra J; Mukherjee, Pinku

2010-12-01

Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1-tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1.

Lubiprostone Reverses the Inhibitory Action of Morphine on Mucosal Secretion in Human Small Intestine

PubMed Central

Sun, Xiaohong; Wang, Xiyu; Wang, Guo-Du; Xia, Yun; Liu, Sumei; Qu, Meihua; Needleman, Bradley J.; Mikami, Dean J.; Melvin, W. Scott; Bohn, Laura M.; Ueno, Ryuji; Wood, Jackie D.

2016-01-01

Background and Aims Treatments with morphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipation-predominant IBS in adult women. We tested whether lubiprostone can reverse morphine-suppression of mucosal secretion in human intestine and explored the mechanism of action. Methods Fresh segments of jejunum discarded during Roux-En-Y gastric bypass surgeries were used. Changes in short-circuit current (ΔIsc) were recorded in Ussing flux chambers as a marker for electrogenic chloride secretion during pharmacological interactions between morphine, prostaglandin receptor antagonists, chloride channel blockers and lubiprostone. Results Morphine suppressed basal Isc. Lubiprostone reversed morphine suppression of basal Isc. Lubiprostone, applied to the mucosa in concentrations ranging from 3 nM to 30 μM, evoked increases in Isc in concentration-dependent manner when applied to the mucosal side of muscle-stripped preparations. Blockade of enteric nerves did not change stimulation of Isc by lubiprostone. Removal of chloride or application of bumetanide or NPPB suppressed or abolished responses to lubiprostone. Antagonists acting at CFTR channels and prostaglandin EP4 receptors, but not at E1, EP1-3 receptors, partially suppressed stimulation of Isc by lubiprostone. Conclusions Antisecretory action of morphine results from suppression of excitability of secretomotor neurons in the enteric nervous system. Lubiprostone, which does not affect enteric neurons directly, bypasses the action of morphine by directly opening mucosal chloride channels. PMID:21181441

Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine.

PubMed

Sun, Xiaohong; Wang, Xiyu; Wang, Guo-Du; Xia, Yun; Liu, Sumei; Qu, Meihua; Needleman, Bradley J; Mikami, Dean J; Melvin, W Scott; Bohn, Laura M; Ueno, Ryuji; Wood, Jackie D

2011-02-01

Treatments with morphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipation-predominant IBS in adult women. We tested whether lubiprostone can reverse morphine-suppression of mucosal secretion in human intestine and explored the mechanism of action. Fresh segments of jejunum discarded during Roux-En-Y gastric bypass surgeries were used. Changes in short-circuit current (ΔIsc) were recorded in Ussing flux chambers as a marker for electrogenic chloride secretion during pharmacological interactions between morphine, prostaglandin receptor antagonists, chloride channel blockers and lubiprostone. Morphine suppressed basal Isc. Lubiprostone reversed morphine suppression of basal Isc. Lubiprostone, applied to the mucosa in concentrations ranging from 3 nM to 30 μM, evoked increases in Isc in concentration-dependent manner when applied to the mucosal side of muscle-stripped preparations. Blockade of enteric nerves did not change stimulation of Isc by lubiprostone. Removal of chloride or application of bumetanide or NPPB suppressed or abolished responses to lubiprostone. Antagonists acting at CFTR channels and prostaglandin EP(4) receptors, but not at E(1), EP(1-3) receptors, partially suppressed stimulation of Isc by lubiprostone. Antisecretory action of morphine results from suppression of excitability of secretomotor neurons in the enteric nervous system. Lubiprostone, which does not affect enteric neurons directly, bypasses the action of morphine by directly opening mucosal chloride channels.

Effect of Conjugated Linoleic Acid-enriched Butter After 24 hours of Intestinal Mucositis Induction.

PubMed

Barros, Patrícia Aparecida Vieira de; Generoso, Simone de Vasconcelos; Andrade, Maria Emília Rabelo; da Gama, Marco Antonio Sundfeld; Lopes, Fernando Cesar Ferraz; de Sales E Souza, Éricka Lorenna; Martins, Flaviano Dos Santos; Miranda, Sued Eustáquio Mendes; Fernandes, Simone Odília Antunes; Cardoso, Valbert Nascimento

2017-01-01

Mucositis is the most common side effect due to chemotherapy or radiotherapy. It refers to the inflammation of intestinal mucous membranes, and it is associated with complications such as diarrhea, weight loss, and increased intestinal permeability (IP). This study was designed to evaluate the effect of diet containing conjugated linoleic acid (CLA)-enriched butter on intestinal damage and inflammatory response after 24 h of 5-fluorouracil (5-FU)-induced mucositis. Mice were divided into four groups: CTL; CLA; 5-FU, and CLA 5-FU, and they were fed for 31 days. On the 30th experimental day, mucositis was induced by unique injection of 300 mg/kg of 5-FU. After 24 h (31st experimental day), IP was evaluated; ileum and fecal material were collected to determine cytokine level and myeloperoxidase (MPO) activity and secretory immunoglobulin A (sIgA). The 5-FU group showed an increase in IP and MPO activity (CTL vs. 5-FU: P < 0.05). Additionally, increased levels of IP and MPO were observed in CLA 5-FU group compared to those in the test groups (P < 0.05). Animals in the CLA 5-FU group showed reduced concentrations of sIgA (CTL vs. CLA 5-FU: P < 0.05). CLA-enriched butter exacerbating the 5-FU-induced intestinal damage. Safety concerns regarding the use of CLA require further investigation.

Natural Products for Management of Oral Mucositis Induced by Radiotherapy and Chemotherapy

PubMed Central

Aghamohamamdi, Azar; Hosseinimehr, Seyed Jalal

2015-01-01

Oral mucositis is a common side effect of systemic chemotherapy and radiotherapy of head and neck in patients with cancer. Severe oral mucositis is painful and affects oral functions, including intake of food and medications and speech. Prevention of oral mucositis affects the life quality of patients. Recent studies have been focused on natural products to improve or reduce this complication. Many clinical trials have been performed to assess natural products for treatment of mucositis and their results are promising. The authors reviewed the evidence for natural products in the prevention and treatment of oral mucositis induced by radiation therapy and chemotherapy. PMID:26306626

Effect of nabumetone and aspirin on colonic mucosal bleeding time.

PubMed

Basson, M D; Panzini, L; Palmer, R H

2001-04-01

The management of patients taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) who require colonoscopy remains controversial because of concerns over bleeding after biopsy or polypectomy. To determine whether patients using the NSAID nabumetone, a non-acidic prodrug with mixed activity against cyclooxygenase-1 (COX-1) and COX-2, exhibited prolonged mucosal bleeding times and how this might compare with mucosal bleeding times in patients using aspirin. We assessed triplicate mucosal bleeding times in patients undergoing screening flexible sigmoidoscopy. We compared 90 patients who had taken no aspirin or NSAIDs within the previous 2 weeks, to 60 patients who had received nabumetone 1 g b.d. by mouth for the previous 2 weeks, and 30 patients who had taken 325 mg aspirin daily for the previous 2 weeks. In each case, the investigator performing the study was blinded to the patient's medication. Mucosal bleeding times did not differ significantly among control or nabumetone-using patients. However, the patients receiving aspirin exhibited significant prolongation. Mucosal bleeding time correlated statistically significantly, but weakly, with skin bleeding time. Nabumetone does not appear to prolong mucosal bleeding time after mucosal pinch biopsy, and skin bleeding time does not reliably screen for prolonged mucosal bleeding time.

GNAQ mutation in a patient with metastatic mucosal melanoma.

PubMed

Kim, Chung-Young; Kim, Dae Won; Kim, Kevin; Curry, Jonathan; Torres-Cabala, Carlos; Patel, Sapna

2014-07-16

Mucosal melanomas represent about 1% of all melanoma cases and classically have a worse prognosis than cutaneous melanomas. Due to the rarity of mucosal melanomas, only limited clinical studies with metastatic mucosal melanoma are available. Mucosal melanomas most commonly contain mutations in the gene CKIT, and treatments have been investigated using targeted therapy for this gene. Mutations in mucosal melanoma are less common than in cutaneous or uveal melanomas and occur in descending order of frequency as: CKIT (20%), NRAS (5%) or BRAF (3%). Mutations in G-alpha proteins, which are associated with activation of the mitogen-activated protein kinase pathway, have not been reported in mucosal melanomas. These G-alpha protein mutations occur in the genes GNAQ and GNA11 and are seen at a high frequency in uveal melanomas, those melanomas that begin in the eye. A 59-year old Caucasian male was diagnosed with a mucosal melanoma after evaluation for what was thought to be a hemorrhoid. Molecular analysis of the tumor revealed a GNAQ mutation. Ophthalmologic exam did not disclose a uveal melanoma. Here we report, to our knowledge, the first known case of GNAQ mutation in a patient with metastatic mucosal melanoma.

GNAQ mutation in a patient with metastatic mucosal melanoma

PubMed Central

2014-01-01

Background Mucosal melanomas represent about 1% of all melanoma cases and classically have a worse prognosis than cutaneous melanomas. Due to the rarity of mucosal melanomas, only limited clinical studies with metastatic mucosal melanoma are available. Mucosal melanomas most commonly contain mutations in the gene CKIT, and treatments have been investigated using targeted therapy for this gene. Mutations in mucosal melanoma are less common than in cutaneous or uveal melanomas and occur in descending order of frequency as: CKIT (20%), NRAS (5%) or BRAF (3%). Mutations in G-alpha proteins, which are associated with activation of the mitogen-activated protein kinase pathway, have not been reported in mucosal melanomas. These G-alpha protein mutations occur in the genes GNAQ and GNA11 and are seen at a high frequency in uveal melanomas, those melanomas that begin in the eye. Case presentation A 59-year old Caucasian male was diagnosed with a mucosal melanoma after evaluation for what was thought to be a hemorrhoid. Molecular analysis of the tumor revealed a GNAQ mutation. Ophthalmologic exam did not disclose a uveal melanoma. Conclusion Here we report, to our knowledge, the first known case of GNAQ mutation in a patient with metastatic mucosal melanoma. PMID:25030020

Chemotherapy- and radiotherapy-induced oral mucositis: review of preventive strategies and treatment.

PubMed

Saadeh, Claire E

2005-04-01

Oral mucositis is a frequently encountered and potentially severe complication associated with administration of chemotherapy and radiotherapy. Although many pharmacologic interventions have been used for the prevention and treatment of oral mucositis, there is not one universally accepted strategy for its management. Most preventive and treatment strategies are based on limited, often anecdotal, clinical data. Basic oral hygiene and comprehensive patient education are important components of care for any patient with cancer at risk for development of oral mucositis. Nonpharmacologic approaches for the prevention of oral mucositis include oral cryotherapy for patients receiving chemotherapy with bolus 5-fluorouracil, and low-level laser therapy for patients undergoing hematopoietic stem cell transplantation. Chlorhexidine, amifostine, hematologic growth factors, pentoxifylline, glutamine, and several other agents have all been investigated for prevention of oral mucositis. Results have been conflicting, inconclusive, or of limited benefit. Treatment of established mucositis remains a challenge and focuses on a palliative management approach. Topical anesthetics, mixtures (also called cocktails), and mucosal coating agents have been used despite the lack of experimental evidence supporting their efficacy. Investigational agents are targeting the specific mechanisms of mucosal injury; among the most promising of these is recombinant human keratinocyte growth factor.

Effects of mucosal loading on vocal fold vibration.

PubMed

Tao, Chao; Jiang, Jack J

2009-06-01

A chain model was proposed in this study to examine the effects of mucosal loading on vocal fold vibration. Mucosal loading was defined as the loading caused by the interaction between the vocal folds and the surrounding tissue. In the proposed model, the vocal folds and the surrounding tissue were represented by a series of oscillators connected by a coupling spring. The lumped masses, springs, and dampers of the oscillators modeled the tissue properties of mass, stiffness, and viscosity, respectively. The coupling spring exemplified the tissue interactions. By numerically solving this chain model, the effects of mucosal loading on the phonation threshold pressure, phonation instability pressure, and energy distribution in a voice production system were studied. It was found that when mucosal loading is small, phonation threshold pressure increases with the damping constant R(r), the mass constant R(m), and the coupling constant R(mu) of mucosal loading but decreases with the stiffness constant R(k). Phonation instability pressure is also related to mucosal loading. It was found that phonation instability pressure increases with the coupling constant R(mu) but decreases with the stiffness constant R(k) of mucosal loading. Therefore, it was concluded that mucosal loading directly affects voice production.

Effects of mucosal loading on vocal fold vibration

NASA Astrophysics Data System (ADS)

Tao, Chao; Jiang, Jack J.

2009-06-01

A chain model was proposed in this study to examine the effects of mucosal loading on vocal fold vibration. Mucosal loading was defined as the loading caused by the interaction between the vocal folds and the surrounding tissue. In the proposed model, the vocal folds and the surrounding tissue were represented by a series of oscillators connected by a coupling spring. The lumped masses, springs, and dampers of the oscillators modeled the tissue properties of mass, stiffness, and viscosity, respectively. The coupling spring exemplified the tissue interactions. By numerically solving this chain model, the effects of mucosal loading on the phonation threshold pressure, phonation instability pressure, and energy distribution in a voice production system were studied. It was found that when mucosal loading is small, phonation threshold pressure increases with the damping constant Rr, the mass constant Rm, and the coupling constant Rμ of mucosal loading but decreases with the stiffness constant Rk. Phonation instability pressure is also related to mucosal loading. It was found that phonation instability pressure increases with the coupling constant Rμ but decreases with the stiffness constant Rk of mucosal loading. Therefore, it was concluded that mucosal loading directly affects voice production.

The mucosal immune system of fish: the evolution of tolerating commensals while fighting pathogens

PubMed Central

Gomez, Daniela; Sunyer, J Oriol; Salinas, Irene

2013-01-01

The field of mucosal immunology research has grown fast over the past few years, and our understanding on how mucosal surfaces respond to complex antigenic cocktails is expanding tremendously. With the advent of new molecular sequencing techniques, it is easier to understand how the immune system of vertebrates is, to a great extent, orchestrated by the complex microbial communities that live in symbiosis with their hosts. The commensal microbiota is now seen as the “extended self” by many scientists. Similarly, fish immunologist are devoting important research efforts to the field of mucosal immunity and commensals. Recent breakthroughs on our understanding of mucosal immune responses in teleost fish open up the potential of teleosts as animal research models for the study of human mucosal diseases. Additionally, this new knowledge places immunologists in a better position to specifically target the fish mucosal immune system while rationally designing mucosal vaccines and other immunotherapies. In this review, an updated view on how teleost skin, gills and gut immune cells and molecules, function in response to pathogens and commensals is provided. Finally, some of the future avenues that the field of fish mucosal immunity may follow in the next years are highlighted. PMID:24099804

Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy--a randomized controlled trial.

PubMed

Svanberg, Anncarin; Birgegård, Gunnar; Ohrn, Kerstin

2007-10-01

Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.

Effects of cold atmospheric plasma on mucosal tissue culture

NASA Astrophysics Data System (ADS)

Welz, Christian; Becker, Sven; Li, Yang-Fang; Shimizu, Tetsuji; Jeon, Jin; Schwenk-Zieger, Sabina; Thomas, Hubertus M.; Isbary, Georg; Morfill, Gregor E.; Harréus, Ulrich; Zimmermann, Julia L.

2013-01-01

Thermal plasmas have been commonly used in medical applications such as plasma ablation and blood coagulation. Newer developments show that plasmas can be generated with ion temperatures close to room temperature: these non-thermal or so-called cold atmospheric plasmas (CAPs) therefore open up a wide range of further biomedical applications. Based on the understanding of the bactericidal, virucidal and fungicidal properties of CAPs, information about the effects of CAP on mucosal cells and tissue is still lacking. Therefore this study focuses on the interaction of CAP with healthy head and neck mucosal cells on a molecular level. To analyse this interaction in detail, fresh tissue samples from healthy nasal and pharyngeal mucosa were harvested during surgery, assembled to a three-dimensional tissue culture model (mini organ cultures) and treated with CAP for different treatment times. Effects on the viability, necrosis induction and mutagenic activity were evaluated with the trypan blue exclusion test, Annexin-V/PI staining and alkaline microgel electrophoresis (comet assay). Trypan blue exclusion test revealed that the CAP treatment significantly decreases the cell viability for all tested treatment times (5, 10, 30, 60 and 120 s p < 0.05), but only a treatment time of 120 s showed a cytotoxic effect as the viability dropped below 90%. Annexin-V/PI staining revealed a significant increase in necrosis in CAP treated pharyngeal tissue cultures for treatment times of 60 and 120 s (p < 0.05). For nasal tissue this effect was already detected for a 30 s treatment (p < 0.05). Comet assay analysis showed no mutagenic effects after exposure to CAP.

Oral Mucositis: Melatonin Gel an Effective New Treatment

PubMed Central

Abdel Moneim, Ahmed Esmat; Guerra-Librero, Ana; Florido, Javier; Shen, Ying-Qiang; Fernández-Gil, Beatriz; Acuña-Castroviejo, Darío; Escames, Germaine

2017-01-01

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, the role of melatonin in the treatment of mucositis has recently been investigated, and offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives. PMID:28481279

Development of plant-based mucosal vaccines against widespread infectious diseases.

PubMed

Salyaev, Rurick K; Rigano, Maria Manuela; Rekoslavskaya, Natalya I

2010-08-01

Mucosal vaccination is a perspective for the control of infectious diseases, since it is capable of inducing humoral and cell-mediated responses. In addition, the delivery of vaccines to mucosal surfaces makes immunization practice safe and acceptable, and eliminates needle-associated risks. Transgenic plants can be used as bioreactors for the production of mucosally delivered protective antigens. This technology shows great promise to simplify and decrease the cost of vaccine delivery. Herein, we review the development of mucosally administered vaccines expressed in transgenic plants. In particular, we evaluate the advantages and disadvantages of using plants for the production of mucosal vaccines against widespread infectious diseases such as HIV, hepatitis B and TB.

Standardized Methods for Detection of Poliovirus Antibodies.

PubMed

Weldon, William C; Oberste, M Steven; Pallansch, Mark A

2016-01-01

Testing for neutralizing antibodies against polioviruses has been an established gold standard for assessing individual protection from disease, population immunity, vaccine efficacy studies, and other vaccine clinical trials. Detecting poliovirus specific IgM and IgA in sera and mucosal specimens has been proposed for evaluating the status of population mucosal immunity. More recently, there has been a renewed interest in using dried blood spot cards as a medium for sample collection to enhance surveillance of poliovirus immunity. Here, we describe the modified poliovirus microneutralization assay, poliovirus capture IgM and IgA ELISA assays, and dried blood spot polio serology procedures for the detection of antibodies against poliovirus serotypes 1, 2, and 3.

Helminthic therapy: improving mucosal barrier function

PubMed Central

Wolff, Martin J.; Broadhurst, Mara J.

2014-01-01

The epidemiology of autoimmune diseases and helminth infections led to suggestions that helminths could improve inflammatory conditions, which was then tested using animal models. This has translated to clinical investigations aimed at the safe and controlled reintroduction of helminthic exposure to patients suffering from autoimmune diseases (so-called “helminthic therapy”) in an effort to mitigate the inflammatory response. In this review, we will summarize the results of recent clinical trials of helminthic therapy, with particular attention to mechanisms of action. Whereas previous reviews have emphasized immune regulatory mechanisms activated by helminths, we propose that enhancement of mucosal barrier function may have an equally important role in improving conditions of inflammatory bowel diseases. PMID:22464690

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the esophageal diagnostic working group.

PubMed

Richter, J E; Pandolfino, J E; Vela, M F; Kahrilas, P J; Lacy, B E; Ganz, R; Dengler, W; Oelschlager, B K; Peters, J; DeVault, K R; Fass, R; Gyawali, C P; Conklin, J; DeMeester, T

2013-01-01

Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence-based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with 'refractory' GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2-receptor antagonists (which are expensive and which carry risks - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non-GERD causes of their extraesophageal symptoms. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Endoscopic mucosal autograft for treating esophageal caustic strictures: preliminary human experience.

PubMed

He, Kexin; Zhao, Lili; Bu, Shoushan; Liu, Li; Wang, Xiang; Wang, Min; Fan, Zhining

2018-06-11

 Esophageal caustic stricture is a stubborn disease and postoperative restenosis limits the clinical efficacy of endoscopic dilation. Autologous mucosal grafts have been successfully applied in the treatment of urethral stricture and in the prevention of stricture after extensive mucosal resection. We aimed to use mucosal autografting performed endoscopically to treat refractory esophageal stricture. METHODS : Three patients with intractable corrosive esophageal stricture were treated endoscopically by combining dilation with autologous mucosal transplantation. RESULTS : All procedures were successful with no severe complications. Mucosal regeneration was shown at the transplanted segments. One patient was able to maintain a normal diet with complete remission after 1 year of follow-up. Intraluminal stenosis and dysphagia were significantly improved in another two patients. CONCLUSIONS : Mucosal autografting can achieve esophageal re-epithelialization, inhibit undesired fibrosis, prevent restenosis, and promote functional regeneration. © Georg Thieme Verlag KG Stuttgart · New York.

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

PubMed Central

Matoba, Nobuyuki; Magérus, Aude; Geyer, Brian C.; Zhang, Yunfang; Muralidharan, Mrinalini; Alfsen, Annette; Arntzen, Charles J.; Bomsel, Morgane; Mor, Tsafrir S.

2004-01-01

A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing the mucosal targeting B subunit of cholera toxin to the conserved galactosylceramide-binding domain (including the ELDKWA-neutralizing epitope) of the HIV-1 gp41 envelope protein, which mediates the transcytosis of HIV-1 across the mucosal epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers that were capable of binding galactosyl-ceramide and GM1 gangliosides. Mucosal (intranasal) administration in mice of the purified chimeric protein followed by an i.p. boost resulted in transcytosis-neutralizing serum IgG and mucosal IgA responses and induced immunological memory. Plant production of mucosally targeted immunogens could be particularly useful for immunization programs in developing countries, where desirable product traits include low cost of manufacture, heat stability, and needle-free delivery. PMID:15347807

Recent advances in microparticle and nanoparticle delivery vehicles for mucosal vaccination.

PubMed

McNeela, E A; Lavelle, E C

2012-01-01

The great potential of mucosal vaccination is widely accepted but progress in the clinical development of subunit mucosal vaccines has been disappointing. Of the available approaches, the use of polymer-based microparticles is attractive because these delivery vehicles can be specifically tailored for vaccines and they offer the potential for integration of adjuvant. Here we address recent developments in the use of particulates as mucosal vaccines and the potential of novel targeting strategies, formulation approaches and adjuvant combinations to enhance the efficacy of particle-based mucosal vaccines. This review discusses the current status of mucosal vaccines based on particles and highlights several of the strategies that are currently under investigation for improving their immunogenicity. These include enhancing the stability of formulations in the luminal environment, increasing uptake by specifically targeting particles to mucosal inductive sites, and augmenting immunogenicity through co-formulation with immunostimulatory agents.

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux.

PubMed

Robertson, Elaine V; Derakhshan, Mohammad H; Wirz, Angela A; Mitchell, David R; Going, James J; Kelman, Andrew W; Ballantyne, Stuart A; McColl, Kenneth E L

2017-07-01

Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH. We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High-resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine, before and after a meal. The SCJ was marked with an endoscopically placed clip and visualised fluoroscopically. Cardiac mucosa was longer in volunteers with HH (3.5 vs 2.5 mm, p=0.01). There was no excessive acid reflux 5 cm above the upper border of the lower oesophageal sphincter (LOS) in either group but those with HH had short segment reflux 11 mm above the pH transition point after the meal when supine (pH<4 for 5.5% vs 0.3% of time, p=0.01). The SCJ and pH transition point were proximally displaced within the gastro-oesophageal junction in those with HH versus controls (p<0.05). The pH transition point was proximal to the peak LOS pressure point in HH subjects but distal to it in controls after the meal (p<0.05). When supine, the postprandial pH transition point crossed the SCJ in those with HH (p=0.03). Healthy volunteers with HH have increased intrasphincteric reflux and lengthening of cardiac mucosa in the absence of traditional transsphincteric reflux. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The mucosal immune system: From dentistry to vaccine development

PubMed Central

KIYONO, Hiroshi; AZEGAMI, Tatsuhiko

2015-01-01

The oral cavity is the beginning of the aero-digestive tract, which is covered by mucosal epithelium continuously under the threat of invasion of pathogens, it is thus protected by the mucosal immune system. In the early phase of our scientific efforts for the demonstration of mucosal immune system, dental science was one of major driving forces due to their foreseeability to use oral immunity for the control of oral diseases. The mucosal immune system is divided functionally into, but interconnected inductive and effector sites. Intestinal Peyer’s patches (PPs) are an inductive site containing antigen-sampling M cells and immunocompetent cells required to initiate antigen-specific immune responses. At effector sites, PP-originated antigen-specific IgA B cells become plasma cells to produce polymeric IgA and form secretory IgA by binding to poly-Ig receptor expressed on epithelial cells for protective immunity. The development of new-generation mucosal vaccines, including the rice-based oral vaccine MucoRice, on the basis of the coordinated mucosal immune system is a promising strategy for the control of mucosal infectious diseases. PMID:26460320

Cryotherapy effect on oral mucositis severity among recipients of bone marrow transplantation: a literature review.

PubMed

Tayyem, Abdel-Qader Mahmoud

2014-08-01

Oral mucositis is a distressing toxic effect of cancer therapy and one of the major side effects of the myeloablative conditioning used to prepare patients for bone marrow transplantation (BMT). Oral cryotherapy is one of the recent modalities used to prevent and manage oral mucositis. The purpose of this review is to clarify the cryotherapy effect on oral mucositis severity among patients receiving myeloablative conditioning followed by BMT. A literature search was performed using six different electronic databases: CINAHL®, MEDLINE®, Nursing Ovid, PubMed, Springer, and Science Direct. Six articles were deemed relevant and included in this review. Oral mucositis increases mortality rate, length of hospital stay, opioid use, and the need for parenteral nutrition usage. It also decreases patient's quality of life and his or her desire to complete treatment. However, oral cryotherapy significantly minimizes the incidence and severity of oral mucositis and decreases secondary oral mucositis complications. Using oral cryotherapy concurrently with a regular oral care protocol can improve its efficacy for preventing and managing oral mucositis. Additional studies should be conducted to create standard oral cryotherapy protocols.

Biology and Mucosal Immunity to Myxozoans

PubMed Central

Gómez, Daniela; Bartholomew, Jerri; Sunyer, J. Oriol

2014-01-01

Myxozoans are among the most abundant parasites in nature. Their life cycles involve two hosts: an invertebrate, usually an annelid, and a vertebrate, usually a fish. They affect fish species in their natural habitats but also constitute a menace for fish aquaculture. Using different strategies they are able to parasitize and cause damage in multiple organs, including mucosal tissues, which they use also as portals of entry. In fish, the main mucosal sites include the intestine, skin and gills. Recently the finding of a specific mucosal immunoglobulin in teleost (IgT), analogous to mammalian IgA, and the capacity of fish to develop a specific mucosal immune response against different pathogens, has highlighted the importance of studying immune responses at mucosal sites. In this review, we describe the major biological characteristics of myxozoan parasites and present the data available regarding immune responses for species that infect mucosal sites. As models for mucosal immunity we review the responses to Enteromyxum spp. and Ceratomyxa shasta, both of which parasitize the intestine. The immune response at the skin and gills is also described, as these mucosal tissues are used by myxozoans as attaching surfaces and portal of entry, and some species also parasitize these sites. Finally, the development of immunoprophylactic strategies is discussed. PMID:23994774

Mucosal vaccines to prevent porcine reproductive and respiratory syndrome: a new perspective.

PubMed

Renukaradhya, Gourapura J; Dwivedi, Varun; Manickam, Cordelia; Binjawadagi, Basavaraj; Benfield, David

2012-06-01

Porcine reproductive and respiratory syndrome (PRRS) is an economically important infectious disease of swine. Constant emergence of variant strains of PRRS virus (PPRSV) and virus-mediated immune evasion followed by viral persistence result in increased incidence and recurrence of PRRS in swine herds. Current live and killed PRRSV vaccines administered by a parenteral route are ineffective in inducing complete protection. Thus, new approaches in design and delivery of PRRSV vaccines are needed to reduce the disease burden of the swine industry. Induction of an effective mucosal immunity to several respiratory pathogens by direct delivery of a vaccine to mucosal sites has proven to be effective in a mouse model. However, there are challenges in eliciting mucosal immunity to PRRS due to our limited understanding of safe and potent mucosal adjuvants, which could potentiate the mucosal immune response to PRRSV. The purpose of this review is to discuss methods for induction of protective mucosal immune responses in the respiratory tract of pigs. The manuscript also discusses how PRRSV modulates innate, adaptive and immunoregulatory responses at both mucosal and systemic sites of infected and/or vaccinated pigs. This information may help in the design of innovative mucosal vaccines to elicit superior cross-protective immunity against divergent field strains of PRRSV.

Functional and structural characteristics of secretory IgA antibodies elicited by mucosal vaccines against influenza virus.

PubMed

Suzuki, Tadaki; Ainai, Akira; Hasegawa, Hideki

2017-09-18

Mucosal tissues are major targets for pathogens. The secretions covering mucosal surfaces contain several types of molecules that protect the host from infection. Among these, mucosal immunoglobulins, including secretory IgA (S-IgA) antibodies, are the major contributor to pathogen-specific immune responses. IgA is the primary antibody class found in many external secretions and has unique structural and functional features not observed in other antibody classes. Recently, extensive efforts have been made to develop novel vaccines that induce immunity via the mucosal route. S-IgA is a key molecule that underpins the mechanism of action of these mucosal vaccines. Thus, precise characterization of S-IgA induced by mucosal vaccines is important, if the latter are to be used successfully in a clinical setting. Intensive studies identified the fundamental characteristics of S-IgA, which was first discovered almost half a century ago. However, S-IgA itself has not gained much attention of late, despite its importance to mucosal immunity; therefore, some important questions remain. This review summarizes the current understanding of the molecular characteristics of S-IgA and its role in intranasal mucosal vaccines against influenza virus infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Prevalence and Investigation of Risk Factors of Oral Mucositis in a Pediatric Oncology Inpatient Population; a Prospective Study.

PubMed

Allen, Gabrielle; Logan, Richard; Revesz, Tom; Keefe, Dorothy; Gue, Sam

2018-01-01

Oral mucositis can be a frequent and severe complication of chemotherapy in children. It can result in pain, infection, depression, prolonged admission, treatment delays, increase in patient morbidity, and increased costs. To record the prevalence and severity of oral mucositis among inpatients and explore the relationship of risks factors and the development of oral mucositis. During an 18-month period 643 clinical inpatient assessments were completed on 73 children who were admitted and had received chemotherapy in the last 14 days. There were 43 episodes of oral mucositis in 31 children; 42.5% of the inpatient population. World Health Organization assessment identified 32.6% of episodes were grade 1, 34.9% grade 2, 14.0% grade 3, and 18.6% grade 4. Analysis revealed significant associations between patient diagnosis (P<0.0001), chemotherapy cycles (P<0.0001), day 8 and 9 of the chemotherapy cycle (P<0.05), and neutropenia (P<0.0001) and oral mucositis. Children had increased length of admission with increasing severity of oral mucositis (P=0.0005). The prevalence of oral mucositis was 42.5% among inpatients and admission length was increased with increasing severity. Patient diagnosis, chemotherapy treatment block, day of chemotherapy cycle, and neutropenic status were shown to influence the risk of developing oral mucositis.

Ionic basis of membrane potentials of epithelial cells in rat small intestine

PubMed Central

Barry, R. J. C.; Eggenton, Jacqueline

1972-01-01

1. Potentials across the mucosal and serosal membranes of the epithelial cells of rat jejunum together with transmural potentials were recorded using everted sac preparations. 2. Ionic changes in either mucosal or serosal fluids affect mucosal or serosal membrane potentials respectively with comparable changes in the transmural potential. The contralateral membrane potential is relatively unaffected. 3. Replacement of mucosal sodium chloride by potassium chloride or lithium chloride had little effect on potentials, but its replacement by mannitol or Tris chloride increased the negativity of the mucosal potential, giving linear relationships against log10[Na]m with slopes of 41·4 and 30·7 mV respectively for tenfold change in [Na]m. 4. At constant [Na]m, potassium or lithium increased the mucosal potential by 25·7 and 19·8 mV respectively for tenfold concentration changes. 5. Qualitatively similar changes occurred in the serosal potential when the ionic composition of the serosal fluid was varied. 6. Mucosal potential changes in response to modifications of the ionic composition of the mucosal fluid were the same in the presence and absence of galactose. 7. Sodium and potassium diffusion potentials largely determine both the mucosal and serosal membrane potentials. For the mucosal membrane, PK:PNa is 1·26:1, and is probably higher for the serosal membrane. Chloride makes no significant contribution to membrane potentials. 8. Potentials generated by the electrogenic sodium pump are superimposed on diffusion potentials across the serosal membrane. PMID:4646579

High-resolution electrical mapping of porcine gastric slow-wave propagation from the mucosal surface.

PubMed

Angeli, T R; Du, P; Paskaranandavadivel, N; Sathar, S; Hall, A; Asirvatham, S J; Farrugia, G; Windsor, J A; Cheng, L K; O'Grady, G

2017-05-01

Gastric motility is coordinated by bioelectrical slow waves, and gastric dysrhythmias are reported in motility disorders. High-resolution (HR) mapping has advanced the accurate assessment of gastric dysrhythmias, offering promise as a diagnostic technique. However, HR mapping has been restricted to invasive surgical serosal access. This study investigates the feasibility of HR mapping from the gastric mucosal surface. Experiments were conducted in vivo in 14 weaner pigs. Reference serosal recordings were performed with flexible-printed-circuit (FPC) arrays (128-192 electrodes). Mucosal recordings were performed by two methods: (i) FPC array aligned directly opposite the serosal array, and (ii) cardiac mapping catheter modified for gastric mucosal recordings. Slow-wave propagation and morphology characteristics were quantified and compared between simultaneous serosal and mucosal recordings. Slow-wave activity was consistently recorded from the mucosal surface from both electrode arrays. Mucosally recorded slow-wave propagation was consistent with reference serosal activation pattern, frequency (P≥.3), and velocity (P≥.4). However, mucosally recorded slow-wave morphology exhibited reduced amplitude (65-72% reduced, P<.001) and wider downstroke width (18-31% wider, P≤.02), compared to serosal data. Dysrhythmias were successfully mapped and classified from the mucosal surface, accorded with serosal data, and were consistent with known dysrhythmic mechanisms in the porcine model. High-resolution gastric electrical mapping was achieved from the mucosal surface, and demonstrated consistent propagation characteristics with serosal data. However, mucosal signal morphology was attenuated, demonstrating necessity for optimized electrode designs and analytical algorithms. This study demonstrates feasibility of endoscopic HR mapping, providing a foundation for advancement of minimally invasive spatiotemporal gastric mapping as a clinical and scientific tool. © 2016 John Wiley & Sons Ltd.

Effects of spaceflight on the proliferation of jejunal mucosal cells

NASA Technical Reports Server (NTRS)

Phillips, Robert W.; Moeller, C. L.; Sawyer, Heywood R.; Smirnov, K. L.

1991-01-01

The purpose of this project was to test the hypothesis that the generalized, whole body decrease in synthetic activity due to microgravity conditions encountered during spaceflight would be demonstrable in cells and tissues characterized by a rapid rate of turnover. Jejunal mucosal cells were chosen as a model since these cells are among the most rapidly proliferating in the body. Accordingly, the percentage of mitotic cells present in the crypts of Lieberkuhn in each of 5 rats flown on the COSMOS 2044 mission were compared to the percentage of mitotic cells present in the crypts in rats included in each of 3 ground control groups (i.e., vivarium, synchronous and caudal-elevated). No significant difference (p greater than .05) was detected in mitotic indices between the flight and vivarium group. Although the ability of jejunal mucosal cells to divide by mitosis was not impaired in flight group, there was, however, a reduction in the length of villi and depth of crypts. The concommitant reduction in villus length and crypth depth in the flight group probably reflects changes in connective tissue components within the core of villi.

[Therapeutic effect of rebamipide for oral mucositis associated with FEC therapy for breast cancer].

PubMed

Enami, Akiko; Masuda, Norikazu; Yamamura, Jun; Mizutani, Makiko; Yasojima, Hiroyuki; Shikata, Ayako; Masaoka, Miyuki; Takada, Seiko; Bamba, Nao; Yamamoto, Mie; Abe, Megumi; Makihara, Katsuya

2014-11-01

No guidelines for supportive drug therapy have been established for oral mucositis occurring during cancer chemotherapy. We retrospectively examined the progression of oral mucositis in 91 patients with breast cancer who received the 5-fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 regimen between September 2007 and August 2008. Daily rebamipide was administered to patients with oral mucositis as per hospital protocol to evaluate the hypothesized preventive and mucosal protective effects of rebamipide(Mucosta®). Oral mucositis was observed in 43 patients (47%)during 4 courses of FEC. The median age of the patients was 55 years(range, 32-76 years). Of the 91 patients, 49 patients who did not receive rebamipide during the 4 FEC courses were classified as group A, 14 patients who received rebamipide before the start of FEC were classified as group B, and 28 patients who received rebamipide after developing oral mucositis were classified as group C. The incidence of oral mucositis at the start of FEC with or without rebamipide administration was observed in 5 patients in group B (36%) and 38 patients in groups A and C (49%) (p=0.3472). The mucositis grade was G1 in 4 patients and G2 in 1 patient in group B, and G1 in 20 patients and G2 plus G3 in 18 patients in groups A and C (p=0.2467). In group C, the grade decreased in 25 patients (89%) and did not occur (G0) in 17 patients (61%) during the next course, and 15 patients (54%) continued to the final course without any occurrence of mucositis. These results suggest that rebamipide is effective for the treatment of oral mucositis. Although significant differences were not observed in the groups, rebamipide has the potential to prevent development of oral mucositis and alleviate its symptoms, and seems promising as a new supportive drug therapy. We hope to verify the preventive and protective effects of rebamipide by conducting a prospective, randomized trial while treating oral mucositis with basic oral care and appropriate interventions provided by a multidisciplinary team.

Evaluation of mast cells, eosinophils, blood capillaries in oral lichen planus and oral lichenoid mucositis.

PubMed

Reddy, D Santhosh; Sivapathasundharam, B; Saraswathi, T R; SriRam, G

2012-01-01

Mast cells are granule containing secretory cells present in oral mucosal and connective tissue environment. Oral lichen planus and oral lichenoid lesions are commonly occurring oral diseases and have some similarity clinically and histologically. Both are characterized by an extensive sub epithelial infiltrate of T cells, together with mast cells, eosinophils and blood capillaries. In this study mast cell and eosinophil densities along with number of blood capillaries were studied to find out if they could aid in histopathological distinction between oral lichen planus and lichenoid mucositis. To enumerate mast cells and compare the status of Mast Cells (Intact or Degranulated) in Lichen planus, Lichenoid mucositis and normal buccal mucosa in tissue sections stained with Toluidine Blue, and also to enumerate Eosinophils and blood capillaries in tissue sections stained with H and E. The study group included 30 cases each of oral lichen planus and oral lichenoid mucositis. 10 cases of clinically normal oral buccal mucosa formed the control group. All the sections were stained with Toluidine blue and H and E separately. Histopathological analysis was done using binocular light microscope equipped with square ocular grid to standardize the field of evaluation. The result of the study showed. · Significant increase in number of mast cells in oral lichen planus and oral lichenoid mucositis compared to normal buccal mucosa. · Significant increase of intact mast cells suepithelially within the inflammatory cell infiltrate in oral lichen planus compared to oral lichenoid mucositis. · Significant increase of degranulated mast cells in oral lichenoid mucositis to oral lichen planus, and increase in number of eosinophil densities in oral lichenoid mucositis compared to oral lichen planus. · Significant increase in number of capillaries in oral lichenoid mucositis compared to oral lichen planus. The findings of increased number of intact mast cells sub epithelially in oral lichen planus to oral lichenoid mucositis and increase in number of degranulated mast cells as well as capillaries subepithelially in oral lichenoid mucositis to oral lichen planus can be used as reliable criteria for histologic distinction between these two lesions. The increase of eosinophils in oral lichenoid mucositis to oral lichen planus could be used as adjunct histologic criterion in the diagnosis of oral lichenoid mucositis.

The role of titanium-prepared platelet-rich fibrin in palatal mucosal wound healing and histoconduction.

PubMed

Ustaoğlu, Gülbahar; Ercan, Esra; Tunali, Mustafa

2016-10-01

We aimed to determine the clinical effects of titanium-prepared, platelet-rich fibrin (T-PRF) on human palatal mucosal wound healing (PMWH) and to identify its effect on time-dependent changes in palatal soft-tissue thickness (PSTT) in terms of histoconduction, which is a new concept. Free gingival graft (FGG) donor sites were treated with T-PRF and compared with an untreated control group. The results of colour match and H 2 O 2 -bubbling tests for complete wound epithelization (CWE) were recorded on days 3, 7, 14 and 21. Pain level, number of analgesics used and bleeding status were recorded for the first 7 days. PSTT was measured at baseline and after 1 and 6 months. Colour match scores of the test group were significantly higher than those of the control group at 7 and 14 days. CWE was observed at a higher frequency in the test group than in the control group on day 14. Post-operative bleeding prevalence was lower in the test group than in the control group for the first 2 days. A time-dependent decrease in PSTT was observed at 1 and 6 months in the control group compared with baseline (baseline, 4.23 ± 0.62 mm; 1 month, 4.01 ± 0.68 mm; and 6 months, 3.93 ± 0.69 mm). However, no significant difference was found in the test group (baseline, 4.29 ± 0.64 mm; 1 month, 4.61 ± 0.51 mm; and 6 months, 4.51 ± 0.58 mm). The T-PRF membrane exhibited positive effects on PMWH. T-PRF, which is a promising autogenous matrix for histoconduction, may also be preferred as an autogenous alternative to connective tissue grafts in the treatment of gingival recessions and peri-implant mucosal recessions.

Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals.

PubMed

Mohan Kumar, M; Joshi, M C; Prabha, T; Dorababu, M; Goel, R K

2006-04-01

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.

Oral disease profiles in chronic graft versus host disease.

PubMed

Bassim, C W; Fassil, H; Mays, J W; Edwards, D; Baird, K; Steinberg, S M; Cowen, E W; Naik, H; Datiles, M; Stratton, P; Gress, R E; Pavletic, S Z

2015-04-01

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials. © International & American Associations for Dental Research 2015.

Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment.

PubMed

Riley, Philip; McCabe, Martin G; Glenny, Anne-Marie

2016-10-01

In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).

Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

ClinicalTrials.gov

2018-05-23

Metastatic Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

Assays to Study the Interaction of Campylobacter jejuni with the Mucosal Surface.

PubMed

Clyne, Marguerite; Duggan, Gina; Dunne, Ciara; Dolan, Brendan; Alvarez, Luis; Bourke, Billy

2017-01-01

Mucosal colonization and overcoming the mucosal barrier are essential steps in the establishment of infection by Campylobacter jejuni. The interaction between C. jejuni and host cells, including binding and invasion, is thought to be the key virulence factor important for pathogenesis of C. jejuni infections in animals or humans. The intestinal mucosal barrier is composed of a polarized epithelium covered by a thick adherent mucus gel layer. There is a requirement for cell culture assays of infection to accurately represent the in vivo mucosal surface. In this chapter, we describe the use of a number of cell culture models and the use of polarized in vitro organ culture to examine the interaction of C. jejuni with mucosal surfaces.

Vaccine-induced mucosal immunity to poliovirus: analysis of cohorts from an open-label, randomised controlled trial in Latin American infants.

PubMed

Wright, Peter F; Connor, Ruth I; Wieland-Alter, Wendy F; Hoen, Anne G; Boesch, Austin W; Ackerman, Margaret E; Oberste, M Steven; Gast, Chris; Brickley, Elizabeth B; Asturias, Edwin J; Rüttimann, Ricardo; Bandyopadhyay, Ananda S

2016-12-01

Identification of mechanisms that limit poliovirus replication is crucial for informing decisions aimed at global polio eradication. Studies of mucosal immunity induced by oral poliovirus (OPV) or inactivated poliovirus (IPV) vaccines and mixed schedules thereof will determine the effectiveness of different vaccine strategies to block virus shedding. We used samples from a clinical trial of different vaccination schedules to measure intestinal immunity as judged by neutralisation of virus and virus-specific IgA in stools. In the FIDEC trial, Latin American infants were randomly assigned to nine groups to assess the efficacy of two schedules of bivalent OPV (bOPV) and IPV and challenge with monovalent type 2 OPV, and stools samples were collected. We selected three groups of particular interest-the bOPV control group (serotypes 1 and 3 at 6, 10, and 14 weeks), the trivalent attenuated OPV (tOPV) control group (tOPV at 6, 10, and 14 weeks), and the bOPV-IPV group (bOPV at 6, 10, and 14 weeks plus IPV at 14 weeks). Neutralising activity and poliovirus type-specific IgA were measured in stool after a monovalent OPV type 2 challenge at 18 weeks of age. Mucosal immunity was measured by in-vitro neutralisation of a type 2 polio pseudovirus (PV2). Neutralisation titres and total and poliovirus-type-specific IgG and IgA concentrations in stools were assessed in samples collected before challenge and 2 weeks after challenge from all participants. 210 infants from Guatemala and Dominican Republic were included in this analysis. Of 38 infants tested for mucosal antibody in the tOPV group, two were shedding virus 1 week after challenge, compared with 59 of 85 infants receiving bOPV (p<0·0001) and 53 of 87 infants receiving bOPV-IPV (p<0·0001). Mucosal type 2 neutralisation and type-specific IgA were noted primarily in response to tOPV. An inverse correlation was noted between virus shedding and both serum type 2 neutralisation at challenge (p<0·0001) and mucosal type 2 neutralisation at challenge (p<0·0001). Mucosal type-2-specific antibodies can be measured in stool and develop in response to receipt of OPV type 2 either in the primary vaccine series or at challenge. These mucosal antibodies influence the amount of virus that is shed in an established infection. Bill & Melinda Gates Foundation. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS.

PubMed

Hering, Rudolf; Kreyer, Stefan; Putensen, Christian

2017-10-27

Lung protective mechanical ventilation with limited peak inspiratory pressure has been shown to affect cardiac output in patients with ARDS. However, little is known about the impact of lung protective mechanical ventilation on regional perfusion, especially when associated with moderate permissive respiratory acidosis. We hypothesized that lung protective mechanical ventilation with limited peak inspiratory pressure and moderate respiratory acidosis results in an increased cardiac output but unequal distribution of blood flow to the different organs of pigs with oleic-acid induced ARDS. Twelve pigs were enrolled, 3 died during instrumentation and induction of lung injury. Thus, 9 animals received pressure controlled mechanical ventilation with a PEEP of 5 cmH 2 O and limited peak inspiratory pressure (17 ± 4 cmH 2 O) versus increased peak inspiratory pressure (23 ± 6 cmH 2 O) in a crossover-randomized design and were analyzed. The sequence of limited versus increased peak inspiratory pressure was randomized using sealed envelopes. Systemic and regional hemodynamics were determined by double indicator dilution technique and colored microspheres, respectively. The paired student t-test and the Wilcoxon test were used to compare normally and not normally distributed data, respectively. Mechanical ventilation with limited inspiratory pressure resulted in moderate hypercapnia and respiratory acidosis (PaCO 2 71 ± 12 vs. 46 ± 9 mmHg, and pH 7.27 ± 0.05 vs. 7.38 ± 0.04, p < 0.001, respectively), increased cardiac output (140 ± 32 vs. 110 ± 22 ml/min/kg, p<0.05) and regional blood flow in the myocardium, brain and spinal cord, adrenal and thyroid glands, the mucosal layers of the esophagus and jejunum, the muscularis layers of the esophagus and duodenum, and the gall and urinary bladders. Perfusion of kidneys, pancreas, spleen, hepatic arterial bed, and the mucosal and muscularis blood flow to the other evaluated intestinal regions remained unchanged. In this porcine model of ARDS mechanical ventilation with limited peak inspiratory pressure resulting in moderate respiratory acidosis was associated with an increase in cardiac output. However, the better systemic blood flow was not uniformly directed to the different organs. This observation may be of clinical interest in patients, e.g. with cardiac, renal and cerebral pathologies.

Detection of familial adenomatous polyposis with polarized spectroscopic imaging and oral vascular density

NASA Astrophysics Data System (ADS)

Basiri, Ali; Edelstein, Daniel L.; Giardiello, Francis M.; Ramella-Roman, J. C.

2011-03-01

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disease characterized by the development of multiple colonic polyps at younger age with a near 100% lifetime risk of colorectal cancer in later years. The determination of FAP is made after extensive clinical evaluation and genetic testing of at risk individuals. Genetic testing is expensive and in some cases deleterious mutations are not found in all patients with a clinical diagnosis of FAP. As such, the early identification of affected individuals could substantially eliminate associated morbidity and mortality. We investigated a novel spectro-polarimetric imaging system to capture images of the oral mucosa at different wavelengths in an attempt to distinguish patients with FAP from controls. Total diffused oral mucosal reflectance (OMR) and oral mucosal vascular density (OMVD) were calculated from spectral data collected from 33 patients with gene positive FAP, 5 patients who tested negative for FAP, and 45 controls. A statistically significant difference in OMVD (p < 0.001) was observed between individuals with FAP and controls. Analysis of OMR showed no significant difference between the two subject groups.

Dietary palmitic acid modulates intestinal re-growth after massive small bowel resection in a rat.

PubMed

Sukhotnik, Igor; Hayari, Lili; Bashenko, Yulia; Chemodanov, Elena; Mogilner, Jorge; Shamir, Raanan; Bar Yosef, Fabiana; Shaoul, Ron; Coran, Arnold G

2008-12-01

Among factors promoting intestinal adaptation after bowel resection, dietary fatty acids have a special role. The purpose of the present study was to evaluate the effects of palmitic acid (PA) on early intestinal adaptation in rats with short bowel syndrome (SBS). Male Sprague-Dawley rats underwent either a bowel transection with re-anastomosis (sham rats) or 75% small bowel resection (SBS rats). Animals were randomly assigned to one of four groups: sham rats fed normal chow (sham-NC); SBS rats fed NC (SBS-NC), SBS rats fed high palmitic acid diet (SBS-HPA), and SBS rats fed low palmitic acid diet (SBS-LPA). Rats were sacrificed on day 14. Parameters of intestinal adaptation, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, cell proliferation and apoptosis were determined at sacrifice. RT-PCR and Western blotting were used to determine the level of bax and bcl-2 mRNA and protein (parameters of apoptosis), and ERK protein levels (parameter of proliferation). Statistical analysis was performed using Kruskal-Wallis test followed by post hoc test for multiple comparisons with P values of less than 0.05 considered statistically significant. SBS-HFD rats demonstrated higher bowel and mucosal weight, mucosal DNA and protein in ileum, while deprivation of PA (SBS-LPA) inhibited intestinal re-growth both in jejunum and ileum compared to SBS-NC rats. A significant up-regulation of ERK protein coincided with increased cell proliferation in SBS-HFD rats (vs. SBS-NC). Also, the initial decreased levels of apoptosis corresponded with the early decrease in bax and increase in bcl-2 at both mRNA and protein levels. Early exposure to HPA both augments and accelerates structural bowel adaptation in a rat model of SBS. Increased cell proliferation and decreased cell apoptosis may be responsible for this effect. Deprivation of PA in the diet inhibits intestinal re-growth.

Shifts in Host Mucosal Innate Immune Function Are Associated with Ruminal Microbial Succession in Supplemental Feeding and Grazing Goats at Different Ages

PubMed Central

Jiao, Jinzhen; Zhou, Chuanshe; Guan, L. L.; McSweeney, C. S.; Tang, Shaoxun; Wang, Min; Tan, Zhiliang

2017-01-01

Gastrointestinal microbiota may play an important role in regulating host mucosal innate immune function. This study was conducted to test the hypothesis that age (non-rumination, transition and rumination) and feeding type [Supplemental feeding (S) vs. Grazing (G)] could alter ruminal microbial diversity and maturation of host mucosal innate immune system in goat kids. MiSeq sequencing was applied to investigate ruminal microbial composition and diversity, and RT-PCR was used to test expression of immune-related genes in ruminal mucosa. Results showed that higher (P < 0.05) relative abundances of Prevotella, Butyrivibrio, Pseudobutyrivibrio, Methanobrevibacter.gottschalkii, Neocallimastix, Anoplodinium–Diplodinium, and Polyplastron, and lower relative abundance of Methanosphaera (P = 0.042) were detected in the rumen of S kids when compared to those in G kids. The expression of genes encoding TLRs, IL1α, IL1β and TICAM2 was down-regulated (P < 0.01), while expression of genes encoding tight junction proteins was up-regulated (P < 0.05) in the ruminal mucosa of S kids when compared to that in G kids. Moreover, irrespective of feeding type, relative abundances of ruminal Prevotella, Fibrobacter, Ruminococcus, Butyrivibrio, Methanobrevibacter, Neocallimastix, and Entodinium increased with age. The expression of most genes encoding TLRs and cytokines increased (P < 0.05) from day 0 to 7, while expression of genes encoding tight junction proteins declined with age (P < 0.05). This study revealed that the composition of each microbial domain changed as animals grew, and these changes might be associated with variations in host mucosal innate immune function. Moreover, supplementing goat kids with concentrate could modulate ruminal microbial composition, enhance barrier function and decrease local inflammation. The findings provide useful information in interpreting microbiota and host interactions, and developing nutritional strategies to improve the productivity and health of rumen during early life. PMID:28912767

Determination of the Chronic Mammalian Toxicological Effects of RDX. Acute Dermal Toxicity Test of Hexehydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) in Rabbits

DTIC Science & Technology

1984-08-01

Typist B. Letica Verified: L_. Pathologist - Date 20 Study Nlumnber L6121.10 Dose (mg/1) Test Animal Number 15 * Accession Number 81-7176 Microscopic...Diffusemoderate necrosis of mucosal epithelium. Mild, diffuse accumulation of inflammatory cells in mucosa and submucosa Typist B. Letica Verified: tk

Laparoscopic Nissen fundoplication mainly reduces the volume of acid reflux and potentially improves mucosal integrity up to the middle esophagus in neurologically impaired children detected by esophageal combined pH-multichannel intraluminal impedance measurements.

PubMed

Fukahori, Suguru; Yagi, Minoru; Ishii, Shinji; Asagiri, Kimio; Saikusa, Nobuyuki; Hashizume, Naoki; Yoshida, Motomu; Masui, Daisuke; Sakamoto, Saki; Tsuruhisa, Shihori; Kurahachi, Tomohiro; Tanaka, Yoshiaki

2016-08-01

The aim of this study was to evaluate detailed changes of gastroesophageal reflux disease (GERD) in children before and after laparoscopic Nissen fundoplication (LNF) utilizing esophageal combined pH-multichannel intraluminal impedance (pH/MII) measurements. Thirteen patients with neurological impairment, who received laparoscopic Nissen fundoplication (LNF) owing to refractory pathological GERD, were enrolled in this study. 24h pH/MII was conducted in all patients before and one year after LNF. Each parameter of the pH/MII was evaluated and compared each other. Both the mean pH index and bolus exposure index after LNF were significantly lower than those before LNF. The mean numbers of total and nonacid reflux episodes after LNF were significantly lower than those before LNF. The mean numbers of total, acid and nonacid proximal reflux episodes after LNF were significantly lower than those before LNF. The mean baseline impedance values from Z3 to Z6 after LNF were significantly higher than those before LNF. The present study provides new insights into the effects of LNF in pediatric patients, which prevents mainly acid reflux episodes from rising to the proximal esophagus, and is expected to improve the mucosal integrity up to the middle esophagus. Copyright © 2016 Elsevier Inc. All rights reserved.

Antioxidant Properties and Gastroprotective Effects of 2-(Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats

PubMed Central

Ariffin, Azhar; Abdulla, Mahmood A.; Abdullah, Zanariah

2016-01-01

A series of new 2-(ethylthio)benzohydrazone derivatives (1–6) were prepared and characterised by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly prepared compounds were screened for their in vitro antioxidant activities using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Among them, most powerful antioxidant, compound 1 has been selected in order to illustrate anti-ulcer effect on ethanol-induced gastric mucosal lesions in rats. Four groups of Sprague Dawley rats were respectively treated with 10% Tween 20 as ulcer control group, 20 mg/kg omeprazole as reference group, 50 mg/kg and 100 mg/kg compound 1 as experimental animals. Macroscopically, ulcer control group showed extensive hemorrhagic lesions of gastric mucosa compared with omeprazole or compound 1. Rats pre-treated with compound 1 showed increased in gastric pH and gastric mucus. Histologically, ulcer control group showed severe damage to gastric mucosa with edema and leucocytes infiltration of submucosal layer. In immunohistochemical analysis, rats which were pre-treated with compound 1 showed up-regulation of HSP70 and down-regulation of Bax proteins. In conclusion, the gastroprotective effect of compound 1 may be due to its antioxidant activity, and/or due to up-regulation of HSP70 and down-regulation of Bax protein in stained tissue section. PMID:27272221

Preparation and evaluation of mesalamine collagen in situ rectal gel: a novel therapeutic approach for treating ulcerative colitis.

PubMed

Ramadass, Satiesh Kumar; Perumal, Sathiamurthi; Jabaris, Sugin Lal; Madhan, Balaraman

2013-01-23

Ulcerative colitis (UC) is a chronic inflammatory disease that primarily affects the colonic mucosa. Mesalamine had been established as a first line drug for treating mild to moderate UC. A continued availability of the drug for treatment of damaged tissues remains a great challenge today. In the present study, a novel mesalamine collagen in situ gel has been prepared using type I collagen, which is pH/temperature sensitive. This hydrogel undergoes sol-gel transition under physiological pH and temperature which was confirmed by rheological studies. The in vitro release profile demonstrated sustained release of mesalamine over a period of 12h. The in vivo efficacy of the in situ gel was performed using dextran sodium sulphate induced ulcerative colitis model in BALB/c mice. The clinical parameters such as, body weight changes, rectal bleeding and stool consistency were evaluated. In addition, the histopathological investigation was conducted to assess severity of mucosal damage and inflammation infiltrate. There was a significant reduction in rectal bleeding and mucosal damage score for collagen-mesalamine in situ gel group compared to the reference group. Apart from releasing mesalamine in controlled manner, the strategy of administering mesalamine through collagen in situ gel facilitates regeneration of damaged mucosa resulting in a synergistic effect for the treatment of ulcerative colitis. Copyright © 2012 Elsevier B.V. All rights reserved.

Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

PubMed

He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

2015-03-01

Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

Long-term mucosal recovery and healing in celiac disease is the rule - not the exception.

PubMed

Hære, Petter; Høie, Ole; Schulz, Tom; Schönhardt, Irina; Raki, Melinda; Lundin, Knut E A

2016-12-01

The prevalence of persistent villous atrophy (VA) in patients with celiac disease (CD) on a gluten-free diet (GFD) varies greatly between studies. Most studies show a relatively high prevalence of mucosal atrophy and inflammation in treated patients, a finding which have led to a concept of non-responsive CD. Few studies have examined the prevalence of long-term mucosal healing. Our study aimed to determine the extent of mucosal healing in a cohort of Norwegian patients with CD treated with GFD for several years. Adult patients diagnosed with VA between 1989 and 2009 were included. We performed a follow-up gastroscopy with duodenal biopsies. Two pathologists evaluated the biopsies according to the Marsh-Oberhuber classification. Mucosal healing was defined as Marsh 0 while mucosal recovery was defined as Marsh 0-2. Duodenal biopsies were obtained from 127 adult patients with established CD. After a follow-up time of 8.1 years (median, range 2.3-22.3), 103 (81%) of the patients showed mucosal healing, 120 patients (94%) showed mucosal recovery, and 7 patients (6%) showed persistent VA. In addition, 103 of the 127 patients (81%) had undergone a routine follow-up biopsy 12.6 months (median, range 5.2-28.8) after diagnosis. At the time of the routine follow-up, only 52 of these patients (50.5%) had achieved mucosal recovery. Although half of the patients had persistent VA at the time of routine follow-up, both long-term mucosal recovery and healing is possible for the vast majority of adult patients with CD.

Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

PubMed

Chen, Joey; Seabrook, Jamie; Fulford, Adrienne; Rajakumar, Irina

2017-03-01

Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p < 0.001). The median oral mucositis severity, assessed using the WHO oral toxicity scale from grade 0-4, experienced in the no group was 2.5 vs. 2 in the cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

Effect of pH Test-Strip Characteristics on Accuracy of Readings.

PubMed

Metheny, Norma A; Gunn, Emily M; Rubbelke, Cynthia S; Quillen, Terrilynn Fox; Ezekiel, Uthayashanker R; Meert, Kathleen L

2017-06-01

Little is known about characteristics of colorimetric pH test strips that are most likely to be associated with accurate interpretations in clinical situations. To compare the accuracy of 4 pH test strips with varying characteristics (ie, multiple vs single colorimetric squares per calibration, and differing calibration units [1.0 vs 0.5]). A convenience sample of 100 upper-level nursing students with normal color vision was recruited to evaluate the accuracy of the test strips. Six buffer solutions (pH range, 3.0 to 6.0) were used during the testing procedure. Each of the 100 participants performed 20 pH tests in random order, providing a total of 2000 readings. The sensitivity and specificity of each test strip was computed. In addition, the degree to which the test strips under- or overestimated the pH values was analyzed using descriptive statistics. Our criterion for correct readings was an exact match with the pH buffer solution being evaluated. Although none of the test strips evaluated in our study was 100% accurate at all of the measured pH values, those with multiple squares per pH calibration were clearly superior overall to those with a single test square. Test strips with multiple squares per calibration were associated with greater overall accuracy than test strips with a single square per calibration. However, because variable degrees of error were observed in all of the test strips, use of a pH meter is recommended when precise readings are crucial. ©2017 American Association of Critical-Care Nurses.

Clinical assessment of oral mucositis and candidiasis compare to chemotherapic nadir in transplanted patients.

PubMed

Patussi, Cleverson; Sassi, Laurindo Moacir; Munhoz, Eduardo Ciliao; Zanicotti, Roberta Targa Stramandinoli; Schussel, Juliana Lucena

2014-01-01

Oral mucositis is a chief complication in patients undergoing hematopoietic stem cell transplantation (HSCT). It is considered a toxic inflammatory reaction that interferes with the patient's recuperation and quality of life. Oral candidiasis is a common fungal infection observed in dental practice, particularly in immunocompromised patients. The aim of this study was to evaluate the presence of oral mucositis and oral candidiasis in patients who underwent HSCT and their correlation with the chemotherapeutic nadir (lowest possible outcome). We evaluated patients with different diagnoses who underwent HSCT at the Hospital Erasto Gaertner. No chemotherapeutic nadir curves could be associated with mucositis, and patients had different presentations of mucositis. No patient developed oral candidiasis during hospitalization. Together with cell counts, we collected demographic data including age, oral hygiene, habits harmful to health, and the use of oral prostheses. It was observed that patients who smoked cigarettes before hospitalization showed less mucositis, resulting in no feeding problems or other comorbid conditions due to the effect of mucositis. However, the nadir of the chemotherapy curve, in isolation, is not a predictive tool for the appearance (or no appearance) of oral mucositis.

[Effectiveness of palifermin in the prevention of oral mucositis in patients with haematological cancers].

PubMed

Ayago Flores, D; Ferriols Lisart, R

2010-01-01

To assess the effectiveness of palifermin for the prevention of oral mucositis in patients with haematological cancers. Retrospective observational study of cohorts of patients with haematological cancer undergoing cytotoxic therapy causing hematopoietic ablation. The main variable assessed was the duration of the oral mucositis. Secondary variables assessed were incidence of mucositis, febrile or septic neutropenia and the administration of opioids and parenteral nutrition. We included 36 patients in this study, 11 in the group that received palifermin and 25 in the control group. The duration of oral mucositis was 4.6+/-3.1 days (median: 5 days) in the patients treated with palifermin in comparison with 7.4+/-4.0 days (median: 6 days) in patients treated with conventional prophylactic therapy (p<0.05). However, no significant differences were seen in the incidence of mucositis, febrile or septic neutropenia, opioid administration of the use of parenteral nutrition. Prophylactic treatment with palifermin reduces the duration of oral mucosities in patients with haematological cancer. Further studies are necessary with larger samples to be able to assess palifermin and its influence on other variables, such as incidence of mucositis, sepsis, febrile neutropenia, etc. Copyright © 2009 SEFH. Published by Elsevier Espana. All rights reserved.

Mucosal Vaccine Development Based on Liposome Technology

PubMed Central

Norling, Karin; Bally, Marta; Höök, Fredrik

2016-01-01

Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines. PMID:28127567

Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy.

PubMed

Baydar, Mustafa; Dikilitas, Mustafa; Sevinc, Alper; Aydogdu, Ismet

2005-08-01

One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis.

Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy.

PubMed Central

Baydar, Mustafa; Dikilitas, Mustafa; Sevinc, Alper; Aydogdu, Ismet

2005-01-01

INTRODUCTION: One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. METHODS: In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. RESULTS: While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). DISCUSSION: Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis. PMID:16173332

Screening and referral of oral mucosal pathology: a check-up of Australian dentists.

PubMed

Allen, K; Farah, C S

2015-03-01

Oral squamous cell carcinomas and potentially malignant oral disorders can be detected early by visually inspecting the oral soft tissues. This study aimed to determine Australian dentists' opinions and practices regarding oral mucosal screening, referral and oral cancer prevention. Nine hundred and ninety-nine randomly selected general dentists were mailed a questionnaire. The questionnaire queried practitioners' opinions and perceptions of oral mucosal screening, their referral practices and their beliefs regarding detection and prevention of oral cancer. A total of n=640 individuals responded, yielding a response rate of 70.2%. Most Australian dentists reported to routinely perform oral mucosal screening. Lack of training, confidence, time and financial incentives were seen as barriers to performing mucosal screening to at least some degree by participants in this study. Most dentists manage referrals for oral mucosal pathology appropriately; however, only about half believe in following up with referred patients. Only half of dentists surveyed believed that they could influence a patient to quit smoking. Australian dentists place importance on oral mucosal screening. Some changes to dental education and training could be made to further improve confidence and ability of dentists in detecting and referring oral mucosal pathology. © 2015 Australian Dental Association.

A double-blind, placebo-controlled, randomised trial of active manuka honey and standard oral care for radiation-induced oral mucositis.

PubMed

Bardy, Joy; Molassiotis, Alex; Ryder, W David; Mais, Kathleen; Sykes, Andrew; Yap, Beng; Lee, Lip; Kaczmarski, Ed; Slevin, Nicholas

2012-04-01

Our aim was to investigate the effect of active manuka honey on radiation-induced mucositis. A total of 131 patients diagnosed with head and neck cancer who were having radiotherapy to the oral cavity or oropharyngeal area were recruited into the study, and were randomly allocated to take either manuka honey or placebo (golden syrup) 20 ml 4 times daily for 6 weeks. Mucositis was assessed according to the Radiation Therapy Oncology Group (RTOG) scale at baseline, weekly during radiotherapy, and twice weekly thereafter until the mucositis resolved. The patient's weight was recorded at the same time as the mucositis was assessed. Throat swabs to identify bacterial or fungal infections were taken at baseline, and during and after radiotherapy. There was no significant difference between honey and golden syrup in their effects on mucositis. Active manuka honey did not improve mucositis, but both the honey and the syrup seemed to be associated with a reduction in bacterial infections. Compliance was a problem after the onset of mucositis, which may have affected the findings. Copyright © 2011 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Candida innate immunity at the mucosa.

PubMed

Richardson, Jonathan P; Moyes, David L; Ho, Jemima; Naglik, Julian R

2018-03-09

The tremendous diversity in microbial species that colonise the mucosal surfaces of the human body is only now beginning to be fully appreciated. Distinguishing between the behaviour of commensal microbes and harmful pathogens that reside at mucosal sites in the body is a complex, and exquisitely fine-tuned process central to mucosal health. The fungal pathobiont Candida albicans is frequently isolated from mucosal surfaces with an asymptomatic carriage rate of approximately 60% in the human population. While normally a benign member of the microbiota, overgrowth of C. albicans often results in localised mucosal infection causing morbidity in otherwise healthy individuals, and invasive infection that often causes death in the absence of effective immune defence. C. albicans triggers numerous innate immune responses at mucosal surfaces, and detection of C. albicans hyphae in particular, stimulates the production of antimicrobial peptides, danger-associated molecular patterns and cytokines that function to reduce fungal burdens during infection. This review will summarise our current understanding of innate immune responses to C. albicans at mucosal surfaces. Copyright © 2018. Published by Elsevier Ltd.

Mucosal vaccination--an old but still vital strategy.

PubMed

Długońska, Henryka; Grzybowski, Marcin

2012-01-01

The basic premise of vaccinology is to achieve strong protective immunity against defined infectious agents by a vaccine mimicking the effects of natural primary exposure to a pathogen. Because an exposure of humans and animals to microbes occurs mostly through mucosal surfaces, targeting the mucosa seems a rational and efficient vaccination strategy. Many experimental and clinical data confirmed that mucosal immunization offers many advantages over widely used in human and veterinary medicine subcutaneous or intramuscular immunization. In the present article selected aspects regarding mucosal vaccination are discussed. The structure and function of mucosa-associated lymphoid tissue (MALT), comprised of four main mucosal compartments forming a structural and functional unity as well as pivotal cellular MALT components (dendritic and M cells) were briefly characterized. Particular attention was focused on the mode of simple but efficacious delivery of vaccine antigens to mucosal surfaces. A few trials to generate potential mucosal vaccines against toxoplasmosis introduced by nasal or oral routes to experimental animals are also presented.

Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat.

PubMed

Sukhotnik, Igor; Helou, Habib; Mogilner, Jorge; Lurie, Michael; Bernsteyn, Aleksander; Coran, Arnold G; Shiloni, Eitan

2005-03-01

Arginine and nitric oxide are critical to the normal physiology of the gastrointestinal tract and maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluate the effects of oral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis following intestinal ischemia-reperfusion (IR) in the rat. Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent laparotomy and superior mesenteric artery mobilization, IR rats underwent superior mesenteric artery occlusion for 30 min following by 24 h of reperfusion, and IR-ARG rats were treated with enteral arginine given in drinking water (2%) 48 h before and following IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with p <0.05 considered statistically significant. IR rats demonstrated a significant decrease in bowel weight in duodenum and jejunum, mucosal weight in jejunum and ileum, and villus height in jejunum and ileum compared with control animals. IR rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in ileum compared with control rats. IR-ARG animals demonstrated greater duodenal and jejunal bowel weight; duodenal, jejunal, and ileal mucosal weight; and jejunal and ileal cell proliferation index compared with IR animals. In conclusion, oral ARG administration improves mucosal recovery following IR injury in the rat.

Differential production of immunoglobulin classes and subclasses by mucosal-type human B-lymphocytes exposed in vitro to CpG oligodeoxynucleotides.

PubMed

Cognasse, Fabrice; Acquart, Sophie; Beniguel, Lydie; Sabido, Odile; Chavarin, Patricia; Genin, Christian; Garraud, Olivier

2005-01-01

As B-lymphocytes play an important role in innate and adaptive immunity, we aimed to examine the effects of CpG oligodeoxynucleotides (ODNs) on purified tonsil-originating CD19+ B-cells, representing mucosal B-cells. We screened various K-type ODNs, reactive with human B-cells, and tested for the production of immunoglobulins in vitro. Using one CpG-ODN, DSP30, we observed that it could upregulate not only Toll-like receptor 9 (TLR9) mRNA expression in activated B-cells, but also the early expression of CD69 followed by the sequential expression of CD80, CD86 and the nuclear factor (NF)-kappaB pathway. Furthermore, mRNA expression of certain B-cell-derived cytokines was influenced by exposure to DSP30, with a strong upregulation of interleukin 6 (IL-6) and downregulation of IL1-beta. Stimulation of B-cells, co-stimulated with IL-2, IL-10 and soluble CD40 ligand (sCD40L) with different CpG-ODNs, had differing effects on the terminal differentiation in vitro of B-cells into immunoglobulin-secreting cells. TLR9 is involved in innate immunity and the recognition of bound CpG DNA from invading bacterial pathogens. As tonsillar B-cells are mucosal-type B-lymphocytes, this study suggests that CpG-ODNs show promise as mucosal adjuvants in modulating the local production of immunoglobulins of certain classes and subclasses, a crucial issue in vaccine perspectives.

Curdlan sulfate-O-linked quaternized chitosan nanoparticles: potential adjuvants to improve the immunogenicity of exogenous antigens via intranasal vaccination.

PubMed

Zhang, Shu; Huang, Shengshi; Lu, Lu; Song, Xinlei; Li, Pingli; Wang, Fengshan

2018-01-01

The development of ideal vaccine adjuvants for intranasal vaccination can provide convenience for many vaccinations. As an ideal intranasal vaccine adjuvant, it should have the properties of assisting soluble antigens to pass the mucosal barrier and potentiating both systemic and mucosal immunity via nasal administration. By using the advantages of polysaccharides, which can promote both T-helper 1 and 2 responses, curdlan sulfate (CS)- O -(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride ( O -HTCC) nanoparticles were prepared by interacting CS with O -HTCC, and the adjuvancy of the nanoparticles was investigated. The results showed that the polysaccharide-based nanoparticles induced the proliferation and activation of antigen-presenting cells. High protein-loading efficiency was obtained by testing with the model antigen ovalbumin (Ova), and the Ova adsorbed onto the cationic CS/ O -HTCC complexes was taken up easily by the epithelium. To evaluate the capacity of the Ova/CS/ O -HTCC nanoparticles for immune enhancement in vivo, we collected and analyzed immunocytes, serum, and mucosal lavage fluid from intranasally vaccinated mice. The results showed that Ova/CS/ O -HTCC nanoparticles induced activation and maturation of antigen-presenting cells and provoked the proliferation and differentiation of lymphocytes more significantly compared to the immunization of Ova mixed with aluminum hydroxide gel. Furthermore, CS/ O -HTCC evoked a significantly higher level of Ova-specific antibodies. Therefore, these results suggest that CS/ O -HTCC nanoparticles are ideal vaccine adjuvants for soluble antigens used in intranasal or mucosal vaccination.

Effects of honey use on the management of radio/chemotherapy-induced mucositis: a meta-analysis of randomized controlled trials.

PubMed

Xu, J-L; Xia, R; Sun, Z-H; Sun, L; Min, X; Liu, C; Zhang, H; Zhu, Y-M

2016-12-01

This meta-analysis aimed to assess the prophylactic effects of honey use on the management of radio/chemotherapy-induced mucositis. PubMed, Cochrane Library, Science Direct, China National Knowledge Infrastructure (CNKI), VIP (Chinese scientific journal database), and China Biology Medicine (CBM) were searched for relevant articles without language restriction. Two reviewers searched and evaluated the related studies independently. Statistical analyses were performed using Stata 11.0, calculating the pooled risk ratio (RR) with the corresponding 95% confidence interval (CI). Begg's funnel plot was used together with Egger's test to detect publication bias. A total of seven randomized controlled trials were finally included. Quality assessment showed one article to have a low risk of bias, two to have a moderate risk, and four to have a high risk. Meta-analysis showed that, compared with blank control, honey treatment could reduce the incidence of oral mucositis after radio/chemotherapy (RR 0.35, 95% CI 0.18-0.70, P=0.003). No meta-analysis was applied for honey vs. lidocaine or honey vs. golden syrup. The sensitivity analysis showed no significant change when any one study was excluded. No obvious publication bias (honey vs. blank control) was detected. In conclusion, honey can effectively reduce the incidence of radio/chemotherapy-induced oral mucositis; however, further multi-centre randomized controlled trials are needed to support the current evidence. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Fibrin sealant for closure of mucosal penetration at the cardia during peroral endoscopic myotomy: A retrospective study at a single center

PubMed Central

Zhang, Wen-Gang; Linghu, En-Qiang; Li, Hui-Kai

2017-01-01

AIM To assess the efficacy and safety of fibrin sealant for closure of mucosal penetration at the cardia during peroral endoscopic myotomy (POEM). METHODS Twenty-four patients who underwent POEM and experienced mucosal injury of the cardia during the procedure were retrospectively identified. Of the 24 patients, 21 had mucosal penetration and 3 had only slight mucosal damage without penetration. The 21 patients with mucosal penetration received fibrin sealant for closure at the site of penetration. Penetration-related characteristics, treatment, and recovery were reviewed for all 21 patients to assess the efficacy and safety of fibrin sealant for closure of mucosal penetration at the cardia. Clinical data, including general characteristics, procedure-related parameters, Eckardt scores, lower esophageal sphincter pressures (LESP), and esophagogastroduodenoscopy (EGD) results, were analyzed to determine their influence on treatment success after mucosal penetration during POEM. RESULTS All 21 patients had a solitary mucosal penetration in the cardia (12 in esophageal region of the cardia, 9 in the stomach region of the cardia, and 1 in both the esophageal and stomach regions). Twelve had a hole-like penetration and 9 had a linear penetration. For those with a hole-like penetration, the mean size was 0.14 cm2 (0.02-0.32 cm2). For those with a linear penetration, the median size was 0.37 cm (0.10-1.00 cm). Closure of the mucosal penetration using fibrin sealant was performed successfully in all 21 patients (two patients required 5 mL fibrin sealant, and the remaining 19 patients required 2.5 mL). Two patients had a nasogastric tube placed for five days after POEM; the remaining 19 patients were kept fasting for 3 d. All 21 patients were discharged after a median of 5 d (range: 5-7 d) postoperatively. During a median 42 mo (range: 9-62 mo) follow-up, all 21 patients with a mucosal penetration successfully healed without the occurrence of infection, ulcer, or esophagitis. Furthermore, the median LESP decreased from 31.9 mmHg (range: 21.9-67.1 mmHg) preoperatively to 20.3 mmHg (range: 6.0-41.0 mmHg) postoperatively (P < 0.05). The median preoperative and postoperative Eckardt scores were 5.0 (range; 4-10) and 1.0 (range: 0-4), respectively (P < 0.05). Of the 21 patients with mucosal penetration, symptom remission, which is defined as a postoperative Eckardt score ≤ 3, was achieved in 20 patients (95.2%) indicating that mucosal penetration did not influence the success of POEM treatment if closed successfully using fibrin sealant. CONCLUSION Fibrin sealant is safe and effective for closure of mucosal penetration during POEM. Mucosal penetrations do not appear to influence the treatment success of POEM if closed successfully using fibrin sealant. Additional studies regarding the feasibility, efficacy, and safety of fibrin sealant for closure of larger mucosal penetrations is warranted. PMID:28321165

Vaginal pH: Home-Use Tests

MedlinePlus

... streptococcus. How accurate is this test? Home vaginal pH tests showed good agreement with a doctor's diagnosis. However, ... to your doctor’s test? Yes. The home vaginal pH tests are practically identical to the ones sold to ...

Shear properties of vocal fold mucosal tissues and their effect on vocal fold oscillation

NASA Astrophysics Data System (ADS)

Chan, Roger Wai Kai

Viscoelastic shear properties of vocal fold mucosal tissues and phonosurgical biomaterials were measured with a parallel-plate rotational rheometer. Elastic, viscous and damping properties were quantified as a function of frequency (0.01 Hz to 15 Hz) for human vocal fold mucosal tissues (N = 15), implantable biomaterials commonly used in the treatment of vocal fold paralysis (Teflon, gelatin, and collagen) (the non-mucosal group), and biomaterials currently or potentially useful in the treatment of vocal fold mucosal defects (adipose tissue or fat, hyaluronic acid, and fibronectin) (the mucosal group). It was found that intersubject differences as large as an order of magnitude were often observed for the shear properties of vocal fold mucosal tissues, part of which may be age- and gender-related. Shear properties of the non-mucosal group biomaterials were often much higher than those of the mucosal group biomaterials, which were relatively close to the shear properties of mucosal tissues. Viscoelastic and rheological modeling showed that shear properties of human vocal fold mucosa may be described by a quasi-linear viscoelastic theory and a statistical network theory, based upon which extrapolations to audio frequencies were possible. A theory of small-amplitude vocal fold oscillation was revisited to describe the effects of tissue shear properties on vocal fold oscillation and phonation threshold pressure, a measure of the 'ease' of phonation and an objective indication of vocal function. It was found that phonation threshold pressure is directly related to the viscous shear modulus or the 'effective damping modulus', a concept proposed to quantify the effective amount of damping in vocal fold oscillation. The mucosal group biomaterials were incorporated into the artificial vocal fold mucosa of a physical model in order to empirically assess their effects on phonation threshold pressure. Results showed that higher threshold pressures were consistently observed for higher concentrations of hyaluronic acid and for hyaluronic acid mixed with fibronectin, in correlation with their differences in viscous shear modulus and effective damping modulus. Implications for phonosurgery were discussed in terms of the choice of optimal biomaterials for the surgical management of vocal fold mucosal defects and lamina propria deficiencies.

[Diagnosis of human brucellosis. Role of pH in the seroagglutination test and influence of pH on the agglutinating activity of IgM, IgG and IgA antibodies].

PubMed

Rubio Vallejo, Manuel; del Pozo, José L; Del Pozo León, José Luis; Hernández-Molina, Juan Manuel; Dorronsoro Ibero, Inés; Marrodán Ciordia, Teresa; Díaz García, Ramón

2002-04-01

To evaluate the role of pH in the seroagglutination test (SAT)and Rose Bengal (RB) test, and to determine the influence of pH on the agglutinating activity of IgM, IgG and IgA antibodies. The SAT was performed at pH 7.2 or pH 5.0 in standard microtiter-type polystyrene plates using Ring Test antigen or the Brucella suspension (BRUCAPT) provided in the Brucellacapt kits. Specific antibodies against native hapten were determined by radial immunodiffusion. Additionally, IgG, IgA and IgM fractions were separated from 8 sera by absorption chromatography and their agglutinating capacity was studied at pH 7.2 and 5.0. We studied 72 sera from patients with clinical brucellosis taken at the time of hospitalization, 16 from persons in contact with infected animals, and 16 from healthy donors. SAT results at pH 5.0 correlated with those obtained with the Rose Bengal test. Four Rose Bengal-positive sera were found to be SAT-negative at pH 7.2 and SAT-positive at pH 5.0. SAT performed at pH 5.0 with BRUCAPT antigen yielded higher titers than tests performed at pH 7.2 or 5.0 with Ring Test antigen (p < 0.001), with highest titers in IDR-positive sera. Among the 8 IgG fractions, all but one agglutinated at pH 7.2, and in 4, IgG titers showed significant increases at pH 5.0. Three IgA fractions were SAT-negative at pH 7.2 and SAT-positive at pH 5.0; the other 5 agglutinated at both pH conditions and were DTT-sensitive. All IgA fractions but one were positive by Rose Bengal. Agglutinating activity of the IgM fraction was not affected by pH. The SAT performed with the buffer and antigen suspension included in the Brucellacapt kit (pH 5.0) is highly useful for detecting agglutinating and non-agglutinating antibodies at pH 7.2.

HIV infection and specific mucosal immunity: workshop 4B.

PubMed

Challacombe, S J; Fidel, P L; Tugizov, S; Tao, L; Wahl, S M

2011-04-01

Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues-namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.

Novel mucosal DNA-MVA HIV vaccination in which DNA-IL-12 plus cholera toxin B subunit (CTB) cooperates to enhance cellular systemic and mucosal genital tract immunity.

PubMed

Maeto, Cynthia; Rodríguez, Ana María; Holgado, María Pía; Falivene, Juliana; Gherardi, María Magdalena

2014-01-01

Induction of local antiviral immune responses at the mucosal portal surfaces where HIV-1 and other viral pathogens are usually first encountered remains a primary goal for most vaccines against mucosally acquired viral infections. Exploring mucosal immunization regimes in order to find optimal vector combinations and also appropriate mucosal adjuvants in the HIV vaccine development is decisive. In this study we analyzed the interaction of DNA-IL-12 and cholera toxin B subunit (CTB) after their mucosal administration in DNA prime/MVA boost intranasal regimes, defining the cooperation of both adjuvants to enhance immune responses against the HIV-1 Env antigen. Our results demonstrated that nasal mucosal DNA/MVA immunization schemes can be effectively improved by the co-delivery of DNA-IL-12 plus CTB inducing elevated HIV-specific CD8 responses in spleen and more importantly in genital tract and genito-rectal draining lymph nodes. Remarkably, these CTL responses were of superior quality showing higher avidity, polyfunctionality and a broader cytokine profile. After IL-12+CTB co-delivery, the cellular responses induced showed an enhanced breadth recognizing with higher efficiency Env peptides from different subtypes. Even more, an in vivo CTL cytolytic assay demonstrated the higher specific CD8 T-cell performance after the IL-12+CTB immunization showing in an indirect manner its potential protective capacity. Improvements observed were maintained during the memory phase where we found higher proportions of specific central memory and T memory stem-like cells T-cell subpopulations. Together, our data show that DNA-IL-12 plus CTB can be effectively employed acting as mucosal adjuvants during DNA prime/MVA boost intranasal vaccinations, enhancing magnitude and quality of HIV-specific systemic and mucosal immune responses.

Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock.

PubMed

Assadi, A; Desebbe, O; Kaminski, C; Rimmelé, T; Bénatir, F; Goudable, J; Chassard, D; Allaouchiche, B

2008-01-01

We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock. Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug. Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP. In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.

Evaluation of the genotoxic effects of fixed appliances on oral mucosal cells and the relationship to nickel and chromium concentrations: an in-vivo study.

PubMed

Natarajan, Madhumitha; Padmanabhan, Sridevi; Chitharanjan, Arun; Narasimhan, Malathi

2011-09-01

The release of metal ions from fixed orthodontic appliances is a source of concern. The aim of this study was to evaluate genotoxic damage in the oral mucosal cells of patients wearing fixed appliance, and the nickel and chromium ion contents in these cells. Twenty patients undergoing orthodontic treatment formed the experimental group, and 20 untreated subjects comprised the control group. Oral mucosal smears were collected at 2 times: at debonding and 30 days after debonding. The smears were stained with Papanicolaou stain and studied under a light microscope to evaluate the presence of micronuclei. Inductively coupled plasma-mass spectrometry was used to quantify the presence of metal ions. The data were subjected to the Mann-Whitney U test and the Spearman rank correlation test. The mean micronuclei frequency was significantly higher in the treated group than in the control group at debonding; the difference was smaller and not statistically significant 30 days after debonding. The nickel and chromium ion contents in the experimental group were not significantly higher than in the control group. No correlation could be established between micronuclei frequency and metal ion content. Nickel and chromium alloys of orthodontic appliances emit metal ions in sufficient quantities to induce localized genotoxic effects, but these changes revert on removal of the appliances. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Herbs in Oral Mucositis

PubMed Central

Baharvand, Maryam; Jafari, Soudeh

2017-01-01

Oral mucositis is an inflammatory mucosal destruction as a result of chemotherapy and/or radiation therapy, which in severe cases can impair patients’ quality of life. Moreover, mucosal infection and/or systemic involvement due to compromised immunity leads to delay or discontinuation of the treatment. Many strategies and agents have been suggested for the management of this condition. Because of their lower side effects compared to chemical drugs, general interest in evaluating therapeutic effects of herbs has been increased intensively. Herbal plants apply their effect through different mechanisms of action: antioxidant, analgesic, anti-inflammatory, antifungal, antiseptic, and anticarcinogenic activity. Recently, various natural agents in plants have been noticed in mucositis, which may improve the symptoms through different interventions. The purpose of this review is to focus on the preventive or therapeutic use of herbal medicine to alleviate oral mucositis. PMID:28511530

Oral mucositis: etiology, and clinical and pharmaceutical management.

PubMed

Zur, Eyal

2012-01-01

Oral mucosal damage is one of the common and worst side effects of radiotherapy and chemotherapy treatment for cancer. With prevalence between 10% and 100%, depending on the cytotoxic and/or radiotherapy regimen and patient-associated variables, this morbid condition represents a significant problem in oncology. This article addresses oral mucositis and discusses its prevalence, risk factors, clinical and economical impacts, etiology, and clinical management in view of the most recent evidence. Despite clear progress and the development of clinical guidelines on this topic, what we currently have to offer to patients to manage mucositis and oropharyngeal pain is still inadequate. This article offers two compounded preparations supported by evidence-based data to treat oral mucositis. Expansion of the knowledge of the pathogenesis of mucositis as well as a better insight into individual risk factors will provide opportunities to improve management strategies.

Palifermin in the management of mucositis in hematological malignancies: current evidences and future perspectives.

PubMed

Niscola, Pasquale; Scaramucci, Laura; Giovannini, Marco; Ales, Micaela; Bondanini, Francesco; Cupelli, Luca; Dentamaro, Teresa; Lamanda, Michela; Natale, Giuseppina; Palumbo, Roberto; Romani, Claudio; Tendas, Andrea; Tolu, Barbara; Violo, Leano; de Fabritiis, Paolo

2009-10-01

In the management of hematological malignancies, chemotherapy-induced mucositis is an increasingly recognized problem, leading to potentially severe clinical complications, treatment delays, increased costs and impairment of patient's quality of life. Many forms of cytotoxic treatments given in this setting may induce several degrees of mucositis. In particular, conditioning therapy with hematopoietic stem cell transplantation (HSCT) induces a disruption of the mucosal barrier function throughout the entire gastrointestinal tract facilitating the spreading of bacteria and endotoxin with subsequent increased risk of septicemia and, in the allogeneic setting, a worsening of Graft Versus Host Disease (GVHD). To review the role of palifermin and of other existing and potential treatments for chemotherapy-induced mucositis in the context of current knowledge of pathobiology in the setting of hematological malignancies. We searched for palifermin and mucositis of any region of the gastrointestinal tract using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. The pathobiology of mucositis is complex, and agents that target mechanisms to prevent mucositis or accelerate healing are highly required. In this regard, palifermin (recombinant human keratinocyte growth factor) has been demonstrated to reduce the severity and the duration of oral mucositis and to significantly improve several treatment outcomes in patients submitted to autologous HSCT; data are insufficient to recommend its use in the non-autologous HSCT settings, although interesting properties of this agent deserves other investigations in order to explore other possible indications.

Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination.

PubMed

Holechek, Susan A; McAfee, Megan S; Nieves, Lizbeth M; Guzman, Vanessa P; Manhas, Kavita; Fouts, Timothy; Bagley, Kenneth; Blattman, Joseph N

2016-11-04

In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all-trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8 + T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings. We hypothesized that increasing in vivo production of retinoic acid (RA) during vaccination with a DNA vector expressing retinaldehyde dehydrogenase 2 (RALDH2), the rate-limiting enzyme in RA biosynthesis, could similarly provide enhanced programming of mucosal homing to T cell responses while avoiding teratogenic effects. Administration of a RALDH2- expressing plasmid during immunization with a HIVgag DNA vaccine resulted in increased systemic and mucosal CD8 + T cell numbers with an increase in both effector and central memory T cells. Moreover, mice that received RALDH2 plasmid during DNA vaccination were more resistant to intravaginal challenge with a recombinant vaccinia virus expressing the same HIVgag antigen (VACVgag). Thus, RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection from viral infection at mucosal sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative Efficacy of Aloe vera and Benzydamine Mouthwashes on Radiation-induced Oral Mucositis: A Triple-blind, Randomised, Controlled Clinical Trial.

PubMed

Sahebjamee, Mahnaz; Mansourian, Arash; Hajimirzamohammad, Mohammad; Mohammad, Haji Mirza Mohammad; Zadeh, Mohsen Taghi; Bekhradi, Reza; Kazemian, Ali; Manifar, Soheila; Ashnagar, Sajjad; Doroudgar, Kiavash

2015-01-01

To compare the efficacy of an Aloe vera mouthwash with a benzydamine mouthwash in the alleviation of radiation- induced mucositis in head and neck cancer patients using a triple-blind, randomised controlled trial. Twenty-six eligible head and neck cancer patients who were to receive conventional radiation therapy at the radiation oncology department were randomised to receive an Aloe vera mouthwash or a benzydamine mouthwash. Mucositis severity was assessed during the course of radiation therapy using the WHO grading system. At baseline, there was no difference in the distribution of mucositis severity between the two groups. The mean interval between radiation therapy and onset of mucositis was similar for both groups (Aloe vera 15.69±7.77 days, benzydamine 15.85±12.96 days). The mean interval between the start of radiation therapy and the maximum severity of mucositis were was also similar in both the Aloe vera and benzydamine groups (Aloe vera 23.38±10.75 days, benzydamine 23.54±15.45 days). Mean changes of mucositis severity over time in both groups were statistically similar and the effect of both treatments did not change signficantly with time (p=0.09). Aloe vera mouthwash was as beneficial as benzydamine mouthwash in alleviating the severity of radiation-induced mucositis and showed no side effects. The Aloe vera mouthwash could be an alternative agent in the treatment of radiation-induced mucositis in patients with head and neck cancers.

Extraction and characterization of cashew tree (Anacardium occidentale) gum; use in aceclofenac dental pastes.

PubMed

Hasnain, M Saquib; Rishishwar, Poonam; Rishishwar, Sanjay; Ali, Sadath; Nayak, Amit Kumar

2018-05-20

In the current work, the usefulness of extracted cashew tree gum (CG) as pharmaceutical excipient in dental pastes containing aceclofenac (AC) for the pain management in the periodontitis treatment was investigated. CG was extracted from crude exudate of cashew tree (Anacardium occidentale, family: Anacardiaceae) (yield 19.22%). Physicochemical characteristics like colour, odour, taste, solubility, pH and viscosity of extracted CG were estimated; the phytochemical identification tests indicated the presence of carbohydrates and mucilage within it. It was also characterized by FTIR spectroscopy and 1 H NMR analyses. Using the extracted CG (as natural mucoadhesive polymer) with calcium carbonate (abrasive agent), glycerin (humectant and cosolvent), methyl paraben (preservative), sodium lauryl sulfate (surfactant) and camphor (flavoring agent), 1% w/w AC dental pastes was formulated via conventional trituration. The drug contents, viscosities and pHs, tube extrudabilities and tube spreadabilities of these dental pastes were observed within permissible ranges. The dental pastes demonstrated sustained AC releasing over 6 h, in vitro and also revealed good adhesion to the oral mucosal membrane. These 1% w/w AC dental pastes can be used in the effectual management of dental inflammation and pain through local delivery of AC over a prolonged in the periodontitis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Laparoscopic Heller-Dor for primary esophageal achalasia: outcomes in 173 patients.

PubMed

Rosati, Riccardo; Fumagalli Romario, Uberto; Ceolin, Martina; Massaron, Simonetta; Peracchia, Alberto

2013-01-01

Laparoscopic Heller myotomy combined with anterior (Dor) fundoplication is the most widely-used surgical procedure for treating esophageal achalasia in Europe From November 1992 through May 2010 we performed laparoscopic Heller-Dor on 173 patients Conversion to laparotomy was required in three cases (1.7%) at the beginning of the experience (for mucosal) perforation which was the most frequent intraoperative complication, managed laparoscopically with the increasing experience. Five (2.9%) cases had minor postoperative complications. Clinical results were satisfactory in 99.4% of cases. One patient (0.6%) had severe persistent dysphagia. Mean esophageal diameter decreased from 50 mm ± 12 (range 20- 90) to 25 mm ± 7 (range 15-80). Lower esophageal sphincter pressure decreased from 32 mmHg (median, range 10- 93) pre-operatively to 11 mmHg (median, range 5-21) at one year follow up and residual pressure from 12 mmHg (median, range 3-30) to 4 mmHg (median, range 1-8). Impedance and pH monitoring showed normal levels in 39/47 (83%) patients who agreed to testing. The good outcomes of this experience, in part due to careful adherence to technical aspects of the operation, confirm that the laparoscopic Heller-Dor is the gold standard surgical treatment for esophageal achalasia.

Slowly digestible starch diets alter proximal glucosidase activity and glucose absorption

USDA-ARS?s Scientific Manuscript database

Sucrase-isomaltase (Si) and maltase-glucoamylase (Mgam) are mucosal glucosidases required for digestion of starch to glucose. Ablation of maltase-Mgam reduces in vivo starch digestion. We tested whether slowly digestible starch diets induce changes in glucosidase activities. Rice starch was encaps...

Autoimmune estrogen dermatitis in an infertile female.

PubMed

Elcin, Gonca; Gülseren, Duygu; Bayraktar, Miyase; Gunalp, Serdar; Gurgan, Timur

2017-06-01

Autoimmune estrogen dermatitis is a cyclical cutaneous eruption that occurs premenstrually and goes to the rapid resolution within a few days of menstrual cycles. The disorder has variable clinical manifestations consisting of macules, papules, vesicles, urticarial lesions, bullae, eczematous plaques, and erythema multiforme-like lesions. Herein, we present a case of a 30-year-old woman with attacks of edema and erosions involving the oral and genital mucosal sites on every first day of her menstruation period. She had also multiple endocrinological problems such as hypotroidism and infertility. To determine the sex hormon sensitivity, intradermal skin tests were performed. Based on her personal history and skin test findings, a diagnosis of autoimmune estrogen dermatitis was made. After the oophorectomy, she was free from the skin and mucosal symptoms. We propose that it is important to suspect the diagnosis of autoimmune estrogen dermatitis in patients who present with recurrent cylic eruptions and it must be kept in mind that these patients might have a concomitant infertility.

Concurrent colonic mucosa-associated lymphoid tissue lymphoma and adenoma diagnosed after a positive fecal occult blood test: a case report.

PubMed

Lin, Pei-Chiang; Chen, Jinn-Shiun; Deng, Po; Wang, Chih-Wei; Huang, Chiung-Huei; Tang, Reiping; Chiang, Jy-Ming; Yeh, Chien-Yuh; Hsieh, Pao-Shiu; Tsai, Wen-Sy; Chiang, Sum-Fu

2016-01-27

Colonic lymphoma is an uncommon presentation of extranodal lymphoma. Colonic mucosa-associated lymphoid tissue lymphoma is a different entity from gastric mucosa-associated lymphoid tissue lymphoma, and very rare. The presentation and management of colonic mucosa-associated lymphoid tissue are highly variable in the literature. We report the case of a 59-year-old Taiwanese man who underwent a colonoscopy after a positive test for fecal occult blood. His past history included hypertension and hyperthyroidism. The colonoscopy revealed an adenomatous polyp and mucosa-associated lymphoid tissue lymphoma. We successfully performed a polypectomy and endoscopic mucosal resection. The lymphoma was staged according to the Ann Arbor system modified by Musshoff as E-I. Our patient showed no lymphoma recurrence over a 3-year follow-up. Endoscopic mucosal resection for colonic mucosa-associated lymphoid tissue lymphoma without disseminated disease may be feasible. We successfully used colonoscopic treatment without adjuvant therapy to treat early-stage pathogen-free colonic mucosa-associated lymphoid tissue lymphoma.

Human intestinal mucosal mast cells: expanded population in untreated coeliac disease.

PubMed Central

Strobel, S; Busuttil, A; Ferguson, A

1983-01-01

Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell count in 27 control subjects was 146/mm2, SD 29. Significantly higher values were obtained in untreated coeliac disease (mean 243, SD 41, p less than 0.001) returning to the normal range in coeliacs treated with a gluten-free diet with normal jejunal biopsy morphology. In seven patients mucosal mast cell counts were performed in multiple jejunal biopsies, and these showed that mucosal mast cell distribution was not patchy. There was no evidence of degranulation of intestinal mucosal mast cells under the conditions of routine biopsy (overnight fast). An increase in mucosal mast cells in untreated coeliac disease may be one explanation for the high number of IgE positive stained cells in the intestinal mucosa that has been reported by some authors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6826106

Severity of Oral Mucositis in Children following Chemotherapy and Radiotherapy and Its Implications at a Single Oncology Centre in Durango State, Mexico.

PubMed

Carreón-Burciaga, Ramón G; Castañeda-Castaneira, Enrique; González-González, Rogelio; Molina-Frechero, Nelly; Gaona, Enrique; Bologna-Molina, Ronell

2018-01-01

Mucositis is an adverse effect of chemotherapy (QT) and/or radiotherapy (RT). The purpose of this study was to investigate the occurrence of oral mucositis in children undergoing cancer treatment. Fifty-one children with cancer who had received QT, RT, or both (QT-RT) underwent clinical evaluations; World Health Organization criteria were used to establish the degree and severity of mucositis. The correlations between the clinical data, type of cancer, and therapy were statistically analysed. Mucositis was present in 88.23% of the patients; 57.78%, 7.78%, and 24.44% received QT, RT, and QT-RT, respectively. Severity scores of 1 and 2 were the most common; scores of 3-4 were observed in patients who received QT-RT or more than 7 treatment cycles. There was a significant association between mucositis, the type of treatment, and the number of cycles received ( p < 0.05). It is important to implement therapeutic protocols that help maintain excellent oral health and reduce the risk of oral mucositis. Stomatologists should be consulted to assess patients' oral cavities and provide preventive treatment prior to QT and/or RT administration. It is important to integrate a stomatologist into the oncological working group to focus on preventing and managing oral mucositis.

Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells enhances treatment benefits in radiation-induced oral mucositis.

PubMed

Shen, Zongshan; Wang, Jiancheng; Huang, Qiting; Shi, Yue; Wei, Zhewei; Zhang, Xiaoran; Qiu, Yuan; Zhang, Min; Wang, Yi; Qin, Wei; Huang, Shuheng; Huang, Yinong; Liu, Xin; Xia, Kai; Zhang, Xinchun; Lin, Zhengmei

2018-02-14

Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR 2 -overexpressing MSCs (MSCs CXCR2 ) for mucositis treatment. Indeed, MSCs CXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSC CXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.

Oral Mucosal Lesions in Indians From Northeast Brazil

PubMed Central

Cury, Patricia Ramos; Porto, Lia Pontes Arruda; dos Santos, Jean Nunes; e Ribeiro, Livia Silva Figueiredo; de Aquino Xavier, Flavia Caló; Figueiredo, Andreia Leal; Ramalho, Luciana Maria Pedreira

2014-01-01

Abstract The aim of this cross-sectional study was to evaluate the prevalence of oral mucosal lesions, and their risk indicators in adult Kiriri Indians from Northeast Brazil. Clinical oral examination was performed on a representative sample of 223 Indians (age ≥19 years). A systematic evaluation of lips, labial mucosa and sulcus, commissures, buccal mucosa and sulcus, gingiva and alveolar ridge, tongue, floor of the mouth, and soft and hard palate was performed. Bivariate analysis was conducted to assess associations between mucosal conditions and age, gender, income, educational level, diabetic status, and smoking status. Mucosal lesions were found in 50 participants (22.4%). The most prevalent lesions were fistulae (6.2%) and traumatic ulcers (4.48%). Oral mucosal was associated with higher age (≥35 years; odds ratio [OR] = 1.99, 95% confidence interval [CI]: 1.05–3.76, P = 0.03) and lower education level (<9 years; OR = 2.13, 95% CI: 0.96–4.71, P = 0.06). Mucosal conditions are prevalent in Kiriri Indians and the presence of mucosal lesions is associated with advanced age and lower education. A public health program aimed at preventing and treating mucosal lesions and targeted toward the high-risk group is vital to improve the oral health status of this population. PMID:25501053

Current and Future Targets for Mucosal Healing in Inflammatory Bowel Disease

PubMed Central

Atreya, Raja; Neurath, Markus F.

2017-01-01

The induction and subsequent maintenance of mucosal healing has emerged as one of the central therapeutic goals in the management of patients with inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis). Current and novel treatment options are assessed regarding their therapeutic efficacy on the basis of their ability to induce mucosal healing. However, there is still substantial debate about the precise definition of mucosal healing. Here, we will give an overview regarding the definitions of mucosal healing as well as its probable effects on long-term disease behavior and finally focus on current and potential therapeutic targets to achieve this therapeutic goal in IBD patients. PMID:28612022

Coupling between H+ transport and anaerobic glycolysis in turtle urinary bladder: effect of inhibitors of H+ ATPase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinmetz, P.R.; Husted, R.F.; Mueller, A.

1981-03-15

The coupling between H+ transport (JH) and anaerobic glycolysis was examined in vitro in an anaerobic preparation of turtle urinary bladder. JH was measured as the short-circuit current after Na+ transport was abolished with ouabain and by pH stat titration. The media were gassed with N2 and 1% CO2 (PO2 less than 0.5 mm Hg) and contained 10 mM glucose. Under these conditions, JH was not inhibited by 3 mM serosal (S) cyanide or by 0.1 mM mucosal (M) dinitrophenol. Control anaerobic lactate production (Jlac) of 47 bladders was plotted as a function of simultaneously measured JH. The slope ofmore » Jlac on JH was 0.58« less

Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma.

PubMed

Furney, Simon J; Turajlic, Samra; Stamp, Gordon; Nohadani, Mahrokh; Carlisle, Anna; Thomas, J Meirion; Hayes, Andrew; Strauss, Dirk; Gore, Martin; van den Oord, Joost; Larkin, James; Marais, Richard

2013-07-01

Mucosal melanoma displays distinct clinical and epidemiological features compared to cutaneous melanoma. Here we used whole genome and whole exome sequencing to characterize the somatic alterations and mutation spectra in the genomes of ten mucosal melanomas. We observed somatic mutation rates that are considerably lower than occur in sun-exposed cutaneous melanoma, but comparable to the rates seen in cancers not associated with exposure to known mutagens. In particular, the mutation signatures are not indicative of ultraviolet light- or tobacco smoke-induced DNA damage. Genes previously reported as mutated in other cancers were also mutated in mucosal melanoma. Notably, there were substantially more copy number and structural variations in mucosal melanoma than have been reported in cutaneous melanoma. Thus, mucosal and cutaneous melanomas are distinct diseases with discrete genetic features. Our data suggest that different mechanisms underlie the genesis of these diseases and that structural variations play a more important role in mucosal than in cutaneous melanomagenesis. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Sequential Combination Chemotherapy of Dacarbazine (DTIC) with Carboplatin and Paclitaxel for Patients with Metastatic Mucosal Melanoma of Nasal Cavity and Paranasal Sinuses.

PubMed

Omata, W; Tsutsumida, A; Namikawa, K; Takahashi, A; Oashi, K; Yamazaki, N

2017-01-01

By the recent introduction of molecular targeting drugs against BRAF mutation and immune checkpoint inhibitors, the prognosis of patients with melanoma in advanced stage is now improving, but still in the minority. Mucosal melanoma lacks the BRAF mutations, and hence conventional chemotherapeutic regimens must be improved. We have conventionally used dacarbazine (DTIC) for patients with metastatic mucosal melanoma. However, the efficacy of DTIC in patients with metastatic mucosal melanoma has been limited. Therefore, we explored other possibilities to improve the prognosis of patients suffering from metastatic mucosal melanoma. In this communication, we present a retrospective analysis of the sequential combination chemotherapy of DTIC with carboplatin and paclitaxel (CP) for metastatic mucosal melanoma of nasal cavity and paranasal sinuses. The objective response rate of seven patients is 14.3% by RECIST 1.1 and the overall survival (OS) is 12.5 months. These data indicate that the sequential combination chemotherapy of DTIC with CP could be an option for patients with metastatic mucosal melanoma of nasal cavity and paranasal sinuses who are currently ending into dismal prognosis.

The effect of oral mucositis on morbidity and mortality in bone marrow transplant.

PubMed

Gabriel, Don A; Shea, Thomas; Olajida, Oludamilola; Serody, Jonathan S; Comeau, Terrance

2003-12-01

Oral mucosal ulceration is a frequent complication in bone marrow transplantation, resulting from epithelial injury caused by cytotoxic chemotherapy and radiation conditioning, as well as from pre-existing infection. Oral mucositis causes pain, interferes with patient nutrition, and can lead to systemic infection and other complications that increase patient morbidity and mortality; this complication also markedly increases the expense of bone marrow transplantation. A variety of interventions have been assessed for preventing oral mucositis or reducing the severity of mucositis and its sequelae. These include meticulous pretransplantation and ongoing mouth care, calcium phosphate solution, near-infrared light and lower-energy laser treatment, interleukin-11, sucralfate, oral glutamine, granulocyte-macrophage colony-stimulating factor rinse, tretinoin, and keratinocyte growth factor; particularly promising results have been observed with use of the cytoprotectant/radioprotectant agent amifostine. Reduction in the severity and duration of oral mucositis and its sequelae in patients undergoing bone marrow transplantation can have a substantial impact on morbidity and mortality and cost of care. Further systematic evaluation of approaches to prevention and management of oral mucositis is necessary to define optimal strategies in the transplantation setting.

Effect of oral glutamine on enterocyte turnover during methotrexate-induced mucositis in rats.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Karry, Rahel; Shamian, Benhoor; Lurie, Michael; Kokhanovsky, Natalie; Ure, Benno M; Coran, Arnold G

2009-01-01

The objective of this study was to evaluate the effects of oral glutamine in preventing intestinal mucosal damage caused by methotrexate (MTX) in rats. Male Sprague-Dawley rats were divided into 3 experimental groups: control rats, rats treated intraperitoneally with MTX (MTX rats) and rats treated with oral glutamine in the drinking water (2%) 72 h following intraperitoneal injection of a single dose of MTX (MTX-glutamine rats). Intestinal mucosal damage (Park's injury score), mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 h following MTX injection. RT-PCR was used to determine Bax and Bcl-2 mRNA expression. MTX-glutamine rats demonstrated greater jejunal and ileal mucosal weight and mucosal DNA, greater ileal villus height and crypt depth, and a greater index of proliferation in the jejunum and ileum compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-glutamine rats (vs. MTX) was accompanied by decreased Bax and increased Bcl-2 mRNA expression. Treatment with oral glutamine prevents mucosal injury and improves intestinal recovery following MTX injury in the rat.

Intestinal mucositis: mechanisms and management.

PubMed

Keefe, Dorothy M

2007-07-01

To describe the advances in the rapidly evolving field of intestinal (or alimentary) mucositis during the past year. Major advances have been made in both the clinical and preclinical setting, with the publication of a suite of articles regarding the pathobiology and management of mucositis, as well as several articles on important basic research in the area. The mechanism of mucositis development is now understood to be much more complex than previously thought, with an interplay of host and drug factors leading to overt damage, and variation in manifestation of that damage depending on the specific region of the gut. The MASCC/ISOO management guidelines for mucositis have been updated: a recommendation for the use of palifermin in the hematology transplant setting has been added, and a couple of previous recommendations have been revoked. This marks an important milestone in mucositis, as it is the first time a drug has been available that substantially reduces the occurrence and severity of mucositis. There is still much to be done to abolish the severe toxicity of chemotherapy and radiotherapy; however, progress is accelerating, and new targeted drugs are becoming available.

Enteral Arginine Does Not Increase Superior Mesenteric Arterial Blood Flow but Induces Mucosal Growth in Neonatal Pigs123

PubMed Central

Puiman, Patrycja J.; Stoll, Barbara; van Goudoever, Johannes B.; Burrin, Douglas G.

2011-01-01

Arginine is an essential amino acid in neonates synthesized by gut epithelial cells and a precursor for NO that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemia-reperfusion models and low plasma levels are associated with necrotizing enterocolitis. We hypothesized that enteral arginine is a specific stimulus for neonatal intestinal blood flow and mucosal growth under conditions of total parenteral nutrition (TPN) or partial enteral nutrition (PEN). We first tested the dose dependence and specificity of acute (3 h) enteral arginine infusion on superior mesenteric artery (SMA) blood flow in pigs fed TPN or PEN. We then determined whether chronic (4 d) arginine supplementation of PEN increases mucosal growth and if this was affected by treatment with the NO synthase inhibitor, NG-nitro-l-arginine methyl ester (L-NAME). Acute enteral arginine infusion increased plasma arginine dose dependently in both TPN and PEN groups, but the plasma response was markedly higher (100–250%) in the PEN group than in the TPN group at the 2 highest arginine doses. Baseline SMA blood flow was 90% higher in the PEN (2.37 ± 0.32 L⋅kg−1⋅h−1) pigs than in the TPN pigs (1.23 ± 0.17 L⋅kg−1⋅h−1), but was not affected by acute infusion individually of arginine, citrulline, or other major gut fuels. Chronic dietary arginine supplementation in PEN pigs induced mucosal growth in the intestine, but this effect was not prevented by treatment with L-NAME. Intestinal crypt cell proliferation, protein synthesis, and phosphorylation of mammalian target of rapamycin and p70S6 kinase were not affected by dietary arginine. We conclude that partial enteral feeding, but not acute enteral arginine, increases SMA blood flow in the neonatal pig. Furthermore, supplementing arginine in partial enteral feeding modestly increases intestinal mucosal growth and was NO independent. PMID:21106927

Role of the Mdm2 SNIP 309 Polymorphism in Gastric Mucosal Morphologic Patterns of Patients with Helicobacter pylori Associated Gastritis.

PubMed

Tongtawee, Taweesak; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

2016-01-01

The tumor suppressor p53 is as a regulator of cell proliferation, apoptosis and many other biological processes as well as external and internal stress responses. Mdm2 SNIP309 is a negative regulator of 53. Therefore, this study aimed to determine the role of the Mdm2 SNIP 309 polymorphism in the gastric mucosal morphological patterns in patients with Helicobacter pylori associated gastritis. A prospective cross-sectional study was carried out from November 2014 through November 2015. Biopsy specimens were obtained from patients and infection was proven by positive histology. Gastric mucosa specimens were sent to the Molecular Genetics Unit, Institute of Medicine, Suranaree University of Technology where they were tested by molecular methods to detect the patterns of Mdm2 SNIP 309 polymorphism using the real-time PCR hybridization probe method. The results were analyzed and correlated with gastric mucosal morphological patterns by using C-NBI endoscopy. A total of 300 infected patients were enrolled and gastric mucosa specimens were collected. In this study the percentage of Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygous was 78% and 19 % respectively whereas Mdm2 SNIP309 G/G homozygous was 3%. Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygosity correlated with type 1 to type 3 gastric mucosal morphological patterns (P<0.01) whereas Mdm2 SNIP309 G/G homozygous correlated with type 4 and type 5 (P<0.01). Our study finds the frequency of Mdm2 SNIP309 G/G in a Thai population is very low, and suggests that this can explain ae Thailand enigma. Types 1 to type 3 are the most common gastric mucosal morphological patterns according to the unique genetic polymorphism of MDM2 SNIP 309 in the Thai population.

Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states

PubMed Central

Levitt, David G; Levitt, Michael D

2017-01-01

Protein losing enteropathy (PLE) has been associated with more than 60 different conditions, including nearly all gastrointestinal diseases (Crohn’s disease, celiac, Whipple’s, intestinal infections, and so on) and a large number of non-gut conditions (cardiac and liver disease, lupus, sarcoidosis, and so on). This review presents the first attempt to quantitatively understand the magnitude of the PLE in relation to the associated pathology for three different disease categories: 1) increased lymphatic pressure (e.g., lymphangiectasis); 2) diseases with mucosal erosions (e.g., Crohn’s disease); and 3) diseases without mucosal erosions (e.g., celiac disease). The PLE with lymphangiectasis results from rupture of the mucosal lymphatics, with retrograde drainage of systemic lymph into the intestinal lumen with the resultant loss of CD4 T cells, which is diagnostic. Mucosal erosion PLE results from macroscopic breakdown of the mucosal barrier, with the epithelial capillaries becoming the rate-limiting factor in albumin loss. The equation derived to describe the relationship between the reduction in serum albumin (CP) and PLE indicates that gastrointestinal albumin clearance must increase by at least 17 times normal to reduce the CP by half. The strengths and limitations of the two quantitative measures of PLE (51Cr-albumin or α1-antitrypsin [αAT] clearance) are reviewed. αAT provides a simple quantitative diagnostic test that is probably underused clinically. The strong, unexplained correlation between minor decreases in CP and subsequent mortality in seemingly healthy individuals raises the question of whether subclinical PLE could account for the decreased CP and, if so, could the mechanism responsible for PLE play a role in the increased mortality? A large-scale study correlating αAT clearance with serum albumin concentrations will be required in order to determine the role of PLE in the regulation of the serum albumin concentration of seemingly healthy subjects. PMID:28761367

Which PCDAI Version Best Reflects Intestinal Inflammation in Pediatric Crohn Disease?

PubMed

Turner, Dan; Levine, Arie; Walters, Thomas D; Focht, Gili; Otley, Anthony; López, Victor Navas; Koletzko, Sibylle; Baldassano, Robert; Mack, David; Hyams, Jeffrey; Griffiths, Anne M

2017-02-01

There is increasing interest in measuring mucosal inflammation in Crohn disease (CD), but there are minimal data correlating the Pediatric Crohn's Disease Activity Index (PCDAI) versions (PCDAI, weighted Pediatric Crohn's Disease Activity Index [wPCDAI], abbreviated Pediatric Crohn's Disease Activity Index [abbrPCDAI], and the short Pediatric Crohn's Disease Activity Index [shPCDAI]) with mucosal inflammation. We aimed to compare the 4 PCDAI versions head to head with endoscopic degree of inflammation as measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD), fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and to explore cut-off values that are associated with mucosal healing. We used the prospectively collected data from the ImageKids study on 100 children with CD undergoing colonoscopy and from the Growth Relapse and Outcomes with Therapy study (n = 222), in which 145 children had calprotectin data at week 12 after diagnosis. All 4 PCDAI versions had fair correlation with the SES-CD (r = 0.42-0.45, all P < 0.001) and CRP (r = 0.32-0.45, all P < 0.01); the wPCDAI and PCDAI were superior to the shorter versions when comparing the blood tests. All versions had poor correlation with calprotectin, and only the wPCDAI reached significance (r = 0.26, P = 0.002 vs r = 0.15, P = 0.07 for PCDAI; r = 0.08, P = 0.37 for shPCDAI; r = 0.06, P = 0.5 for abbrPCDAI). The best cut-off to identify endoscopic mucosal healing was <12.5 points for the wPCDAI (sensitivity 58% and specificity 84%) and <10 for PCDAI (sensitivity 63% and specificity 77%). The more feasible wPCDAI and the PCDAI had comparable correlation with measures of endoscopic inflammation. These were slightly superior to the other 2 shorter versions, but still none of the PCDAI versions can give a valid assessment of mucosal healing.

Analysis of the Genotoxic Effects of Mobile Phone Radiation using Buccal Micronucleus Assay: A Comparative Evaluation.

PubMed

Banerjee, Sumita; Singh, Narendra Nath; Sreedhar, Gadiputi; Mukherjee, Saikat

2016-03-01

Micronucleus (MN) is considered to be a reliable marker for genotoxic damage and it determines the presence and the extent of the chromosomal damage. The MN is formed due to DNA damage or chromosomal disarrangements. The MN has a close association with cancer incidences. In the new era, mobile phones are constantly gaining popularity specifically in the young generation, but this device uses radiofrequency radiation that may have a possible carcinogenic effect. The available reports related to the carcinogenic effect of mobile radiation on oral mucosa are contradictory. To explore the effects of mobile phone radiation on the MN frequency in oral mucosal cells. The subjects were divided into two major groups: low mobile phone users and high mobile phone users. Subjects who used their mobile phone since less than five years and less than three hours a week comprised of the first group and those who used their mobile since more than five years and more than 10 hours a week comprised of the second group. Net surfing and text messaging was not considered in this study. Exfoliated buccal mucosal cells were collected from both the groups and the cells were stained with DNA-specific stain acridine orange. Thousand exfoliated buccal mucosal cells were screened and the cells which were positive for micronuclei were counted. The micronucleus frequency was represented as mean±SD, and unpaired Student t-test was used for intergroup comparisons. The number of micronucleated cells/ 1000 exfoliated buccal mucosal cells was found to be significantly increased in high mobile phone users group than the low mobile phone users group. The use of mobile phone with the associated complaint of warmth around the ear showed a maximum increase in the number of micronucleated cells /1000 exfoliated buccal mucosal cells. Mobile phone radiation even in the permissible range when used for longer duration causes significant genotoxicity. The genotoxicity can be avoided to some extent by the regular use of headphones.

Effect of Paneer and Cheese Consumption on Salivary Acidogenicity and Calcium Concentration: A Comparative Study.

PubMed

Somaraj, Vinej; Shenoy, Rekha P; Panchmal, Ganesh Shenoy; Jodalli, Praveen S; Sonde, Laxminarayan; Nagaraj, Kundapur

2018-01-01

To assess and compare the salivary pH reversal phenomenon and calcium concentration in subjects consuming paneer and cheese after an acidogenic challenge and also to compare the salivary pH measurements using pH strips and a portable pen-type pH meter. Sixty caries free undergraduate students were randomly selected and divided into two group: 1. paneer; 2. cheese. After determining the resting salivary pH using pH strips and a pen-type pH meter, participants were subjected to an acidogenic challenge (10% sucrose). Following consumption of test foods (10-gram cubes), salivary pH was measured at intervals of 5, 10, 15, 30 and 60 min to record the time taken for the salivary pH to return to baseline. Colorimetric salivary calcium concentration was estimated (Biochemical Analyzer) at baseline and after 60 min of test food consumption. The statistical tests used were Shapiro-Wilk's test for normality, repeated measures ANOVA, and the independent t-test. Test meals reversed the fall in pH after acidogenic challenge starting at 5 min and returning to baseline values after 30 min in both groups (p = 1.000). Colorimetric estimates showed higher salivary calcium concentrations with paneer (p < 0.001). The pen-type pH meter showed superior efficiency in terms of time (p < 0.001) compared to pH strips. The salivary pH reversal phenomenon was evident after consumption of both paneer and cheese following the acidogenic challenge. Consumption of paneer significantly increased salivary calcium concentration. The pen-type pH meter proved to be more efficient.

Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with polyps.

PubMed

Miljkovic, Dijana; Psaltis, Alkis; Wormald, Peter-John; Vreugde, Sarah

2018-01-01

Recent studies demonstrated that B cells and their chemoattractants are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP). However, the presence of naive B cells and of plasmablasts and memory B-cell subsets in the mucosa and periphery of the same patient with CRS is yet to be characterized. Here we sought to quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP), and control patients. Polyps, mucosa, and peripheral blood samples were prospectively collected from the patients with CRS and from the non-CRS controls. We used flow cytometry to distinguish among naive, plasmablast, and memory B cells in sinus tissue and peripheral blood. A total of 45 patients were recruited for the study. The patients with CRSwNP had significantly increased mucosal B-cell numbers versus the controls (3.39 ± 4.05% versus 0.39 ± 1.05% of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61 ± 0.94 versus 0.11 ± 0.24% of live cells; p < 0.03, Kruskal-Wallis test), plasmablasts (0.06 ± 0.26 versus 0.00 ± 0.00% of live cells; p < 0.055, Kruskal-Wallis test), and memory B cells (0.62 ± 1.26 versus 0.05 ± 0.15% of live cells; p < 0.02, Kruskal-Wallis test). Our study identified increased frequencies of different B-cell subtypes in the mucosa of patients with CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP had significantly increased B-cell subtypes compared with the patients with CRSsNP and the controls. These results implied a potential role for mucosal B cells in the ongoing inflammation in patients with CRSwNP.

Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with polyps

PubMed Central

Miljkovic, Dijana; Psaltis, Alkis; Wormald, Peter-John

2018-01-01

Background: Recent studies demonstrated that B cells and their chemoattractants are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP). However, the presence of naive B cells and of plasmablasts and memory B-cell subsets in the mucosa and periphery of the same patient with CRS is yet to be characterized. Objective: Here we sought to quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP), and control patients. Methods: Polyps, mucosa, and peripheral blood samples were prospectively collected from the patients with CRS and from the non-CRS controls. We used flow cytometry to distinguish among naive, plasmablast, and memory B cells in sinus tissue and peripheral blood. Results: A total of 45 patients were recruited for the study. The patients with CRSwNP had significantly increased mucosal B-cell numbers versus the controls (3.39 ± 4.05% versus 0.39 ± 1.05% of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61 ± 0.94 versus 0.11 ± 0.24% of live cells; p < 0.03, Kruskal-Wallis test), plasmablasts (0.06 ± 0.26 versus 0.00 ± 0.00% of live cells; p < 0.055, Kruskal-Wallis test), and memory B cells (0.62 ± 1.26 versus 0.05 ± 0.15% of live cells; p < 0.02, Kruskal-Wallis test). Conclusion: Our study identified increased frequencies of different B-cell subtypes in the mucosa of patients with CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP had significantly increased B-cell subtypes compared with the patients with CRSsNP and the controls. These results implied a potential role for mucosal B cells in the ongoing inflammation in patients with CRSwNP. PMID:29336281

Phase II clinical trial of local use of GM-CSF for prevention and treatment of chemotherapy- and concomitant chemoradiotherapy-induced severe oral mucositis in advanced head and neck cancer patients: an evaluation of effectiveness, safety and costs.

PubMed

Mantovani, Giovanni; Massa, Elena; Astara, Giorgio; Murgia, Viviana; Gramignano, Giulia; Lusso, Maria Rita; Camboni, Paolo; Ferreli, Luca; Mocci, Miria; Perboni, Simona; Mura, Loredana; Madeddu, Clelia; Macciò, Antonio

2003-01-01

In the present open non-randomized phase II study we looked for effectiveness, safety, tolerability and costs of locally applied GM-CSF in preventing or treating mucositis in patients receiving chemotherapy or chemoradiotherapy for head and neck cancer. In addition to clinical mucositis scoring system, the effects of treatment with GM-CSF were evaluated by its impact on patient quality of life and by laboratory immunological assays such as serum proinflammatory cytokines, IL-2 and leptin. The trial was designed to assess the effectiveness of local GM-CSF treatment in two different settings: i) prophylaxis of mucositis; ii) treatment of mucositis. Prophylaxis was chosen for chemoradiotherapy treatments of high mucosatoxic potential, while curative treatment was reserved for chemotherapy or chemoradiotherapy treatments of lesser potential of inducing mucositis. From January 1998 to December 2001, 68 patients entered the study. The great majority of patients of both groups had head and neck cancer, were stage IV, PS ECOG 0-1, were habitual smokers and were treated with chemotherapy and concomitant (or sequential) chemoradiotherapy. Forty-six patients were included in the 'prophylactic' setting and 22 patients in the 'curative' setting. The main findings of our study are: only 50% of patients included in the 'prophylactic' setting developed mucositis; the duration of oral mucositis from appearance until complete remission was significantly shorter in the 'prophylactic' than in the 'curative' setting; the mean grade of oral mucositis at baseline, on day 3 of therapy and on day 6 of therapy was significantly lower in the 'prophylactic' than in the 'curative' setting; 24 (55.82%) patients in the 'prophylactic' setting had grade 3/4 oral mucositis at baseline compared to 25 (80.60%) patients in the 'curative' setting (p=0.048). Thirteen (30.23%) patients in the 'prophylactic' setting had grade 3/4 oral mucositis on day 3 of therapy compared to 19 (61.29%) patients in the 'curative' setting (p=0.015); 'prophylactic' setting was able to shorten grade 3/4 oral mucositis to grade 0/1 more effectively than the 'curative' one on day 6 of therapy (p=0.05). The present clinical trial is to date by far the largest study assessing the effectiveness of topical GM-CSF and it is the first study comparing the efficacy of topical GM-CSF in the 'prophylactic' setting, i.e., with the aim to prevent the chemoradiotherapy-induced oral mucositis, with that in the 'curative' treatment, i.e., the therapy for established oral mucositis. The topical application of GM-CSF was demonstrated to be effective for oral mucositis induced by chemotherapy and chemoradiotherapy regimens. Moreover, the 'prophylactic' setting was demonstrated to be more effective than the 'curative' one.

Biodistribution and photodynamic effect of protoporphyrin IX in rat urinary bladders after intravesical instillation of 5-aminolaevulinic acid

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Bown, Stephen G.

1995-03-01

Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Complications such as scarring of the detrusor muscle and prolonged cutaneous photosensitivity may be reduced by using the new photosensitizer precursor, 5- aminolaevulinic acid (ALA). After instillation of ALA, the concentration, pH, and time of bladder retention of ALA solution were found to be the key factors to a satisfactory PpIX buildup in the mucosa. The optimum PpIX fluorescence intensity ratio between mucosa and muscle layer is 10 to 1 with a pH 5.5, 1% ALA solution retained for 5 hours. Higher concentration resulted in more mucosal PpIX formation, but less selectivity. Unbuffered ALA was unsuitable for bladder instillation. Two days after laser treatment with 25 J/cm2 at 630 nm with optimal sensitization, typical histological findings were urothelial sloughing and lamina propria edema without obvious muscle damage. After 7 days, recovery of the urothelium was almost complete and fibroblast infiltration was minimal. ALA induced PpIX after bladder instillation may be an appropriate photosensitizer for future management of superficial bladder cancer.

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

PubMed Central

Sorsby, Eleanor; Mahtey, Nabeel; Brown, Ian

2017-01-01

Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection. PMID:28542528

Why mucosal health?

USDA-ARS?s Scientific Manuscript database

Aquaculture species depend more heavily on mucosal barriers than their terrestrial agricultural counterparts as they are continuously interacting with the aquatic microbiota. Unlike classical immune centers, such as the spleen and kidney, the accessibility of mucosal surfaces through immersion/dip t...

Update on primary mucosal melanoma.

PubMed

Tacastacas, Joselin D; Bray, Julie; Cohen, Yoon K; Arbesman, Joshua; Kim, Julian; Koon, Henry B; Honda, Kord; Cooper, Kevin D; Gerstenblith, Meg R

2014-08-01

Mucosal melanomas are aggressive cancers of mucosal surfaces with clinical and pathologic characteristics distinct from cutaneous melanomas, warranting different staging systems and treatment approaches. Surgical resection is performed frequently for the primary tumor, although the utility of lymph node surgery and radiation therapy is not established. Therapies targeted against C-KIT activating mutations, identified in many mucosal melanomas, are emerging as promising treatments. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Induction of mucosal IgA by a novel jet delivery technique for HIV-1 DNA.

PubMed

Lundholm, P; Asakura, Y; Hinkula, J; Lucht, E; Wahren, B

1999-04-09

Novel ways of delivering plasmid DNA to elicit humoral IgA, IgG and cell-mediated immune responses in mice were investigated. Intraoral administration of DNA in the cheek, using a jet immunization technique, elicited the highest IgA mucosal responses. Intranasal immunization gave strong mucosal IgA responses and persistent systemic IgG. Immunoglobulin isotype analysis revealed an IgG1 profile for intramuscular tongue and gene gun immunizations and an IgG2a profile following oral jet injection and intranasal application. The route of delivery was of importance for the characteristics and quality of the mucosal immune response following DNA immunization. For DNA vaccine delivery, the intraoral jet injection technique has the advantages of being a simple and rapid way of administering the DNA in solution and of provoking specific mucosal IgA when administered in the mucosal associated lymphoid tissue.

21 CFR 862.1120 - Blood gases (PCO2, PO2) and blood pH test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Blood gases (PCO2, PO2) and blood pH test system... Test Systems § 862.1120 Blood gases (PCO2, PO2) and blood pH test system. (a) Identification. A blood gases (PCO2, PO2) and blood pH test system is a device intended to measure certain gases in blood, serum...

Acid-base relations in epithelium of turtle bladder: site of active step in acidification and role of metabolic CO2.

PubMed

Steinmetz, P R

1969-07-01

The acid-base relations across the two surfaces of the epithelium of the turtle bladder were examined. By means of the 5,5-dimethyl-2,4-oxazolidinedione (DMO) technique the intracellular OH(-) concentration was measured in the presence and absence of a transepithelial pH gradient. When both sides of the bladder were bathed with solutions free of exogenous CO(2) and bicarbonate at pH 7.41 ([OH(-)] = 239 nmoles/liter), the epithelial cells were alkaline, the mean intracellular [OH(-)] being 347nmoles/liter. This alkalinity of the cells was preserved in bladders that secreted H(+) against a gradient of over 2 pH units. In bathing solutions stirred with 4.85% CO(2) and buffered with 25 mM HCO(3) (-) at pH 7.41 the intracellular [OH(-)] was lower than in CO(2)-free solutions and close to the extracellular [OH(-)]. In the CO(2)-free system anaerobiosis caused increased alkalinity of the cells and inhibition of H(+) secretion presumably by decreased metabolic CO(2) production. Carbonic acid inhibitors reduced H(+) secretion, but had no significant effect on the alkalinity of the cells. An inactive analogue of acetazolamide had no effect on H(+) secretion. The results indicate that the active step in acidification is located near the mucosal surface of the epithelium and that the alkali formed within the epithelial cells moves passively into the serosal solution along an electro-chemical gradient. The inhibitory effect of certain sulfonamides on H(+) secretion by the bladder is directly correlated with their known carbonic anhydrase inhibitory activity, but not associated with a measurable change in the mean intracellular [OH(-)].

The impact of gastric distension on the lower esophageal sphincter and its exposure to acid gastric juice.

PubMed

Ayazi, Shahin; Tamhankar, Anand; DeMeester, Steven R; Zehetner, Joerg; Wu, Calvin; Lipham, John C; Hagen, Jeffrey A; DeMeester, Tom R

2010-07-01

The lower esophageal sphincter (LES) in patients with gastroesophageal reflux disease often has a low resting pressure and a short abdominal length. The mechanism by which this occurs is unknown. We hypothesize that gastric distension causes progressive effacement of the abdominal portion of the LES, exposing it to acid injury resulting in mucosal and sphincter damage. Our aim was to assess in normal subjects the effect of gastric distension on the LES length and pressure and its exposure to acid gastric juice. Eleven asymptomatic volunteers had their LES length and pressure measured before and during gastric distension. The location of the pH step-up point (shift from gastric pH to a pH >4) was also measured before and after distension. Progressive gastric distension with air resulted in progressive shortening of LES (R = 0.89, P < 0.0001). After infusion of 750 cc of air there was a significant reduction in the median LES length from 4 to 2.6 cm (P = 0.001). This change occurred in the abdominal length of the LES (2.6-1.4 cm [P = 0.001]) and not in the thoracic length. At rest the pH step-up point was 0.5 cm above the lower border of the LES and with distension moved a median of 1 cm cephalad within the LES. Simultaneously with the loss of length there was a reduction in LES pressure (27.4-23.4 mm Hg, P = 0.02). Gastric distension causes progressive shortening of the abdominal length of the LES and a reduction in its pressure. The process exposes the effaced mucosa and sphincter to acid gastric juice.

Testing the Carcinogenic Potential of Water Disinfectant Byproducts in a Human Colon Mucosal Culture System

EPA Science Inventory

Epidemiological studies have linked the consumption of disinfected surface waters to an increased risk of colorectal cancer. Approximately 600 disinfection byproducts (DBPs) have been identified for a number of disinfectants currently in use. An in-depth mechanism-based structure...

Milk glucosidase activity enables suckled pup starch digestion

USDA-ARS?s Scientific Manuscript database

Starch requires six enzymes for digestion to free glucose: two amylases (salivary and pancreatic) and four mucosal maltase activities; sucrase-isomaltase and maltase-glucoamylase. All are deficient in suckling rodents. The objective of this study is to test (13)C-starch digestion before weaning by m...

Identification of risk factors for mucosal injury during laparoscopic Heller myotomy for achalasia.

PubMed

Tsuboi, Kazuto; Omura, Nobuo; Yano, Fumiaki; Hoshino, Masato; Yamamoto, Se-Ryung; Akimoto, Shusuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2016-02-01

Mucosal injury during myotomy is the most frequent complication seen with the Heller-Dor procedure for achalasia. The present study aimed to examine risk factors for such mucosal injury during this procedure. This was a retrospective analysis of patients who underwent the laparoscopic Heller-Dor procedure for achalasia at a single facility. Variables for evaluation included patient characteristics, preoperative pathophysiological findings, and surgeon's operative experience. Logistic regression was used to identify risk factors. We also examined surgical outcomes and the degree of patient satisfaction in relation to intraoperative mucosal injury. Four hundred thirty-five patients satisfied study criteria. Intraoperative mucosal injury occurred in 67 patients (15.4%). In univariate analysis, mucosal injury was significantly associated with the patient age ≥60 years, disease history ≥10 years, prior history of cardiac diseases, preoperative esophageal transverse diameter ≥80 mm, and surgeon's operative experience with fewer than five cases. In multivariate analysis involving these factors, the following variables were identified as risk factors: age ≥60 years, esophageal transverse diameter ≥80 mm, and surgeon's operative experience with fewer than five cases. The mucosal injury group had significant extension of the operative time and increased blood loss. However, there were no significant differences between the two groups in the incidence of reflux esophagitis or the degree of symptom alleviation postoperatively. The fragile esophagus caused by advanced patient age and/or dilatation were risk factor for mucosal injury during laparoscopic Heller-Dor procedure. And novice surgeon was also identified as an isolated risk factor for mucosal injury.

Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation.

PubMed

Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda; Chaiyarit, Ponlatham

2017-06-01

The existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Sections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n=30), and control subjects (n=30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects. AANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p=0.002, p<0.001, and p=0.031, respectively). Increased levels of AANAT, melatonin, and MT1 in the inflamed oral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Esophageal mucosal breaks in gastroesophageal reflux disease partially responsive to proton pump inhibitor therapy.

PubMed

Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Silberg, Debra G

2013-04-01

Approximately 20-30% of patients with gastroesophageal reflux disease (GERD) do not experience complete symptom resolution during proton pump inhibitor (PPI) therapy. The aim of this study was to determine the prevalence of esophageal mucosal breaks among patients who have a partial response to PPI therapy. This was an analysis of data from a phase 2b clinical trial carried out to assess the efficacy and safety of a reflux inhibitor, lesogaberan (AZD3355), as an add-on to PPI therapy in this patient population (clinicaltrials.gov reference: NCT01005251). A total of 661 patients with persistent GERD symptoms who had received a minimum of 4 weeks of PPI therapy were included in the study. The prevalence of esophageal mucosal breaks was assessed according to (i) the most recent endoscopy results from within the previous 24 months, if available ("historical" endoscopies), and (ii) the results of endoscopies performed at study baseline ("baseline" endoscopies). Baseline endoscopies were not carried out in patients who had a historical endoscopy showing an absence of esophageal mucosal breaks. Historical endoscopy results were available for 244 patients, of whom 48 (19.7%) had esophageal mucosal breaks. Baseline endoscopies were carried out in 465 patients, of whom 146 (31.4%) had esophageal mucosal breaks. Sensitivity analyses showed a prevalence of esophageal mucosal breaks of 20-30%. In both the historical and baseline endoscopies, most esophageal mucosal breaks were Los Angeles grades A or B. In patients with GERD symptoms partially responsive to PPI therapy, mild-to-moderate severity esophageal mucosal breaks are common (prevalence 20-30%), and may contribute to symptom etiology.

Impact of Mucositis on Absorption and Systemic Drug Exposure of Isavuconazole.

PubMed

Kovanda, Laura L; Marty, Francisco M; Maertens, Johan; Desai, Amit V; Lademacher, Christopher; Engelhardt, Marc; Lu, Qiaoyang; Hope, William W

2017-06-01

Isavuconazonium sulfate is the water-soluble prodrug of isavuconazole. Population analyses have demonstrated relatively predictable pharmacokinetic (PK) behavior in diverse patient populations. We evaluated the impact of mucositis on the oral isavuconazole exposure using population PK modeling. This study included patients treated in two phase 3 trials of isavuconazole, SECURE for treatment of invasive aspergillosis (IA) and other filamentous fungi and VITAL for patients with mucormycosis, invasive fungal disease (IFD) caused by other rare fungi, or IA and renal impairment. Mucositis was reported by site investigators and its impact on oral bioavailability was assessed. Use of the oral formulation was at the discretion of the investigator. Patients with plasma samples collected during the use of isavuconazonium sulfate were included in the construction of population PK model. Of 250 patients included, 56 patients had mucositis at therapy onset or as an adverse event during oral isavuconazole therapy. Levels of oral bioavailability were comparable, at 98.3% and 99.8%, respectively. The average drug exposures (average area under the curve [AUC ave ]) calculated from either the mean or median parameter estimates were not different between patients with and without mucositis. Mortality and overall clinical responses were similar between patients receiving oral therapy with and without mucositis. We found that isavuconazole exposures and clinical outcomes in this subset of patients with mucositis who were able to take oral isavuconazonium sulfate were comparable to those in patients without mucositis, despite the difference in oral bioavailability. Therefore, mucositis may not preclude use of the oral formulation of isavuconazonium sulfate. Copyright © 2017 Kovanda et al.

Impact of Mucositis on Absorption and Systemic Drug Exposure of Isavuconazole

PubMed Central

Marty, Francisco M.; Maertens, Johan; Desai, Amit V.; Lademacher, Christopher; Engelhardt, Marc; Lu, Qiaoyang

2017-01-01

ABSTRACT Isavuconazonium sulfate is the water-soluble prodrug of isavuconazole. Population analyses have demonstrated relatively predictable pharmacokinetic (PK) behavior in diverse patient populations. We evaluated the impact of mucositis on the oral isavuconazole exposure using population PK modeling. This study included patients treated in two phase 3 trials of isavuconazole, SECURE for treatment of invasive aspergillosis (IA) and other filamentous fungi and VITAL for patients with mucormycosis, invasive fungal disease (IFD) caused by other rare fungi, or IA and renal impairment. Mucositis was reported by site investigators and its impact on oral bioavailability was assessed. Use of the oral formulation was at the discretion of the investigator. Patients with plasma samples collected during the use of isavuconazonium sulfate were included in the construction of population PK model. Of 250 patients included, 56 patients had mucositis at therapy onset or as an adverse event during oral isavuconazole therapy. Levels of oral bioavailability were comparable, at 98.3% and 99.8%, respectively. The average drug exposures (average area under the curve [AUCave]) calculated from either the mean or median parameter estimates were not different between patients with and without mucositis. Mortality and overall clinical responses were similar between patients receiving oral therapy with and without mucositis. We found that isavuconazole exposures and clinical outcomes in this subset of patients with mucositis who were able to take oral isavuconazonium sulfate were comparable to those in patients without mucositis, despite the difference in oral bioavailability. Therefore, mucositis may not preclude use of the oral formulation of isavuconazonium sulfate. PMID:28289034

Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis.

PubMed

Flores, Brisas M; O'Connor, Anthony; Moss, Alan C

2017-12-01

Long-standing ulcerative colitis is an established risk factor for colorectal neoplasia. A number of observational studies have suggested that evidence of mucosal inflammation (endoscopic or histologic) is associated with a greater risk for colorectal neoplasia than is mucosal healing. Our goal was to systematically analyze the risk of colorectal neoplasia in patients with ulcerative colitis who have ongoing mucosal inflammation to better inform surveillance strategies. We performed a systematic review and meta-analysis of the effect of endoscopic and/or histologic inflammation on the risk of colorectal neoplasia in cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. Six studies met the inclusion criteria, incorporating outcomes in 1443 patients. No study used a single validated measure for mucosal inflammation. The pooled odds ratio for colorectal neoplasia was 3.5 (95% confidence interval [CI], 2.6-4.8; P < .001) in those with any mucosal inflammation and 2.6 (95% CI, 1.5-4.5; P = .01) in those with histologic inflammation, when compared with those with mucosal healing. The overall quality of the studies was good. The presence of objective evidence of mucosal inflammation during follow-up in patients with ulcerative colitis is associated with a greater risk of subsequent colorectal neoplasia than in those with mucosal healing. This risk factor should be considered in guidelines on surveillance intervals for these patients. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

CON4EI: Slug Mucosal Irritation (SMI) test method for hazard identification and labelling of serious eye damaging and eye irritating chemicals.

PubMed

Adriaens, E; Guest, R; Willoughby, J A; Fochtman, P; Kandarova, H; Verstraelen, S; Van Rompay, A R

2018-06-01

Assessment of ocular irritancy is an international regulatory requirement in the safety evaluation of industrial and consumer products. Although many in vitro ocular irritation assays exist, alone they are incapable of fully categorizing chemicals. The objective of CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for eye irritation assessment that can lead to complete replacement of the in vivo Draize rabbit eye test (OECD TG 405). A set of 80 reference chemicals was tested with seven test methods, one method was the Slug Mucosal Irritation (SMI) test method. The method measures the amount of mucus produced (MP) during a single 1-hour contact with a 1% and 10% dilution of the chemical. Based on the total MP, a classification (Cat 1, Cat 2, or No Cat) is predicted. The SMI test method correctly identified 65.8% of the Cat 1 chemicals with a specificity of 90.5% (low over-prediction rate for in vivo Cat 2 and No Cat chemicals). Mispredictions were predominantly unidirectional towards lower classifications with 26.7% of the liquids and 40% of the solids being underpredicted. In general, the performance was better for liquids than for solids with respectively 76.5% vs 57.1% (Cat 1), 61.5% vs 50% (Cat 2), and 87.5% vs 85.7% (No Cat) being identified correctly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using a Bedside Video-assisted Test Tube Test to Assess Stoma Viability: A Report of 4 Cases.

PubMed

Ahmad, Sarwat; Turner, Keli; Shah, Paulesh; Diaz, Jose

2016-07-01

Mucosal discoloration of an intestinal stoma may indicate self-limited venous congestion or necrosis necessitating operative revision. A common bedside technique to assess stoma viability is the "test tube test". A clear tube is inserted into the stoma and a hand-held light is used to assess the color of the stoma. A technique (video-assisted test tube test [VATTT]) developed by the authors utilizes a standard video bronchoscope inserted into a clear plastic blood collection tube to visually inspect and assess the mucosa. This technique was evaluated in 4 patients (age range 49-72 years, all critically ill) with a discolored stoma after emergency surgery. In each case, physical exam revealed ischemic mucosa at the surface either immediately after surgery or after worsening hypotension weeks later. Serial test tube test assessments were ambiguous when trying to assess deeper mucosa. The VATTT assessment showed viable pink mucosa beneath the surface and until the fascia was revealed in 3 patients. One (1) patient had mucosal ischemia down to the fascia, which prompted operative revision of the stoma. The new stoma was assessed with a VATTT and was viable for the entire length of the stoma. VATTT provided an enhanced, magnified, and clearer way to visually assess stoma viability in the postoperative period that can be performed at the bedside with no adverse events. It may prevent unnecessary relaparotomy or enable earlier diagnosis of deep ostomy necrosis. Validity and reliability studies are warranted.

Enhancement of Antituberculosis Immunity in a Humanized Model System by a Novel Virus-Vectored Respiratory Mucosal Vaccine.

PubMed

Yao, Yushi; Lai, Rocky; Afkhami, Sam; Haddadi, Siamak; Zganiacz, Anna; Vahedi, Fatemeh; Ashkar, Ali A; Kaushic, Charu; Jeyanathan, Mangalakumari; Xing, Zhou

2017-07-01

The translation of preclinically promising novel tuberculosis vaccines to ultimate human applications has been challenged by the lack of animal models with an immune system equivalent to the human immune system in its genetic diversity and level of susceptibility to tuberculosis. We have developed a humanized mice (Hu-mice) tuberculosis model system to investigate the clinical relevance of a novel virus-vectored (VV) tuberculosis vaccine administered via respiratory mucosal or parenteral route. We find that VV vaccine activates T cells in Hu-mice as it does in human vaccinees. The respiratory mucosal route for delivery of VV vaccine in Hu-mice, but not the parenteral route, significantly reduces the humanlike lung tuberculosis outcomes in a human T-cell-dependent manner. Our results suggest that the Hu-mouse can be used to predict the protective efficacy of novel tuberculosis vaccines/strategies before they proceed to large, expensive human trials. This new vaccine testing system will facilitate the global pace of clinical tuberculosis vaccine development. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Oral mucosal lesions and their association with sociodemographic, behavioral, and health status factors.

PubMed

Gheno, José Nicolau; Martins, Marco Antonio Trevizani; Munerato, Maria Cristina; Hugo, Fernando Neves; Sant'ana Filho, Manoel; Weissheimer, Camila; Carrard, Vinicius Coelho; Martins, Manoela Domingues

2015-01-01

The aim of this study was to evaluate the frequency of oral mucosal lesions and their associations with sociodemographic, health, and behavioral factors in a southern Brazilian population. Information was collected from participants (n = 801) using a structured questionnaire during an oral cancer screening campaign held at an agribusiness show in southern Brazil in 2009. Data were described using frequency distributions or means and standard deviations. Associations between independent variables and outcomes were assessed using the Chi-squared test. A total of 465 lesions were detected (actinic cheilitis: n = 204, 25.5%; candidiasis: n = 50, 6.2%; fibrous inflammatory hyperplasia: n = 42, 5.2%; ulceration, n = 33, 4.1%; hemangioma: n = 14, 1.7%; leukoplakia: n = 11, 1.4%). Candidiasis, actinic cheilitis, and fibrous inflammatory hyperplasia were associated significantly with literacy. Actinic cheilitis was also associated significantly with sun exposure and hat use, and leukoplakia was associated with smoking. The high frequency of oral mucosal lesions observed highlights the importance of education about risk factors. Additionally, training of health professionals, mainly those from public health services, in the use of preventive and community education strategies is needed.

Frequency of Addictive Habits and its Association with Oral Diseases Among a Cross Section of Indian Police Personnel Connotation.

PubMed

Singh, Aishwarya; Bhambal, Ajay; Saxena, Sudhanshu; Tiwari, Vidhatri; Tiwari, Utkarsh

2016-05-01

To assess the frequency of adverse addictive habits, specially alcohol and tobacco usage, among police personnel of Bhopal City, Central India and its association with the frequency of oral mucosal lesions and periodontal diseases. Across-sectional analytical study. Bhopal City, Capital of Madhya Pradesh State, Central India, from February to April 2013. All the police personnel posted at various police stations were interviewed and clinically examined. Police personnel who did not cooperate or were not willing, were excluded from the study. Chi-square test was used to analyze categorical variables. Atotal of 781 subjects were interviewed for the various forms of adverse habits, followed by clinical assessment of oral mucosal lesions and periodontal status using WHO 1997 criteria. The mean age of study subjects was 40.58 ±9.84 years. Usage of tobacco was found among 55% and only 1.3% of subjects consumed alcohol. The prevalence of oral mucosal lesions and periodontal diseases was significantly higher among tobacco users. There was high usage of tobacco among police personnel in Bhopal City, India with a detrimental effect on oral health.

Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Sang-wook; Jung, Kwon Il; Kim, Yeun Wha B.S.

2007-03-15

Purpose: We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model. Methods and Materials: Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 {+-} 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 {mu}g/mL (Group 3), or 100 {mu}g/mLmore » (Group 4) rhEGF three times per day. Results: Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 {mu}g/mL or 100 {mu}g/mL rhEGF. Conclusion: These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats.« less

Experiment K-7-17: Effects of Spaceflight on the Proliferation of Jejunal Mucosal Cells

NASA Technical Reports Server (NTRS)

Phillips, R. W.; Moeller, C. L.; Sawyer, H. R.; Smirnov, K. L.

1994-01-01

The purpose of this project was to test the hypothesis that the generalized, whole body decrease in synthetic activity due to microgravity conditions encountered during spaceflight would be demonstrable in cells and tissues characterized by a rapid rate of turnover. Jejunal mucosal cells were chosen as a model since these cells are among the most rapidly proliferating in the body. Accordingly, the percentage of mitotic cells present in the crypts of Lieberkuhn in each of 5 rats flown on the COSMOS 2044 mission were compared to the percentage of mitotic cells present in the crypts in rats included in each of 3 ground control groups (i.e., vivarium, synchronous and caudal-elevated). No significant difference (p greater than .05) was detected in mitotic indices between the flight and vivarium group. Although the ability of jejunal mucosal cells to divide by mitosis was not impaired in flight group, there was, however, a reduction in the length of villi and depth of crypts. The concommitant reduction in villus length and crypth depth in the flight group probably reflects changes in connective tissue components within the core of villi.

Chemotherapy-Induced and/or Radiation Therapy-Induced Oral Mucositis—Complicating the Treatment of Cancer

PubMed Central

Naidu, Maddireddy Umameshwar Rao; Ramana, Gogula Venkat; Rani, Pingali Usha; Mohan, Iyyapu Krishna; Suman, Avula; Roy, Priyadarshni

2004-01-01

Abstract The term mucositis is coined to describe the adverse effects of radiation and chemotherapy treatments. Mucositis is one of the most common adverse reactions encountered in radiation therapy for head and neck cancers, as well as in chemotherapy, in particular with drugs affecting DNA synthesis (S-phase-specific agents such as fluorouracil, methotrexate, and cytarabine). Mucositis may limit the patient's ability to tolerate chemotherapy or radiation therapy, and nutritional status is compromised. It may drastically affect cancer treatment as well as the patient's quality of life. The incidence and severity of mucositis will vary from patient to patient. It will also vary from treatment to treatment. It is estimated that there is 40% incidence of mucositis in patients treated with standard chemotherapy and this will not only increase with the number of treatment cycles but also with previous episodes. Similarly, patients who undergo bone marrow transplantation and who receive high doses of chemotherapy have a 76% chance of getting mucositis. Patients receiving radiation, in particular to head and neck cancers, have a 30% to 60% chance. The exact pathophysiology of development is not known, but it is thought to be divided into direct and indirect mucositis. Chemotherapy and/or radiation therapy will interfere with the normal turnover of epithelial, cells leading to mucosal injury; subsequently, it can also occur due to indirect invasion of Gram-negative bacteria and fungal species because most of the cancer drugs will cause changes in blood counts. With the advancement in cytology, a more precise mechanism has been established. With this understanding, we can select and target particular mediators responsible for the mucositis. Risk factors such as age, nutritional status, type of malignancy, and oral care during treatment will play important roles in the development of mucositis. Many treatment options are available to prevent and treat this condition, but none of them can completely prevent or treat mucositis. More and more pathological methods are being developed to understand this condition so that better therapeutic regimens can be selected. Emphasis also should be made in assessing the patient's psychologic condition, particular depressive disorders. This is important because treatment with antidepressants will not only contribute in lifting depression but also reduces pain somatization. Although mucositis is rarely life-threatening, it will interfere with treatment of cancer to a great extent. PMID:15548350

21 CFR 862.1550 - Urinary pH (nonquantitative) test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Urinary pH (nonquantitative) test system. 862.1550 Section 862.1550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1550 Urinary pH (nonquantitative) test system. (a) Identification. A urinary pH...

Easiness of Use and Validity Testing of VS-SENSE Device for Detection of Abnormal Vaginal Flora and Bacterial Vaginosis

PubMed Central

Donders, Gilbert G. G.; Marconi, Camila; Bellen, Gert

2010-01-01

Accessing vaginal pH is fundamental during gynaecological visit for the detection of abnormal vaginal flora (AVF), but use of pH strips may be time-consuming and difficult to interpret. The aim of this study was to evaluate the VS-SENSE test (Common Sense Ltd, Caesarea, Israel) as a tool for the diagnosis of AVF and its correlation with abnormal pH and bacterial vaginosis (BV). The study population consisted of 45 women with vaginal pH ≥ 4.5 and 45 women with normal pH. Vaginal samples were evaluated by VS-SENSE test, microscopy and microbiologic cultures. Comparing with pH strips results, VS-SENSE test specificity was 97.8% and sensitivity of 91%. All severe cases of BV and aerobic vaginitis (AV) were detected by the test. Only one case with normal pH had an unclear result. Concluding, VS-SENSE test is easy to perform, and it correlates with increased pH, AVF, and the severe cases of BV and AV. PMID:20953405

Easiness of use and validity testing of VS-SENSE device for detection of abnormal vaginal flora and bacterial vaginosis.

PubMed

Donders, Gilbert G G; Marconi, Camila; Bellen, Gert

2010-01-01

Accessing vaginal pH is fundamental during gynaecological visit for the detection of abnormal vaginal flora (AVF), but use of pH strips may be time-consuming and difficult to interpret. The aim of this study was to evaluate the VS-SENSE test (Common Sense Ltd, Caesarea, Israel) as a tool for the diagnosis of AVF and its correlation with abnormal pH and bacterial vaginosis (BV). The study population consisted of 45 women with vaginal pH ≥ 4.5 and 45 women with normal pH. Vaginal samples were evaluated by VS-SENSE test, microscopy and microbiologic cultures. Comparing with pH strips results, VS-SENSE test specificity was 97.8% and sensitivity of 91%. All severe cases of BV and aerobic vaginitis (AV) were detected by the test. Only one case with normal pH had an unclear result. Concluding, VS-SENSE test is easy to perform, and it correlates with increased pH, AVF, and the severe cases of BV and AV.

Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination

PubMed Central

Nochi, Tomonori; Takagi, Hidenori; Yuki, Yoshikazu; Yang, Lijun; Masumura, Takehiro; Mejima, Mio; Nakanishi, Ushio; Matsumura, Akiko; Uozumi, Akihiro; Hiroi, Takachika; Morita, Shigeto; Tanaka, Kunisuke; Takaiwa, Fumio; Kiyono, Hiroshi

2007-01-01

Capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle, mucosal vaccination is considered ideal for the global control of infectious diseases. In this study, we developed a rice-based oral vaccine expressing cholera toxin B subunit (CTB) under the control of the endosperm-specific expression promoter 2.3-kb glutelin GluB-1 with codon usage optimization for expression in rice seed. An average of 30 μg of CTB per seed was stored in the protein bodies, which are storage organelles in rice. When mucosally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches and induced CTB-specific serum IgG and mucosal IgA antibodies with neutralizing activity. When expressed in rice, CTB was protected from pepsin digestion in vitro. Rice-expressed CTB also remained stable and thus maintained immunogenicity at room temperature for >1.5 years, meaning that antigen-specific mucosal immune responses were induced at much lower doses than were necessary with purified recombinant CTB. Because they require neither refrigeration (cold-chain management) nor a needle, these rice-based mucosal vaccines offer a highly practical and cost-effective strategy for orally vaccinating large populations against mucosal infections, including those that may result from an act of bioterrorism. PMID:17573530

Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

NASA Astrophysics Data System (ADS)

Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

1999-04-01

Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

Treatment of oral mucositis due to chemotherapy

PubMed Central

Bagán-Sebastián, José V

2016-01-01

Introduction The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the management of oral mucositis caused by chemotherapy in cancer patients. Material and Methods An exhaustive search was made of the PubMed-Medline, Cochrane Library and Scopus databases, crossing the key words “oral mucositis”, “prevention” and “treatment” with the terms “chemotherapy” and “radiotherapy” by means of the boolean operators “AND” and “NOT”. A total of 268 articles were obtained, of which 96 met the inclusion criteria. Results Several interventions for the prevention of oral mucositis, such as oral hygiene protocols, amifostine, benzidamine, calcium phosphate, cryotherapy and iseganan, among others, were found to yield only limited benefits. Other studies have reported a decrease in the appearance and severity of mucositis with the use of cytoprotectors (sucralfate, oral glutamine, hyaluronic acid), growth factors, topical polyvinylpyrrolidone, and low power laser irradiation. Conclusions Very few interventions of confirmed efficacy are available for the management of oral mucositis due to chemotherapy. However, according to the reviewed literature, the use of palifermin, cryotherapy and low power laser offers benefits, reducing the incidence and severity of oral mucositis – though further studies are needed to confirm the results obtained. Key words:Chemotherapy-Induced Oral Mucositis Treatment. PMID:27034762

Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperature.

PubMed

Lindemann, J; Leiacker, R; Wiesmiller, K; Rettinger, G; Keck, T

2004-08-01

Benzalkonium chloride is a preservative commonly used in nasal decongestant sprays. It has been suggested that benzalkonium chloride may be harmful to the nasal mucosa. Decongestion with the vasoconstrictor xylometazoline containing benzalkonium chloride has been shown to cause a significant reduction of the nasal mucosal temperature. The purpose of the present study was to determine the short-term influence of xylometazoline nasal spray with and without benzalkonium chloride on the nasal mucosal temperature. Healthy volunteers (30) were included in the study. Fifteen volunteers received xylometazoline nasal spray (1.0 mg/mL) containing benzalkonium chloride (0.1 mg/mL) and 15 age-matched subjects, received xylometazoline nasal spray without benzalkonium chloride. Using a miniaturized thermocouple the septal mucosal temperature was continuously measured at defined intranasal detection sites before and after application of the nasal spray. The mucosal temperature values did not significantly differ between the group receiving xylometazoline containing benzalkonium chloride and the group receiving xylometazoline spray without benzalkonium chloride before and after decongestion (P > 0.05). In both study groups septal mucosal temperatures significantly decreased after decongestion (P < 0.05) because of a reduction of the nasal mucosal blood flow following vasoconstriction. This study indicates that benzalkonium chloride itself does not seem to influence nasal blood flow and nasal mucosal temperature in topical nasal decongestants.

[The value of the thermocouple in the measurement of the gastric mucosal blood-flow. The influence of the occlusion of the celiac artery and prostaglandin E1 on the gastric mucosal blood flow. An experimental study in animals (author's transl)].

PubMed

Koch, H; Demling, L

1976-02-27

The study has been carried out to ensure the positive evidence of the measurement of the gastric mucosal blood-flow with the aid of the thermocouple (heat-clearance technique). The experiments have shown that the suction pressure of 600 mm mercury column which was used to fix the Thermocouple to the mucosa was indispensable in order to assess the blood-flow in the entire depth of the mucosa. Changes in the mucosal blood-flow are measuured at the same rate in all quadrants of the gastric corpus. The measuring of the blood-flow of a well circumscribed area of the mucosa is therefore representative for the entire corpus. Vasopressin led to a significant reduction of the gastric mucosal blood-flow measured with heat-clearance as well aminopyrine-clearance. There was a linear correlation between the results of both methods. Vasopressin selectively reduces the blood-flow of the gastric mucosa but not of the submucosa, the muscular layer and the serosa. Therefore it seems to be probable that changes in mucosal blood-flow selectively can be measured with the aid of the thermocouple. After previous stimulation with pentagastrin neither mucosal blood-flow nor acid secretion of the stomach were influenced by the occlusion of the celiac artery by 25 %. The occlusion of the celiac artery by 50 % reduced significantly the pentagastrin-stimulated gastric mucosal blood-flow whereas the acid secretion was not influenced. Prostaglandin E1 at a dose rate of 2 mug/kg-h increased significantly arterial and mucosal blood-flow as well as acid secretion of the stomach. In comparison PGE1 administered at a dose rate of 4 mug/kg-h reduced significantly gastric mucosal blood-flow and gastric secretion. PGE1 at a dose rate of 8 mug/kg-h did not produce any significant changes in blood-flow and secretion. The results suggested that the changes of gastric secretion observed with PGE1 were the consequence of primary changes in the gastric mucosal blood-flow.

Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet.

PubMed

Kang, Won-Ho; Nguyen, Hien Van; Park, Chulhun; Choi, Youn-Woong; Lee, Beom-Jin

2017-05-01

This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasmadiafiltration ameliorating gut mucosal barrier dysfunction and improving survival in porcine sepsis models.

PubMed

Li, Ming Xin; Liu, Jun Feng; Lu, Jian Da; Zhu, Ying; Kuang, Ding Wei; Xiang, Jian Bing; Sun, Peng; Wang, Wei; Xue, Jun; Gu, Yong; Hao, Chuan Ming

2016-12-01

The object of this study is to explore whether the plasmadiafiltration (PDF) is more effective in improving the intestinal mucosal barrier function by removing more key large molecular inflammatory mediators and then prolonging the survival time. Totally, 24 porcine sepsis models induced by cecal ligation and puncture (CLP) operation were randomly divided into three groups: PDF group, high-volume hemofiltration (HVHF) group, and control group, and received 8 h treatment, respectively. The expression of ZO-1 and occludin in intestinal mucosal epithelial cells were detected by immunohistochemistry, and apoptotic protein caspase-3-positive lymphocytes were signed in mesenteric lymph nodes by TUNEL staining. The hemodynamic parameters were measured by invasive cavity detection. The tumor necrosis factor alpha (TNFα) and high-mobility group protein 1 (HMGB1) were tested by ELISA method. And then, the survival curves with all-cause death were compared with three groups. PDF led to a superior reversal of sepsis-related hemodynamic impairment and serum biochemistry abnormalities and resulted in longer survival time compared with HVHF and control (p < 0.01). Definitive protection from excessive TNF-α and HMGB1 response were only achieved by PDF. A more regular distribution pattern of ZO-1 and occludin along the epithelium was found in PDF animals (p < 0.01). The presence of apoptotic lymphocytes was significantly reduced in the PDF animals (p < 0.01). PDF can effectively eliminate more pivotal inflammatory mediators of TNFα and HMGB1 and reduce the inflammation damage of the intestinal mucosal barrier and apoptosis of lymphocyte then improve the circulation function and prolong the survival time.

Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins.

PubMed

Dyawanapelly, Sathish; Koli, Uday; Dharamdasani, Vimisha; Jain, Ratnesh; Dandekar, Prajakta

2016-08-01

The main aim of the present study was to compare mucoadhesion and cellular uptake efficiency of chitosan (CS) and chitosan oligosaccharide (COS) surface-modified polymer nanoparticles (NPs) for mucosal delivery of proteins. We have developed poly (D, L-lactide-co-glycolide) (PLGA) NPs, surface-modified COS-PLGA NPs and CS-PLGA NPs, by using double emulsion solvent evaporation method, for encapsulating bovine serum albumin (BSA) as a model protein. Surface modification of NPs was confirmed using physicochemical characterization methods such as particle size and zeta potential, SEM, TEM and FTIR analysis. Both surface-modified PLGA NPs displayed a slow release of protein compared to PLGA NPs. Furthermore, we have explored the mucoadhesive property of COS as a material for modifying the surface of polymeric NPs. During in vitro mucoadhesion test, positively charged COS-PLGA NPs and CS-PLGA NPs exhibited enhanced mucoadhesion, compared to negatively charged PLGA NPs. This interaction was anticipated to improve the cell interaction and uptake of NPs, which is an important requirement for mucosal delivery of proteins. All nanoformulations were found to be safe for cellular delivery when evaluated in A549 cells. Moreover, intracellular uptake behaviour of FITC-BSA loaded NPs was extensively investigated by confocal laser scanning microscopy and flow cytometry. As we hypothesized, positively charged COS-PLGA NPs and CS-PLGA NPs displayed enhanced intracellular uptake compared to negatively charged PLGA NPs. Our results demonstrated that CS- and COS-modified polymer NPs could be promising carriers for proteins, drugs and nucleic acids via nasal, oral, buccal, ocular and vaginal mucosal routes.

Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

PubMed

Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

2010-02-01

Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats

PubMed Central

Whittaker, Alexandra L; Zhu, Ying; Howarth, Gordon S; Loung, Chi S; Bastian, Susan E P; Wirthensohn, Michelle G

2017-01-01

AIM To determine if almond extracts reduce the severity of chemotherapy-induced mucositis as determined through biochemical, histological and behavioural markers. METHODS Intestinal mucositis is a debilitating condition characterized by inflammation and ulceration of the gastrointestinal mucosa experienced by cancer patients undergoing chemotherapy. Certain bioactive plant products have shown promise in accelerating mucosal repair and alleviating clinical symptoms. This study evaluated almond extracts for their potential to reduce the severity of chemotherapy-induced mucositis in Dark Agouti rats. Female Dark Agouti rats were gavaged (days 3-11) with either PBS, almond hull or almond blanched water extract at two doses, and were injected intraperitoneally with 5-fluorouracil (5-FU-150 mg/kg) or saline on day 9 to induce mucositis. Burrowing behavior, histological parameters and myeloperoxidase activity were assessed. RESULTS Bodyweight was significantly reduced in rats that received 5-FU compared to saline-treated controls (P < 0.05). Rats administered 5-FU significantly increased jejunal and ileal MPO levels (1048%; P < 0.001 and 409%; P < 0.001), compared to healthy controls. Almond hull extract caused a pro-inflammatory response in rats with mucositis as evidenced by increased myeloperoxidase activity in the jejunum when compared to 5-FU alone (rise 50%, 1088 ± 96 U/g vs 723 ± 135 U/g, P = 0.02). Other extract-related effects on inflammatory activity were minimal. 5-FU significantly increased histological severity score compared to healthy controls confirming the presence of mucositis (median of 9.75 vs 0; P < 0.001). The extracts had no ameliorating effect on histological severity score in the jejunum or ileum. Burrowing behavior was significantly reduced in all chemotherapy-treated groups (P = 0.001). The extracts failed to normalize burrowing activity to baseline levels. CONCLUSION Almond extracts at these dosages offer little beneficial effect on mucositis severity. Burrowing provides a novel measure of affective state in studies of chemotherapy-induced mucositis. PMID:29184703

Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence.

PubMed

O'Regan, Kevin; Breen, Micheál; Ramaiya, Nikhil; Jagannathan, Jyothi; DiPiro, Pamela J; Hodi, F Stephen; Van den Abbeele, Annick D

2013-12-30

Mucosal melanoma is a rare but aggressive subtype of melanoma with unique clinicopathologic features. We hypothesize that mucosal melanoma shows predilection for separate and unique metastatic pathways. This was a retrospective analysis of 19 patients (5 men and 14 women; median age 60 years, range 38-76 years) with metastatic mucosal melanoma presenting to a tertiary oncology center between 2005 and 2010. We performed a review of medical records and histologic and imaging studies to evaluate the natural history, metastatic patterns and the role of imaging in the management of patients with advanced mucosal melanoma. At presentation, disease was confined to the primary site (58%, n = 11) or to the regional lymph nodes (32%, n = 6) in most patients. The most common site of metastasis was the lungs (89%, n = 16), followed by the liver (67%, n = 12) and peritoneum (44%, n = 8). Sinonasal melanoma preferentially spread to the liver (100%, n = 4), vaginal melanoma to the lungs (100%, n = 7) and anal melanoma to the inguinal lymph nodes (100%, n = 4). Pathways of metastatic spread in mucosal melanoma may differ from other forms of melanoma and between different primary sites of mucosal origin.

Close association between oral Candida species and oral mucosal disorders in patients with xerostomia.

PubMed

Shinozaki, S; Moriyama, M; Hayashida, J-N; Tanaka, A; Maehara, T; Ieda, S; Nakamura, S

2012-10-01

Heightened interest in oral health has lead to an increase in patients complaining of xerostomia, which is associated with various oral mucosal disorders. In this study, we investigated the relationship between Candida species and oral mucosal disorders in patients with xerostomia. We evaluated whole salivary flow rate and presence of oral mucosal disorders in 48 patients with xerostomia and 15 healthy controls. The number of Candida species was measured as colony-forming units after propagation on selective medium. Identification of Candida at the species level was carried out by polymerase chain reaction and restriction fragment length polymorphism analysis. We then examined the relationship between Candida species and oral mucosal symptoms. Compared with controls, patients with xerostomia exhibited significantly decreased whole salivary flow rate, increased rate of oral mucosal symptoms, and higher numbers of Candida. Salivary flow rate negatively correlated with the number Candida. Among patients with oral candidiasis, Candida albicans was isolated from the tongue mucosa and Candida glabrata was isolated from the angle of the mouth. These results suggest that particular Candida species are involved in the pathogenesis of oral mucosal disorders in patients with xerostomia. © 2012 John Wiley & Sons A/S.

[Precancerous conditions in the ENT area].

PubMed

Gál, B; Mrzena, L; Hort, P

2013-01-01

An important part of tumor prevention is early detection, dia-gnosis, treatment and screening of precancerous conditions. Correct detection and screening of premalignant lesions leads to early dia-gnosis of a malignant process which provides a better chance to completely cure the patient and also predicts better quality of life. Precancerous conditions look like whitish, red or mixed mucose lesions (leukoplakia, erytroplakia, erytroleukoplakia) which are visible during clinical examination. Nevertheless, these mucose changes are not absolutely conclusive. Therefore, histological testing is necessary for dia-gnosis and determination of bio-logical potencial of precancerous lesions. Precancerous lesions as a term of histological terminology means dysplasia. The risk of progression of dysplasia into a carcinoma depends on a grade of dysplasia. The conservative or surgical treatment is chosen according to localisation and grade of dysplasia.

Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats

PubMed Central

Halabi, Mohammed Farouq; Shakir, Raied Mustafa; Bardi, Daleya Abdulaziz; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Hassandarvish, Pouya; Hajrezaie, Maryam; Norazit, Anwar; Abdulla, Mahmood Ameen

2014-01-01

Background The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats. Methodology/Principal Findings The cytotoxic effect of ETHAB was assessed using a MTT cleavage assay on a WRL68 cell line, while its antioxidant activity was evaluated in vitro. In the anti-ulcer study, rats were divided into six groups. Group 1 and group 2 received 10% Tween 20 (vehicle). Group 3 received 20 mg/kg Omeprazole. Groups 4, 5 and 6 received ETHAB at doses of 5, 10, and 20 mg/kg, respectively. After an hour, group 1 received the vehicle. Groups 2–6 received absolute ethanol to induce gastric mucosal lesions. In the WRL68 cell line, an IC50 of more than 100 µg/mL was observed. ETHAB results showed antioxidant activity in the DPPH, FRAP, nitric oxide and metal chelating assays. There was no acute toxicity even at the highest dosage (1000 mg/kg). Microscopy showed that rats pretreated with ETHAB revealed protection of gastric mucosa as ascertained by significant increases in superoxide dismutase (SOD), pH level, mucus secretion, reduced gastric lesions, malondialdehyde (MDA) level and remarkable flattened gastric mucosa. Histologically, pretreatment with ETHAB resulted in comparatively better gastric protection, due to reduction of submucosal edema with leucocyte infiltration. PAS staining showed increased intensity in uptake of Alcian blue. In terms of immunohistochemistry, ETHAB showed down-expression of Bax proteins and over-expression of Hsp70 proteins. Conclusion/Significance The gastroprotective effect of ETHAB may be attributed to antioxidant activity, increased gastric wall mucus, pH level of gastric contents, SOD activity, decrease in MDA level, ulcer area, flattening of gastric mucosa, reduction of edema and leucocyte infiltration of the submucosal layer, increased PAS staining, up-regulation of Hsp70 protein and suppressed expression of Bax. Key words: ethyl 4-(3, 5-di-ter-butyl-2-hydroxybenzylamino) benzoate; toxicity; antioxidant; gastric-ulcer; anti-ulcer; histology; immunohistochemistry. PMID:24800807

Acid loading test (pH)

MedlinePlus

... medlineplus.gov/ency/article/003615.htm Acid loading test (pH) To use the sharing features on this page, please enable JavaScript. The acid loading test (pH) measures the ability of the kidneys to send ...

Colonization and effector functions of innate lymphoid cells in mucosal tissues

PubMed Central

Kim, Myunghoo; Kim, Chang H.

2016-01-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bossi, Paolo, E-mail: Paolo.bossi@istitutotumori.mi.it; Bergamini, Cristiana; Miceli, Rosalba

Purpose: We assessed the presence of salivary cytokines, their modulation during chemoradiation therapy (CTRT), and their association with oral mucositis severity in patients with head and neck cancer (HNC). Methods and Materials: The present prospective observational study enrolled 55 patients with locally advanced HNC requiring CTRT. We also studied 10 healthy volunteers and 10 patients with other cancers. The salivary levels of 13 cytokines were analyzed. We constructed a cytokine predictive score of oral mucositis severity. Results: The baseline salivary cytokine levels were not associated with the severity of treatment-induced oral mucositis. The cytokine levels overall increased during treatment, especiallymore » in patients with worse mucositis. In particular, on univariable analysis, an increase of interleukin (IL)-1β (area under the curve [AUC] 0.733; P=.009), IL-6 (AUC 0.746; P=.005), and tumor necrosis factor-α (AUC 0.710; P=.005) at the third week of treatment was significantly associated with the development of severe oral mucositis. On multivariable analysis, the predictive score based on the IL-1β and IL-6 changes from baseline to week 3 was an early strong predictor of higher grade oral mucositis. Conclusions: The treatment of HNC patients with concurrent CTRT induces a significant increase in the salivary levels of IL-1β, IL-6, and tumor necrosis factor-α, all positively associated with the severity of mucosal toxicity. A greater increase of IL-1β and IL-6 3 weeks after treatment initiation is predictive of worse oral mucositis, representing a potential tool for the early identification of patients at risk.« less

Analysis of TSC1 mutation spectrum in mucosal melanoma.

PubMed

Ma, Meng; Dai, Jie; Xu, Tianxiao; Yu, Sifan; Yu, Huan; Tang, Huan; Yan, Junya; Wu, Xiaowen; Yu, Jiayi; Chi, Zhihong; Si, Lu; Cui, Chuanliang; Sheng, Xinan; Kong, Yan; Guo, Jun

2018-02-01

Mucosal melanoma is a relatively rare subtype of melanoma for which no clearly established therapeutic strategy exists. The genes of the mTOR signalling pathway have drawn great attention as key targets for cancer treatment, including melanoma. In this study, we aimed to investigate the mutation status of the upstream mTOR regulator TSC1 and evaluated its correlation with the clinicopathological features of mucosal melanoma. We collected 91 mucosal melanoma samples for detecting TSC1 mutations. All the coding exons of TSC1 were amplified by PCR and subjected to Sanger sequencing. Expression level of TSC1 encoding protein (hamartin) was detected by immunohistochemistry. The activation of mTOR pathway was determined by evaluating the phosphorylation status of S6RP and 4E-BP1. The overall mutation frequency of TSC1 was found to be 17.6% (16/91 patients). TSC1 mutations were more inclined to occur in advanced mucosal melanoma (stages III and IV). In the 16 patients with TSC1 mutations, 14 different mutations were detected, affecting 11 different exons. TSC1 mutations were correlated with upregulation of S6RP phosphorylation but were unrelated to 4E-BP1 phosphorylation or hamartin expression. Mucosal melanoma patients with TSC1 mutations had a worse outcome than patients without TSC1 mutations (24.0 versus 34.0 months, P = 0.007). Our findings suggest that TSC1 mutations are frequent in mucosal melanoma. TSC1 mutations can activate the mTOR pathway through phospho-S6RP and might be a poor prognostic predictor of mucosal melanoma. Our data implicate the potential significance of TSC1 mutations for effective and specific drug therapy for mucosal melanoma.

Mucosal complications of modified osteo-odonto keratoprosthesis in chronic Stevens-Johnson syndrome.

PubMed

Basu, Sayan; Pillai, Vinay Sukumara; Sangwan, Virender S

2013-11-01

To describe clinical outcomes of complications afflicting the autologous oral mucous membrane graft after modified osteo-odonto keratoprosthesis surgery in chronic Stevens-Johnson syndrome (SJS). Prospective case series. This study included 30 eyes of 30 patients with SJS-induced dry keratinized ocular surfaces; the patients underwent various stages of this procedure between August 2009 and February 2012. Mucosal complications were classified as either necrosis or overgrowth. Mucosal necrosis was managed according to a predesigned algorithm based on timing (pre- and postimplantation) and location (central or peripheral) of necrosis. Cases with mucosal overgrowth underwent mucosal debulking and trimming. Mucosal necrosis developed in 15 (50%) eyes and overgrowth in 4 (13.3%) eyes. Preimplantation necrosis (n = 7) was initially managed conservatively, but 2 eyes required free labial-mucous membrane grafting for persistent corneal exposure. Free labial-mucous membrane grafting was performed in all cases of postimplantation necrosis (n = 10), but 8 eyes required additional tarsal pedicle flaps (n = 6, for peripheral necrosis) or through-the-lid revisions (n = 2, for central necrosis). Debulking and trimming effectively managed all cases of mucosal overgrowth, but 3 eyes required repeat procedures. At 24.1 ± 6.5 months postimplantation, the keratoprosthesis was retained in all eyes, and the probability of maintaining 20/60 or better vision was similar in eyes with or without mucosal necrosis (86 ± 8.8% vs 80 ± 10.3%). Mucosal complications, especially necrosis, occurred commonly following modified osteo-odonto keratoprosthesis surgery in dry keratinized post-SJS eyes. The algorithm-based management approach described in this study was successful in treating these complications, retaining the prosthesis and preserving useful vision. Copyright © 2013 Elsevier Inc. All rights reserved.

Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation.

PubMed

Onseng, Kittipong; Johns, Nutjaree Pratheepawanit; Khuayjarernpanishk, Thanut; Subongkot, Suphat; Priprem, Aroonsri; Hurst, Cameron; Johns, Jeffrey

2017-12-01

Oral mucositis is a major cause of pain and delayed cancer treatment leading to poor survival in head and neck cancer patients receiving concurrent chemoradiation. The study evaluated the effect of adjuvant melatonin on minimizing oral mucositis complications to reduce these treatment delays and interruptions. A randomized, double-blind, double dummy, placebo-controlled clinical trial. Ubon Ratchathani Cancer Hospital, Thailand. Thirty-nine head and neck cancer patients receiving concurrent chemoradiation (5 days/week of radiation plus chemotherapy three or six cycles). Patients were randomized to receive 20 mg melatonin gargle (or matched placebo) before each irradiation, and 20 mg melatonin capsules (or matched placebo) taken nightly during 7 weeks of concurrent chemoradiation. Endpoints were oral mucositis events (incidence and time to grade 3 mucositis or grade 2 xerostomia), pain medication consumption and quality of life (QOL). Melatonin group reported lower incidence of grade 3 oral mucositis (42% vs. 55%) and grade 2 xerostomia (20% vs. 21%); no statistical significance was detected. Melatonin regimen delayed onset of grade 3 mucositis (median 34 days vs. 50 days; p = 0.0318), allowing median time of 16 more patient visits before its onset and fewer interrupted treatments due to oral mucositis were reported (n = 1 vs. n = 5). There was no difference of grade 2 xerostomia (median 32 days vs. 50 days; p = 0.624). Morphine consumption was also reduced (median 57 mg vs. 0 mg; p = 0.0342), while QOL was comparable during the study period. Adjuvant melatonin delayed the onset of oral mucositis, which enables uninterrupted cancer treatment and reduced the amount of morphine used for pain treatment.

The effect of royal jelly on oral mucositis in patients undergoing radiotherapy and chemotherapy.

PubMed

Erdem, Ozden; Güngörmüş, Zeynep

2014-01-01

This study was conducted to evaluate the effect of royal jelly on oral mucositis in patients undergoing radiotherapy and chemotherapy. The study population consisted of 103 patients undergoing radiotherapy and chemotherapy. Oral mucositis was graded according to the World Health Organization criteria, and patients were divided into 2 groups. All patients received mouthwash therapy with benzydamine hydrochloride and nystatin rinses. In addition, patients in the experimental group received royal jelly. The mean resolution time of oral mucositis in the royal jelly group was significantly shorter than that of the control group. As a result, the study results demonstrate that royal jelly administrated by a certain procedure improved the signs and symptoms of oral mucositis and markedly shortened its healing time.

Endobronchial Mucosal Neuroma with Sarcoidosis.

PubMed

Erdem, Ipek; Duman, Dildar; Eroglu, Selma; Agca, Meltem; Erdagi, Aykut; Turker, Hatice; Hazar, Armagan

2018-02-01

A first case of endobronchial mucosal neuroma with sarcoidosis is hereby reported. A 67-year female patient, who was diagnosed as sarcoidosis previously, was admitted to our hospital with symptoms of dyspnea, chest pain and fatigue. Middle lobe atelectasis and endobronchial lesion were observed in thorax computed tomography (CT). Fiberoptic bronchoscopy revealed polypoid lesions and histopathological examination of biopsy material showed clustered nerve bundles consistent with mucosal neuroma and non-necrotising granulomas consistent with sarcoidosis. Mucosal neuromas are pathognomonic features of multiple endocrine neoplasia (MEN) type 2B. But other components of MEN type 2B such as medullary tyroid carcinoma or pheochromocytoma were not detected in our patient. Hence, a diagnosis of solitary mucosal neuroma and sarcoidosis in the bronchi was made.

Dimensional changes in soft tissues around dental implants following free gingival grafting: an experimental study in dogs.

PubMed

Bengazi, Franco; Lang, Niklaus P; Caroprese, Marino; Urbizo Velez, Joaquin; Favero, Vittorio; Botticelli, Daniele

2015-02-01

To study the buccal dimensional tissue changes at oral implants following free gingival grafting, with or without including the keratin layer, performed at the time of implant installation into alveolar mucosa. The mandibular premolars and first molars were extracted bilaterally in six Beagle dogs. In the right side of the mandible (Test), flaps were first elevated, and the buccal as well as part of the lingual masticatory mucosa was removed. An incision of the periosteum at the buccal aspect was performed to allow the flap to be coronally repositioned. Primary wound closure was obtained. In the left side, the masticatory (keratinized) mucosa was left in situ, and no sutures were applied (Control). After 3 months of healing, absence of keratinized mucosa was confirmed at the test sites. Two recipient sites were prepared at each side of the mandible in the region of the third and fourth premolars. All implants were installed with the shoulder placed flush with the buccal alveolar bony crest, and abutments were connected to allow a non-submerged healing. Two free gingival mucosal grafts were harvested from the buccal region of the maxillary canines. One graft was left intact (gingival mucosal graft), while for the second, the epithelial layer was removed (gingival connective tissue graft). Subsequently, the grafts were fixed around the test implants in position of the third and fourth premolars, respectively. After 3 months, the animals were euthanized and ground sections obtained. Similar bony crest resorption and coronal extension of osseointegration were found at test and control sites. Moreover, similar dimensions of the peri-implant soft tissues were obtained at test and control sites. The increase in the alveolar mucosal thickness by means of a gingival graft affected the peri-implant marginal bone resorption and soft tissue recession around implants. This resulted in outcomes that were similar to those at implants surrounded by masticatory mucosa, indicating that gingival grafting in the absence of keratinized mucosa around implants may reduce the resorption of the marginal crest and soft tissue recession. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PH DEPENDENT TOXICITY OF FIVE METALS TO THREE MARINE ORGANISMS

EPA Science Inventory

The pH of natural marine systems is relatively stable; this may explain why metal toxicity changes with pH have not been well documented. However, changes in metal toxicity with pH in marine waters are of concern in toxicity testing. During porewater toxicity testing pH can chang...

Low level laser therapy in the treatment of oral mucositis in cancer patients: systematic review of literature

NASA Astrophysics Data System (ADS)

El-Sabbagh, Rula Fawzi; Selting, Wayne J.

2016-03-01

Oral mucositis is a debilitating and dose limiting side effect of oncotherapy in cancer patients. Low Level Laser Therapy (LLLT) is a promising new intervention for the treatment of oral mucositis. Aims and objectives: 1. Perform a systematic review of available literature on the therapeutic effect of LLLT on established oral mucositis. 2. Formulate recommendations for future studies based on results of review. Methods: Electronic search oflow level laser therapy in the treatment of oral mucositis was conducted and eligible studies reviewed. Results: Four studies met the inclusion criteria and were analyzed. A total of 109 patients were included, 59 of which received LLLT as a therapeutic measure. An overall success rate of 81.4% success rate was reported in regard to OM. Conclusion: The review demonstrated the positive therapeutic effect of LLLT on oral mucositis. However, the need for future studies with standardized reporting of parameters and methods is needed to increase the level of evidence of this intervention.

[Cryotherapy is useful and safe in the prevention of oral mucositis after high-dose melphalan (L-PAM)].

PubMed

Inagaki, Noriko; Ohue, Yukiko; Shigeta, Hiroe; Tasaka, Taizo

2006-11-01

We prospectively assessed the effectiveness of cryotherapy after high-dose L-PAM to prevent oral mucositis. Cryotherapy with ice tips was commenced 15 minutes before L-PAM administration, and continued until the end of administration. Twenty-six patients were enrolled in this study. Thirteen patients with myeloma were treated with 200 mg/m2 L-PAM followed by autologous peripheral blood stem cell transplantation, and 13 patients (4 AML, 4 MDS, 2 ALL, 2 lymphoma and 1 CML) were treated with 140 mg/m2 L-PAM followed by allogeneic stem cell transplantation. Grade 1 mucositis occurred in four of 13 patients (31%) with 200 mg/m2 L-PAM, and 2 of 13 patients (16%) with 140 mg/m2 L-PAM. Only one patient had grade 2 mucositis, and no grade 3 mucositis were observed. The procedure was well tolerated in all patients. These data suggest that cryotherapy is effective to minimize L-PAM-induced oral mucositis.

Mucosal immunoglobulins at respiratory surfaces mark an ancient association that predates the emergence of tetrapods

PubMed Central

Xu, Zhen; Takizawa, Fumio; Parra, David; Gómez, Daniela; von Gersdorff Jørgensen, Louise; LaPatra, Scott E.; Sunyer, J. Oriol

2016-01-01

Gas-exchange structures are critical for acquiring oxygen, but they also represent portals for pathogen entry. Local mucosal immunoglobulin responses against pathogens in specialized respiratory organs have only been described in tetrapods. Since fish gills are considered a mucosal surface, we hypothesized that a dedicated mucosal immunoglobulin response would be generated within its mucosa on microbial exposure. Supporting this hypothesis, here we demonstrate that following pathogen exposure, IgT+ B cells proliferate and generate pathogen-specific IgT within the gills of fish, thus providing the first example of locally induced immunoglobulin in the mucosa of a cold-blooded species. Moreover, we demonstrate that gill microbiota is predominantly coated with IgT, thus providing previously unappreciated evidence that the microbiota present at a respiratory surface of a vertebrate is recognized by a mucosal immunoglobulin. Our findings indicate that respiratory surfaces and mucosal immunoglobulins are part of an ancient association that predates the emergence of tetrapods. PMID:26869478

Suitability of the isolated chicken eye test for classification of extreme pH detergents and cleaning products.

PubMed

Cazelle, Elodie; Eskes, Chantra; Hermann, Martina; Jones, Penny; McNamee, Pauline; Prinsen, Menk; Taylor, Hannah; Wijnands, Marcel V W

2015-04-01

A.I.S.E. investigated the suitability of the regulatory adopted ICE in vitro test method (OECD TG 438) with or without histopathology to identify detergent and cleaning formulations having extreme pH that require classification as EU CLP/UN GHS Category 1. To this aim, 18 extreme pH detergent and cleaning formulations were tested covering both alkaline and acidic extreme pHs. The ICE standard test method following OECD Test Guideline 438 showed good concordance with in vivo classification (83%) and good and balanced specificity and sensitivity values (83%) which are in line with the performances of currently adopted in vitro test guidelines, confirming its suitability to identify Category 1 extreme pH detergent and cleaning products. In contrast to previous findings obtained with non-extreme pH formulations, the use of histopathology did not improve the sensitivity of the assay whilst it strongly decreased its specificity for the extreme pH formulations. Furthermore, use of non-testing prediction rules for classification showed poor concordance values (33% for the extreme pH rule and 61% for the EU CLP additivity approach) with high rates of over-prediction (100% for the extreme pH rule and 50% for the additivity approach), indicating that these non-testing prediction rules are not suitable to predict Category 1 hazards of extreme pH detergent and cleaning formulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of three acute stress models for simulating the pathophysiology of stress-related mucosal disease.

PubMed

Saxena, Bhagawati; Singh, Sanjay

2017-05-30

Stress-related mucosal disease (SRMD) is highly prevalent in intensive care patients leading to increasing treatment cost and mortality. SRMD is a disease elusive of ideal treatment. Evaluation of drugs is very pertinent for the efficient and safe treatment of SRMD. It relies mainly on in vivo screening models. There are various stress models, and till date, none of them is validated for simulating the SRMD pathophysiology. The present study aims to choose the best model, which reproduce pathophysiology of SRMD, among previously established stress models. This study evaluates ulcer index, hexosamine content, microvascular permeability, and gastric content in three acute stress models (cold-restraint, restraint, and water immersion restraint). Macroscopic pictures of the ulcerogenic stomach explain that in contrast to other models, cold-restraint stress (CRS) exposure produced marked ulcers on the fundic area of the stomach. Results of the present study depicted that each stress model significantly increased ulcer index, microvascular permeability and decreased hexosamine level, however, the maximum in the case of CRS-exposed rats. Total acidity and pH of the gastric content remains unchanged in all the stress models. On the contrary, the gastric volume significantly decreased only in case of CRS, while unchanged in other stress models. The overall results revealed that the CRS resembles the pathophysiology of SRMD closely. It is the best and feasible model among all the models to evaluate drugs for the treatment of SRMD.

Rebamipide gargle in preventive management of chemo-radiotherapy induced oral mucositis.

PubMed

Chaitanya, B; Pai, Keerthilatha M; Yathiraj, Prahlad H; Fernandes, Donald; Chhaparwal, Yogesh

2017-09-01

Oral mucositis is inflammation of mucosa of oral cavity which is an inevitable and acute side effect in patients undergoing chemoradiotherapy for head & neck cancer. Though many agents have been tried in prevention & treatment of oral mucositis, until date no single agent exists that is universally established to be effective. 60 Patients diagnosed with Head & Neck cancer recruited for concurrent chemo-radiotherapy were assigned in a double blind fashion into 2 groups using computer based 1:1 ratio randomization. Subjects in Group 1 were given Rebamipide gargle while subjects in Group 2 were given Placebo gargle in similar colour coded bottles to gargle 6 times/day. Subjective assessment of oral mucositis was done by Numeric Rating Scale (NRS) and objective scoring according to RTOG system. All subjects in the Group 1 reported good treatment compliance but 4 subjects in Group 2 developed burning sensation to gargle and were excluded. Onset of oral mucositis was 3.5days earlier in Group 2 (mean=11.17) as compared to Group 1 (mean=14.63). At the end of chemo-radiotherapy, severity of oral mucositis was significantly lower in Group 1 (mean=1.97) than in Group 2 (mean=2.81). Findings of this study revealed that Rebamipide gargle may be an effective means to prolong the onset of oral mucositis and may reduce the severity of oral mucositis in undergoing chemo-radiotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Induction of pneumococcal polysaccharide-specific mucosal immune responses by oral immunization.

PubMed

VanCott, J L; Kobayashi, T; Yamamoto, M; Pillai, S; McGhee, J R; Kiyono, H

1996-04-01

Liposome and cholera toxin (CT) are considered to be effective antigen delivery vehicles and adjuvants for mucosal vaccines. The effect of these antigen delivery systems on adjuvant responses to mucosally administered pneumococcal polysaccharide (Pnup) was investigated in this study. Both mucosal (e.g. oral) and systemic (i.p.) immunization of mice with purified preparations of Pnup type 23F induced antigen-specific IgM responses in sera. Interestingly, oral immunization of as little as 10 micrograms of Pnup type 23F was sufficient to induce systemic IgM responses. Pnup-specific IgM antibodies peaked by day 7 and no booster responses were evident after a second dose on day 14. In order to examine whether IgG and IgA Pnup-specific immune responses are induced by mucosal immunization, the mucosal adjuvant CT was mixed with Pnup type 23 as an oral vaccine. Co-oral administration of CT and Pnup type 23F resulted in the induction of Pnup-specific faecal IgA antibodies. These results were confirmed by detecting antigen-specific IgA-spot-forming cells in mononuclear cell suspensions prepared from the intestine of immunized mice. These findings suggest that oral immunization with Pnup in the presence of mucosal adjuvants, such as CT, could induce Pnup-specific IgA responses whereas Pnup alone did not. In an attempt to further enhance antigen-specific antibody responses, Pnup type 23F was encapsulated in liposomes and used as mucosal vaccine. However, immunogenicity of Pnup was not improved.

Multi-scale Finite Element Modeling of Eustachian Tube Function: Influence of Mucosal Adhesion

PubMed Central

Malik, J.E.; Swarts, J.D.; Ghadiali, S. N.

2017-01-01

The inability to open the collapsible Eustachian tube (ET) leads to the development of chronic Otitis Media (OM). Although mucosal inflammation during OM leads to increased mucin gene expression and elevated adhesion forces within the ET lumen, it is not known how changes in mucosal adhesion alter the biomechanical mechanisms of ET function. In this study, we developed a novel multi-scale finite element model of ET function in adults that utilizes adhesion spring elements to simulate changes in mucosal adhesion. Models were created for six adult subjects and dynamic patterns in muscle contraction were used to simulate the wave-like opening of the ET that occurs during swallowing. Results indicate that ET opening is highly sensitive to the level of mucosal adhesion and that exceeding a critical value of adhesion leads to rapid ET dysfunction. Parameter variation studies and sensitivity analysis indicate that increased mucosal adhesion alters the relative importance of several tissue biomechanical properties. For example, increases in mucosal adhesion reduced the sensitivity of ET function to tensor veli palatini muscle forces but did not alter the insensitivity of ET function to levator veli palatini muscle forces. Interestingly, although changes in cartilage stiffness did not significantly influence ET opening under low adhesion conditions, ET opening was highly sensitive to changes in cartilage stiffness under high adhesion conditions. Therefore, our multi-scale computational models indicate that changes in mucosal adhesion as would occur during inflammatory OM alter the biomechanical mechanisms of ET function. PMID:26891171

Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

PubMed Central

Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

2013-01-01

Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

Isolation of HIV-1-Neutralizing Mucosal Monoclonal Antibodies from Human Colostrum

PubMed Central

Friedman, James; Alam, S. Munir; Shen, Xiaoying; Xia, Shi-Mao; Stewart, Shelley; Anasti, Kara; Pollara, Justin; Fouda, Genevieve G.; Yang, Guang; Kelsoe, Garnett; Ferrari, Guido; Tomaras, Georgia D.; Haynes, Barton F.; Liao, Hua-Xin

2012-01-01

Background Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody responses may play a role in protection of the majority of HIV-exposed, breastfeeding infants. Therefore, characterization of HIV-specific antibodies produced by B cells in milk could guide the development of vaccines that elicit protective mucosal antibody responses. Methods We isolated B cells from colostrum of an HIV-infected lactating woman with a detectable neutralization response in milk and recombinantly produced and characterized the resulting HIV-1 Envelope (Env)-specific monoclonal antibodies (mAbs). Results The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds to linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast, colostrum mAb CH08 is a nonpolyreactive CD4-inducible (CD4i) gp120-specific mAb with moderate breadth of neutralization. Conclusions These novel HIV-neutralizing mAbs isolated from a mucosal compartment provide insight into the ability of mucosal B cell populations to produce functional anti-HIV antibodies that may contribute to protection against virus acquisition at mucosal surfaces. PMID:22624058

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.

PubMed

Lalla, Rajesh V; Bowen, Joanne; Barasch, Andrei; Elting, Linda; Epstein, Joel; Keefe, Dorothy M; McGuire, Deborah B; Migliorati, Cesar; Nicolatou-Galitis, Ourania; Peterson, Douglas E; Raber-Durlacher, Judith E; Sonis, Stephen T; Elad, Sharon

2014-05-15

Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis. A literature search was conducted to identify eligible published articles, based on predefined inclusion/exclusion criteria. Each article was independently reviewed by 2 reviewers. Studies were rated according to the presence of major and minor flaws as per previously published criteria. The body of evidence for each intervention, in each treatment setting, was assigned a level of evidence, based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. The literature search identified 8279 papers, 1032 of which were retrieved for detailed evaluation based on titles and abstracts. Of these, 570 qualified for final inclusion in the systematic reviews. Sixteen new guidelines were developed for or against the use of various interventions in specific treatment settings. In total, the MASCC/ISOO Mucositis Guidelines now include 32 guidelines: 22 for oral mucositis and 10 for gastrointestinal mucositis. This article describes these updated guidelines. The updated MASCC/ISOO Clinical Practice Guidelines for mucositis will help clinicians provide evidence-based management of mucositis secondary to cancer therapy. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Lactobacillus brevis CD2 lozenges prevent oral mucositis in patients undergoing high dose chemotherapy followed by haematopoietic stem cell transplantation

PubMed Central

Sharma, Atul; Tilak, TVSVGK; Bakhshi, Sameer; Raina, Vinod; Kumar, Lalit; Chaudhary, Surendra Pal; Sahoo, Ranjit Kumar; Gupta, Ritu; Thulkar, Sanjay

2016-01-01

Background Oral mucositis is a common inflammatory complication in patients undergoing high-dose chemotherapy and radiation followed by haematopoietic stem cell transplantation (HSCT). Lactobacillus brevis CD2 has been proven efficacious in preventing chemoradiotherapy-induced oral mucositis in squamous cell carcinoma of head and neck. Methods This phase II study aimed to evaluate the safety and efficacy of L. brevis CD2 lozenges in preventing oral mucositis in patients undergoing HSCT. Eligible patients received four to six lozenges of L. brevis CD2 per day, beginning from 4 to 7 days before initiation of chemotherapy and continuing until resolution of mucositis or till day +24. Results Of 31 patients enrolled, 7 (22.6%) patients did not develop any mucositis, 6 (19.4%) patients developed grade 1, 12 (38.7%) patients developed grade 2, 4 (12.9%) and 2 (6.5%) patients developed grade 3 and grade 4 mucositis, respectively. Median time to onset and for resolution of mucositis were 6 days and 8 days, respectively. No adverse events were reported with usage of study drug. However, one patient died of Klebsiella sepsis. Conclusion Promising results from the study encourage the use of L. brevis CD2 lozenges as a supportive care treatment option; however, a randomised, double-blind, multicentric trial in a larger population is warranted. Trials registration number NCT01480011 at https://www.clinicaltrials.gov/ (Registered on Nov 04, 2011). PMID:28848667

Recurrent symptoms after fundoplication with a negative pH study--recurrent reflux or functional heartburn?

PubMed

Thompson, Sarah K; Cai, Wang; Jamieson, Glyn G; Zhang, Alison Y; Myers, Jennifer C; Parr, Zoe E; Watson, David I; Persson, Jenny; Holtmann, Gerald; Devitt, Peter G

2009-01-01

A small cohort of patients present after antireflux surgery complaining of recurrent heartburn. Over two thirds of these patients will have a negative 24-h pH study. The aim of our study is to determine whether these patients have an associated functional disorder or abnormal cytokine activity and to examine the reproducibility of pH testing. A prospective analysis was carried out on a cohort of patients who had undergone a fundoplication and postoperative pH testing for recurrent heartburn: group A--patients with recurrent heartburn and a negative 24-h pH study and group B (control group)--patients with recurrent heartburn and a positive pH study. Questionnaires, a blood sample, and repeat pH testing were completed. Sixty-nine patients were identified. Group A's depression score (8.6 +/- 4.1) was significantly higher than group B's (5.9 +/- 4.2; P = 0.03). Cytokine levels were similar in both groups. Forty-seven of 49 (96%) patients who underwent repeat pH testing had a negative study. Symptom-reflux correlation was highly significant (P < 0.001). Some patients with recurrent heartburn and a negative pH study have associated functional or psychiatric comorbidities such as depression. Reproducibility of 24-h pH testing in these patients is excellent.

Mucosal immune response in broilers following vaccination with inactivated influenza and recombinant Bacillus subtilis

USDA-ARS?s Scientific Manuscript database

Mucosal and systemic immunity were observed in broilers vaccinated with mannosylated chitosan adjuvated (MCA) inactivated A/Turkey/Virginia/158512/2002 (H7N2) and administered with and without recombinant Bacillus subtilis to elicit heterologous influenza strain protection. Previously, mucosal immu...

Sick building syndrome (SBS) among office workers in a Malaysian university--Associations with atopy, fractional exhaled nitric oxide (FeNO) and the office environment.

PubMed

Lim, Fang-Lee; Hashim, Zailina; Md Said, Salmiah; Than, Leslie Thian-Lung; Hashim, Jamal Hisham; Norbäck, Dan

2015-12-01

There are few studies on sick building syndrome (SBS) including clinical measurements for atopy and fractional exhaled nitric oxide (FeNO). Our aim was to study associations between SBS symptoms, selected personal factors, office characteristics and indoor office exposures among office workers from a university in Malaysia. Health data were collected by a questionnaire (n=695), skin prick test (SPT) (n=463) and FeNO test (n=460). Office settled dust was vacuumed and analyzed for endotoxin, (1,3)-β-glucan and house dust mites (HDM) allergens group 1 namely Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1). Office indoor temperature, relative air humidity (RH), carbon monoxide (CO) and carbon dioxide (CO2) were measured by a direct reading instrument. Associations were studied by two-levels multiple logistic regression with mutual adjustment and stratified analysis. The prevalence of weekly dermal, mucosal and general symptoms was 11.9%, 16.0% and 23.0% respectively. A combination of SPT positivity (allergy to HDM or cat) and high FeNO level (≥25 ppb) was associated with dermal (p=0.002), mucosal (p<0.001) and general symptoms (p=0.05). Der f1 level in dust was associated with dermal (p<0.001), mucosal (p<0.001) and general (p=0.02) symptoms. Among those with allergy to D. farinae, associations were found between Der f 1 levels in dust and dermal (p=0.003), mucosal (p=0.001) and general symptoms (p=0.007). Office-related symptoms were associated with Der f 1 levels in dust (p=0.02), low relative air humidity (p=0.04) and high office temperature (p=0.05). In conclusion, a combination of allergy to cat or HDM and high FeNO is a risk factor for SBS symptoms. Der f 1 allergen in dust can be a risk factor for SBS in the office environment, particularly among those sensitized to Der f 1 allergen. Copyright © 2015 Elsevier B.V. All rights reserved.

Intranasal Administration of a Therapeutic HIV Vaccine (Vacc-4x) Induces Dose-Dependent Systemic and Mucosal Immune Responses in a Randomized Controlled Trial

PubMed Central

Brekke, Kristin; Lind, Andreas; Holm-Hansen, Carol; Haugen, Inger Lise; Sørensen, Birger; Sommerfelt, Maja; Kvale, Dag

2014-01-01

Background Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant. Methods Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β. Results Vacc-4x proliferative T cell responses increased only among the vaccinated (p≤0.031). The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037) and developed larger DTH (p = 0.005) than the adjuvant group. Rectal (distal) Vacc-4x IgA and IgG antibodies also increased (p = 0.043) in this group. In contrast, the high dose generated higher nasal (local) Vacc-4x IgA (p = 0.028) and serum IgG (p = 0.030) antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = −0.82, p<0.001) and high regulation (r = 0.61, p = 0.010) at baseline. Conclusion Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation. Trial Registration ClinicalTrials.gov NCT01473810 PMID:25398137

Effect of individual SCFA on the epithelial barrier of sheep rumen under physiological and acidotic luminal pH conditions.

PubMed

Greco, Gabriele; Hagen, Franziska; Meißner, Svenja; Shen, Zanming; Lu, Zhongyan; Amasheh, Salah; Aschenbach, Jörg R

2018-02-15

The objective of this study was to investigate whether individual short-chain fatty acids (SCFA) have a different potential to either regulate the formation of the ruminal epithelial barrier (REB) at physiological pH or to damage the REB at acidotic ruminal pH. Ruminal epithelia of sheep were incubated in Ussing chambers on their mucosal side in buffered solutions (pH 6.1 or 5.1) containing no SCFA (control), 30 mM of either acetate, propionate or butyrate, or 100 mM acetate. Epithelial conductance (Gt), short-circuit current (Isc), and fluorescein flux rates were measured over 7 h. Thereafter, mRNA and protein abundance, as well as localization of the tight junction proteins claudin (Cldn)-1, -4, -7, and occludin were analyzed. At pH 6.1, butyrate increased Gt and decreased Isc, with additional decreases in claudin-7 mRNA and protein abundance (each P < 0.05) and disappearance of Cldn-7 immunosignals from the stratum corneum. By contrast, the mRNA abundance of Cldn-1 and/or Cldn-4 were upregulated by 30 mM propionate, 30 mM butyrate, or 100 mM acetate (P < 0.05), however, without coordinated changes in protein abundance. At luminal pH 5.1, neither Gt, Isc, nor TJ protein abundance was altered in the absence of SCFA; only fluorescein flux rates were slightly increased (P < 0.05) and fluorescein signals were no longer restricted to the stratum corneum. The presence of acetate, propionate, or butyrate at pH 5.1 increased fluorescein flux rates and Gt, and decreased Isc (each P < 0.05). Protein abundance of Cldn-1 was decreased in all SCFA treatments but 30 mM butyrate; abundance of Cldn -4 and -7 was decreased in all SCFA treatments but 30 mM acetate; and abundance of occludin was decreased in all SCFA treatments but 30 mM propionate (each P < 0.05). Immunofluorescence staining of SCFA-treated tissues at pH 5.1 showed disappearance of Cldn-7, discontinuous pattern for Cldn-4 and blurring of occludin and Cldn-1 signals in tight junction complexes. The fluorescein dye appeared to freely diffuse into deeper cell layers. The strongest increase in Gt and consistent decreases in the abundance and immunosignals of tight junction proteins were observed with 100 mM acetate at pH 5.1. We conclude that SCFA may contribute differently to the REB formation at luminal pH 6.1 with possible detrimental effects of butyrate at 30 mM concentration. At luminal pH 5.1, all SCFA elicited REB damage with concentration appearing more critical than SCFA species.

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

PubMed

Kim, Myunghoo; Kim, Chang H

2016-10-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Vigilance or Subversion? Constitutive and Inducible M Cells in Mucosal Tissues.

PubMed

Lo, David D

2018-03-01

Microfold (M) cells are epithelial cells present in mucosal tissues and specialized for the capture of luminal microparticles and their delivery to underlying immune cells; thus, they are crucial participants in mucosal immune surveillance. Multiple phenotypic subsets of M cells have now been described, all sharing a unique apical morphology that provides clues to their ability to capture microbial particles. The existence of diverse M cell phenotypes, especially inflammation-inducible M cells, provides an intriguing puzzle: some variants may augment luminal surveillance to boost mucosal immunity, while others may promote microbial access to tissues. Here, I consider the unique induction requirements of each M cell subset and functional differences, highlighting the potentially distinct consequences in mucosal immunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microbiota and Mucosal Immunity in Amphibians

PubMed Central

Colombo, Bruno M.; Scalvenzi, Thibault; Benlamara, Sarah; Pollet, Nicolas

2015-01-01

We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence different aspects of mucosal development and function. Yet, the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: (i) the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and (ii) the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small-animal model to improve the fundamental knowledge on immunological functions of gut microbiota. PMID:25821449

Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

PubMed

Saito, H; Kimura, T; Takeda, T; Kishimoto, S; Oguma, T; Shimamura, K

1990-01-01

The pharmacokinetics of flomoxef in serum and in the mucosal tissue of the middle ear and mastoid were studied in 9 patients undergoing tympanoplasties. All patients received 1 g of flomoxef intravenously. Flomoxef levels in serum and in mucosal tissue were determined by a bioassay method. The peak value of mean concentrations of flomoxef in the mucosal tissue was 30.3 +/- 11.7 micrograms/ml at 10 min after the administrations. Pharmacokinetic analyses showed that the concentration of flomoxef in the mucosal tissue was over 1.56 micrograms/ml (which is the MIC90 for the common pathogens of otitis media) for more than 2 h and decreased parallel with serum concentration with a half-life of about 40 min.

Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat.

PubMed

Koppelmann, Tal; Pollak, Yulia; Mogilner, Jorge; Bejar, Jacob; Coran, Arnold G; Sukhotnik, Igor

2012-04-30

Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat. Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression. MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels. Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.

Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

PubMed

Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Kajiwara, Eiji; Nishida, Ryuichi

2013-01-01

Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

Mucosal Cysts of the Maxillary Sinus in Solid Organ Transplant Population: Computerised Tomography Follow-Up Results

PubMed Central

Aydın, Erdinç; Yerli, Hasan; Tanrıkulu, Suna; Hizal, Evren

2013-01-01

Background: The clinical significance of maxillary sinus mucosal cysts in liver and kidney transplant recipients remains unclear. Aim: To investigate the course of maxillary mucosal cysts in liver and kidney transplantation patients. Study Design: Retrospective clinical study Methods: Paranasal sinus computed tomography scans of 169 renal and 43 hepatic transplant recipients were reviewed. The incidence, size and growth characteristics of maxillary mucosal cysts in the renal and hepatic transplant population were noted. Results: Overall incidence of maxillary sinus mucosal cyst in transplantation patients was found to be 24.5%, with a male to female ratio of 2:1 (p<0.05). Follow-up views of 26 patients showed that the size of the cysts increased in 19, decreased in 4, and remained the same in 3 patients. Mean growth rate of the cysts was calculated to be 6.30 ± 7.02 mm2 per month. Most of the cysts were located on the inferior wall of the maxillary sinus. Conclusion: Incidence of the maxillary mucosal cysts in renal and hepatic transplant recipients does not differ from general population, but these cysts have a greater tendency to grow. Specific measures are not needed for isolated, asymptomatic maxillary mucosal cysts in transplant populations. PMID:25207125

Effect of dietary fat on the distribution of mucosal mass and cell proliferation along the small intestine.

PubMed Central

Jenkins, A P; Thompson, R P

1992-01-01

This study investigated how substitution of long chain triglycerides for glucose in a mixed diet affects the overall small intestinal mucosal mass and the distribution of mucosal mass and cell proliferation along the small intestine. Four groups of eight female Wistar rats (180-200 g) were isocalorically fed mixed diets containing the essential fatty acid rich oil Efamol substituted for glucose at concentrations of 1.2%, 10%, 25%, and 50% total calories for 20 to 23 days. The small intestine was divided into three equal length segments and whole gut weights, mucosal weights, protein and DNA determined. Cell proliferation was estimated from the two hour accumulation of vincristine arrested metaphases in microdissected crypts at points 0%, 17%, 33%, 50%, 66%, and 100% small intestinal length. There were no differences between groups in parameters of overall small intestinal or distal segment mucosal mass. With increasing levels of fat, however, there was a significant trend for the mucosal mass of the proximal segment to fall and that of the middle segment to rise. The pattern of two hour metaphase accumulation reflected these changes. These regional changes in mucosal mass and cell proliferation may reflect differences in the sites of absorption of fat and glucose. PMID:1541418

Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence

PubMed Central

O’Regan, Kevin; Ramaiya, Nikhil; Jagannathan, Jyothi; DiPiro, Pamela J.; Stephen Hodi, F.; Van den Abbeele, Annick D.

2013-01-01

Abstract Purpose: Mucosal melanoma is a rare but aggressive subtype of melanoma with unique clinicopathologic features. We hypothesize that mucosal melanoma shows predilection for separate and unique metastatic pathways. Materials and methods: This was a retrospective analysis of 19 patients (5 men and 14 women; median age 60 years, range 38–76 years) with metastatic mucosal melanoma presenting to a tertiary oncology center between 2005 and 2010. We performed a review of medical records and histologic and imaging studies to evaluate the natural history, metastatic patterns and the role of imaging in the management of patients with advanced mucosal melanoma. Results: At presentation, disease was confined to the primary site (58%, n = 11) or to the regional lymph nodes (32%, n = 6) in most patients. The most common site of metastasis was the lungs (89%, n = 16), followed by the liver (67%, n = 12) and peritoneum (44%, n = 8). Sinonasal melanoma preferentially spread to the liver (100%, n = 4), vaginal melanoma to the lungs (100%, n = 7) and anal melanoma to the inguinal lymph nodes (100%, n = 4). Conclusion: Pathways of metastatic spread in mucosal melanoma may differ from other forms of melanoma and between different primary sites of mucosal origin. PMID:24434078

Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations.

PubMed

Cosgarea, Ioana; Ugurel, Selma; Sucker, Antje; Livingstone, Elisabeth; Zimmer, Lisa; Ziemer, Mirjana; Utikal, Jochen; Mohr, Peter; Pfeiffer, Christiane; Pföhler, Claudia; Hillen, Uwe; Horn, Susanne; Schadendorf, Dirk; Griewank, Klaus G; Roesch, Alexander

2017-06-20

Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutaneous melanomas. For the majority of mucosal melanomas oncogenic driver mutations remain unknown. In our study, 75 tumor tissues from patients diagnosed with mucosal melanoma were analyzed, applying a targeted next generation sequencing panel covering 29 known recurrently mutated genes in melanoma. NF1 and RAS mutations were identified as the most frequently mutated genes occurring in 18.3% and 16.9% of samples, respectively. Mutations in BRAF were identified in 8.4% and KIT in 7.0% of tumor samples. Our study identifies NF1 as the most frequently occurring driver mutation in mucosal melanoma. RAS alterations, consisting of NRAS and KRAS mutations, were the second most frequent mutation type. BRAF and KIT mutations were rare with frequencies below 10% each. Our data indicate that in mucosal melanomas RAS/NF1 alterations are frequent, implying a significant pathogenetic role for MAPK and potentially PI3K pathway activation in these tumors.

Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations

PubMed Central

Cosgarea, Ioana; Ugurel, Selma; Sucker, Antje; Livingstone, Elisabeth; Zimmer, Lisa; Ziemer, Mirjana; Utikal, Jochen; Mohr, Peter; Pfeiffer, Christiane; Pföhler, Claudia; Hillen, Uwe; Horn, Susanne; Schadendorf, Dirk

2017-01-01

Purpose Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutaneous melanomas. For the majority of mucosal melanomas oncogenic driver mutations remain unknown. Experimental Design and Results In our study, 75 tumor tissues from patients diagnosed with mucosal melanoma were analyzed, applying a targeted next generation sequencing panel covering 29 known recurrently mutated genes in melanoma. NF1 and RAS mutations were identified as the most frequently mutated genes occurring in 18.3% and 16.9% of samples, respectively. Mutations in BRAF were identified in 8.4% and KIT in 7.0% of tumor samples. Conclusions Our study identifies NF1 as the most frequently occurring driver mutation in mucosal melanoma. RAS alterations, consisting of NRAS and KRAS mutations, were the second most frequent mutation type. BRAF and KIT mutations were rare with frequencies below 10% each. Our data indicate that in mucosal melanomas RAS/NF1 alterations are frequent, implying a significant pathogenetic role for MAPK and potentially PI3K pathway activation in these tumors. PMID:28380455

Prevention of gastrointestinal side-effects in paediatric oncology: what are the guidelines?

PubMed

Cheng, Karis K F

2017-06-01

Gastrointestinal side-effects, particularly with regard to alimentary tract mucositis and chemotherapy-induced nausea and vomiting (CINV), continue to be frequent and debilitating symptomatic conditions among children and adolescents receiving cytotoxic cancer therapy. Further avenues of progress for mucositis and CINV prevention in paediatric oncology setting are warranted. The current article reviews the major guidelines and literature published in 2016 pertaining to the prevention of mucositis and CINV. Considerable professional organizational efforts have been made to develop consensus-based or evidence-based guidelines that periodically update to define basic standards of mucositis and CINV prevention. There are a few published works in 2016 that may contribute to the emerging evidence on prevention of mucositis and CINV in the paediatric setting for future guideline updates. The concomitant use of 5-HT3 receptor antagonist and dexamethasone are effective to prevent acute and delayed CINV in children who are to receive highly or moderately emetogenic chemotherapy. Optimal control of acute and delayed CINV can prevent anticipatory CINV. Oral care protocols would be beneficial to prevent mucositis in children across all cancer treatment modalities. Cryotherapy or low-level light therapy may be applied to cooperative children undergoing chemotherapy or haematological stem cell transplant conditioning regimens with a high rate of mucositis.

Elemental Diet Accelerates the Recovery From Oral Mucositis and Dermatitis Induced by 5-Fluorouracil Through the Induction of Fibroblast Growth Factor 2.

PubMed

Harada, Koji; Ferdous, Tarannum; Kobayashi, Hiroaki; Ueyama, Yoshiya

2018-06-01

Mucositis and dermatitis induced by anticancer agents are common complications of anticancer therapies. In this study, we evaluated the efficacy of Elental (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis and dermatitis was induced through a combination of 5-FU treatment and mild abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice respectively. These animals received saline, dextrin or Elental suspension (18 kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral mucositis and dermatitis more effectively than dextrin in the animal model. Moreover, growth facilitating effects of Elental on HaCaT cells were examined in vitro. MTT assay, wound healing assay, and migration assay revealed that Elental could enhance the growth, invasion, and migration ability of HaCaT. ELISA and Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings suggest that Elental is effective for the treatment of mucositis and dermatitis, and may accelerate mucosal and skin recovery through FGF2 induction and reepithelization.

Effect of dietary fat on the distribution of mucosal mass and cell proliferation along the small intestine.

PubMed

Jenkins, A P; Thompson, R P

1992-02-01

This study investigated how substitution of long chain triglycerides for glucose in a mixed diet affects the overall small intestinal mucosal mass and the distribution of mucosal mass and cell proliferation along the small intestine. Four groups of eight female Wistar rats (180-200 g) were isocalorically fed mixed diets containing the essential fatty acid rich oil Efamol substituted for glucose at concentrations of 1.2%, 10%, 25%, and 50% total calories for 20 to 23 days. The small intestine was divided into three equal length segments and whole gut weights, mucosal weights, protein and DNA determined. Cell proliferation was estimated from the two hour accumulation of vincristine arrested metaphases in microdissected crypts at points 0%, 17%, 33%, 50%, 66%, and 100% small intestinal length. There were no differences between groups in parameters of overall small intestinal or distal segment mucosal mass. With increasing levels of fat, however, there was a significant trend for the mucosal mass of the proximal segment to fall and that of the middle segment to rise. The pattern of two hour metaphase accumulation reflected these changes. These regional changes in mucosal mass and cell proliferation may reflect differences in the sites of absorption of fat and glucose.

Cellular Energetical Actions of “Chemical” and “Surgical” Vagotomy in Gastrointestinal Mucosal Damage and Protection: Similarities, Differences and Significance for Brain-Gut Function

PubMed Central

Szabo, Imre L.; Czimmer, Jozsef; Mozsik, Gyula

2016-01-01

Background The authors, as internists, registered significant difference in the long lasting actions of surgical and chemical (atropine treatment) vagotomy in patients with peptic ulcer during second half of the last century (efficency, gastric acid secretion, gastrointestinal side effects, briefly benefical and harmful actions were examined). Aims 1. Since the authors participated in the establishing of human clinical pharmacology in this field, they wanted to know more and more facts of the acute and chronic effects of surgical and chemical (atropine treatment) on the gastrointestinal mucosal biochemisms and their actions altered by bioactive compounds and scavengers regarding the development of gastric mucosal damage and protection. Methods The observations were carried out in animals under various experimental conditions (in intact, pylorus-ligated rats, in different experimental ulcer models, together with application of various mucosal protecting compounds) without and with surgical vagotomy and chemical vagotomy produced by atropine treatment. Results 1. No changes were obtained in the cellular energy systems (ATP, ADP, AMP, cAMP, “adenylate pool”, “energy charge“ [(ATP+ 0.5 ADP)/ (ATP+ADP+AMP)] of stomach (glandular part, forestomach) in pylorus ligated rats after surgical vagotomy in contrast to those produced by only chemical vagotomy; 2. The effects of the gastric mucosal protective compounds [atropine, cimetidine, prostaglandins, scavengers (like vitamin A, β-carotene), capsaicin] disappeared after surgical vagotomy; 3. The extents of different chemical agents induced mucosal damaging effects were enhanced by surgical vagotomy and was not altered by chemical vagotomy; 4. The existence of feedback mechanisms of pharmacological (cellular and intracellular) regulatory mechanisms between the membrane-bound ATP-dependent energy systems exists in the gastric mucosa of intact animals, and after chemical vagotomy, but not after surgical vagotomy. Conclusions 1. Increased vagal nerve activity takes place in the gastric mucosal damage; 2 both surgical and chemical vagotomy result mucosal protective affect on the gastric mucosal in different damaging experimental models; 3. The capsaicin-induced gastric mucosal damage depends on the applied doses, presence of anatomically intact vagal nerve (but independent from the chemical vagotomy), 4. The central and pheripheral neural regulations differ during gastric mucosal damage and protection induced by drugs, bioactive compounds, scavengers. PMID:27440445

HIF evaluation of In-Situ Aqua TROLL 400

USGS Publications Warehouse

Tillman, Evan F.

2017-10-18

The In-Situ Aqua TROLL 400 (Aqua TROLL 400) was tested at the U.S. Geological Survey (USGS) Hydrologic Instrumentation Facility (HIF) against known standards over the Aqua TROLL 400’s operating temperature to verify the manufacturer’s stated accuracy specifications and the USGS recommendations for pH, dissolved oxygen (DO), and specific conductance (SC). The Aqua TROLL 400 manufacturer’s specifications are within the USGS recommendations for all parameters tested, except for DO, which is outside the USGS recommendation at DO concentrations of 8.0 milligrams per liter (mg/L) and higher. The Aqua TROLL 400 was compliant with Serial Digital Interface at 1200 baud (SDI-12) version 1.3. During laboratory testing of pH, the Aqua TROLL 400 sonde met the U.S. Geological Survey “National Field Manual for the Collection of Water-Quality Data” (NFM) recommendations for pH at all values tested, except at 4 degrees Celsius (°C) at pH 9.395 and pH 3.998. The Aqua TROLL 400 met the manufacturer specifications for pH at all values tested, except for pH buffers 3.998, 9.395, and 10.245 at 4 °C; pH 2.990 and 3.998 at 15 °C; and pH 3.040 at 40 °C. The Aqua TROLL 400 met the NFM recommendations at 93.7 percent of the SC values tested and met the manufacturer’s accuracy specifications at 56.3 percent of the SC values tested. During the laboratory testing for DO, the Aqua TROLL 400 met the manufacturer specifications, except at 5.55 mg/L, and met the NFM recommendations at all concentrations tested. An Aqua TROLL 400 was field tested at USGS Station 02492620, National Space Technology Laboratories (NSTL) Station, Mississippi, on the Pearl River for 6 weeks and showed good agreement with the well-maintained site sonde data for pH, DO, temperature, and SC.

Time- and concentration-dependent increases in cell proliferation in rats and mice administered vinyl acetate in drinking water.

PubMed

Valentine, Rudolph; Bamberger, J R; Szostek, B; Frame, S R; Hansen, J F; Bogdanffy, M S

2002-06-01

Chronic administration of vinyl acetate (VA) in drinking water to rats and mice has produced upper digestive tract neoplasms. These tumors were believed to arise from the intracellular metabolism of VA by carboxylesterases to cytotoxic and genotoxic compounds. We hypothesized that prolonged VA exposure at high concentrations would induce cytotoxicity and a restorative cell proliferation (CP). These endpoints were measured in F-344 rats and BDF1 mice administered drinking water containing 0, 1000, 5000, 10,000, or 24,000 ppm VA for 92 days. On test days, Days 1, 8, 29, and 92, upper digestive tract histopathology and oral cavity CP (pulsed 5-bromodeoxyuridine [BrdU] to measure S-phase DNA synthesis) were evaluated. Analysis of test solutions showed that VA spontaneously hydrolyzed, slowly releasing acetic acid and thereby lowering pH. Statistically significant, concentration-related increases in CP occurred in basal cells of the mandibular oral cavity mucosa of mice at 10,000 and 24,000 ppm but only after 92 days. CP increases were approximately 2.4- and 3.4-fold above controls and were considered to be toxicologically significant. Some statistically significant increases in CP were also measured in the oral cavity mucosa of rats; however, these changes were considered to be of equivocal biological relevance. No histopathological evidence of mucosal injury was seen in either species. The absence of cytotoxicity in the upper digestive tract mucosa suggests that the increased CP at high administered VA concentrations may be due to a mitogenic response, ostensibly from the loss of cell growth controls in oral cavity mucosa.

Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals

PubMed Central

Bailey, Ryan S.; Casey, Kevin P.; Pawar, Sachin S.; Garcia, Guilherme J. M.

2016-01-01

Importance Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. Objective To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy subjects. Design, Setting, and Participants Twenty-two healthy adults were recruited for this study. Subjects first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale (VAS) to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in two locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Results The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (ΔTexp-insp = 6.2 ± 2.6°C) than during resting breathing (ΔTexp-insp = 4.2 ± 2.3°C) in both locations (p < 10−13). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side VAS score (Pearson r = −0.55, p=0.0076) and NOSE score (Pearson r = −0.47, p=0.028). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower in the first cavity to be measured, which was the right cavity in all subjects. Conclusions and Relevance The greater mucosal temperature oscillations during deep breathing is consistent with the common experience that airflow sensation is enhanced during deep breaths, thus supporting the hypothesis that mucosal cooling plays a central role in nasal airflow sensation. A possible correlation was found between subjective nasal patency scores and nasal mucosal temperature, but our results were inconsistent. The higher temperature in the left cavity suggests that the sensor irritated the nasal mucosa, affecting the correlation between patency scores and mucosal temperature. Future studies should consider non-contact temperature sensors to prevent mucosa irritation. PMID:27918749

HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation

PubMed Central

Heron, Samantha E.; Elahi, Shokrollah

2017-01-01

Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to “inflammaging” that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome. Therefore, unraveling how HIV compromises the integrity of the oral mucosal tissues and innate immune components of the oral cavity and its association with induction of chronic inflammation are critical for the development of effective preventive interventions and therapeutic strategies. PMID:28326084

HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation.

PubMed

Heron, Samantha E; Elahi, Shokrollah

2017-01-01

Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to "inflammaging" that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome. Therefore, unraveling how HIV compromises the integrity of the oral mucosal tissues and innate immune components of the oral cavity and its association with induction of chronic inflammation are critical for the development of effective preventive interventions and therapeutic strategies.

Effects of ε-viniferin, a dehydrodimer of resveratrol, on transepithelial active ion transport and ion permeability in the rat small and large intestinal mucosa.

PubMed

Karaki, Shin-Ichiro; Ishikawa, Junji; Tomizawa, Yuka; Kuwahara, Atsukazu

2016-05-01

ε-Viniferin is a dehydrodimer of resveratrol, a polyphenol synthesized in many plants, including grapevine. The present study investigated the effects of ε-viniferin and resveratrol on epithelial secretory and barrier functions in isolated rat small and large intestinal mucosa. Mucosa-submucosa tissue preparations of various segments of the rat large and small intestines were mounted on Ussing chambers, and short-circuit current (Isc) and tissue conductance (Gt) were continuously measured. The mucosal addition of ε-viniferin (>10(-5) mol/L) and resveratrol (>10(-4) mol/L) to the cecal mucosa, which was the most sensitive region, induced an increase in Isc and a rapid phase decrease (P-1) followed by rapid (P-2) and broad (P-3) peak increases in Gt in concentration-dependent manners. Mucosal ε-viniferin (10(-4) mol/L), but not resveratrol (10(-4) mol/L), increased the permeability of FITC-conjugated dextran (4 kDa). The mucosal ε-viniferin-evoked changes in Isc (Cl(-) secretion), but not in Gt, were attenuated by a selective cyclooxygenase (COX)-1 inhibitor and a selective EP4 prostaglandin receptor. The mucosal ε-viniferin-evoked increase in Isc was partially attenuated, and P-2, but not P-1 or P-3, change in Gt was abolished by a transient receptor potential cation channel, subfamily A, member 1 (TRPA1) inhibitor. Moreover, the mucosal ε-viniferin concentration-dependently attenuated the mucosal propionate (1 mmol/L)-evoked increases in Isc and Gt Immunohistochemical studies revealed COX-1-immunoreactive epithelial cells in the cecal crypt. The present study showed that mucosal ε-viniferin modulated transepithelial ion transport and permeability, possibly by activating sensory epithelial cells expressing COX-1 and TRPA1. Moreover, mucosal ε-viniferin decreased mucosal sensitivity to other luminal molecules such as short-chain fatty acids. In conclusion, these results suggest that ε-viniferin modifies intestinal mucosal transport and barrier functions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

A pilot study of mitochondrial DNA point mutation A3243G in a sample of Croatian patients having type 2 diabetes mellitus associated with maternal inheritance.

PubMed

Martin-Kleiner, I; Pape-Medvidović, E; Pavlić-Renar, I; Metelko, Z; Kusec, R; Gabrilovac, J; Boranić, M

2004-12-01

In this work, patients having type 2 diabetes mellitus and diabetic mothers were tested for the presence of mitochondrial DNA point mutation A3243G. This mutation is associated with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), diabetes and deafness. Twenty-two diabetic persons were screened. DNA was isolated from peripheral blood lymphocytes and from swabs of oral mucosa. The mitochondrial DNA point mutation A3243G was detected using PCR-RFLP test. The mutation was detected in oral mucosal DNA of two patients (but not from lymphocyte DNA). One patient was a man with hearing and visual impairments and proteinuria; the other was a woman having proteinuria but no hearing impairment. The mutation was not detectable in oral mucosal DNA from the control persons: 20 diabetic patients having diabetic fathers and 22 healthy, nondiabetic volunteers. The incidence of mitochondrial DNA point mutation A3243G in this study of Croatian diabetic patients is in line with data in the literature.

Distinct shifts in the oral microbiota are associated with the progression and aggravation of mucositis during radiotherapy.

PubMed

Hou, Jin; Zheng, HuiMin; Li, Pan; Liu, HaiYue; Zhou, HongWei; Yang, XiaoJun

2018-05-04

Oral mucositis remains one of the most common complications of radiation therapy for patients with head and neck cancer. This study aimed to investigate the dynamic shifts in the oral mucosal microbiota and their association with the progression and aggravation of mucositis in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. In this study, oropharyngeal mucosa of patients were examined regularly, and sampled longitudinally in eight stages of their radiation treatment program: before radiation, and then after 10, 20, 30, 40, 50, 60, and 70 Gy. Based on 16S rRNA gene sequencing and bioinformatics analysis, the characteristics of dynamic variations in oral microbiota during their treatment were investigated. The results showed that the mucosal bacterial alpha diversity (richness and evenness) did not change significantly during the entire course of these patient treatments. Notwithstanding 20 genera were found to be significantly positively associated with their radiation dose, whereas 10 genera were negatively associated with it. Notably, two bacterial co-abundance groups (CAG 1 and 2) were identified and the majority of bacteria clustered within the CAG 2 were indeed periodontal disease-associated genera. Most strikingly, many of them, especially Prevotella, Fusobacterium, Treponema and Porphyromonas, showed obvious dynamic synchronous variations in their abundances throughout the course of radiation therapy, where their peaks frequently coincided with the onset of severe mucositis. Our results suggest that dysbiosis of oral mucosal microbiota may contribute to exacerbating the severity of mucositis in patients undergoing radiotherapy for nasopharyngeal carcinoma. Copyright © 2018 Elsevier B.V. All rights reserved.

Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

PubMed Central

Schuetz, Alexandra; Deleage, Claire; Sereti, Irini; Rerknimitr, Rungsun; Phanuphak, Nittaya; Phuang-Ngern, Yuwadee; Estes, Jacob D.; Sandler, Netanya G.; Sukhumvittaya, Suchada; Marovich, Mary; Jongrakthaitae, Surat; Akapirat, Siriwat; Fletscher, James L. K.; Kroon, Eugene; Dewar, Robin; Trichavaroj, Rapee; Chomchey, Nitiya; Douek, Daniel C.; O′Connell, Robert J.; Ngauy, Viseth; Robb, Merlin L.; Phanuphak, Praphan; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat

2014-01-01

Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. PMID:25503054

Multi-scale finite element modeling of Eustachian tube function: influence of mucosal adhesion.

PubMed

Malik, J E; Swarts, J D; Ghadiali, S N

2016-12-01

The inability to open the collapsible Eustachian tube (ET) leads to the development of chronic Otitis Media (OM). Although mucosal inflammation during OM leads to increased mucin gene expression and elevated adhesion forces within the ET lumen, it is not known how changes in mucosal adhesion alter the biomechanical mechanisms of ET function. In this study, we developed a novel multi-scale finite element model of ET function in adults that utilizes adhesion spring elements to simulate changes in mucosal adhesion. Models were created for six adult subjects, and dynamic patterns in muscle contraction were used to simulate the wave-like opening of the ET that occurs during swallowing. Results indicate that ET opening is highly sensitive to the level of mucosal adhesion and that exceeding a critical value of adhesion leads to rapid ET dysfunction. Parameter variation studies and sensitivity analysis indicate that increased mucosal adhesion alters the relative importance of several tissue biomechanical properties. For example, increases in mucosal adhesion reduced the sensitivity of ET function to tensor veli palatini muscle forces but did not alter the insensitivity of ET function to levator veli palatini muscle forces. Interestingly, although changes in cartilage stiffness did not significantly influence ET opening under low adhesion conditions, ET opening was highly sensitive to changes in cartilage stiffness under high adhesion conditions. Therefore, our multi-scale computational models indicate that changes in mucosal adhesion as would occur during inflammatory OM alter the biomechanical mechanisms of ET function. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Mucosal immunogenicity of plant lectins in mice

PubMed Central

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O’Hagan, D T

2000-01-01

The mucosal immunogenicity of a number of plant lectins with different sugar specificities was investigated in mice. Following intranasal (i.n.) or oral administration, the systemic and mucosal antibody responses elicited were compared with those induced by a potent mucosal immunogen (cholera toxin; CT) and a poorly immunogenic protein (ovalbumin; OVA). After three oral or i.n. doses of CT, high levels of specific serum antibodies were measured and specific IgA was detected in the serum, saliva, vaginal wash, nasal wash and gut wash of mice. Immunization with OVA elicited low titres of serum IgG but specific IgA was not detected in mucosal secretions. Both oral and i.n. delivery of all five plant lectins investigated [Viscum album (mistletoe lectin 1; ML‐1), Lycospersicum esculentum (tomato lectin; LEA), Phaseolus vulgaris (PHA), Triticum vulgaris (wheat germ agglutinin (WGA), Ulex europaeus I (UEA‐1)] stimulated the production of specific serum IgG and IgA antibody after three i.n. or oral doses. Immunization with ML‐1 induced high titres of serum IgG and IgA in addition to specific IgA in mucosal secretions. The response to orally delivered ML‐1 was comparable to that induced by CT, although a 10‐fold higher dose was administered. Immunization with LEA also induced high titres of serum IgG, particularly after i.n. delivery. Low specific IgA titres were also detected to LEA in mucosal secretions. Responses to PHA, WGA and UEA‐1 were measured at a relatively low level in the serum, and little or no specific mucosal IgA was detected. PMID:10651938

The effect of honey on mucositis induced by chemoradiation in head and neck cancer.

PubMed

Maiti, Pradip Kumar; Ray, Amitabh; Mitra, Tarak Nath; Jana, Utpal; Bhattacharya, Jibak; Ganguly, Subir

2012-07-01

The aim of this study was to evaluate the effect of pure natural honey on radiation-induced mucositis. Fifty-five patients diagnosed with head and neck cancer requiring radiation to the oropharyngeal mucosal area were divided into two groups (study arm-28 and control arm-27) to receive either chemoradiation or chemoradiation plus topical application of honey. Patients were treated using a telecobalt machine at 2 Gy per day, five times a week up to a total dose of 66 Gy. in the study arm, patients were advised to take 20 ml of honey 15 minutes before, 15 minutes after and similar amount at bed time. Patients were evaluated every week for the development of radiation mucositis using the WHO grading system. There was significant reduction in the symptomatic grades 3 and 4 mucositis in honey-treated patients compared to controls ie, 18% versus 41% for grade 3 and 4% versus 22% for grade 4 mucositis. Seventy-one per cent of patients treated with topical honey showed no change or a positive gain in body weight. In the control group also 22% had no weight loss, though none showed weight gain. Furthermore, it didn't affect blood sugar level when initial fasting blood sugar level was < 150 mg%. Honey is a cheap, simple, easily available and effective agent in reducing radiation-induced mucositis. Within the limits of this study the results showed the application of natural honey is effective in managing radiation induced mucositis, which warrants further multicentric randomised trials to validate the findings.

Effects of n-3 polyunsaturated fatty acids and vitamin E on colonic mucosal leukotriene generation, lipid peroxidation, and microcirculation in rats with experimental colitis.

PubMed

Shimizu, T; Igarashi, J; Ohtuka, Y; Oguchi, S; Kaneko, K; Yamashiro, Y

2001-01-01

We investigated the effect of n-3 polyunsaturated fatty acids (PUFAs) on mucosal levels of leukotrienes (LTs) and lipid peroxide (LPO), and on mucosal microcirculation, in rats with experimental colitis induced by dextran sulfate sodium (DSS). We fed Wistar rats a perilla oil-enriched diet containing alpha-linolenic acid (63.2% of total fatty acids) with various doses of vitamin E for 4 weeks, with 4% DSS added to the drinking water during the last week. Control rats were fed a diet produced from soybean oil containing alpha-linolenic acid (5.1% of total fatty acids). Colonic mucosal blood flow was measured with a laser Doppler flowmeter. The mucosal level of arachidonic acid was significantly lower and that of eicosapentaenoic acid was significantly higher in the experimental group. The mucosal level of LPO in the experimental group fed a trace or ordinary dose of vitamin E was significantly higher than that of the controls. The production of LTB(4) and LTC(4) from the colonic mucosa in the experimental group was significantly lower than that in controls. However, only the experimental group fed a vitamin E dose 4-fold higher than that given to the controls showed a significant increase in mucosal blood flow. These results suggest that n-3 PUFAs increase mucosal blood flow by inhibiting LT production when there is sufficient vitamin E to inhibit lipid peroxidation in rats with experimental colitis. Copyright 2001 S. Karger AG, Basel

New frontiers in mucositis.

PubMed

Peterson, Douglas E; Keefe, Dorothy M; Sonis, Stephen T

2012-01-01

Mucositis is among the most debilitating side effects of radiotherapy, chemotherapy, and targeted anticancer therapy. Research continues to escalate regarding key issues such as etiopathology, incidence and severity across different mucosae, relationships between mucosal and nonmucosal toxicities, and risk factors. This approach is being translated into enhanced management strategies. Recent technology advances provide an important foundation for this continuum. For example, evolution of applied genomics is fostering development of new algorithms to rapidly screen genomewide single-nucleotide polymorphisms (SNPs) for patient-associated risk prediction. This modeling will permit individual tailoring of the most effective, least toxic treatment in the future. The evolution of novel cancer therapeutics is changing the mucositis toxicity profile. These agents can be associated with unique mechanisms of mucosal damage. Additional research is needed to optimally manage toxicity caused by agents such as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors, without reducing antitumor effect. There has similarly been heightened attention across the health professions regarding clinical practice guidelines for mucositis management in the years following the first published guidelines in 2004. New opportunities exist to more effectively interface this collective guideline portfolio by capitalizing upon novel technologies such as an Internet-based Wiki platform. Substantive progress thus continues across many domains associated with mucosal injury in oncology patients. In addition to enhancing oncology patient care, these advances are being integrated into high-impact educational and scientific venues including the National Cancer Institute Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference on mucosal health and disease scheduled for June 2013.

Glutamine prevents oxidative stress in a model of portal hypertension.

PubMed

Zabot, Gilmara Pandolfo; Carvalhal, Gustavo Franco; Marroni, Norma Possa; Licks, Francielli; Hartmann, Renata Minuzzo; da Silva, Vinícius Duval; Fillmann, Henrique Sarubbi

2017-07-07

To evaluate the protective effects of glutamine in a model of portal hypertension (PH) induced by partial portal vein ligation (PPVL). Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum . Twenty-four male Wistar rats were divided into four experimental groups: (1) control group (SO) - rats underwent exploratory laparotomy; (2) control + glutamine group (SO + G) - rats were subjected to laparotomy and were treated intraperitoneally with glutamine; (3) portal hypertension group (PPVL) - rats were subjected to PPVL; and (4) PPVL + glutamine group (PPVL + G) - rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase (GPx), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) after PPVL. Lipid peroxidation of the membrane was increased in the animals subjected to PH ( P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups ( P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH ( P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH ( P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification (44 pixel = 1 μm) were captured. The sum means of all areas, of each group were calculated. The mean areas of eNOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for eNOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group ( P < 0.01). For iNOS, the control (SO) and control + G (SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of iNOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine ( P < 0.01). Treatment with glutamine prevents gut mucosal injury after PH in rats.

Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

ERIC Educational Resources Information Center

Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

2006-01-01

Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

Branch pattern of starch internal structure influences the glucogenesis by mucosal Nt-maltase-glucoamylase

USDA-ARS?s Scientific Manuscript database

To produce sufficient amounts of glucose from food starch, both alpha-amylase and mucosal alpha-glucosidases are required. We found previously that the digestion rate of starch is influenced by its susceptibility to mucosal alpha-glucosidases. In the present study, six starches and one glycogen were...

Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine

USDA-ARS?s Scientific Manuscript database

In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally co-administered with an antigen to pigs. Detoxified E. coli enterotoxins LTK63 and LTR72 enhanced mucosal and systemic immunity to the model peptide, exhibiting their efficacy as mucosal adjuvants for...

Mucosal maltase-glucoamylase plays a crucial role in starch digestion and prandial glucose homeostasis of mice

USDA-ARS?s Scientific Manuscript database

Starch is the major source of food glucose, and its digestion requires small intestinal alpha-glucosidic activities provided by the 2 soluble amylases and 4 enzymes bound to the mucosal surface of enterocytes. Two of these mucosal activities are associated with sucrase-isomaltase complex, while anot...

Unexpected high digestion rate of cooked starch by the Ct-Maltase-Glucoamylase small intestine mucosal alpha-glucosidase subunit

USDA-ARS?s Scientific Manuscript database

For starch digestion to glucose, two luminal alpha-amylases and four gut mucosal alpha-glucosidase subunits are employed. The aim of this research was to investigate, for the first time, direct digestion capability of individual mucosal alpha-glucosidases on cooked (gelatinized) starch. Gelatinized ...

A lumped mucosal wave model of the vocal folds revisited: Recent extensions and oscillation hysteresis

PubMed Central

Lucero, Jorge C.; Koenig, Laura L.; Lourenço, Kelem G.; Ruty, Nicolas; Pelorson, Xavier

2011-01-01

This paper examines an updated version of a lumped mucosal wave model of the vocal fold oscillation during phonation. Threshold values of the subglottal pressure and the mean (DC) glottal airflow for the oscillation onset are determined. Depending on the nonlinear characteristics of the model, an oscillation hysteresis phenomenon may occur, with different values for the oscillation onset and offset threshold. The threshold values depend on the oscillation frequency, but the occurrence of the hysteresis is independent of it. The results are tested against pressure data collected from a mechanical replica of the vocal folds, and oral airflow data collected from speakers producing intervocalic ∕h∕. In the human speech data, observed differences between voice onset and offset may be attributed to variations in voice pitch, with a very small or inexistent hysteresis phenomenon. PMID:21428520

Detection of Leishmania in Unaffected Mucosal Tissues of Patients with Cutaneous Leishmaniasis Caused by Leishmania (Viannia) Species

PubMed Central

Figueroa, Roger Adrian; Lozano, Leyder Elena; Romero, Ibeth Cristina; Cardona, Maria Teresa; Prager, Martin; Pacheco, Robinson; Diaz, Yira Rosalba; Tellez, Jair Alexander; Saravia, Nancy Gore

2016-01-01

Background Leishmania (Viannia) species are the principal cause of mucosal leishmaniasis. The natural history and pathogenesis of mucosal disease are enigmatic. Parasitological evaluation of mucosal tissues has been constrained by the invasiveness of conventional sampling methods. Methods We evaluated the presence ofLeishmania in the mucosa of 26 patients with cutaneous leishmaniasis and 2 patients with mucocutaneous leishmaniasis. Swab samples of the nasal mucosa, tonsils, and conjunctiva were analyzed using polymerase chain reaction with LV-B1 primers and Southern blot hybridization. Results Two patients with mucocutaneous leishmaniasis and 21 (81%) of 26 patients with cutaneous leishmaniasis had Leishmania kinetoplast minicircle DNA (kDNA) in mucosal tissues. kDNA was amplified from swab samples of nasal mucosa from 14 (58%) of 24 patients, tonsils from 13 (46%) of 28 patients, and conjunctiva from 6 (25%) of 24 patients. kDNA was detected in the mucosa of patients with cutaneous disease caused by Leishmania panamensis, Leishmania guyanensis, and Leishmania braziliensis. Conclusion The asymptomatic presence of parasites in mucosal tissues may be common in patients with Leishmania (Viannia) infection. PMID:19569974

Pharmacokinetics of Antiretrovirals in Mucosal Tissue

PubMed Central

Cottrell, M.L.; Srinivas, N.; Kashuba, A.D.M.

2015-01-01

Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

Irinotecan-induced mucositis: the interactions and potential role of GLP-2 analogues.

PubMed

Mayo, Bronwen J; Stringer, Andrea M; Bowen, Joanne M; Bateman, Emma H; Keefe, Dorothy M

2017-02-01

A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention. This is a review of current literature on irinotecan-induced mucositis and GLP-2 analogues mechanisms of action. Recent studies have found alterations that appear to be crucial in the development of severe intestinal mucositis, including early apoptosis, alterations in proliferation and cell survival pathways, as well as induction of inflammatory cascades. Several studies have indicated a possible role for glucagon-like peptide-2 analogues in treating this toxicity, due to its proven intestinotrophic, anti-apoptotic and anti-inflammatory effects in other models of gastrointestinal disease. This review provides evidence as to why and how this treatment may improve mucositis through the possible molecular crosstalk that may be occurring in models of severe intestinal mucositis.

Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

PubMed Central

Keller, Marla J.; Carpenter, Colleen A.; Lo, Yungtai; Einstein, Mark H.; Liu, Congzhou; Fredricks, David N.; Herold, Betsy C.

2012-01-01

Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. Results The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). Conclusions Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels of antimicrobial (lactoferrin) and anti-inflammatory (IL-1ra) proteins. These findings indicate the need for additional safety studies of this candidate non-hormonal contraceptive. Trial Registration ClinicalTrials.gov NCT00850837 PMID:23056520

Microbiota Separation and C-reactive protein Elevation in Treatment Naïve Pediatric Granulomatous Crohn Disease

PubMed Central

Kellermayer, Richard; Mir, Sabina A. V.; Nagy-Szakal, Dorottya; Cox, Stephen B.; Dowd, Scot E.; Kaplan, Jess L.; Sun, Yan; Reddy, Sahna; Bronsky, Jiri; Winter, Harland S.

2012-01-01

Objectives In patients with inflammatory bowel diseases (IBD), the presence of non-caseating mucosal granuloma is sufficient for diagnosing Crohn disease (CD) and may represent a specific immune response or microbial-host interaction. The cause of granulomas in CD is unknown and their association with the intestinal microbiota has not been addressed with high-throughput methodologies. Methods The mucosal microbiota from three different pediatric centers was studied with 454 pyrosequencing of the bacterial 16S rRNA gene and the fungal small subunit (SSU) ribosomal region in transverse colonic biopsy specimens from 26 controls and 15 treatment naïve pediatric CD cases. Mycobacterium avium subspecies paratuberculosis (MAP) was tested with real-time PCR. The correlation of granulomatous inflammation with C-reactive protein (CRP) was expanded to 86 treatment naïve CD cases. Results The CD microbiota separated from controls by distance based redundancy analysis (dbRDA; p=0.035). Mucosal granulomata found in any portion of the intestinal tract associated with an augmented colonic bacterial microbiota divergence (p=0.013). The granuloma based microbiota separation persisted even when research center bias was eliminated (p=0.04). Decreased Roseburia and Ruminococcus in granulomatous CD were important in this separation. However, principal coordinates analysis (PCoA) did not reveal partitioning of the groups. CRP levels above 1mg/dl predicted the presence of mucosal granulomata (OR: 28 [6–134.32]; 73% sensitivity, 91% specificity). Conclusions Granulomatous CD associates with microbiota separation and CRP elevation in treatment naïve children. However, overall dysbiosis in pediatric CD appears rather limited. Geographical/center bias should be accounted for in future multi-center microbiota studies. PMID:22699834

Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene.

PubMed

Goupil, Mathieu; Cousineau-Côté, Vincent; Aumont, Francine; Sénéchal, Serge; Gaboury, Louis; Hanna, Zaher; Jolicoeur, Paul; de Repentigny, Louis

2014-10-26

The tissue-signaling cytokines IL-17 and IL-22 are critical to host defense against oral Candida albicans infection, by their induction of oral antimicrobial peptide expression and recruitment of neutrophils. Mucosal Th17 cells which produce these cytokines are preferentially depleted in HIV-infected patients. Here, we tested the hypothesis that defective IL-17- and IL-22-dependent host responses to C. albicans determine the phenotype of susceptibility to oropharyngeal candidiasis (OPC) in transgenic (Tg) mice expressing HIV-1. Naïve CD4+ T-cells and the differentiated Th1, Th2, Th17, Th1Th17 and Treg lineages were all profoundly depleted in cervical lymph nodes (CLNs) of these Tg mice. However, naive CD4+ cells from Tg mice maintained the capacity to differentiate into these lineages in response to polarizing cytokines in vitro. Expression of Il17, Il22, S100a8 and Ccl20 was enhanced in oral mucosal tissue of non-Tg, but not of Tg mice, after oral infection with C. albicans. Treatment of infected Tg mice with the combination of IL-17 and IL-22, but not IL-17 or Il-22 alone, significantly reduced oral burdens of C. albicans and abundance of Candida hyphae in the epithelium of tongues of infected Tg mice, and restored the ability of the Tg mice to up-regulate expression of S100a8 and Ccl20 in response to C. albicans infection. These findings demonstrate that defective IL-17- and IL-22-dependent induction of innate mucosal immunity to C. albicans is central to the phenotype of susceptibility to OPC in these HIV transgenic mice.

Classification of atrophic mucosal patterns on Blue LASER Imaging for endoscopic diagnosis of Helicobacter pylori-related gastritis: A retrospective, observational study.

PubMed

Nishikawa, Yoshiyuki; Ikeda, Yoshio; Murakami, Hidehiro; Hori, Shin-Ichiro; Hino, Kaori; Sasaki, Chise; Nishikawa, Megumi

2018-01-01

Atrophic gastritis can be classified according to characteristic mucosal patterns observed by Blue LASER Imaging (BLI) in a medium-range to distant view. To facilitate the endoscopic diagnosis of Helicobacter pylori (HP)-related gastritis, we investigated whether atrophic mucosal patterns correlated with HP infection based on the image interpretations of three endoscopists blinded to clinical features. This study included 441 patients diagnosed as having atrophic gastritis by upper gastrointestinal endoscopy at Nishikawa Gastrointestinal Clinic between April 1, 2015 and March 31, 2016. The presence/absence of HP infection was not taken into consideration. Endoscopy was performed using a Fujifilm EG-L580NW scope. Atrophic mucosal patterns observed by BLI were classified into Spotty, Cracked and Mottled. Image interpretation results were that 89, 122 and 228 patients had the Spotty, Cracked and Mottled patterns, respectively, and 2 patients an undetermined pattern. Further analyses were performed on 439 patients, excluding the 2 with undetermined patterns. The numbers of patients testing negative/positive for HP infection in the Spotty, Cracked and Mottled pattern groups were 12/77, 105/17, and 138/90, respectively. The specificity, positive predictive value and positive likelihood ratio for endoscopic diagnosis with positive HP infection based on the Spotty pattern were 95.3%, 86.5% and 8.9, respectively. In all patients with the Spotty pattern before HP eradication, the Cracked pattern was observed on subsequent post-eradication endoscopy. The Spotty pattern may represent the presence of HP infection, the Cracked pattern, a post-inflammatory change as seen after HP eradication, and the Mottled pattern, intestinal metaplasia.

Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1.

PubMed

Daniel, C; Repa, A; Wild, C; Pollak, A; Pot, B; Breiteneder, H; Wiedermann, U; Mercenier, A

2006-07-01

Probiotic lactic acid bacteria (LAB) are able to modulate the host immune system and clinical trials have demonstrated that specific strains have the capacity to reduce allergic symptoms. Therefore, we aimed to evaluate the potential of recombinant LAB producing the major birch pollen allergen Bet v 1 for mucosal vaccination against birch pollen allergy. Recombinant Bet v 1-producing Lactobacillus plantarum and Lactococcus lactis strains were constructed. Their immunogenicity was compared with purified Bet v 1 by subcutaneous immunization of mice. Intranasal application of the live recombinant strains was performed to test their immunomodulatory potency in a mouse model of birch pollen allergy. Bet v 1 produced by the LAB was recognized by monoclonal anti-Bet v 1 and IgE antibodies from birch pollen-allergic patients. Systemic immunization with the recombinant strains induced significantly lower IgG1/IgG2a ratios compared with purified Bet v 1. Intranasal pretreatment led to reduced allergen-specific IgE vs enhanced IgG2a levels and reduced interleukin (IL)-5 production of splenocytes in vitro, indicating a shift towards non-allergic T-helper-1 (Th1) responses. Airway inflammation, i.e. eosinophils and IL-5 in lung lavages, was reduced using either Bet v 1-producing or control strains. Allergen-specific secretory IgA responses were enhanced in lungs and intestines after pretreatment with only the Bet v 1-producing strains. Mucosal vaccination with live recombinant LAB, leading to a shift towards non-allergic immune responses along with enhanced allergen-specific mucosal IgA levels offers a promising approach to prevent systemic and local allergic immune responses.