Salivary agglutinin/DMBT1SAG expression is up-regulated in the presence of salivary gland tumors

DEFF Research Database (Denmark)

Bikker, F J; van der Wal, J E; Ligtenberg, A J M

2004-01-01

Salivary agglutinin (SAG) is encoded by the gene Deleted in Malignant Brain Tumors 1 (DMBT1) and represents the salivary variant of DMBT1 (DMBT1(SAG)). While SAG is a bona fide anti-caries factor, DMBT1 was proposed as a candidate tumor-suppressor for brain, digestive tract, and lung cancer. Thou...

DMBT1 promotes basal and meconium-induced nitric oxide production in human lung epithelial cells in vitro

DEFF Research Database (Denmark)

Müller, Hanna; Weiss, Christel; Renner, Marcus

2017-01-01

Meconium aspiration syndrome (MAS) is characterized by surfactant inactivation and inflammation. As lung epithelial cells up-regulate nitric oxide (NO) in response to inflammation, the NO production following meconium exposition was examined in relation to expression of Deleted in Malignant Brain...... NO production than the DMBT1- cells (p = 0.0090). Meconium led in DMBT1- and DMBT1+ cells to elevated NO levels (p production in DMBT1+ cells (p = 0.0476), but NO levels remained above...... NO production from DMBT1- cells (p = 0.0289). Dexamethasone diminished NO production in DMBT1+ cells after meconium exposition (p = 0.0076). Combined addition of LPS and meconium significantly increased NO production in both cell types (p

Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells

DEFF Research Database (Denmark)

Müller, Hanna; Nagel, Christian; Weiss, Christel

2015-01-01

between VEGF and IL-6 levels to DMBT1 expression in the lungs of preterm and term infants and in lung epithelial cells in vitro. METHODS: We examined by ELISA VEGF levels in 120 tracheal aspirates of 57 preterm and term infants and tested for correlation with different perinatal factors as well...... as with DMBT1 levels. To examine the effect of DMBT1 on VEGF and IL-6 expression we compared type II lung epithelial A549 cells stably transfected with a DMBT1 expression plasmid (DMBT1+ cells) to A549 cells stably transfected with an empty expression plasmid (DMBT1- cells). The concentrations of VEGF and IL-6...... that DMBT1 promotes VEGF and suppresses IL-6 production in alveolar tissues, which could point to DMBT1 having a possible role in the transition from inflammation to regeneration and being a potentially useful clinical marker....

Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

DEFF Research Database (Denmark)

Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

2010-01-01

,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

An integrative model on the role of DMBT1 in epithelial cancer

DEFF Research Database (Denmark)

Mollenhauer, Jan; Helmke, Burkhard; Müller, Hanna

2002-01-01

The gene, deleted in malignant brain tumors 1 (DMBT1), has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumor suppressor gene. We have proposed that its presumptive dual function in protection and differentiation is of importance to under......The gene, deleted in malignant brain tumors 1 (DMBT1), has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumor suppressor gene. We have proposed that its presumptive dual function in protection and differentiation is of importance...... displayed presumable mutations. However, none of the alterations would be predicted to lead to a complete inactivation of the gene. DMBT1 is mucin-like and shows tissue-specific expression and secretion, pointing to a function in the protection of monolayered epithelia and to an additional function...... in the differentiation of multilayered epithelia. The expression patterns in carcinomas arising from the respective structures support this view. Accepting this functional dualism gives rise to an initial model on the role of DMBT1 in epithelial cancer....

Homozygous deletion and expression of PTEN and DMBT1 in human primary neuroblastoma and cell lines.

Science.gov (United States)

Muñoz, Jorge; Lázcoz, Paula; Inda, María Mar; Nistal, Manuel; Pestaña, Angel; Encío, Ignacio J; Castresana, Javier S

2004-05-01

Neuroblastoma is the most common pediatric solid tumor. Although many allelic imbalances have been described, a bona fide tumor suppressor gene for this disease has not been found yet. In our study, we analyzed 2 genes, PTEN and DMBT1, mapping 10q23.31 and 10q25.3-26.1, respectively, which have been found frequently altered in other kinds of neoplasms. We screened both genes for homozygous deletions in 45 primary neuroblastic tumors and 12 neuroblastoma cell lines. Expression of these genes in cell lines was assessed by RT-PCR analysis. We could detect 2 of 41 (5%) primary tumors harboring PTEN homozygous deletions. Three of 41 (7%) primary tumors and 2 of 12 cell lines presented homozygous losses at the g14 STS on the DMBT1 locus. All cell lines analyzed expressed PTEN, but lack of DMBT1 mRNA expression was detected in 2 of them. We tried to see whether epigenetic mechanisms, such as aberrant promoter hypermethylation, had any role in DMBT1 silencing. The 2 cell lines lacking DMBT1 expression were treated with 5-aza-2'-deoxycytidine; DMBT1 expression was restored in only one of them (MC-IXC). From our work, we can conclude that PTEN and DMBT1 seem to contribute to the development of a small fraction of neuroblastomas, and that promoter hypermethylation might have a role in DMBT1 gene silencing. Copyright 2004 Wiley-Liss, Inc.

PTEN and DMBT1 homozygous deletion and expression in medulloblastomas and supratentorial primitive neuroectodermal tumors.

Science.gov (United States)

Inda, María Mar; Mercapide, Javier; Muñoz, Jorge; Coullin, Philippe; Danglot, Giséle; Tuñon, Teresa; Martínez-Peñuela, José María; Rivera, José María; Burgos, Juan J; Bernheim, Alain; Castresana, Javier S

2004-12-01

Medulloblastoma, which accounts for 20-25% of all childhood brain tumors, is defined as a primitive neuroectodermal tumor (PNET) located in the cerebellum. Supratentorial PNET are less frequent than medulloblastoma. But their clinical outcome is worse than in medulloblastomas. Chromosome 10q contains at least 2 tumor suppressor genes that might play a role in brain tumor development: PTEN and DMBT1. The aim of this study was to compare the status of homozygous deletion and expression of PTEN and DMBT1 genes in PNET primary tumor samples and cell lines. Homozygous deletions of PTEN and DMBT1 were studied in 32 paraffin-embedded PNET samples (23 medulloblastomas and 9 supratentorial PNET) and in 7 PNET cell lines, by differential PCR and by FISH. PTEN homozygous losses were demonstrated in 7 medulloblastomas (32%) and in no supratentorial PNET, while homozygous deletions of DMBT1 appeared in 1 supratentorial PNET (20%) and in 7 medulloblastomas (33%). No homozygous deletion of PTEN or DMBT1 was detected in any of the PNET cell lines either by differential PCR or by FISH. Expression study of the 2 genes was performed in the 7 PNET cell lines by RT-PCR. One PNET cell line lacked PTEN and DMBT1 expression, while 2 medulloblastoma cell lines did not express DMBT1. Our results add some positive data to the hypothesis that supratentorial PNETs and medulloblastomas might be genetically different.

DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands

NARCIS (Netherlands)

End, C.; Bikker, F.J.; Renner, M.; Bergmann, G.; Lyer, S.; Blaich, S.; Hudler, M.; Helmke, B.; Gassler, N.; Autschbach, F.; Ligtenberg, A.J.M.; Benner, A.; Holmskov, U.; Schirmacher, P.; Nieuw Amerongen, A.V.; Rosenstiel, P.; Sina, C.; Franke, A.; Hafner, M.; Kioschis, P.; Schreiber, S.; Poustka, A.; Mollenhauer, J.

2009-01-01

Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-kappaB activation and to the pathogenesis of Crohn's disease. Here, we aimed at

DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands

NARCIS (Netherlands)

End, C.; Bikker, F.; Renner, M.; Bergmann, G.; Lyer, S.; Blaich, S.; Hudler, M.; Helmke, B.; Gassler, N.; Autschbach, F.; Ligtenberg, A.J.M.; Benner, A.; Holmskov, U.; Schirmacher, P.; Nieuw Amerongen, A.V.; Rosenstiel, P.; Sina, C.; Franke, A.; Hafner, A.; Kioschis, P.; Schreiber, S.; Poustka, A.; Mollenhauer, J.

2009-01-01

Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-κB activation and to the pathogenesis of Crohn's disease. Here, we aimed at

Deleted in malignant brain tumour 1 (DMBT1) is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

DEFF Research Database (Denmark)

Ambruosi, Barbara; Accogli, Gianluca; Douet, Cecile

2013-01-01

fertilization rate, and that this effect is cancelled by the addition of antibodies, in both porcine and equine species. Moreover, pre-incubation of oocytes with recombinant DMBT1 induces an increase of the monospermic fertilization rate in the pig, confirming an involvement of DMBT1 in the fertilization...... allowed us to identify the DMBT1 protein as well as a DMBT1-like protein in several mammals. Our results strongly suggest an important role of DMBT1 in the process of fertilization.......Oviductal environment affects preparation of gametes for fertilization, fertilization itself, and the subsequent embryo development. The aim of this study is to evaluate the effect of oviductal fluid and the possible involvement of Deleted in Malignant Brain Tumours 1 (DMBT1) on in vitro...

DMBT1 encodes a protein involved in the immune defense and in epithelial differentiation and is highly unstable in cancer

DEFF Research Database (Denmark)

Mollenhauer, J; Herbertz, S; Holmskov, U

2000-01-01

in the respiratory immune defense. Immunohistochemical analyses revealed that DMBT1 is produced by both tumor-associated macrophages and tumor cells and that it is deregulated in glioblastoma multiforme in comparison to normal brain tissue. Our data further suggest that the proteins CRP-ductin and hensin, both...... of which have been implicated in epithelial differentiation, are the DMBT1 orthologs in mice and rabbits, respectively. These findings and the spatial and temporal distribution of DMBT1 in fetal and adult epithelia suggest that DMBT1 further plays a role in epithelial development. Rearrangements of DMBT1......, DMBT1 is a gene that is highly unstable in cancer and encodes for a protein with at least two different functions, one in the immune defense and a second one in epithelial differentiation....

DMBT1 expression is down-regulated in breast cancer

DEFF Research Database (Denmark)

Braidotti, P; Nuciforo, P G; Mollenhauer, J

2004-01-01

and hyperplastic mammary cells positive with DMBTh12 were also MCM5-positive. CONCLUSIONS: The redistribution and up-regulation of DMBT1 in normal and hyperplastic tissues flanking malignant tumours and its down-regulation in carcinomas suggests a potential role in breast cancer. Moreover, the concomitant......BACKGROUND: We studied the expression of DMBT1 (deleted in malignant brain tumor 1), a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle. METHODS: Sections from 17 benign lesions and 55 carcinomas were immunostained...... expression was down-regulated in the cancerous lesions compared to the normal and/or hyperplastic epithelium adjacent to carcinomas (3/55 positive carcinomas versus 33/42 positive normal/hyperplastic epithelia; p = 0.0001). In 72% of cases RT-PCR confirmed immunohistochemical results. Most of normal...

Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant

DEFF Research Database (Denmark)

Müller, Hanna; End, Caroline; Renner, Marcus

2007-01-01

BACKGROUND: Deleted in Malignant Brain Tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome...

DMBT1 is frequently downregulated in well-differentiated gastric carcinoma but more frequently upregulated across various gastric cancer types

DEFF Research Database (Denmark)

Conde, Ana R; Martins, Ana P; Brito, Miguel

2007-01-01

in cell differentiation and protection and has been proposed as a candidate tumour suppressor for brain and epithelial cancer. One study reported a loss of DMBT1 expression in 12.5% (5/40) of gastric cancer samples. Here, we examined in more detail DMBT1 protein and mRNA expression in 78 primary gastric...... preferentially take place in well-differentiated gastric carcinoma. However, an upregulation of DMBT1 expression is more frequently found across all gastric cancer types.......Well-differentiated gastric carcinomas are considered to represent a distinct entity emerging via specific molecular changes different from those found in other gastric carcinoma types. The gene deleted in malignant brain tumours 1 (DMBT1) at 10q25.3-q26.1 codes for a protein presumably involved...

Molecular characterization of the porcine deleted in malignant brain tumors 1 gene (DMBT1)

DEFF Research Database (Denmark)

Haase, Bianca; Humphray, Sean J; Lyer, Stefan

2006-01-01

The human gene deleted in malignant brain tumors 1 (DMBT1) is considered to play a role in tumorigenesis and pathogen defense. It encodes a protein with multiple scavenger receptor cysteine-rich (SRCR) domains, which are involved in recognition and binding of a broad spectrum of bacterial pathogens...

Cardiac amyloidosis induces up-regulation of Deleted in Malignant Brain Tumors 1 (DMBT1)

DEFF Research Database (Denmark)

Müller, Hanna; Renner, Marcus; Bergmann, Frank

2013-01-01

Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense compo...... components, i.e., Deleted in Malignant Brain Tumors 1 (DMBT1) and the complement system, in different types of cardiac amyloidosis....

Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis

DEFF Research Database (Denmark)

Kaemmerer, Elke; Schneider, Ursula; Klaus, Christina

2012-01-01

Kaemmerer E, Schneider U, Klaus C, Plum P, Reinartz A, Adolf M, Renner M, Wolfs T G A M, Kramer B W, Wagner N, Mollenhauer J & Gassler N (2012) Histopathology Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis Aims:  Deleted in malignant brain...

The SRCR/SID region of DMBT1 defines a complex multi-allele system representing the major basis for its variability in cancer

DEFF Research Database (Denmark)

Mollenhauer, Jan; Müller, Hanna; Kollender, Gaby

2002-01-01

Deleted in malignant brain tumors 1 (DMBT1) at 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain and epithelial cancer. DMBT1 encodes a multifunctional mucin-like protein presumably involved in epithelial differentiation and protection. The gene consists of highly...... homologous and repeating exon and intron sequences. This specifically applies to the region coding for the repetitive scavenger receptor cysteine-rich (SRCR) domains and SRCR-interspersed domains (SIDs) that constitutes the major part of the gene. This particular structure may previously have interfered...... with the delineation of DMBT1 alterations in cancer. Uncovering these, however, is of mechanistic importance. By a combined approach, we conducted a detailed mutational analysis, starting from a panel of 51 tumors, including 46 tumor cell lines and five primary tumors. Alterations in the repetitive region were present...

A variant form of the human deleted in malignant brain tumor 1 (DMBT1 gene shows increased expression in inflammatory bowel diseases and interacts with dimeric trefoil factor 3 (TFF3.

Directory of Open Access Journals (Sweden)

Jens Madsen

Full Text Available The protein deleted in malignant brain tumors (DMBT1 and the trefoil factor (TFF proteins have all been proposed to have roles in epithelial cell growth and cell differentiation and shown to be up regulated in inflammatory bowel diseases. A panel of monoclonal antibodies was raised against human DMBT1(gp340. Analysis of lung washings and colon tissue extracts by Western blotting in the unreduced state, two antibodies (Hyb213-1 and Hyb213-6 reacted with a double band of 290 kDa in lung lavage. Hyb213-6, in addition, reacted against a double band of 270 kDa in colon extract while Hyb213-1 showed no reaction. Hyb213-6 showed strong cytoplasmic staining in epithelial cells of both the small and large intestine whereas no staining was seen with Hyb213-1. The number of DMBT1(gp340 positive epithelial cells, stained with Hyb213-6, was significantly up regulated in inflammatory colon tissue sections from patients with ulcerative colitis (p<0.0001 and Crohn's disease (p = 0.006 compared to normal colon tissue. Immunohistochemical analysis of trefoil factor TFF1, 2 and 3 showed that TFF1 and 3 localized to goblet cells in both normal colon tissue and in tissue from patients with ulcerative colitis or Crohn's disease. No staining for TFF2 was seen in goblet cells in normal colon tissue whereas the majority of tissue sections in ulcerative colitis and Crohn's disease showed sparse and scattered TFF2 positive goblet cells. DMBT1 and TFF proteins did therefore not co-localize in the same cells but localized in adjacent cells in the colon. The interaction between DMBT1(gp340 and trefoil TFFs proteins was investigated using an ELISA assay. DMBT1(gp340 bound to solid-phase bound recombinant dimeric TFF3 in a calcium dependent manner (p<0.0001 but did not bind to recombinant forms of monomeric TFF3, TFF2 or glycosylated TFF2. This implies a role for DMBT1 and TFF3 together in inflammatory bowel disease.

Identification of the bacteria-binding peptide domain on salivary agglutinin (gp-340/DMBT1), a member of the scavenger receptor cysteine-rich superfamily

DEFF Research Database (Denmark)

Bikker, Floris J; Ligtenberg, Antoon J M; Nazmi, Kamran

2002-01-01

Salivary agglutinin is encoded by DMBT1 and identical to gp-340, a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Salivary agglutinin/DMBT1 is known for its Streptococcus mutans agglutinating properties. This 300-400 kDa glycoprotein is composed of conserved peptide motifs: 14...... containing exclusively SRCR and SID domains that binds to S. mutans. To define more closely the S. mutans-binding domain, consensus-based peptides of the SRCR domains and SIDs were designed and synthesized. Only one of the SRCR peptides, designated SRCRP2, and none of the SID peptides bound to S. mutans....... Strikingly, this peptide was also able to induce agglutination of S. mutans and a number of other bacteria. The repeated presence of this peptide in the native molecule endows agglutinin/DMBT1 with a general bacterial binding feature with a multivalent character. Moreover, our studies demonstrate...

Human DMBT1-Derived Cell-Penetrating Peptides for Intracellular siRNA Delivery

DEFF Research Database (Denmark)

Tuttolomondo, Martina; Casella, Cinzia; Hansen, Pernille Lund

2017-01-01

tumor 1) is a pattern recognition molecule that interacts with polyanions and recognizes and aggregates bacteria. Taking advantage of these properties, we investigated whether specific synthetic DMBT1-derived peptides could be used to formulate nanoparticles for siRNA administration. Using......-potential, circular dichroism, dynamic light scattering, and transmission electron microscopy revealed negatively charged nanoparticles with an average diameter of 10-800 nm, depending on the reaction conditions, and a spherical or rice-shaped morphology, depending on the peptide and β-helix conformation. We...

The pattern recognition molecule deleted in malignant brain tumors 1 (DMBT1) and synthetic mimics inhibit liposomal nucleic acid delivery

DEFF Research Database (Denmark)

Lund Hansen, Pernille; Blaich, Stephanie; End, Caroline

2011-01-01

Liposomal nucleic acid delivery is a preferred option for therapeutic settings. The cellular pattern recognition molecule DMBT1, secreted at high levels in various diseases, and synthetic mimics efficiently inhibit liposomal nucleic acid delivery to human cells. These findings may have relevance...

SU-F-T-30: Comprehensive Dosimetric Characterization of the Novel Direction Modulation Brachytherapy (DMBT) Tandem Applicator Using Monte Carlo Simulations

Energy Technology Data Exchange (ETDEWEB)

Safigholi, H; Mashouf, S; Soliman, Abraam; Owrangi, A; Song, W Y [Deprtment of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Han, D [Deprtment of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Department of Radiation Oncology, University of California San Francisco, San Francisco, CA (United States)

2016-06-15

Purpose: To characterize the dosimetric properties/distributions of the novel proposed direction modulated brachytherapy (DMBT) tandem applicator in combination with 192Ir HDR source, and compare against conventional tandem design, using Monte Carlo simulations. Methods: The proposed DMBT tandem applicator is designed for image-guided adaptive brachytherapy, especially MRI, of cervical cancer. It has 6 peripheral holes of 1.3-mm width, grooved along a 5.4-mm diameter nonmagnetic tungsten alloy rod of density 18.0 g/cc, capable of generating directional dose profiles – leading to enhanced dose sculpting capacity through inverse planning. In-water dosimetric parameters for the DMBT and conventional tandems have been calculated for various radial distances away and around the tandems. For the DMBT tandem, the cumulative dose from the 192Ir source occupying 1) one and 2) all six holes in equal dwell times was calculated and normalized to match the dose rate of the open source (in conventional tandem) at 1 cm from the center. This is done to compare and contrast the characteristic dose distributions to that of the isotropic TG43-based 192Ir source. Results: All dose rates were normalized at 1-cm radius from the center of the applicators, containing source(s). The normalized dose rates at 0.5, 3.0, and 5.0-cm radiuses were then 388, 11.3, and 4.1% for conventional tandem, 657, 8.1, and 2.7% for DMBT tandem with the source in one hole at front entrance, and 436, 10.9, and 3.8% for DMBT tandem with the source in all six holes. For the DMBT tandem case with the source in one hole, the backside transmissions were 47, 2.4, and 0.9%, respectively. Conclusion: The DMBT tandem is able to generate closely similar dosimetric characteristics as that of the single-channel conventional tandem if needed (with the source occupying all six holes), at the same time, generate directional radiation profile(s) for favorably enabling 3D dose sculpting capability.

DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours

DEFF Research Database (Denmark)

Mollenhauer, J; Wiemann, S; Scheurlen, W

1997-01-01

Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80% of the tumo......Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80....... Intragenic homozygous deletions has been detected in 2/20 medulloblastomas and in 9/39 glioblastomas multiformes. Lack of DMBT1 expression has been demonstrated in 4/5 brain-tumour cell lines. We suggest that DMBT1 is a putative tumour-suppressor gene implicated in the carcinogenesis of medulloblastoma...

High DMBT1 concentrations in breast milk correlate with increased risk of infection in preterm and term neonates

DEFF Research Database (Denmark)

Ronellenfitsch, Sebastian; Weiß, Christel; Frommhold, David

2012-01-01

by Western blotting and its concentration was quantified by ELISA in 95 breast milk samples collected from mothers of preterm and term neonates during the first four weeks after delivery. Possible effects of maternal or neonatal parameters were analyzed by different statistical tests. Results: The mean DMBT1...

SU-G-201-11: Exploring the Upper Limits of Dose Sculpting Capacity of the Novel Direction Modulated Brachytherapy (DMBT) Tandem Applicator

International Nuclear Information System (INIS)

Han, D; Safigholi, H; Soliman, A; Song, W

2016-01-01

Purpose: To explore and quantify the upper limits in dose sculpting capacity of the novel direction modulated brachytherapy (DMBT) tandem applicator compared with conventional tandem design for "1"9"2Ir-based HDR planning. Methods: The proposed DMBT tandem applicator is designed for image-guided adaptive brachytherapy (IGABT), especially MRI, of cervical cancer. It has 6 peripheral holes of 1.3-mm width, grooved along a 5.4-mm diameter nonmagnetic tungsten alloy rod of density 18.0 g/cc, capable of generating directional dose profiles – leading to enhanced dose sculpting capacity through inverse planning. The external dimensions are identical to that of conventional tandem design to ensure clinical compatibility. To explore the expansive dose sculpting capacity, we constructed a hypothetical circular target with 20-mm radius and positioned the DMBT and conventional tandems at the center. We then incrementally shifted the positions laterally away from the center of up to 15 mm, at 1-mm steps. The in-house coded gradient projection-based inverse planning system was then used to generate inverse optimized plans ensuring identical V100=100% coverage. Conformity index (CI) was calculated for all plans. Results: Overall, the DMBT tandem generates more conformal dose distributions than conventional tandem for all lateral positional shifts of 0-15 mm (CI=0.91–0.52 and 0.99–0.34, respectively), with an exception at the central position due to the ideal circular dose distribution, generated by the "1"9"2Ir, fitting tightly around the circular target (CI = 0.91 and 0.99, respectively). The DMBT tandem is able to generate dose conformity of CI>0.8 at up to 6-mm positional shift while the conventional tandem violates this past 2-mm shift. Also, the CI ratio (=DMBT/conv.) increases rapidly until about 8 mm and then stabilizes beyond. Conclusion: A substantial enhancement in the dose sculpting capacity has been demonstrated for the novel DMBT tandem applicator. While

Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis.

Science.gov (United States)

Chen, Chun-Yuan; Rao, Shan-Shan; Ren, Lu; Hu, Xiong-Ke; Tan, Yi-Juan; Hu, Yin; Luo, Juan; Liu, Yi-Wei; Yin, Hao; Huang, Jie; Cao, Jia; Wang, Zhen-Xing; Liu, Zheng-Zhao; Liu, Hao-Ming; Tang, Si-Yuan; Xu, Ran; Xie, Hui

2018-01-01

Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism. Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses. USC-Exos were isolated from the conditioned media of USCs and identified by transmission electron microscopy and flow cytometry. A series of functional assays in vitro were performed to assess the effects of USC-Exos on the activities of wound healing-related cells. Protein profiles in USC-Exos and USCs were examined to screen the candidate molecules that mediate USC-Exos function. The effects of USC-Exos on wound healing in streptozotocin-induced diabetic mice were tested by measuring wound closure rates, histological and immunofluorescence analyses. Meanwhile, the role of the candidate protein in USC-Exos-induced regulation of angiogenic activities of endothelial cells and diabetic wound healing was assessed. Results: USCs were positive for CD29, CD44, CD73 and CD90, but negative for CD34 and CD45. USCs were able to differentiate into osteoblasts, adipocytes and chondrocytes. USC-Exos exhibited a cup- or sphere-shaped morphology with a mean diameter of 51.57 ± 2.93 nm and positive for CD63 and TSG101. USC-Exos could augment the functional properties of wound healing-related cells including the angiogenic activities of endothelial cells. USC-Exos were enriched in the proteins that are involved in regulation of wound healing-related biological processes. Particularly, a pro-angiogenic protein called deleted in malignant brain tumors 1 (DMBT1) was highly expressed in USC-Exos. Further functional assays showed that DMBT1 protein was required for USC

Site-characteristic expression and induction of trefoil factor family 1, 2 and 3 and malignant brain tumor-1 in normal and diseased intrahepatic bile ducts relates to biliary pathophysiology

DEFF Research Database (Denmark)

Sasaki, Motoko; Tsuneyama, Koichi; Saito, Takahito

2004-01-01

BACKGROUND/AIM: Trefoil factor family (TFF)1,2,3 are involved in a homeostasis/repair process of mucosal epithelia. In this study, the significance of TFF family and deleted in the malignant brain tumor-1 (DMBT1), a putative receptor of TFF2, in the intrahepatic biliary tree was investigated...

One-step FPLC-size-exclusion chromatography procedure for purification of rDMBT1 6 kb with increased biological activity

DEFF Research Database (Denmark)

Tuttolomondo, Martina; Hansen, Pernille Lund; Mollenhauer, Jan

2018-01-01

from saliva or produced in vitro and purified by a multistep affinity purification procedure using bacteria, followed by FPLC. Here, we compared a simple, one-step FPLC-SEC protocol for purification of recombinant DMBT1 6 kb, with that of the standard bacteria affinity purification-based protocol. Our...

SU-G-201-11: Exploring the Upper Limits of Dose Sculpting Capacity of the Novel Direction Modulated Brachytherapy (DMBT) Tandem Applicator

Energy Technology Data Exchange (ETDEWEB)

Han, D [University of California San Francisco, San Francisco, CA (United States); Department of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Safigholi, H; Soliman, A [Department of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Song, W [Department of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); University of Toronto, Toronto, ON (Canada)

2016-06-15

Purpose: To explore and quantify the upper limits in dose sculpting capacity of the novel direction modulated brachytherapy (DMBT) tandem applicator compared with conventional tandem design for {sup 192}Ir-based HDR planning. Methods: The proposed DMBT tandem applicator is designed for image-guided adaptive brachytherapy (IGABT), especially MRI, of cervical cancer. It has 6 peripheral holes of 1.3-mm width, grooved along a 5.4-mm diameter nonmagnetic tungsten alloy rod of density 18.0 g/cc, capable of generating directional dose profiles – leading to enhanced dose sculpting capacity through inverse planning. The external dimensions are identical to that of conventional tandem design to ensure clinical compatibility. To explore the expansive dose sculpting capacity, we constructed a hypothetical circular target with 20-mm radius and positioned the DMBT and conventional tandems at the center. We then incrementally shifted the positions laterally away from the center of up to 15 mm, at 1-mm steps. The in-house coded gradient projection-based inverse planning system was then used to generate inverse optimized plans ensuring identical V100=100% coverage. Conformity index (CI) was calculated for all plans. Results: Overall, the DMBT tandem generates more conformal dose distributions than conventional tandem for all lateral positional shifts of 0-15 mm (CI=0.91–0.52 and 0.99–0.34, respectively), with an exception at the central position due to the ideal circular dose distribution, generated by the {sup 192}Ir, fitting tightly around the circular target (CI = 0.91 and 0.99, respectively). The DMBT tandem is able to generate dose conformity of CI>0.8 at up to 6-mm positional shift while the conventional tandem violates this past 2-mm shift. Also, the CI ratio (=DMBT/conv.) increases rapidly until about 8 mm and then stabilizes beyond. Conclusion: A substantial enhancement in the dose sculpting capacity has been demonstrated for the novel DMBT tandem applicator. While

A Variant Form of the Human Deleted in Malignant Brain Tumor 1 (DMBT1) Gene Shows Increased Expression in Inflammatory Bowel Diseases and Interacts with Dimeric Trefoil Factor 3 (TFF3)

DEFF Research Database (Denmark)

Madsen, Jens; Sorensen, Grith Lykke; Nielsen, Ole Stig

2013-01-01

The protein deleted in malignant brain tumors (DMBT1) and the trefoil factor (TFF) proteins have all been proposed to have roles in epithelial cell growth and cell differentiation and shown to be up regulated in inflammatory bowel diseases. A panel of monoclonal antibodies was raised against human...

Salivary agglutinin/glycoprotein-340/DMBT1

DEFF Research Database (Denmark)

Ligtenberg, Antoon J M; Veerman, Enno C I; Nieuw Amerongen, Arie V

2007-01-01

and Helicobacter pylori, influenza viruses and HIV, but also with mucosal defence proteins, such as IgA, surfactant proteins and MUC5B. Stimulation of alveolar macrophage migration, suppression of neutrophil oxidative burst and activation of the complement cascade point further to an important role...

Long-term evaluation of mucosal and systemic immunity and protection conferred by different polio booster vaccines.

Science.gov (United States)

Xiao, Yuhong; Daniell, Henry

2017-09-25

Oral polio vaccine (OPV) and Inactivated Polio Vaccine (IPV) have distinct advantages and limitations. IPV does not provide mucosal immunity and introduction of IPV to mitigate consequences of circulating vaccine-derived polio virus from OPV has very limited effect on transmission and OPV campaigns are essential for interrupting wild polio virus transmission, even in developed countries with a high coverage of IPV and protected sewer systems. The problem is magnified in many countries with limited resources. Requirement of refrigeration for storage and transportation for both IPV and OPV is also a major challenge in developing countries. Therefore, we present here long-term studies on comparison of a plant-based booster vaccine, which is free of virus and cold chain with IPV boosters and provide data on mucosal and systemic immunity and protection conferred by neutralizing antibodies. Mice were primed subcutaneously with IPV and boosted orally with lyophilized plant cells containing 1μg or 25μg polio viral protein 1 (VP1), once a month for three months or a single booster one year after the first prime. Our results show that VP1-IgG1 titers in single or double dose IPV dropped to background levels after one year of immunization. This decrease correlated with >50% reduction in seropositivity in double dose and <10% seropositivity in single dose IPV against serotype 1. Single dose IPV offered no or minimal protection against serotype 1 and 2 but conferred protection against serotype 3. VP1-IgA titers were negligible in IPV single or double dose vaccinated mice. VP1 antigen with two plant-derived adjuvants induced significantly high level and long lasting VP1-IgG1, IgA and neutralizing antibody titers (average 4.3-6.8 log2 titers). Plant boosters with VP1 and plant derived adjuvants maintained the same level titers from 29 to 400days and conferred the same level of protection against all three serotypes throughout the duration of this study. Even during period, when

Systemic Immunization with Papillomavirus L1 Protein Completely Prevents the Development of Viral Mucosal Papillomas

Science.gov (United States)

Suzich, Joann A.; Ghim, Shin-Je; Palmer-Hill, Frances J.; White, Wendy I.; Tamura, James K.; Bell, Judith A.; Newsome, Joseph A.; Bennett Jenson, A.; Schlegel, Richard

1995-12-01

Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

Host responses to Candida albicans: Th17 cells and mucosal candidiasis

OpenAIRE

Conti, Heather R.; Gaffen, Sarah L.

2010-01-01

Candida albicans causes mucosal and disseminated candidiasis, which represent serious problems for the rapidly expanding immunocompromised population. Until recently, Th1-mediated immunity was thought to confer the primary protection, particularly for oral candidiasis. However, emerging data indicate that the newly-defined Th17 compartment appears to play the predominant role in mucosal candidiasis.

SU-F-BRA-05: Utility of the Combined Use of Two Types of HDR Sources with the Direction Modulation Brachytherapy (DMBT) Tandem Applicator for Cervical Cancer Treatment

Energy Technology Data Exchange (ETDEWEB)

Safigholi, H; Soliman, A; Song, W [Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, U of T, Toronto, Ontario (Canada); Han, D [Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, U of T, Toronto, Ontario (Canada); University of California, San Diego, La Jolla, CA (United States); Meigooni, A Soleimani [Comprehensive Cancer Center of Nevada, Las Vegas, Nevada (United States); Scanderbeg, D [UCSD Medical Center, La Jolla, CA (United States)

2015-06-15

Purpose: To maximize the dose to HRCTV while minimizing dose to the OARs, the combination of two HDR brachytherapy sources, 192-Ir and 169-Yb, used in combination with the recently-proposed novel direction modulated brachytherapy (DMBT) tandem applicator were examined. Methods: The DMBT tandem, made from nonmagnetic tungsten-alloy rod, with diameter of 5.4mm, has 6 symmetric peripheral holes of 1.3mm diameter. The 0.3mm thick bio-compatible plastic tubing wraps the tandem. MCNPX v.2.6 was used to simulate the mHDR 192-Ir V2 and 4140 HDR 169-Yb sources inside the DMBT applicator. Thought was by combining the higher energy 192-Ir (380keV) and lower energy 169-Yb (92.7keV) sources could create unprecedented level of dose conformality when combined with the high-degree intensity modulation capable DMBT tandem applicator. 3D dose matrices, with 1 mm3 resolution, were imported into an in-house-coded inverse optimization planning system to evaluate plan quality of 19 clinical patient cases. Prescription dose was 15Gy. All plans were normalized to receive the same HRCTV D90. Results: Generally, the use of dual sources produced better plans than using either of the sources alone, with significantly better performance in some patients. The mean D2cc for bladder, rectum, and sigmoid were 11.65±2.30Gy, 7.47±3.05Gy, and 9.84±2.48Gy for 192-Ir-only, respectively. For 169 -Yb-only, they were 11.67±2.26Gy, 7.44±3.02Gy, and 9.83±2.38Gy, respectively. The corresponding data for the dual sources were 11.51±2.24Gy, 7.30±3.00Gy, and 9.68 ±2.39Gy, respectively. The HRCTV D98 and V100 were 16.37±1.86Gy and 97.37±1.92Gy for Ir-192-only, respectively. For 169-Yb-only, they were 16.43±1.86Gy, and 97.51±1.91Gy, respectively. For the dual source, they were 16.42±1.87Gy and 97.47±1.93Gy, respectively. Conclusion: The plan quality improves, in some cases quite significantly, for when dual 192-Ir and 169-Yb sources are used in combination with highly intensity modulation capable

SU-E-T-523: Investigation of Various MR-Compatible Shielding Materials for Direction Modulated Brachytherapy (DMBT) Tandem Applicator for Cervical Cancer Treatment

Energy Technology Data Exchange (ETDEWEB)

Safigholi, H; Soliman, A; Song, W [Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, U of T, Toronto, Ontario (Canada); Han, D [Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, U of T, Toronto, Ontario (Canada); University of California, San Diego, La Jolla, CA (United States); Meigooni, A Soleimani [Comprehensive Cancer Center of Nevada, Las Vegas, NV (United States); Scanderbeg, D [UCSD Medical Center, La Jolla, CA (United States)

2015-06-15

Purpose: To evaluate various shielding materials such as Gold (Au), Osmium (Os), Tantalum (Ta), and Tungsten (W) based alloys for use with a novel intensity modulation capable direction modulated brachytherapy (DMBT) tandem applicator for image guided cervical cancer HDR brachytherapy. Methods: The novel MRI-compatible DMBT tandem, made from nonmagnetic tungsten-alloy rod with diameter of 5.4 mm, has 6 symmetric peripheral holes of 1.3 mm diameter with 2.05 mm distance from the center for a high degree intensity modulation capacity. The 0.3 mm thickness of bio-compatible plastic tubing wraps the tandem. MCNPX was used for Monte Carlo simulations of the shields and the mHDR Ir-192 V2 source. MC-generated 3D dose matrices of different shielding materials of Au, Os, Ta, and W with 1 mm3 resolution were imported into an in-house-coded inverse optimization planning system to evaluate 19 clinical patient plans. Prescription dose was 15Gy. All plans were normalized to receive the same HRCTV D90. Results: In general, the plan qualities for various shielding materials were similar. The OAR D2cc for bladder was very similar for Au, Os, and Ta with 11.64±2.30Gy. For W, it was very close 11.65±2.30Gy. The sigmoid D2cc was 9.82±2.46Gy for Au and Os while it was 9.84±2.48Gy for Ta and W. The rectum D2cc was 7.44±3.06Gy for Au, 7.43±3.07Gy for Os, 7.48±3.05Gy for Ta, and 7.47±3.05Gy for W. The HRCTV D98 and V100 were very close with 16.37±1.87 Gy and 97.37±1.93 Gy, on average, respectively. Conclusion: Various MRI-compatible shielding alloys were investigated for the DMBT tandem applicator. The clinical plan qualities were not significantly different among these various alloys, however. Therefore, the candidate metals (or in combination) can be used to select best alloys for MRI image guided cervical cancer brachytherapy using the novel DMBT applicator that is capable of unprecedented level of intensity modulation.

SU-E-T-523: Investigation of Various MR-Compatible Shielding Materials for Direction Modulated Brachytherapy (DMBT) Tandem Applicator for Cervical Cancer Treatment

International Nuclear Information System (INIS)

Safigholi, H; Soliman, A; Song, W; Han, D; Meigooni, A Soleimani; Scanderbeg, D

2015-01-01

Purpose: To evaluate various shielding materials such as Gold (Au), Osmium (Os), Tantalum (Ta), and Tungsten (W) based alloys for use with a novel intensity modulation capable direction modulated brachytherapy (DMBT) tandem applicator for image guided cervical cancer HDR brachytherapy. Methods: The novel MRI-compatible DMBT tandem, made from nonmagnetic tungsten-alloy rod with diameter of 5.4 mm, has 6 symmetric peripheral holes of 1.3 mm diameter with 2.05 mm distance from the center for a high degree intensity modulation capacity. The 0.3 mm thickness of bio-compatible plastic tubing wraps the tandem. MCNPX was used for Monte Carlo simulations of the shields and the mHDR Ir-192 V2 source. MC-generated 3D dose matrices of different shielding materials of Au, Os, Ta, and W with 1 mm3 resolution were imported into an in-house-coded inverse optimization planning system to evaluate 19 clinical patient plans. Prescription dose was 15Gy. All plans were normalized to receive the same HRCTV D90. Results: In general, the plan qualities for various shielding materials were similar. The OAR D2cc for bladder was very similar for Au, Os, and Ta with 11.64±2.30Gy. For W, it was very close 11.65±2.30Gy. The sigmoid D2cc was 9.82±2.46Gy for Au and Os while it was 9.84±2.48Gy for Ta and W. The rectum D2cc was 7.44±3.06Gy for Au, 7.43±3.07Gy for Os, 7.48±3.05Gy for Ta, and 7.47±3.05Gy for W. The HRCTV D98 and V100 were very close with 16.37±1.87 Gy and 97.37±1.93 Gy, on average, respectively. Conclusion: Various MRI-compatible shielding alloys were investigated for the DMBT tandem applicator. The clinical plan qualities were not significantly different among these various alloys, however. Therefore, the candidate metals (or in combination) can be used to select best alloys for MRI image guided cervical cancer brachytherapy using the novel DMBT applicator that is capable of unprecedented level of intensity modulation

The Salivary Scavenger and Agglutinin in Early Life: Diverse Roles in Amniotic Fluid and in the Infant Intestine

NARCIS (Netherlands)

Reichhardt, M.P.; Jarva, H.; Been, de M.; Rodriguez, J.M.; Quintana, E.J.; Loimaranta, V.; Vos, de W.M.; Meri, S.

2014-01-01

The salivary scavenger and agglutinin (SALSA), also known as gp340 and dmbt1, is an antimicrobial and inflammation-regulating molecule located at the mucosal surfaces. The present study revealed that SALSA was present in the amniotic fluid (AF) and exceptionally enriched in both meconium and feces

SU-G-IeP1-09: MRI Evaluation of a Direction-Modulated Brachytherapy (DMBT) Tandem Applicator for Cervical Cancer On 3T

Energy Technology Data Exchange (ETDEWEB)

Soliman, A; Safigholi, H [Sunnybrook Research Institute, Toronto, ON (Canada); Sunnybrook Health Sciences Centre, Toronto, ON (Canada); Han, D [University of California San Francisco, San Francisco, CA (United States); Elzibak, A; Mashouf, S; Owrangi, A; Ravi, A [Sunnybrook Health Sciences Centre, Toronto, ON (Canada); University of Toronto, Toronto, ON (Canada); Song, W [Sunnybrook Research Institute, Toronto, ON (Canada); Sunnybrook Health Sciences Centre, Toronto, ON (Canada); University of Toronto, Toronto, ON (Canada)

2016-06-15

Purpose: To assess image quality and artifact extent of a novel direction modulated brachytherapy (DMBT) tandem applicator on a 3T MRI using various clinical imaging sequences. Methods: The tandem applicator is composed of a tungsten alloy with 6 peripheral grooves covered with a PEEK tip. An MR-compatible phantom with similar dimensions to the female pelvis was manufactured. To visually assess the spatial shift of the applicator’s tip, a mountable radial-fiducial with 4 plastic rods, each of 3mm diameter, was designed to tightly fit on the applicator. The rods are separated by 16 mm and mounted at 90-degree relative to one another. The pelvis phantom was filled with a solution of MnCl2 to mimic T2 relaxation time of the cervix (60-80 ms at 3T).Imaging was performed on a 3T Philips Achieva using a 16-channel Torso coil array. Four MR sequences were tested: T2-weighted fast spin-echo (T2w-FSE), proton density weighted FSE (PDw-FSE), T1-weighted FSE (T1w-FSE) and T1 weighted spoiled gradient echo (T1w-GE). The spatial resolution was kept the same between all sequences: 0.6 × 0.6 × 3 mm{sup 3} with no slice gaps. Para-sagittal images were acquired with the applicator fixed at a 30-degree angle anterior to the B0- field to mimic clinical settings. Results: Minimal artifacts were observed on T2w-FSE, PDw-FSE and T1-FSE, while significant artifacts were seen on T1w-GE images. Artifacts induced in all 3 FSE sequences did not hinder accurate localisation of the tip and the applicator boundaries. The drift of the applicator’s centreline from the radial fiducials was measured and found to be < 1 mm for the 3 FSE sequences. Conclusion: The tungsten–based DMBT applicator can be potentially used on 3T with various clinical sequences without inducing significant artifacts. Further validation on patients as well as the evaluation of relative SNR among the different sequences is required.

New frontiers in mucositis.

Science.gov (United States)

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.

Mucosal vaccination by adenoviruses displaying reovirus sigma 1

Energy Technology Data Exchange (ETDEWEB)

Weaver, Eric A. [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Camacho, Zenaido T. [Department of Cell Biology, Department of Natural Sciences, Western New Mexico University, Silver City, NM 88062 (United States); Hillestad, Matthew L. [Nephrology Training Program, Mayo Clinic, Rochester, MN 55902 (United States); Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J. [Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902 (United States); Mercier, George T. [Department of Physics, University of Houston, Houston, TX 77004 (United States); Barry, Michael A., E-mail: mab@mayo.edu [Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902 (United States); Department of Immunology and Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902 (United States)

2015-08-15

We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.

Mucosal vaccination by adenoviruses displaying reovirus sigma 1

International Nuclear Information System (INIS)

Weaver, Eric A.; Camacho, Zenaido T.; Hillestad, Matthew L.; Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J.; Mercier, George T.; Barry, Michael A.

2015-01-01

We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5

Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis

DEFF Research Database (Denmark)

Müller-Enbergs, Helmut; Hu, Jiong; Popp, Rüdiger

2012-01-01

OBJECTIVE: Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated in innate immunity, cell polarity, and differentiation. Here we studied the role of DMBT1 in endothelial cells. METHODS AND RESULTS: DMBT1 was secreted ...... and promote adhesion, migration, proliferation, and angiogenesis as well as vascular repair. Mechanistically, DMBT1 interacts with galectin-3 and modulates the Notch signaling pathway as well as the differential expression of ephrin-B2 and EphB4....

Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis

DEFF Research Database (Denmark)

Kissow, Hannelouise; Hartmann, Bolette; Holst, Jens Juul

2012-01-01

: To determine whether endogenous GLP-1 contributes to the healing processes and if exogenous GLP-1 has a potential role in treating mucositis. METHODS: Mice were injected with 5-fluorouracil (5-FU) or saline to induce mucositis and were then treated with GLP-1, GLP-2, GLP-2 (3-33), exendin (9-39) or vehicle....... The mice were sacrificed 48 or 96 h after the 5-FU injections. The end points were intestinal weight, villus height, proliferation and histological scoring of mucositis severity. Rats were injected with 5-FU or saline, and after 48 h, blood was drawn and analysed for GLP-1 and GLP-2 concentration. RESULTS......: GLP-1 and GLP-2 significantly prevented the loss of mucosal mass and villus height and significantly decreased the mucositis severity score in the duodenum and jejunum 48 h after chemotherapy. The effect was equivalent. Exendin (9-39) reduced the intestinal weight 96 h after chemotherapy. The GLP-1...

Deleted in Malignant Brain Tumors 1 is a versatile mucin-like molecule likely to play a differential role in digestive tract cancer

DEFF Research Database (Denmark)

Mollenhauer, J; Herbertz, S; Helmke, B

2001-01-01

Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a candidate tumor suppressor gene for brain, lung, and digestive tract cancer. In particular, alterations of the gene and/or a loss of expression have been observed in gastric, colorectal, and esophageal carcinomas. Initial evidence...... has accumulated that DMBT1 may represent a multifunctional protein. Because the consequences of a loss of DMBT1 function may be different depending on its original function in a particular tissue, we wondered if it is appropriate to assume a uniform role for DMBT1 in digestive tract carcinomas. We...... hypothesized that a systematic characterization of DMBT1 in the human alimentary tract would be useful to improve the understanding of this molecule and its role in digestive tract carcinomas. Our data indicate that the expression pattern and subcellular distribution of DMBT1 in the human alimentary tract...

Quasi-Dual-Packed-Kerneled Au49 (2,4-DMBT)27 Nanoclusters and the Influence of Kernel Packing on the Electrochemical Gap.

Science.gov (United States)

Liao, Lingwen; Zhuang, Shengli; Wang, Pu; Xu, Yanan; Yan, Nan; Dong, Hongwei; Wang, Chengming; Zhao, Yan; Xia, Nan; Li, Jin; Deng, Haiteng; Pei, Yong; Tian, Shi-Kai; Wu, Zhikun

2017-10-02

Although face-centered cubic (fcc), body-centered cubic (bcc), hexagonal close-packed (hcp), and other structured gold nanoclusters have been reported, it was unclear whether gold nanoclusters with mix-packed (fcc and non-fcc) kernels exist, and the correlation between kernel packing and the properties of gold nanoclusters is unknown. A Au 49 (2,4-DMBT) 27 nanocluster with a shell electron count of 22 has now been been synthesized and structurally resolved by single-crystal X-ray crystallography, which revealed that Au 49 (2,4-DMBT) 27 contains a unique Au 34 kernel consisting of one quasi-fcc-structured Au 21 and one non-fcc-structured Au 13 unit (where 2,4-DMBTH=2,4-dimethylbenzenethiol). Further experiments revealed that the kernel packing greatly influences the electrochemical gap (EG) and the fcc structure has a larger EG than the investigated non-fcc structure. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Science.gov (United States)

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.

Induction of influenza-specific mucosal immunity by an attenuated recombinant Sendai virus.

Directory of Open Access Journals (Sweden)

Thuc-vy L Le

2011-04-01

Full Text Available Many pathogens initiate infection at the mucosal surfaces; therefore, induction of mucosal immune responses is a first level of defense against infection and is the most powerful means of protection. Although intramuscular injection is widely used for vaccination and is effective at inducing circulating antibodies, it is less effective at inducing mucosal antibodies.Here we report a novel recombinant, attenuated Sendai virus vector (GP42-H1 in which the hemagglutinin (HA gene of influenza A virus was introduced into the Sendai virus genome as an additional gene. Infection of CV-1 cells by GP42-H1 resulted in cell surface expression of the HA protein. Intranasal immunization of mice with 1,000 plaque forming units (pfu of GP42-H1 induced HA-specific IgG and IgA antibodies in the blood, bronchoalveolar lavage fluid, fecal pellet extracts and saliva. The HA-specific antibody titer induced by GP42-H1 closely resembles the titer induced by sublethal infection by live influenza virus; however, in contrast to infection by influenza virus, immunization with GP42-H1 did not result in disease symptoms or the loss of body weight. In mice that were immunized with GP42-H1 and then challenged with 5LD(50 (1250 pfu of influenza virus, no significant weight loss was observed and other visual signs of morbidity were not detected.These results demonstrate that the GP42-H1 Sendai virus recombinant is able to confer full protection from lethal infection by influenza virus, supporting the conclusion that it is a safe and effective mucosal vaccine vector.

Mucosal immunity to poliovirus.

Science.gov (United States)

Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

2011-10-01

The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

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

Science.gov (United States)

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.

Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses.

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Campo, Judith Del; Zayas, Caridad; Romeu, Belkis; Acevedo, Reinaldo; González, Elizabeth; Bracho, Gustavo; Cuello, Maribel; Cabrera, Osmir; Balboa, Julio; Lastre, Miriam

2009-12-01

Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen. Therefore, we used female mice immunized by intragastric, intravaginal, intranasal or intramuscular routes with both structures alone or incorporated with ovalbumin (OVA). High levels of specific IgG antibody were detected in all sera and in vaginal washes, but specific IgA antibody in external secretions was only detected in mucosally immunized mice. Furthermore, antigen specific IgG1 and IgG2a isotypes were all induced. AFPL1 and AFCo1 are capable of inducing IFN-gamma responses, and chemokine secretions, like MIP-1alpha and MIP-1beta. However, AFCo1 is a better alternative to induce immune responses at mucosal level. Even when we use a heterologous antigen, the AFCo1 response was better than with AFPL1 in inducing mucosal and systemic immune responses. These results support the use of AFCo1 as a potent Th1 inducing adjuvant particularly suitable for mucosal immunization.

CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization.

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Sundling, Christopher; Schön, Karin; Mörner, Andreas; Forsell, Mattias N E; Wyatt, Richard T; Thorstensson, Rigmor; Karlsson Hedestam, Gunilla B; Lycke, Nils Y

2008-12-01

Strategies to induce potent and broad antibody responses against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) at both systemic and mucosal sites represent a central goal for HIV-1 vaccine development. Here, we show that the non-toxic CTA1-DD adjuvant promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal (i.n.) immunizations with trimeric or monomeric forms of HIV-1 Env in mice and in non-human primates. Env-specific IgG subclasses in the serum of immunized mice reflected a balanced Th1/Th2 type of response. Strikingly, i.n. immunizations with Env and the CTA1-DD adjuvant induced substantial levels of mucosal anti-Env IgA in bronchial alveolar lavage and also detectable levels in vaginal secretions. By contrast, parenteral immunizations of Env formulated in Ribi did not stimulate mucosal IgA responses, while the two adjuvants induced a similar distribution of Env-specific IgG-subclasses in serum. A single parenteral boost with Env in Ribi adjuvant into mice previously primed i.n. with Env and CTA1-DD, augmented the serum anti-Env IgG levels to similar magnitudes as those observed after three intraperitoneal immunizations with Env in Ribi. The augmenting potency of CTA1-DD was similar to that of LTK63 or CpG oligodeoxynucleotides (ODN). However, in contrast to CpG ODN, the effect of CTA1-DD and LTK63 appeared to be independent of MyD88 and toll-like receptor signalling. This is the first demonstration that CTA1-DD augments specific immune responses also in non-human primates, suggesting that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for humoral and cell-mediated immunity against HIV-1 Env.

Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells.

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Bomsel, Morgane; Ganor, Yonatan

2017-12-01

The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans -infect CD4 + T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans -infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans -infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans -infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans -infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans -infection, infectious virions escaping degradation are transferred

Neutrophil Interactions with Epithelial Expressed ICAM-1 Enhances Intestinal Mucosal Wound Healing

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Sumagin, R; Brazil, JC; Nava, P; Nishio, H; Alam, A; Luissint, AC; Weber, DA; Neish, AS; Nusrat, A; Parkos, CA

2015-01-01

A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. While epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 plays an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing. PMID:26732677

Neutrophil interactions with epithelial-expressed ICAM-1 enhances intestinal mucosal wound healing.

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Sumagin, R; Brazil, J C; Nava, P; Nishio, H; Alam, A; Luissint, A C; Weber, D A; Neish, A S; Nusrat, A; Parkos, C A

2016-09-01

A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. Although epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 has an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing.

Mucosal immunity induced by adenovirus-based H5N1 HPAI vaccine confers protection against a lethal H5N2 avian influenza virus challenge

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Park, Ki Seok; Lee, Jiyeung; Ahn, So Shin; Byun, Young-Ho; Seong, Baik Lin; Baek, Yun Hee; Song, Min-Suk; Choi, Young Ki; Na, Yun Jeong; Hwang, Inhwan; Sung, Young Chul; Lee, Chang Geun

2009-01-01

Development of effective vaccines against highly pathogenic avian influenza (HPAI) H5N1 viruses is a global public health priority. Considering the difficulty in predicting HPAI H5N1 pandemic strains, one strategy used in their design includes the development of formulations with the capacity of eliciting broad cross-protective immunity against multiple viral antigens. To this end we constructed a replication-defective recombinant adenovirus-based avian influenza virus vaccine (rAdv-AI) expressing the codon-optimized M2eX-HA-hCD40L and the M1-M2 fusion genes from HPAI H5N1 human isolate. Although there were no significant differences in the systemic immune responses observed between the intramuscular prime-intramuscular boost regimen (IM/IM) and the intranasal prime-intramuscular boost regimen (IN/IM), IN/IM induced more potent CD8 + T cell and antibody responses at mucosal sites than the IM/IM vaccination, resulting in more effective protection against lethal H5N2 avian influenza (AI) virus challenge. These findings suggest that the strategies used to induce multi-antigen-targeted mucosal immunity, such as IN/IM delivery of rAdv-AI, may be a promising approach for developing broad protective vaccines that may be more effective against the new HPAI pandemic strains.

Prior mucosal exposure to heterologous cells alters the pathogenesis of cell-associated mucosal feline immunodeficiency virus challenge

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Leavell Sarah

2010-05-01

Full Text Available Abstract Background Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control and then cats were vaginally challenged with cell-associated or cell-free FIV. Results Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls. Conclusions The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus can be modulated by mucosal exposure to uninfected heterologous cells.

Mucosal effects of tenofovir 1% gel.

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Hladik, Florian; Burgener, Adam; Ballweber, Lamar; Gottardo, Raphael; Vojtech, Lucia; Fourati, Slim; Dai, James Y; Cameron, Mark J; Strobl, Johanna; Hughes, Sean M; Hoesley, Craig; Andrew, Philip; Johnson, Sherri; Piper, Jeanna; Friend, David R; Ball, T Blake; Cranston, Ross D; Mayer, Kenneth H; McElrath, M Juliana; McGowan, Ian

2015-02-03

Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored.

Cell-associated flagella enhance the protection conferred by mucosally-administered attenuated Salmonella Paratyphi A vaccines.

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Orit Gat

2011-11-01

Full Text Available Antibiotic-resistant Salmonella enterica serovar Paratyphi A, the agent of paratyphoid A fever, poses an emerging public health dilemma in endemic areas of Asia and among travelers, as there is no licensed vaccine. Integral to our efforts to develop a S. Paratyphi A vaccine, we addressed the role of flagella as a potential protective antigen by comparing cell-associated flagella with exported flagellin subunits expressed by attenuated strains.S. Paratyphi A strain ATCC 9150 was first deleted for the chromosomal guaBA locus, creating CVD 1901. Further chromosomal deletions in fliD (CVD 1901D or flgK (CVD 1901K were then engineered, resulting in the export of unpolymerized FliC, without impairing its overall expression. The virulence of the resulting isogenic strains was examined using a novel mouse LD(50 model to accommodate the human-host restricted S. Paratyphi A. The immunogenicity of the attenuated strains was then tested using a mouse intranasal model, followed by intraperitoneal challenge with wildtype ATCC 9150.Mucosal (intranasal immunization of mice with strain CVD 1901 expressing cell-associated flagella conferred superior protection (vaccine efficacy [VE], 90% against a lethal intraperitoneal challenge, compared with the flagellin monomer-exporting mutants CVD 1901K (30% VE or CVD 1901D (47% VE. The superior protection induced by CVD 1901 with its cell-attached flagella was associated with an increased IgG2a:IgG1 ratio of FliC-specific antibodies with enhanced opsonophagocytic capacity.Our results clearly suggest that enhanced anti-FliC antibody-mediated clearance of S. Paratyphi A by phagocytic cells, induced by vaccines expressing cell-associated rather than exported FliC, might be contributing to the vaccine-induced protection from S. Paratyphi A challenge in vivo. We speculate that an excess of IgG1 anti-FliC antibodies induced by the exported FliC may compete with the IgG2a subtype and block binding to specific phagocyte Fc

Mucosal immunogenicity of plant lectins in mice

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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

Role of lipoxygenases and the lipoxin A(4)/annexin 1 receptor in ischemia-reperfusion-induced gastric mucosal damage in rats.

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Peskar, Brigitta M; Ehrlich, Karlheinz; Schuligoi, Rufina; Peskar, Bernhard A

2009-01-01

Rat gastric mucosal damage was induced by ischemia-reperfusion. The 5-lipoxygenase inhibitors MK886 and A63162, the 12-lipoxygenase inhibitor baicalein, the 15-lipoxygenase inhibitor PD146176 and the lipoxin (LX) A(4)/annexin 1 antagonist Boc1 increased mucosal damage in a dose-dependent manner. Low doses of these compounds, which have no effects on mucosal integrity, cause severe damage when combined with low doses of indomethacin, celecoxib or dexamethasone. 16,16-Dimethylprostaglandin (PG) E(2) and LXA(4) can replace each other in preventing mucosal injury induced by either cyclooxygenase or lipoxygenase inhibitors. The results suggest that not only cyclooxygenases, but also lipoxygenases have a role in limiting gastric mucosal damage during ischemia-reperfusion. Copyright 2009 S. Karger AG, Basel.

Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

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Carvalho, Agostinho; Giovannini, Gloria; De Luca, Antonella; D'Angelo, Carmen; Casagrande, Andrea; Iannitti, Rossana G; Ricci, Giovanni; Cunha, Cristina; Romani, Luigina

2012-01-01

The recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling. PMID:22543832

Allopurinol gel mitigates radiation-induced mucositis and dermatitis

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Kitagawa, Junichi; Nasu, Masanori; Okumura, Hayato; Matsumoto, Shigeji; Shibata, Akihiko; Makino, Kimiko; Terada, Hiroshi

2008-01-01

It has not been verified whether allopurinol application is beneficial in decreasing the severity of radiation-induced oral mucositis and dermatitis. Rats were divided into 4 groups and received 15 Gy irradiation on the left whisker pad. Group 1 received only irradiation. Group 2 was maintained by applying allopurinol/carrageenan-mixed gel (allopurinol gel) continuously from 2 days before to 20 days after irradiation. Group 3 had allopurinol gel applied for 20 days after radiation. Group 4 was maintained by applying carrageenan gel continuously from 2 days before to 20 days after irradiation. The intra oral mucosal and acute skin reactions were assessed daily using mucositis and skin score systems. The escape thresholds for mechanical stimulation to the left whisker pad were measured daily. In addition, the irradiated tissues at the endpoint of this study were compared with naive tissue. Escape threshold in group 2 was significantly higher than that in group 1, and mucositis and skin scores were much improved compared with those of group 1. Concerning escape threshold, mucositis and skin scores in group 3 began to improve 10 days after irradiation. Group 4 showed severe symptoms of mucositis and dermatitis to the same extent as that observed in group 1. In the histopathological study, the tissues of group 1 showed severe inflammatory reactions, compared with those of group 2. These results suggest that allopurinol gel application can mitigate inflammation reactions associated with radiation-induced oral mucositis and dermatitis. (author)

Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

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Geert Leroux-Roels

Full Text Available Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101. Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1.ClinicalTrials.gov NCT01084343.

The analysis of bacterial culture in radiation mucositis

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Wen Zunbei; Su Deqing; Liang Yuxue

2006-01-01

Objective: To investigate pathogen dose existing or not in patients with radiation mucositis. Methods: From Juanary 2004 to August 2005, from 46 patients with radiation mucositis some pharynx secretion were taken for culture. Then they were treated with antibiotics selected by the cultured results and gargle. Results: 5 patients with grade 0 of radiation mucositis were with no cultured pathogen, and the results of some other patients with radiation mucositis include 8 cases of epiphyte, 1 cases of p. vulgaris and 3 cases of Staphylococcus. the positive rate is 29.2% (12/41); Conclusion: Some patients with radiation mucositis do exist pathogen, and we must slect antibiotics by the bacterial cultured results. (authors)

Correlation between presence of Leishmania RNA virus 1 and clinical characteristics of nasal mucosal leishmaniosis.

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Ito, Marcos Massayuki; Catanhêde, Lilian Motta; Katsuragawa, Tony Hiroshi; Silva Junior, Cipriano Ferreira da; Camargo, Luis Marcelo Aranha; Mattos, Ricardo de Godoi; Vilallobos-Salcedo, Juan Miguel

2015-01-01

Mucosal leishmaniosis (ML) is a severe clinical form of leishmaniosis. Complex factors related to the parasite and the host are attributed to the development of mucosal lesions. Leishmania RNA virus 1 (LRV1) can disrupt immune response, and may be the main determinant of severity of the disease; it should be investigated. To study the existence of clinical differences between patients with ML with endosymbiosis by LRV1 and. those without it. A cross-sectional cohort study with clinical evaluation, polymerase chain reaction (PCR) detection of Leishmania, species classification, and search of LRV1 was performed. Only patients with confirmed diagnosis of ML by positive PCR and with nasal mucosa injuries were included in this analysis. Out of 37 patients, 30 (81.1%) were diagnosed with Leishmania braziliensis, five (13.5%) with Leishmania guyanensis, and two (5.4%) with mixed infection of L. braziliensis and L. guyanensis. LVR1 virus was present in 26 (70.3%) of the cases. Correlation between clinical phenotype and presence of LRV1 was not observed, although the frequency of the virus is two-fold higher in mucosal lesions than that found in the literature on skin lesions in the same geographical area. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

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

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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.

Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation.

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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, poral 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.

Irradiation mucositis and oral flora

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Spijkervet, F.K.L.

1989-01-01

This study, which is motivated by the substantial morbidity of local signs of mucositis and generalized symptoms that result from mucositis induced by therapeutic irradiation, has the following objectives: To investigate if it is possible to prevent irradiation mucositis via oral flora elimination, and, if it is true that flora plays a role in irradiation mucositis, what fraction of the oral flora may be involved; to evaluate oral Gram-negative bacillary carriage; to investigate the possibility to eradicate Gram-negative bacilli from the oral cavity; to evaluate oral yeast carriage; to investigate the possibility to eradicate yeasts stomatitis and the 'selectivity' of elimination of flora. Two methods are described for monitoring alterations of mucositis of the oral cavity and changes in oral flora. Chlorhexidine has been tested as the commonly used prophylaxis. The effect of chlorhexidine 0.1% rinses on oral flora and mucositis has been studied in a prospective placebo controlled double blind randomized programme. The results of the influence of saliva on the antimicrobial activity of chlorhexidine and the results of selective elimination of oral flora in irradiated patients who have head and neck cancer are reported. Salivary inactivation of the topical antimicrobials used for selective elimination of oral flora has been studied and the results are reported. Finally, the objectives that have been achieved (or not) are delineated. The significance of the results of the study are discussed in terms of published information and further lines of research are suggested. (author). 559 refs.; 29 figs.; 20 tabs

New Pathways for Alimentary Mucositis

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Joanne M. Bowen

2008-01-01

Full Text Available Alimentary mucositis is a major dose-limiting toxicity associated with anticancer treatment. It is responsible for reducing patient quality of life and represents a significant economic burden in oncology. The pathobiology of alimentary mucositis is extremely complex, and an increased understanding of mechanisms and pathway interactions is required to rationally design improved therapies. This review describes the latest advances in defining mechanisms of alimentary mucositis pathobiology in the context of pathway activation. It focuses particularly on the recent genome-wide analyses of regimen-related mucosal injury and the identification of specific regulatory pathways implicated in mucositis development. This review also discusses the currently known alimentary mucositis risk factors and the development of novel treatments. Suggestions for future research directions have been raised.

Radiation induced oral mucositis

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P S Satheesh Kumar

2009-01-01

Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

XRCC1 codon 399Gln polymorphism is associated with radiotherapy-induced acute dermatitis and mucositis in nasopharyngeal carcinoma patients

International Nuclear Information System (INIS)

Li, Haijun; You, Yanjie; Lin, Canfeng; Zheng, Mingzhang; Hong, Chaoqun; Chen, Jiongyu; Li, Derui; Au, William W; Chen, Zhijian

2013-01-01

To evaluate the association between single nucleotide polymorphisms (SNPs) at the 194 and 399 codons of XRCC1, and the risk of severe acute skin and oral mucosa reactions in nasopharyngeal carcinoma patients in China. 114 patients with nasopharyngeal carcinoma were sequentially recruited in this study. Heparinized peripheral blood samples were taken for SNPs analysis before the start of radiation treatment. SNPs in XRCC1 (194Arg/Trp and 399Arg/Gln) gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Dermatitis at upper neck and oral mucositis were clinically recorded according to the Common Terminology Criteria for Adverse Events v.3.0. The variant allele frequencies were 0.289 for XRCC1 194Trp and 0.263 for XRCC1 399Gln. Of the 114 patients, 24 experienced grade 3 acute dermatitis and 48 had grade 3 acute mucositis. The XRCC1 399Arg/Gln was significantly associated with the development of grade 3 dermatitis (Odds Ratio, 2.65; 95% CI, 1.04–6.73; p = 0.037, χ2 = 4.357). In addition, it was also associated with higher incidence of grade 3 mucositis with a borderline statistical significance (Odds Ratio, 2.11; 95% CI, 0.951–4.66; p = 0.065, χ2 = 3.411). The relationship between XRCC1 194Arg/Trp and acute dermatitis, and mucositis was not found. Our investigation shows, for the first time, that patients with the XRCC1 399Arg/Gln genotype were more likely to experience severe acute dermatitis and oral mucositis. With further validation, the information can be used to determine personalized radiotherapy strategy

Brain-gut axis and mucosal immunity: a perspective on mucosal psychoneuroimmunology.

LENUS (Irish Health Repository)

Shanahan, F

2012-02-03

The role of the brain-gut axis has traditionally been investigated in relation to intestinal motility, secretion, and vascularity. More recently, the concept of brain-gut dialogue has extended to the relationship between the nervous system and mucosal immune function. There is compelling evidence for a reciprocal or bi-directional communication between the immune system and the neuroendocrine system. This is mediated, in part, by shared ligands (chemical messengers) and receptors that are common to the immune and nervous systems. Although the concept of psychoneuroimmunology and neuroimmune cross-talk has been studied primarily in the context of the systemic immune system, it is likely to have special significance in the gut. The mucosal immune system is anatomically, functionally, and operationally distinct from the systemic immune system and is subject to independent regulatory signals. Furthermore, the intestinal mucosal immune system operates in a local milieu that depends on a dense innervation for its integrity, with juxtaposition of neuroendocrine cells and mucosal immune cells. An overview of evidence for the biologic plausibility of a brain-gut-immune axis is presented and its potential relevance to mucosal inflammatory disorders is discussed.

Gastric Mucosal Erosions - Radiologic evaluation -

International Nuclear Information System (INIS)

Kim, Seung Hyup

1985-01-01

70 cases of gastric mucosal erosions were diagnosed by double contrast upper gastrointestinal examinations and endoscopic findings. Analyzing the radiologic findings of these 70 cases of gastric mucosal erosions, the following results were obtained. 1. Among the total 70 cases, 65 cases were typical varioliform erosions showing central depressions and surrounding mucosal elevations. Remaining 5 cases were erosions of acute phase having multiple irregular depressions without surrounding elevations. 2. The gastric antrum was involved alone or in part in all cases. Duodenal bulb was involved with gastric antrum in 4 cases. 3. The majority of the cases had multiple erosions. There were only 2 cases of single erosion. 4. In 65 cases of varioliform erosions; 1) The diameter of the surrounding elevations varied from 3 to 20 mm with the majority (47 cases) between 6 and 10 mm. 2) In general, the surrounding elevations with sharp margin on double contrast films were also clearly demonstrated on compression films but those with faint margin were not. 3) The size of the central barium collections varied from pinpoint to 10 mm with the majority under 5 mm. The shape of the central barium collections in majority of the cases were round with a few cases of linear, triangular or star-shape. 5. In 5 cases of acute phase erosions; 1) All the 5 cases were females. 2) On double contrast radiography, all the cases showed multiple irregular depressed lesions without surrounding elevations. 3) 1 case had the history of hematemesis. 4) In 1 case, there was marked radiological improvement on follow-up study of 2 months interval. 6. In 23 cases, there were coexistent diseases with gastric mucosal erosions. These were 13 cases of duodenal bulb ulcers,7 cases of benign gastric ulcers and 3 others

Chemotherapy induced intestinal mucositis; from bench to bed

NARCIS (Netherlands)

B.A.E. Koning, de (Barbara)

2008-01-01

textabstractPart 1 focuses primarily on the pathophysiology of mucositis, in order to gain more insight different experimental mouse models were used. Chapter 2 describes mucositis induced by high dose doxorubicin (DOX)- treatment. DOX is a frequently used cytostatic drug in childhood cancer,

Mucosal melanosis associated with chemoembolization

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Ali Alkan

2015-06-01

Full Text Available Mucosal lesions due to underlying disease or drug toxicity, are important part of oncology practice. Patient with a diagnosis of hepatocellular carcinoma was treated with chemoembolisation. She presented with new onset of mucosal hyperpigmented lesion all through her oral cavity. Biopsy was consistent with mucosal melanosis, which was associated with the chemotherapeutics used in the chemoembolisation procedure. Lesion progressively improved without any treatment. Here we present an mucosal melanosis experience after chemoembolisation. J Clin Exp Invest 2015; 6 (2: 189-191

Primary and Chronic HIV Infection Differently Modulates Mucosal Vδ1 and Vδ2 T-Cells Differentiation Profile and Effector Functions.

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Eleonora Cimini

Full Text Available Gut-associated immune system has been identified as a major battlefield during the early phases of HIV infection. γδ T-cells, deeply affected in number and function after HIV infection, are able to act as a first line of defence against invading pathogens by producing antiviral soluble factors and by killing infected cells. Despite the relevant role in mucosal immunity, few data are available on gut-associated γδ T-cells during HIV infection. Aim of this work was to evaluate how primary (P-HIV and chronic (C-HIV HIV infection affects differentiation profile and functionality of circulating and gut-associated Vδ1 and Vδ2 T-cells. In particular, circulating and mucosal cells were isolated from respectively whole blood and residual gut samples from HIV-infected subjects with primary and chronic infection and from healthy donors (HD. Differentiation profile and functionality were analyzed by multiparametric flow cytometry. P-HIV and C-HIV were characterized by an increase in the frequency of effector Vδ1-T cells both in circulating and mucosal compartments. Moreover, during P-HIV mucosal Vδ1 T-cells expressed high levels of CD107a, suggesting a good effector cytotoxic capability of these cells in the early phase of infection that was lost in C-HIV. P-HIV induced an increase in circulating effector Vδ2 T-cells in comparison to C-HIV and HD. Notably, P-HIV as well as HD were characterized by the ability of mucosal Vδ2 T-cells to spontaneously produce IFN-γ that was lost in C-HIV. Altogether, our data showed for the first time a functional capability of mucosal Vδ1 and Vδ2 T-cells during P-HIV that was lost in C-HIV, suggesting exhaustion mechanisms induced by persistent stimulation.

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1.

Science.gov (United States)

Silva, Viviane Carvalho da; Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Martins, Conceição da Silva; Freire, Gildenio Estevam; Aragão, Karoline Saboia; Wanderley, Carlos Wagner de Souza; Freitas, Marcos Rabelo de

2017-09-01

To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

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

Science.gov (United States)

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.

CCL28 induces mucosal homing of HIV-1-specific IgA-secreting plasma cells in mice immunized with HIV-1 virus-like particles.

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Veronica Rainone

Full Text Available Mucosae-associated epithelial chemokine (MEC or CCL28 binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASCs in the mucosal lamina propria. The ability of this chemokine to enhance migration of IgA-ASCs to mucosal sites was assessed in a mouse immunization model using HIV-1(IIIB Virus-like particles (VLPs. Mice receiving either HIV-1(IIIB VLPs alone, CCL28 alone, or the irrelevant CCL19 chemokine were used as controls. Results showed a significantly increased CCR3 and CCR10 expression on CD19(+ splenocytes of HIV-1(IIIB VPL-CCL28-treated mice. HIV-1 Env-specific IFN-γ, IL-4 and IL-5 production, total IgA, anti-Env IgA as well as gastro-intestinal mucosal IgA-secreting plasma cells were also significantly augmented in these mice. Notably, sera and vaginal secretions from HIV-1(IIIB VLP-CCL28-treated mice exhibited an enhanced neutralizing activity against both a HIV-1/B-subtype laboratory strain and a heterologous HIV-1/C-subtype primary isolate. These data suggest that CCL28 could be useful in enhancing the IgA immune response that will likely play a pivotal role in prophylactic HIV vaccines.

The Mucosal Immune System of Teleost Fish

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Irene Salinas

2015-08-01

Full Text Available Teleost fish possess an adaptive immune system associated with each of their mucosal body surfaces. Evidence obtained from mucosal vaccination and mucosal infection studies reveal that adaptive immune responses take place at the different mucosal surfaces of teleost. The main mucosa-associated lymphoid tissues (MALT of teleosts are the gut-associated lymphoid tissue (GALT, skin-associated lymphoid tissue (SALT, the gill-associated lymphoid tissue (GIALT and the recently discovered nasopharynx-associated lymphoid tissue (NALT. Teleost MALT includes diffuse B cells and T cells with specific phenotypes different from their systemic counterparts that have co-evolved to defend the microbe-rich mucosal environment. Both B and T cells respond to mucosal infection or vaccination. Specific antibody responses can be measured in the gills, gut and skin mucosal secretions of teleost fish following mucosal infection or vaccination. Rainbow trout studies have shown that IgT antibodies and IgT+ B cells are the predominant B cell subset in all MALT and respond in a compartmentalized manner to mucosal infection. Our current knowledge on adaptive immunity in teleosts is limited compared to the mammalian literature. New research tools and in vivo models are currently being developed in order to help reveal the great intricacy of teleost mucosal adaptive immunity and help improve mucosal vaccination protocols for use in aquaculture.

A randomised clinical trial of misoprostol for radiation mucositis

International Nuclear Information System (INIS)

Faroudi, F.; Timms, I.; Sathiyuaseelan, Y.; Cakir, B.; Tiver, K.W.; Gebski, V.; Veness, M.

2003-01-01

Radiation mucositis is a major acute toxicity of radiation therapy for head and neck malignancies. We tested whether Misoprostol, a synthetic prostaglandin E 1 analogue given prophylactically decreased intensity of radiation mucositis. A double blind randomized trial was conducted. The intervention consisted of swishing dissolved drug or placebo as a mouthwash, and then swallowing two hours prior to radiation treatment. Patients were stratified based on concurrent chemotherapy, altered fractionation, smoking, extent of oral mucosa in radiation field, and institution. The main end point was the extent of RTOG grade III mucositis, taking into account both time and duration of mucositis. 42 patients were randomized to active drug, and 41 patients to placebo. The trial was designed to have 70 patients in each arm. The trial closed due to poor accrual. In the Misoprostol group 18/42 (43%) had grade III/IV mucositis, and in the placebo group 17/40 (42%). The mean difference between the areas under the curve was 0.38 (p-value: 0.38). For grade II mucositis the corresponding figures were 18 (42%) and 19 (47%). The time from commencement of radiation therapy to the development of peak mucositis was 49 days in the misoprostol patients and 51 days in the placebo group. The duration of grade III mucositis 12.5 days in the Misoprostol patients and 7 days in the placebo patients. In the Misoprostol arm 4 patients had an interruption to their Radiation Therapy, in the Placebo arm 5 had interruptions. Patients average weight loss was 8.1 and 8.2kg. Average self-assessment was via a 10cm LASA scale for soreness of throat and overall well-being. Misoprostol showed a worse QoL on soreness of mouth (mean difference: 0.84 units (p-value .03), but overall well-being was similar on both treatment arms 1 patient withdrew in the Misoprostol arm and 2 in the placebo arm. Misoprostol given prophylactically does not reduce the incidence of Grade III/IV mucositis, is associated with a shorter

Comparative Immunogenicity of HIV-1 gp140 Vaccine Delivered by Parenteral, and Mucosal Routes in Female Volunteers; MUCOVAC2, A Randomized Two Centre Study.

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Catherine A Cosgrove

Full Text Available Defining optimal routes for induction of mucosal immunity represents an important research priority for the HIV-1 vaccine field. In particular, it remains unclear whether mucosal routes of immunization can improve mucosal immune responses.In this randomized two center phase I clinical trial we evaluated the systemic and mucosal immune response to a candidate HIV-1 Clade C CN54gp140 envelope glycoprotein vaccine administered by intramuscular (IM, intranasal (IN and intravaginal (IVAG routes of administration in HIV negative female volunteers. IM immunizations were co-administered with Glucopyranosyl Lipid Adjuvant (GLA, IN immunizations with 0.5% chitosan and IVAG immunizations were administered in an aqueous gel.Three IM immunizations of CN54 gp140 at either 20 or 100 μg elicited significantly greater systemic and mucosal antibodies than either IN or IVAG immunizations. Following additional intramuscular boosting we observed an anamnestic antibody response in nasally primed subjects. Modest neutralizing responses were detected against closely matched tier 1 clade C virus in the IM groups. Interestingly, the strongest CD4 T-cell responses were detected after IN and not IM immunization.These data show that parenteral immunization elicits systemic and mucosal antibodies in women. Interestingly IN immunization was an effective prime for IM boost, while IVAG administration had no detectable impact on systemic or mucosal responses despite IM priming.EudraCT 2010-019103-27 and the UK Clinical Research Network (UKCRN Number 11679.

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

Science.gov (United States)

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.

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

OpenAIRE

Maeto, Cynthia Alejandra; Rodríguez, Ana María; Holgado, María Pía; Falivene, Juliana; Gherardi, Maria Magdalena

2017-01-01

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 thei...

Uptake of genital mucosal sampling in HVTN 097, a phase 1b HIV vaccine trial in South Africa.

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Erica Maxine Lazarus

Full Text Available Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female were screened at three sites in South Africa: Soweto (n = 70, 33%, Cape Town (n = 68, 32% and Klerksdorp (n = 73, 35%. Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n = 149. Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03-0.25 p<0.001 and Klerksdorp OR 0.13 CI: 0.04-0.41 p = 0.001. In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13-5.08, p = 0.02. Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies.ClinicalTrials.gov: NCT02109354.

Modulation of radiation-induced oral mucositis by pentoxifylline: Preclinical studies

International Nuclear Information System (INIS)

Gruber, Sylvia; Bozsaky, Eva; Schmidt, Margret; Doerr, Wolfgang

2015-01-01

Oral mucositis is a frequent early side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is accompanied by inflammatory reactions; their interaction with epithelial processes remains unclear. The aim of the present study was to investigate the effect of pentoxifylline (PTX) on the oral mucosal radiation response in the mouse tongue model. Irradiation comprised fractionation (5 fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), followed by graded local top-up doses (day 7/14), in order to generate complete dose-effect curves. PTX (15 mg/kg subcutaneously) was applied once daily over varying time intervals. Ulceration of mouse tongue epithelium, corresponding to confluent mucositis, was analyzed as the clinically relevant endpoint. With fractionated irradiation over 1 week, PTX administration significantly reduced the incidence of mucosal reactions when initiated before (day - 5) the onset of fractionation; a trend was observed for start of PTX treatment on day 0. Similarly, PTX treatment combined with 2 weeks of fractionation had a significant effect on ulcer incidence in all but one experiment. This clearly illustrates the potential of PTX to ameliorate oral mucositis during daily fractionated irradiation. PTX resulted in a significant reduction of oral mucositis during fractionated irradiation, which may be attributed to stimulation of mucosal repopulation processes. The biological basis of this effect, however, needs to be clarified in further, detailed mechanistic studies. (orig.) [de

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

Science.gov (United States)

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.

Differential Apoptosis in Mucosal and Dermal Wound Healing

Science.gov (United States)

Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

2014-01-01

Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; phealing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

Perspectives toward oral mucositis prevention from parents and health care professionals in pediatric cancer.

Science.gov (United States)

Ethier, Marie-Chantal; Regier, Dean A; Tomlinson, Deborah; Judd, Peter; Doyle, John; Gassas, Adam; Naqvi, Ahmed; Sung, Lillian

2012-08-01

The objectives of this study were: (1) to describe parents and health care professionals (HCPs) perceived importance of oral mucositis prevention in children with cancer; (2) To describe utilities and willingness-to-pay (WTP) to prevent mucositis. Respondents included parents of children receiving intensive chemotherapy for leukemia/lymphoma or undergoing stem cell transplantation and HCPs caring for children with cancer. Importance of mild and severe oral mucositis was estimated using a visual analogue scale (VAS). Mucositis-associated utilities were elicited using the time trade-off technique (TTO). WTP to avoid mucositis was obtained using contingent valuation. These techniques quantify how much time or money the participant is willing to relinquish in order to prevent mucositis. Eighty-two parents and 60 HCPs were included. Parents and HCPs believed mild mucositis to be of similar importance (median VAS 2.5 versus 3.6; P = 0.357) while parents considered severe mucositis less important than HCPs (median VAS 8.3 versus 9.0; P parent versus HCP responses were seen with TTO (mild or severe mucositis) and most parents were not willing to trade any survival time to prevent severe mucositis. Parents were willing to pay significantly more than HCPs to prevent mild mucositis (average median WTP $1,371 CAN vs. $684 CAN, P = 0.031). No differences were seen in WTP to prevent severe mucositis. Parents and HCP believe severe mucositis to be important, although it is more important to HCPs. Parents would not be willing to reduce life expectancy to eliminate mucositis.

GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.

Directory of Open Access Journals (Sweden)

Peter T Loudon

2010-06-01

Full Text Available The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques.Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.

Oral mucositis frequency in head and neck chemoradiotherapy

International Nuclear Information System (INIS)

Hata, Hironobu; Ota, Yojiro; Ueno, Takao; Kurihara, Kinue; Nishimura, Tetsuo; Onozawa, Yusuke; Zenda, Sadamoto

2007-01-01

A retrospective study was performed to determine the frequency and risk factors of oral mucositis in patients receiving radiotherapy or chemoradiotherapy for head and neck tumors. We classified all patients into three groups according to the radiation dose given in the oral cavity (Group A: 0 Gy; 73 patients, Group B: <40 Gy; 66 patients, Group C: ≥40 Gy; 110 patients). In group C, the odds ratio of oral mucositis (≥Gr.2) was 5.6 times in the concomitant chemotherapy group (62 patients) (odds ratio (OR) of 5.6; 95% confidence interval (CI): 2.1-14.9) compared with the radiotherapy (RT) only group (48 patients). In the case of concomitant chemotherapy group in Group C, the odds ratio of oral mucositis (≥Gr.2) was 17 times (OR of 17.1; 95% CI: 2.8-106.0) that in the group using 5-fluorouracil (FU) (50 patients) compared with the group that did not use it (12 patients). For patients whose accumulated radiation dose in the oral cavity was more than 40 Gy, 5-FU was found to be a significant risk factor for oral mucositis. (author)

Finding evidences on oncohematological patients (1st part: Mucositis, pain and satisfaction

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Josefa Solano Antolinos

2008-11-01

Full Text Available Evidence Based Practice (EBP is used as a tool to update nursing knowledge. It increases nurses´critical appraisal skills, to use the best available investigations and improve quality care in the medium to long term.In order to evaluate the repercussion of the EBP on quality daily cares, it is necessary to asses the impact on patients’ health; in regards to oncohematological nursing, some health outcomes would be: secondary effects, psychosocial factors influence on the admission time and patients satisfaction with nursing carers.Oral Mucositis, and pain associated to it, is one of main secondary effects of treatments for cancer. This complication appears in approximately 40% of the cases.There are countless studies on the subject of Oral Mucositis. However, not much has been published about Nurse Care Patient Satisfaction and Psychosocial Impact.As a consequence, our objective has been: to find and summarize the evidences about Mucositis, Pain associated, and Satisfaction; in order to encourage the spread of knowledge and promote changes in practice.Databases as CINAHL, MEDLINE, Cochrane Library, EMBASE, Pascal Biomed, LILACS, CUIDEN, CUIDEN qualitative y CUIDATGE were revised in Spanish, French and English. No time restrictions were applied.

Mucosal healing in ulcerative colitis

DEFF Research Database (Denmark)

Seidelin, Jakob Benedict; Coskun, Mehmet; Nielsen, Ole Haagen

2013-01-01

. With the introduction of the tumor necrosis factor-alpha inhibitors for the treatment of UC, it has become increasingly evident that the disease course is influenced by whether or not the patient achieves mucosal healing. Thus, patients with mucosal healing have fewer flare-ups, a decreased risk of colectomy......, and a lower probability of developing colorectal cancer. Understanding the mechanisms of mucosal wound formation and wound healing in UC, and how they are affected therapeutically is therefore of importance for obtaining efficient treatment strategies holding the potential of changing the disease course of UC....... This review is focused on the pathophysiological mechanism of mucosal wound formation in UC as well as the known mechanisms of intestinal wound healing. Regarding the latter topic, pathways of both wound healing intrinsic to epithelial cells and the wound-healing mechanisms involving interaction between...

Effect of gene time on acute radiation mucositis and dermatitis

International Nuclear Information System (INIS)

Li Suyan; Gao Li; Yin Weibo; Xu Guozhen; Xiao Guangli

2002-01-01

Objective: To evaluate the effect of recombinant human epidermal growth factor (Gene Time) on acute mucositis and dermatitis induced by radiation. Methods: 120 head and neck cancer patients were randomized into 3 groups: 1. Mucositis prophylactic application (MPA) group with control, 2. Mucositis therapeutic application (MTA) group with control and 3. Dermatitis therapeutic application (DTA) group with control. Prophylactic application of drug consisted of spraying the Gene Time preparation on the irradiated skin or mucous membrane as radiotherapy was being carried out. This was compared with control patients who received routine conventional skin care. Therapeutic application was started as grade I radiation mucositis or dermatitis appeared. The evaluation of acute radiation mucositis and dermatitis was done according to the systems proposed by RTOG or EORTC. Results: The results showed that in the MPA group, the rate of radiation mucositis at ≤10 Gy was 20% (4/20) as compared to the 70% (14/20) of the control (P = 0.004). During the course of radiation, the incidences of grade III, IV acute radiation mucositis and dermatitis were always lower than the control. In therapeutic application of Gene Time, the response rate of acute radiation mucositis was also better than the control (90% vs 50%) (P = 0.016) and that of acute dermatitis was similar (95% vs 50%) (P = 0.005). Moreover, the ≤3 d rate of healing of grade III dermatitis in the application group was 3/7 as compared to the 0/14 of the control. Conclusion: Prophylactic application of recombinant human epidermal growth factor is able to postpone the development of radiation mucositis. This preparation is also able to lower the incidence of grade III, IV mucositis and dermatitis both by therapeutic and prophylactic application in addition to the hastened healing of grade III dermatitis

Serum and mucosal immune responses to an inactivated influenza virus vaccine induced by epidermal powder immunization.

Science.gov (United States)

Chen, D; Periwal, S B; Larrivee, K; Zuleger, C; Erickson, C A; Endres, R L; Payne, L G

2001-09-01

Both circulating and mucosal antibodies are considered important for protection against infection by influenza virus in humans and animals. However, current inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder delivery system elicits both serum and mucosal antibodies to an inactivated influenza virus vaccine. Serum antibody responses to influenza vaccine following EPI were enhanced by codelivery of cholera toxin (CT), a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the small intestine, trachea, and vaginal tract, although the titers were much lower than the IgG titers. The local origin of the sIgA antibodies was further shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influenza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, whereas a prime and boost immunizations were required for protection in the absence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.

Prevalence of oral mucosal lesions among chewing tobacco users: A cross-sectional study

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Sujatha S Reddy

2015-01-01

Statistical Analysis Used: Chi-square and Fisher′s exact tests were used to assess the statistical significance. Results: Of the 901 subjects with CT habits, 55.8% revealed no clinically detectable oral mucosal changes and 44.1% showed mucosal changes of which 63.8% were males and 36.1% were females. The most common finding was chewers mucositis (59.5% followed by submucous fibrosis (22.8%, leukoplakia (8%, lichenoid reaction (6.5%, oral cancer (2.7%, and lichen planus (0.5%. Conclusion: This study provides information about different CT habits and associated mucosal lesions among this population.

12 CFR 414.1 - Collection of conference and other fees.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Collection of conference and other fees. 414.1 Section 414.1 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES CONFERENCE AND OTHER FEES § 414.1 Collection of conference and other fees. Ex-Im Bank may impose and collect reasonable fees to cover the costs...

The therapeutic effect of PLAG against oral mucositis in hamster and mouse model

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Ha-Reum Lee

2016-10-01

Full Text Available Chemotherapy-induced mucositis can limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In this study, we investigated the therapeutic effect of PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride in 5-fluorouracil (5-FU-induced oral mucositis animal models. Hamsters were administered 5-FU (80 mg/kg intraperitoneally on days 0, 6, and 9. The animals’ cheek pouches were then scratched equally with the tip of an 18-gauge needle on days 1, 2, and 7. PLAG was administered daily at 250 mg/kg/day. PLAG administration significantly reduced 5-FU/scratching–induced mucositis. Dramatic reversal of weight loss in PLAG-treated hamsters with mucositis was observed. Histochemical staining data also revealed newly differentiated epidermis and blood vessels in the cheek pouches of PLAG-treated hamsters, indicative of recovery. Whole blood analyses indicated that PLAG prevents 5-FU–induced excessive neutrophil transmigration to the infection site and eventually stabilizes the number of circulating neutrophils. In a mouse mucositis model, mice with 5-FU–induced disease treated with PLAG exhibited resistance to body-weight loss compared with mice that received 5-FU or 5-FU/scratching alone. PLAG also dramatically reversed mucositis-associated weight loss and inhibited mucositis-induced inflammatory responses in the tongue and serum. These data suggest that PLAG enhances recovery from 5-FU–induced oral mucositis and may therefore be a useful therapeutic agent for treating side effects of chemotherapy, such as mucositis and cachexia.

Mucosal IgA Responses: Damaged in Established HIV Infection—Yet, Effective Weapon against HIV Transmission

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Viraj Kulkarni

2017-11-01

Full Text Available HIV infection not only destroys CD4+ T cells but also inflicts serious damage to the B-cell compartment, such as lymphadenopathy, destruction of normal B-cell follicle architecture, polyclonal hypergammaglobulinemia, increased apoptosis of B cells, and irreversible loss of memory B-cell responses with advanced HIV disease. Subepithelial B cells and plasma cells are also affected, which results in loss of mucosal IgG and IgA antibodies. This leaves the mucosal barrier vulnerable to bacterial translocation. The ensuing immune activation in mucosal tissues adds fuel to the fire of local HIV replication. We postulate that compromised mucosal antibody defenses also facilitate superinfection of HIV-positive individuals with new HIV strains. This in turn sets the stage for the generation of circulating recombinant forms of HIV. What can the mucosal B-cell compartment contribute to protect a healthy, uninfected host against mucosal HIV transmission? Here, we discuss proof-of-principle studies we have performed using passive mucosal immunization, i.e., topical administration of preformed anti-HIV monoclonal antibodies (mAbs as IgG1, dimeric IgA1 (dIgA1, and dIgA2 isotypes, alone or in combination. Our data indicate that mucosally applied anti-HIV envelope mAbs can provide potent protection against mucosal transmission of simian-human immunodeficiency virus. Our review also discusses the induction of mucosal antibody defenses by active vaccination and potential strategies to interrupt the vicious cycle of bacterial translocation, immune activation, and stimulation of HIV replication in individuals with damaged mucosal barriers.

Buccal mucosal urethroplasty for balanitis xerotica obliterans related urethral strictures: the outcome of 1 and 2-stage techniques.

Science.gov (United States)

Dubey, Deepak; Sehgal, Anand; Srivastava, Aneesh; Mandhani, Anil; Kapoor, Rakesh; Kumar, Anant

2005-02-01

Balanitis xerotica obliterans (BXO) related strictures are complex and generally managed by 2-staged urethroplasty. We present our results with 1-stage dorsal onlay and 2-stage buccal mucosal urethroplasty for such strictures. Between January 2000 and April 2004, 39 patients underwent buccal mucosal urethroplasty for BXO related anterior urethral strictures. The 25 patients with a salvageable urethral plate (group 1) were treated with 1-stage dorsal onlay urethroplasty using a cosmetic incision. The 14 patients with a severely scarred urethral plate, focally dense segments or active infection (group 2) underwent 2-stage urethroplasty. Outcomes in terms of cosmetic appearance, stricture recurrence and complications in the 2 groups were assessed. At a mean followup of 32.5 months (range 3 to 52) 3 patients (12%) in group 1 had recurrent stricture, of which 2 and 1 were treated with optical urethrotomy and urethral dilation, respectively. All patients had a normal slit-like meatus and none had chordee or erectile dysfunction. Four group 2 patients (28.6%) required stomal revision and 2 had glans cleft narrowing after stage 1 urethroplasty. Following stage 2, 3 patients had recurrent stricture, of whom 2 were treated with optical urethrotomy and 1 underwent repeat urethroplasty. In BXO related strictures with a viable urethral plate 1-stage dorsal onlay buccal mucosal urethroplasty provides excellent intermediate term results. The cosmetic incision described provides a normal, wide caliber, slit-like glans. Two-stage procedures provide satisfactory outcomes but they are associated with a higher revision rate.

Mucosal vaccines: recent progress in understanding the natural barriers.

Science.gov (United States)

Borges, Olga; Lebre, Filipa; Bento, Dulce; Borchard, Gerrit; Junginger, Hans E

2010-02-01

It has long been known that protection against pathogens invading the organism via mucosal surfaces correlates better with the presence of specific antibodies in local secretions than with serum antibodies. The most effective way to induce mucosal immunity is to administer antigens directly to the mucosal surface. The development of vaccines for mucosal application requires antigen delivery systems and immunopotentiators that efficiently facilitate the presentation of the antigen to the mucosal immune system. This review provides an overview of the events within mucosal tissues that lead to protective mucosal immune responses. The understanding of those biological mechanisms, together with knowledge of the technology of vaccines and adjuvants, provides guidance on important technical aspects of mucosal vaccine design. Not being exhaustive, this review also provides information related to modern adjuvants, including polymeric delivery systems and immunopotentiators.

Rectal mucosal electrosensitivity - what is being tested?

Science.gov (United States)

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

Mast cells contribute to the mucosal adjuvant effect of CTA1-DD after IgG-complex formation.

Science.gov (United States)

Fang, Yu; Larsson, Lisa; Mattsson, Johan; Lycke, Nils; Xiang, Zou

2010-09-01

Mast cell activation is one of the most dramatic immune-mediated responses the body can encounter. In the worst scenario (i.e., anaphylaxis), this response is fatal. However, the importance of mast cells as initiators and effectors of both innate and adaptive immunity in healthy individuals has recently been appreciated. It was reported that mast cell activation can be used as an adjuvant to promote Ag-specific humoral immune responses upon vaccination. In this study, we have used a clinically relevant mucosal adjuvant, cholera toxin A1 subunit (CTA1)-DD, which is a fusion protein composed of CTA1, the ADP-ribosylating part of cholera toxin, and DD, two Ig-binding domains derived from Staphylococcus aureus protein A. CTA1-DD in combination with polyclonal IgG induced degranulation and production of TNF-alpha from mouse mast cells. Furthermore, CTA1-DD and polyclonal IgG complex induced mast cell degranulation in mouse skin tissue and nasal mucosa. We also found that intranasal immunization with hapten (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to chicken gammaglobulin admixed with CTA1-DD complexed with polyclonal IgG greatly enhanced serum IgG anti-NP Ab responses and stimulated higher numbers of NP-specific plasma cells in the bone marrow as compared with that observed in mice immunized with NP-chicken gammaglobulin with CTA1-DD alone. This CTA1-DD/IgG complex-mediated enhancement was mast cell dependent because it was absent in mast cell-deficient Kit(W-sh/W-sh) mice. In conclusion, our data suggest that a clinically relevant adjuvant, CTA1-DD, exerts additional augmenting effects through activation of mucosal mast cells, clearly demonstrating that mast cells could be further exploited for improving the efficacy of mucosal vaccines.

Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity.

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Sya N Ukena

2007-12-01

Full Text Available Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs.To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order to analyze beneficial effects of EcN under inflammatory conditions, the probiotic was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up-regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to DSS-treated mice reduced the loss of body weight and colon shortening. In addition, infiltration of the colon with leukocytes was ameliorated in EcN inoculated mice. Acute DSS colitis did not result in an anion secretory defect, but abrogated the sodium absorptive function of the mucosa. Additionally, intestinal barrier function was severely affected as evidenced by a strong increase in the mucosal uptake of Evans blue in vivo. Concomitant administration of EcN to DSS treated animals resulted in a significant protection against intestinal barrier dysfunction and IECs isolated from these mice exhibited a more pronounced expression of ZO-1.This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.

Abstracts of the Canadian Society for Civil Engineering annual conference including the general conference, the 1. international structural specialty conference, the 1. international construction specialty conference, and the 1. specialty conference on disaster mitigation : towards a sustainable future

International Nuclear Information System (INIS)

El-Badry, M.; Loov, R.E.; Ruwanpura, J.; El-Hacha, R.; Kroman, J.; Rankin, J.

2006-01-01

This conference provided a forum for national and international practicing engineers, researchers and technical experts to discuss sustainable solutions to infrastructure development. Discussions focused on recent developments in new technologies for building more economic and sustainable infrastructure, while improving the safety of buildings, bridges, roads, water supply and sewage treatment systems. The conference was held in conjunction with associated specialty conferences, including a first international structures specialty conference, a first international construction specialty conference, and a first specialty conference on disaster mitigation. This book of abstracts highlights all the specialty conferences and accompanies a CD-ROM that has the full text of all the papers. Manuscripts of the full papers submitted to the specialty conferences were peer-reviewed by international scientific committees. The general conference provided a forum to learn about new technologies and future directions in various areas of civil engineering. It included a special theme session on sustainable development and a special session on innovation and information technology. Other technical sessions focused on topics such as civil engineering history and education; infrastructure management and renewal; asset management; risk assessment and management; engineering materials and mechanics; environmental engineering and science; hydrotechnical engineering; cold region engineering; and, transportation engineering. The general conference featured 88 presentations, of which 15 have been catalogued separately for inclusion in this database

Prolonged protection against Intranasal challenge with influenza virus following systemic immunization or combinations of mucosal and systemic immunizations with a heat-labile toxin mutant.

Science.gov (United States)

Zhou, Fengmin; Goodsell, Amanda; Uematsu, Yasushi; Vajdy, Michael

2009-04-01

Seasonal influenza virus infections cause considerable morbidity and mortality in the world, and there is a serious threat of a pandemic influenza with the potential to cause millions of deaths. Therefore, practical influenza vaccines and vaccination strategies that can confer protection against intranasal infection with influenza viruses are needed. In this study, we demonstrate that using LTK63, a nontoxic mutant of the heat-labile toxin from Escherichia coli, as an adjuvant for both mucosal and systemic immunizations, systemic (intramuscular) immunization or combinations of mucosal (intranasal) and intramuscular immunizations protected mice against intranasal challenge with a lethal dose of live influenza virus at 3.5 months after the second immunization.

Superfund XV conference proceedings. Volume 1

International Nuclear Information System (INIS)

Anon.

1994-01-01

This conference was held November 29--December 1, 1994 in Washington, D.C..The purpose of this conference was to provide a forum for exchange of state-of-the-art information on Superfund. Papers are included on the following topics: bioremediation; building decontamination; environmental policy issues; federal environmental restoration; groundwater remediation; innovative sampling and analytical technologies; laboratory methods; metals management; mixed wastes; PCB waste management; remediation technology and case studies; and risk assessment. Individual papers have been processed separately for inclusion in the appropriate data bases

Radiation-induced mucositis pain in laryngeal cancer

International Nuclear Information System (INIS)

Takahashi, Atsuhito; Shoji, Kazuhiko; Iki, Takehiro; Mizuta, Masanobu; Matsubara, Mami

2009-01-01

Radiation therapy in those with head and neck malignancies often triggers painful mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). To better understand how radiation-induced pain develops over time, we studied the numerical rating scale (NRS 0-5) pain scores from 32 persons undergoing radiation therapy of 60-72 Gy for newly diagnosed laryngeal cancer. The degree of mucositis was evaluated using Common Terminology Criteria for Adverse Events version3.0 (CTCAE v3.0). We divided the 32 into a conventional fractionation (CF) group of 14 and a hyperfractionation (HF) group of 18, and further divided laryngeal cancer into a small-field group of 23 and a large-field group of 9. The mucositis pain course was similar in CF and HF, but mucositis pain was severer in the HF group, which also required more NSAIDs. Those in the large-field group had severer pain and mucositis and required more NSAIDs than those in the small-field group. We therefore concluded that small/large-field radiation therapy, rather fractionation type, was related to the incidence of radiation-induced mucositis pain. (author)

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

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Reda RI

2017-03-01

Full Text Available Rana Ihab Reda,1 Ming Ming Wen,2 Amal Hassan El-Kamel1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 2Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt 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

Respuesta inmune mucosal inducida por proteoliposoma y cocleato derivados de N. meningitidis serogrupo B

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Judith del Campo

2009-08-01

Full Text Available Mucosal vaccination offers attractive advantages to conventional systemic vaccination. Most pathogens enter or establish infection at mucosal surfaces. This represents an enormous challenge for vaccine development. Nevertheless, the availability of safe and effective adjuvants that function mucosally is the major limitation. Therefore, we investigated the impact of mucosal immunization with the Neisseria meningitidis B proteoliposome (AFPL1, Adjuvant Finlay Proteoliposome 1 and its-derived cochleate (Co, AFCo1. They contain multiple PAMPs as immunopotentiators and have delivery system ability as well as Th1 polarization activity. Groups of female mice were immunized by nasal, oral, intravaginal, or intramuscular routes with three doses with AFPL1/AFCo1 alone or containing ovalbumin or glycoprotein (g D2 from Herpes Simplex Virus type 2 (HSV-2. High levels of specific IgG antibodies were detected in sera of mice vaccinated with either route. However, specific IgA antibodies were produced in saliva and vaginal wash only following mucosal delivering. The polarization to a Th1 pattern was confirmed by testing the induction of IgG2a/IgG2c antibody, positive delayed-type hypersensitivity reactions, and gIFN production. Additionally, AFCo1gD2 showed practically no vaginal HSV-2 replication and 100% protection against lethal vaginal HSV-2 challenge. In conclusion, the results support the use of AFCo1 as potent Th1 adjuvant for mucosal vaccines, particularly for nasal route.

Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection

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Wu Li

2012-01-01

Full Text Available Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis (TB, is one of the world's leading infectious causes of morbidity and mortality. As a mucosal-transmitted pathogen, Mtb infects humans and animals mainly through the mucosal tissue of the respiratory tract. Apart from providing a physical barrier against the invasion of pathogen, the major function of the respiratory mucosa may be to serve as the inductive sites to initiate mucosal immune responses and sequentially provide the first line of defense for the host to defend against this pathogen. A large body of studies in the animals and humans have demonstrated that the mucosal immune system, rather than the systemic immune system, plays fundamental roles in the host’s defense against Mtb infection. Therefore, the development of new vaccines and novel delivery routes capable of directly inducing respiratory mucosal immunity is emphasized for achieving enhanced protection from Mtb infection. In this paper, we outline the current state of knowledge regarding the mucosal immunity against Mtb infection, including the development of TB vaccines, and respiratory delivery routes to enhance mucosal immunity are discussed.

Can the oral microflora affect oral ulcerative mucositis?

NARCIS (Netherlands)

Laheij, A.M.G.A.; de Soet, J.J.

2014-01-01

Purpose of review: Oral mucositis is one of the most prevalent toxicities after hematopoietic stem cell transplantation. Mucositis is initiated by the chemotherapy or radiotherapy preceding the transplantation. It is commonly accepted that microorganisms play a role in the process of oral mucositis.

Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor 1

DEFF Research Database (Denmark)

Bisgaard, H.C.; Holmskov, U.; Santoni-Rugiu, E.

2002-01-01

The regenerative capacity of mammalian adult liver reflects the ability of a number of cell populations within the hepatic lineage to take action. Limited information is available regarding factors and mechanisms that determine the specific lineage level at which liver cells contribute to liver......), were specifically associated with the emergence of ductular (oval) cell populations in injured liver. Subsequent cloning and characterization of the rat DMBT1 homologue revealed a highly inducible expression in ductular reactions composed of transit-amplifying ductular (oval) cells, but not in ductular...... reactions after ligation of the common bile duct. In human liver diseases, DMBT1 was expressed in ductular reactions after infection with hepatitis B and acetaminophen intoxication, but not in primary biliary cirrhosis, primary sclerosing cholangitis, and obstruction of the large bile duct. The expression...

The identification of plant lectins with mucosal adjuvant activity

Science.gov (United States)

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'hagan, D T

2001-01-01

To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic. PMID:11168640

Scoring irradiation mucositis in head and neck cancer patients

International Nuclear Information System (INIS)

Spijkervet, F.K.L.; Panders, A.K.; Saene, H.K.F. van; Vermey, A.; Mehta, D.M.

1989-01-01

Irradiation mucositis is defined as an inflammatory-like process of the oropharyngeal mucosa following therapeutic irradiation of patients who have head and neck cancer. Clinically, it is a serious side effect because severe mucositis can cause generalized problems (weight loss, nasogastic tube feedings) and interferes with the well-being of the patient seriously. Grading mucositis is important for the evaluation of preventive and therapeutic measures. The object of this study was to develop a scoring method based on local mucositis signs only. Four clinical local signs of mucositis were used in this score: white discoloration, erythema, pseudomembranes and ulceration. Mucositis of the oral cavity was calcualted during conventional irradiation protocol for 8 distinguishable areas using the 4 signs and their extent. A prospective evaluation of this method in 15 irradiated head and neck cancer patients displayed an S-curve reflecting a symptomless first irradiation week, followed by a rapid and steady increase of white discoloration, erythema and pseudomembranes during the second and third week. Oral candidiasis, generalized symptoms such as weight loss and the highest mucositis scores were seen after 3 weeks irradiation. The novel mucositis scoring method may be of value in studying the effect of hygiene programs, topical application of disinfectans or antibiotics on oral mucositis. (author)

Scoring irradiation mucositis in head and neck cancer patients

Energy Technology Data Exchange (ETDEWEB)

Spijkervet, F.K.L.; Panders, A.K. (Departments of Oral and Maxillofacial Surgery, University Hospital Groningen (Netherlands)); Saene, H.K.F. van (Medical Microbiology, University of Liverpool (UK)); Vermey, A. (Department of Surgery Oncology Division, University Hospital Groningen (Netherlands)); Mehta, D.M. (Department of Radiotherapy, University Hospital Groningen (Netherlands))

1989-01-01

Irradiation mucositis is defined as an inflammatory-like process of the oropharyngeal mucosa following therapeutic irradiation of patients who have head and neck cancer. Clinically, it is a serious side effect because severe mucositis can cause generalized problems (weight loss, nasogastic tube feedings) and interferes with the well-being of the patient seriously. Grading mucositis is important for the evaluation of preventive and therapeutic measures. The object of this study was to develop a scoring method based on local mucositis signs only. Four clinical local signs of mucositis were used in this score: white discoloration, erythema, pseudomembranes and ulceration. Mucositis of the oral cavity was calcualted during conventional irradiation protocol for 8 distinguishable areas using the 4 signs and their extent. A prospective evaluation of this method in 15 irradiated head and neck cancer patients displayed an S-curve reflecting a symptomless first irradiation week, followed by a rapid and steady increase of white discoloration, erythema and pseudomembranes during the second and third week. Oral candidiasis, generalized symptoms such as weight loss and the highest mucositis scores were seen after 3 weeks irradiation. The novel mucositis scoring method may be of value in studying the effect of hygiene programs, topical application of disinfectans or antibiotics on oral mucositis. (author).

BISPHOSPHONATE - RELATED MUCOSITIS (BRM: A CASE REPORT

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Pavel Stanimirov

2017-03-01

Full Text Available Bisphosphonates (BPs are the most widely used and effective antiresorptive agents for the treatment of diseases in which there is an increase in osteoclastic resorption, including post-menopausal osteoporosis, Paget’s disease, and tumor-associated osteolysis. Oral and maxillofacial surgeons are well aware of the side effects of bisphosphonates and mainly with bisphosphonate-related osteonecrosis of the jaws (BRONJ. Less known are the mucosal lesions associated with the use of these agents. In the scientific literature, there are only few reports of mucosal lesions due to the direct contact of the oral form of BPs with the mucosa (bisphosphonate-related mucositis. They are mostly related to improper use of bisphosphonate tablets that are chewed, sucked or allowed to melt in the mouth before swallowing. Lesions are atypical and need to be differentiated from other mucosal erosions. We present a case of bisphosphonate-related mucositis due to the improper use of alendronate.

ٍEvaluating Baremoom Mouthwash Efficacy in Treatment of Chemotherapy-Induced Mucositis

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MH Akhavan Karbasi

2016-03-01

Full Text Available Introduction: Chemotherapy-induced oral mucositis is regarded as a painful and discomforting chemotherapy complication , affecting patient’s quality of life and endurance to continue the treatment. Hence, treatment of mucositis is of great significance. The present study was conducted to evaluate the effect of Baremoom mouthwash in treatment of chemotherapy-induced mucositis . Methods: This interventional double-blinded randomized clinical trial study was performed on 40 adult patients under chemotherapy in blood and oncology department of Shahid Sadouqhi hospital. The total of 40 patients were randomly divided into two groups: an experimental baremoom group and a control placebo group each containing 20 subjects. Baremoom mouthwash (30% extract, Soren Tektoos, Mashhad and placebo mouthwash ( Sterile water with allowable additives ,Soren Tektoos, Mashhad with same apparent properties were given to the patients (3 times a day for 7 days after mucositis detection. The patients were evaluated in regard with mucositis grade (0-4 WHO and wounds extension on 1th , 3th and 7th days after the study begining. In order to statistically analyze the collected data, Freidman, Mann–Whitney, and wilcoxon W tests were applied utilizing SPSS software (ver, 17. Results: On 3rd  and 7th  days, mean degree of wound extension and mucositis were demonstrated to be significantly different between the two groups. According to Friedman test, both experimental and control groups revealed a significant difference in regard with wound extension and mucositis grade within the three time periods. Conclusion: The study findings indicated that Baremoom mouthwash was more effective in chemotherapy- induced mucositis than placebo. Hence, this agent can be recommended as an appropriate medicine in order to eliminate mucositis symtoms and decrease oral ulcers.

Sixteenth International Laser Radar Conference, Part 1

International Nuclear Information System (INIS)

Mccormick, M.P.

1992-07-01

This publication contains extended abstracts of papers presented at the 16th International Laser Radar Conference. One-hundred ninety-five papers were presented in both oral and poster sessions. The topics of the conference sessions were: (1) Mt. Pinatubo Volcanic Dust Layer Observations; (2) Global Change/Ozone Measurements; (3) GLOBE/LAWS/LITE; (4) Mesospheric Measurements and Measurement Systems; (5) Middle Atmosphere; (6) Wind Measurements and Measurement Systems; (7) Imaging and Ranging; (8) Water Vapor Measurements; (9) Systems and Facilities; and (10) Laser Devices and Technology. This conference reflects the breadth of research activities being conducted in the lidar field. These abstracts address subjects from lidar-based atmospheric investigations relating to global change to the development of new lidar systems and technology

Mimicking herpes simplex virus 1 and herpes simplex virus 2 mucosal behavior in a well-characterized human genital organ culture.

Science.gov (United States)

Steukers, Lennert; Weyers, Steven; Yang, Xiaoyun; Vandekerckhove, Annelies P; Glorieux, Sarah; Cornelissen, Maria; Van den Broeck, Wim; Temmerman, Marleen; Nauwynck, Hans J

2014-07-15

We developed and morphologically characterized a human genital mucosa explant model (endocervix and ectocervix/vagina) to mimic genital herpes infections caused by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Subsequent analysis of HSV entry receptor expression throughout the menstrual cycle in genital tissues was performed, and the evolution of HSV-1/-2 mucosal spread over time was assessed. Nectin-1 and -2 were expressed in all tissues during the entire menstrual cycle. Herpesvirus entry mediator expression was limited mainly to some connective tissue cells. Both HSV-1 and HSV-2 exhibited a plaque-wise mucosal spread across the basement membrane and induced prominent epithelial syncytia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Surgical outcome in headache due to mucosal contact

International Nuclear Information System (INIS)

Goto, Fumiyuki; Yabe, Haruna; Ogawa, Kaoru

2010-01-01

Headaches is classified as primary and secondary, with secondary originating in head and neck conditions, the most important etiology being acute sinusitis. Headache due to mucosal contact, rarely encountered by otorhinolaryngologists, is an important secondary headache, whose criteria are defined by the International Classification of Headache Disorders to include intermittent pain localized in the periorbital and medial canthal or temporozygomatic regions, evidence that pain is attributable to mucosal contact and the presence of mucosal contact in the absence of acute rhinosinusitis, obtained using clinical examinations, nasal endoscopy, and/or computed tomography (CT). After mucosal contact is surgically corrected pain usually disappears permanently within 7 days. We reviewed mucosal contact headaches in 63 subjects undergoing nasal or paranasal surgery from April 2007 to March 2008. Of those 7 were diagnosed with headaches due to contact points in nasal mucosa, ranging from canthal to the temporozygomatic. The most common contact, between the middle turbinate and nasal septum, was seen in 6 of the 7. Surgery eliminated symptoms in 4 and ameliorated them in 3 indicating effective headache management. Subjects with severe headaches or localized periorbital and medial canthal pain regions, mucosal contact involvement is ruled out when CT allows no lesions. When mucosal contact headache is suspected, however surgery should be considered as a last resort. (author)

Microgravity Materials Science Conference 2000. Volume 1

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Ramachandran, Narayanan (Editor); Bennett, Nancy (Editor); McCauley, Dannah (Editor); Murphy, Karen (Editor); Poindexter, Samantha (Editor)

2001-01-01

This is Volume 1 of 3 of the 2000 Microgravity Material Science Conference that was held June 6-8 at the Von Braun Center, Huntsville, Alabama. It was organized by the Microgravity Materials Science Discipline Working Group, sponsored by the Microgravity Research Division (MRD) at NASA Headquarters, and hosted by NASA Marshall Space Flight Center and the Alliance for Microgravity Materials Science and Applications (AMMSA). It was the fourth NASA conference of this type in the microgravity materials science discipline. The microgravity science program sponsored approx. 200 investigators, all of whom made oral or poster presentations at this conference. In addition, posters and exhibits covering NASA microgravity facilities, advanced technology development projects sponsored by the NASA Microgravity Research Division at NASA Headquarters, and commercial interests were exhibited. The purpose of the conference was to inform the materials science community of research opportunities in reduced gravity and to highlight the Spring 2001 release of the NASA Research Announcement (NRA) to solicit proposals for future investigations. It also served to review the current research and activities in materials science, to discuss the envisioned long-term goals. and to highlight new crosscutting research areas of particular interest to MRD. The conference was aimed at materials science researchers from academia, industry, and government. A workshop on in situ resource utilization (ISRU) was held in conjunction with the conference with the goal of evaluating and prioritizing processing issues in Lunar and Martian type environments. The workshop participation included invited speakers and investigators currently funded in the material science program under the Human Exploration and Development of Space (HEDS) initiative. The conference featured a plenary session every day with an invited speaker that was followed by three parallel breakout sessions in subdisciplines. Attendance was

Proximal Gut Mucosal Epithelial Homeostasis in Aged IL-1 Type I Receptor Knockout Mice After Starvation

Science.gov (United States)

2011-08-01

increases whole-body lean mass and insulin sensitivity in elderly subjects with sarcopenia . Am J Cardiol. 2008; 101:69E. [PubMed: 18157968] 11. Iwakiri R...nutritional deficiencies in the elderly can be corrected by nutritional supplementation [5-7], especially among patients who are fed enterally [8-10...mechanistic approach regarding intestinal cell dysfunction in the elderly . Starvation causes mucosal atrophy and loss of mucosal height [32], and glutamine

Experiences with Pontal syrup in mucositis caused by radiotherapy

International Nuclear Information System (INIS)

Miyamoto, Hiroshi; Yamashita, Shoji; Hashimoto, Teisuke; Kunieda, Etsuo; Hashimoto, Shozo

1983-01-01

Pontal syrup was administered at daily dose of 30 ml t. i. d. to 17 patients of mucositis developed due to radiotherapy against malignant tumor. Results were: Remarkably effective-5 cases, effective-8 cases, slightly effective-3 cases, and non-effective-1 case. Certain effects were observed in 16 cases out of 17 cases/94.1%, excluding only one non-effective case. No side-effects were observed in all cases. It is considered that Pontal syrup is a drug useful for mucositis caused by radiotherapy because of its easiness of administration and also of its characteristic of non-stimulant. (author)

The postnatal development of the mucosal immune system and mucosal tolerance in domestic animals

OpenAIRE

Bailey , Mick; Haverson , Karin

2006-01-01

International audience; The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting...

Evidence for a common mucosal immune system in the pig.

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Wilson, Heather L; Obradovic, Milan R

2015-07-01

The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

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Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

Neonatal mucosal immunology.

Science.gov (United States)

Torow, N; Marsland, B J; Hornef, M W; Gollwitzer, E S

2017-01-01

Although largely deprived from exogenous stimuli in utero, the mucosal barriers of the neonate after birth are bombarded by environmental, nutritional, and microbial exposures. The microbiome is established concurrently with the developing immune system. The nature and timing of discrete interactions between these two factors underpins the long-term immune characteristics of these organs, and can set an individual on a trajectory towards or away from disease. Microbial exposures in the gastrointestinal and respiratory tracts are some of the key determinants of the overall immune tone at these mucosal barriers and represent a leading target for future intervention strategies. In this review, we discuss immune maturation in the gut and lung and how microbes have a central role in this process.

Sucralfate for the treatment of radiation induced mucositis

International Nuclear Information System (INIS)

Belka, C.; Hoffmann, W.; Paulsen, F.; Bamberg, M.

1997-01-01

Purpose: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. Patients and Method: The results of available studies are analysed and discussed. Results: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. Conclusion: Nevertheless sucralfate is a save, cheap and active drug for the prevention and treatment of radiation mucositis especially in patients with pelvic irradiation. (orig.) [de

Cutaneous and mucosal pain syndromes

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Siddappa K

2002-01-01

Full Text Available The cutaneous and mucosal pain syndromes are characterized by pain, burning sensation, numbness or paraesthesia of a particular part of the skin or mucosal surface without any visible signs. They are usually sensory disorders, sometimes with a great deal of psychologic overlay. In this article various conditions have been listed and are described. The possible causative mechanisms are discussed when they are applicable and the outline of their management is described.

Management of mucositis in oral irradiation

Energy Technology Data Exchange (ETDEWEB)

Feber, T. [Cookridge Hospital, Leeds (United Kingdom)

1996-10-01

Mucositis significantly affects quality of life and tolerance of treatment in oral irradiation. Effective management of this complication is therefore very important. However, there is a scarcity of up-to-date oral care protocols, with most centres using ritualized regimens. The literature on oral rinses in radiation mucositis is at best inconclusive and at worst confusing. In this study, patients undergoing radical radiotherapy treatment (55-60 Gy in 4 weeks) to more than 50% of the oral cavity and oropharynx were randomized to a research based oral care protocol with either saline 0.9% or hydrogen peroxide 3.5 volumes (HP) as rinses. The results of this study show that, on average, the group receiving saline rinses appeared to do better on some outcomes than the group receiving HP. This suggests that frequent mechanical cleansing of the mouth may be more important than the antiseptic properties of a mouthwash. Antiseptic mouthwashes may be contra-indicated in radiation mucositis. In order to determine best practice in mucositis management, multicentre, multidisciplinary trials should be conducted. (Author).

Management of mucositis in oral irradiation

International Nuclear Information System (INIS)

Feber, T.

1996-01-01

Mucositis significantly affects quality of life and tolerance of treatment in oral irradiation. Effective management of this complication is therefore very important. However, there is a scarcity of up-to-date oral care protocols, with most centres using ritualized regimens. The literature on oral rinses in radiation mucositis is at best inconclusive and at worst confusing. In this study, patients undergoing radical radiotherapy treatment (55-60 Gy in 4 weeks) to more than 50% of the oral cavity and oropharynx were randomized to a research based oral care protocol with either saline 0.9% or hydrogen peroxide 3.5 volumes (HP) as rinses. The results of this study show that, on average, the group receiving saline rinses appeared to do better on some outcomes than the group receiving HP. This suggests that frequent mechanical cleansing of the mouth may be more important than the antiseptic properties of a mouthwash. Antiseptic mouthwashes may be contra-indicated in radiation mucositis. In order to determine best practice in mucositis management, multicentre, multidisciplinary trials should be conducted. (Author)

Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperature.

Science.gov (United States)

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 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.

Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response

Science.gov (United States)

Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin

2010-01-01

Background/Aims Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1 levels could be used to determine the outcome after H. pylori infection. Methods Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression, whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation. PMID:20479912

Suppressed Gastric Mucosal TGF-beta1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response.

Science.gov (United States)

Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin; Hahm, Ki-Baik

2010-03-01

Loss of transforming growth factor beta1 (TGF-beta1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-beta1 levels could be used to determine the outcome after H. pylori infection. Northern blot for the TGF-beta1 transcript, staining of TGF-beta1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-beta1 levels were performed at different times after H. pylori infection. The TGF-beta1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-beta1 levels. SNU-16 cells showing intact TGF-beta signaling exhibited a marked decrease in TGF-beta1 expression, whereas SNU-638 cells defective in TGF-beta signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-beta1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-beta1 is a host defense mechanism to avoid attachment of H. pylori. H. pylori infection was associated with depressed gastric mucosal TGF-beta1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.

An Epidemiological Study of Oral Mucosal Lesions in Karnataka State, India

Directory of Open Access Journals (Sweden)

K. V. V Prasad

2004-01-01

Full Text Available This article presents oral mucosal lesions findings from a state oral health survey of Karnataka, India. A total of 46,579 subjects aged 1-4 to 65+ years were selected by using multistage-cluster-stratified random sampling method and subjects were examined by 32 dentists trained in standardized clinical diagnostic criteria for oral mucosal lesions. In the present study, 7.53% of subjects had one or more oral mucosal lesions, in which, male subjects (9.41 % had a significantly higher prevalence of lesions compared to female subjects (4.38%; urban subjects (11.61% had a significantly higher prevalence than rural subjects (5.01 % and the Christian subjects had a significantly higher prevalence of lesions than the Hindus, Muslims and others (F=211.594, <0.001, S. The observed prevalence of oral mucosal lesions increased with age (r=0.8174, P<0.05, S, which is statistically significant. The most prevalent lesions observed were Leukoplakia (1.73%, Lichen planus (2.02% Ulceration (0.73%, Candidiasis (0.94% and Abscess (1.05%. The maximum number of lesions was seen in sulci (7.33% and the minimum number of lesions was seen in lips (0.02%. Differences in prevalence were analyzed by sex, religion, location and geographical area.

Dysphagia and mucositis after concurrent chemoradiotherapy for head and neck cancer

International Nuclear Information System (INIS)

Tsuneyuki, Miki; Maeda, Tatsuyoshi; Yonezawa, Koichiro; Morimoto, Koichi; Tanimoto, Hitoshi; Saito, Miki; Otsuki, Naoki; Nibu, Ken-ichi

2010-01-01

A speech therapist performs swallowing rehabilitation in this hospital because concurrent chemoradiotherapy (CCRT) for head and neck cancer is commonly associated with, dysphagia. An evaluation of oral mucositis and dysphagia after CCRT was conducted to determine the relationship between swallowing rehabilitation and swallowing disability. A total of 51 patients (44 males and 7 females) with a mean age of 63 years (range, 39 to 80), underwent CCRT with or without neck dissection between April 2008 and November 2009. Oral mucositis and dysphagia were graded at the end of CCRT according to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Seventeen of 51 patients underwent swallowing rehabilitation, exercise and education on muscle strengthening programs before and during CCRT. The average grades of oral mucositis of patients with nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal cancer patients were 1.8, 2.1, 1.8, and 0.8, respectively. There was a lower incidence of oral mucositis in patients with laryngeal cancer than in those with oropharyngeal or hypopharyngeal cancer. The average grades of dysphagia of patients with nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal cancer were 2.4, 2.7, 2.2, and 1.2. Dysphagia was most severe in the patients with oropharyngeal cancer, while it was minimal in those with laryngeal cancer. Seventeen diligent patients that underwent swallowing rehabilitation every day rarely developed severe dysphagia. (author)

Evaluation of edaravone against radiation-induced oral mucositis in mice.

Science.gov (United States)

Nakajima, Noriko; Watanabe, Shinichi; Kiyoi, Takeshi; Tanaka, Akihiro; Suemaru, Katsuya; Araki, Hiroaki

2015-03-01

Oral mucositis induced by radiotherapy for cancers of the head and neck reduce the quality of life of patients. However, effective therapeutic agents are lacking. Symptomatic treatment involves local anesthesia and analgesia. We focused on the antioxidant effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut(®)). Oral mucositis was induced on the tongue tips of mice using a single dose of X-rays (20 Gy). To evaluate the protective effect of edaravone (30 and 300 mg/kg), administration was carried out 30 min before irradiation. Survival, oral mucositis score, myeloperoxidase activity, and levels of 2-Thiobarbituric acid reactive substances were measured, and all were improved compared with those of control mice. A significant difference was not found in terms of survival due to edaravone. Histopathologic findings also highlighted the beneficial features of edaravone. Edaravone reduced the production of reactive oxygen species. These findings suggest that the protective effect of edaravone against radiation-induced oral mucositis is through an antioxidant effect. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Evaluation of edaravone against radiation-induced oral mucositis in mice

Directory of Open Access Journals (Sweden)

Noriko Nakajima

2015-03-01

Full Text Available Oral mucositis induced by radiotherapy for cancers of the head and neck reduce the quality of life of patients. However, effective therapeutic agents are lacking. Symptomatic treatment involves local anesthesia and analgesia. We focused on the antioxidant effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut®. Oral mucositis was induced on the tongue tips of mice using a single dose of X-rays (20 Gy. To evaluate the protective effect of edaravone (30 and 300 mg/kg, administration was carried out 30 min before irradiation. Survival, oral mucositis score, myeloperoxidase activity, and levels of 2-Thiobarbituric acid reactive substances were measured, and all were improved compared with those of control mice. A significant difference was not found in terms of survival due to edaravone. Histopathologic findings also highlighted the beneficial features of edaravone. Edaravone reduced the production of reactive oxygen species. These findings suggest that the protective effect of edaravone against radiation-induced oral mucositis is through an antioxidant effect.

Role of CTA1R7K-COL-DD as a novel therapeutic mucosal tolerance-inducing vector for treatment of collagen-induced arthritis.

Science.gov (United States)

Hasselberg, Annemarie; Schön, Karin; Tarkowski, Andrej; Lycke, Nils

2009-06-01

To determine whether a cholera toxin-derived, novel immunomodulating fusion protein, CTA1R7K-COL-DD, carrying the class II major histocompatibility complex H-2q-restricted type II collagen peptide aa 259-274, can induce therapeutic tolerance and prevent collagen-induced arthritis (CIA) when administered intranasally in DBA/1 mice, and to assess whether ADP-ribosylation at the mucosal membranes exerts a regulatory function such that the outcome of tolerance or immune enhancement can be controlled. DBA/1 mice with CIA were treated intranasally with CTA1R7K-COL-DD. The therapeutic effect was monitored for 46 days after the onset of disease. Clinical scoring of disease, histologic examination of inflammation, and bone erosion were assessed, and cytokine levels were determined in the serum or supernatants from splenocytes stimulated with recall antigen. The protective effect of CTA1R7K-COL-DD resulted in roughly 60% of the mice having no clinical signs or histologic evidence of disease after treatment, and those with CIA had significantly milder disease with less bone erosion. The protective status was associated with lower serum titers of IgG1, IgG2a, IgG2b, and IgG3 anticollagen and a substantial decrease in the production of interleukin-6 (IL-6), IL-17, and interferon-gamma, while levels of IL-10 were markedly up-regulated both in the serum and at the T cell level. The enzymatically inactive mutant fusion protein CTA1R7K-COL-DD provided substantial therapeutic protection against CIA following intranasal administration. The mechanism behind the effect appears to be mediated by peptide-specific regulatory T cells induced by mucosal exposure to the peptide containing CTA1R7K-COL-DD vector. In addition, ADP-ribosylation at the mucosal membranes acts as a key regulator controlling mucosal tolerance or immunity.

Dermoscopic appearance of an amelanotic mucosal melanoma

Science.gov (United States)

Blum, Andreas; Beck-Zoul, Ulrike; Held, Laura; Haase, Sylvie

2016-01-01

Background Hypomelanotic or amelanotic melanomas are challenging to identify, especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal melanomas have been reported to be structureless zones with the presence of blue, gray, or white colors. Case A female in her seventies noted a new lesion on the inside of her right labia that first appeared two months prior. Her past medical history was significant for rheumatoid arthritis requiring ongoing treatment with methotrexate for 20 years and adalimumab for 10 years. After no response to two weeks of local treatment for suspected herpes simplex infection, her gynecologist performed a skin biopsy. Based on the histopathological diagnosis of an amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to dermatology for further assessment. Polarized dermoscopy revealed a distinct asymmetric, sharply demarcated homogenous white papule (4 × 5 mm) as well as polymorphous vessels. Conclusion Dermoscopy may aid in the diagnosis of amelanotic mucosal melanomas. Our case revealed a structureless white area and polymorphous vessels. Additional clues to the diagnosis were the advanced age of the patient and the clinical presentation of a new lesion. PMID:27867742

Probiotic supplements and debridement of peri-implant mucositis

DEFF Research Database (Denmark)

Hallström, Hadar; Lindgren, Susann; Widén, Cecilia

2016-01-01

OBJECTIVE: The aim of this double-blind randomized placebo-controlled trial was to evaluate the effects of probiotic supplements in adjunct to conventional management of peri-implant mucositis. MATERIALS AND METHODS: Forty-nine adult patients with peri-implant mucositis were consecutively recruited...... debridement and oral hygiene reinforcement resulted in clinical improvement of peri-implant mucositis and a reduction in cytokine levels. Probiotic supplements did not provide added benefit to placebo....

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Directory of Open Access Journals (Sweden)

Cielito C Reyes-Gibby

Full Text Available Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA, a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive and thymine degradation pathways (p = 1.06-08 were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis. The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67. In conclusion, gene network analysis identified novel molecules and

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Science.gov (United States)

Reyes-Gibby, Cielito C; Melkonian, Stephanie C; Wang, Jian; Yu, Robert K; Shelburne, Samuel A; Lu, Charles; Gunn, Gary Brandon; Chambers, Mark S; Hanna, Ehab Y; Yeung, Sai-Ching J; Shete, Sanjay

2017-01-01

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06-08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological

Immunology of Gut Mucosal Vaccines

Science.gov (United States)

Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

2011-01-01

Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

7 CFR 1.140 - Conferences and procedure.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Conferences and procedure. 1.140 Section 1.140 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Rules of Practice Governing...) An outline of the case or defense; (ii) The legal theories upon which the party will rely; (iii...

Mucosal complications of modified osteo-odonto keratoprosthesis in chronic Stevens-Johnson syndrome.

Science.gov (United States)

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.

Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis.

Science.gov (United States)

Marie, I; Antonietti, M; Houivet, E; Hachulla, E; Maunoury, V; Bienvenu, B; Viennot, S; Smail, A; Duhaut, P; Dupas, J-L; Dominique, S; Hatron, P-Y; Levesque, H; Benichou, J; Ducrotté, P

2014-07-01

To date, there are no large studies on videocapsule endoscopy in systemic sclerosis (SSc). Consequently, the prevalence and features of gastrointestinal mucosal abnormalities in SSc have not been determined. To determine both prevalence and characteristics of gastrointestinal mucosal abnormalities in unselected patients with SSc, using videocapsule endoscopy. To predict which SSc patients are at risk of developing potentially bleeding gastrointestinal vascular mucosal abnormalities. Videocapsule endoscopy was performed on 50 patients with SSc. Prevalence of gastrointestinal mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were predominant, including: watermelon stomach (34.6%), gastric and/or small intestinal telangiectasia (26.9%) and gastric and/or small intestinal angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P = 0.02), lower levels of ferritin (P correlation between gastrointestinal vascular mucosal lesions and presence of severe extra-digestive vasculopathy (digital ulcers and higher nailfold videocapillaroscopy scores). This latter supports the theory that SSc-related diffuse vasculopathy is responsible for both cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold videocapillaroscopy may be a helpful test for managing SSc patients. In fact, nailfold videocapillaroscopy score should be calculated routinely, as it may result in identification of SSc patients at higher risk of developing potentially bleeding gastrointestinal vascular mucosal lesions. © 2014 John Wiley & Sons Ltd.

A regenerative approach towards mucosal fenestration closure

Science.gov (United States)

Gandi, Padma; Anumala, Naveen; Reddy, Amarender; Viswa Chandra, Rampalli

2013-01-01

Mucosal fenestration is an opening or an interstice through the oral mucosa. A lesion which occurs with greater frequency than generally realised, its occurrence is attributed to a myriad of causes. Mucogingival procedures including connective tissue grafts, free gingival grafts and lateral pedicle grafts are generally considered to be the treatment of choice in the closure of a mucosal fenestration. More often, these procedures are performed in conjunction with other procedures such as periradicular surgery and with bone grafts. However, the concomitant use of gingival grafts and bone grafts in mucosal fenestrations secondary to infections in sites exhibiting severe bone loss is highly debatable. In this article, we report two cases of mucosal fenestrations secondary to trauma and their management by regenerative periodontal surgery with the placement of guided tissue regeneration membrane and bone graft. The final outcome was a complete closure of the fenestration in both the cases. PMID:23749826

1. International four seas conference. Proceedings

Energy Technology Data Exchange (ETDEWEB)

Gougas, A K; Lemoigne, Y; Pepe-Altarelli, M; Petroff, P; Wulz, C E [eds.

1997-07-31

The Frist International Four Seas Conference was held in Trieste, Italy, from June 25th to July 1st, 1995. The principal aim of the Conference was to bring together physicists from the wider Balkan region along with their colleagues from the rest of the world. An overview of the current and future major European and World Physics projects (along with latest experimental results) was presented. Topics included: Physics at FNAL (collider and fixed target), LEP Physics, B and CP violation, presentations from the LHC experiments, AstroParticle Physics, Heavy Ion and Neutrino Physics. Special sessions were devoted to instrumentation projects, to spin-off applications of Particle Physics, while the final session was devoted to presentations connecting Physics and Society. (orig.)

1. International four seas conference. Proceedings

International Nuclear Information System (INIS)

Gougas, A.K.; Lemoigne, Y.; Pepe-Altarelli, M.; Petroff, P.; Wulz, C.E.

1997-01-01

The Frist International Four Seas Conference was held in Trieste, Italy, from June 25th to July 1st, 1995. The principal aim of the Conference was to bring together physicists from the wider Balkan region along with their colleagues from the rest of the world. An overview of the current and future major European and World Physics projects (along with latest experimental results) was presented. Topics included: Physics at FNAL (collider and fixed target), LEP Physics, B and CP violation, presentations from the LHC experiments, AstroParticle Physics, Heavy Ion and Neutrino Physics. Special sessions were devoted to instrumentation projects, to spin-off applications of Particle Physics, while the final session was devoted to presentations connecting Physics and Society. (orig.)

Mucosal CCR1 gene expression as a marker of molecular activity in Crohn's disease: preliminary data.

Science.gov (United States)

Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Ţieranu, Eugen Nicolae; Popa, Caterina; Mănuc, Mircea; Preda, Carmen Monica; Ţieranu, Ioana; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

2017-01-01

A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls. Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array. Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R. Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn's disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.

Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K

1995-01-01

BACKGROUND: Cyclooxygenase inhibitors reduce mucosal bicarbonate secretion in the duodenum, but the evidence for their effect on bicarbonate secretion in the stomach remains controversial. We have, therefore, studied how indomethacin influences gastroduodenal bicarbonate secretion and luminal...... healthy volunteers. Bicarbonate and PGE2 were measured in the gastroduodenal effluents by back-titration and radioimmunoassay, respectively. RESULTS: Vagal stimulation and duodenal luminal acidification (0.1 M HCl; 20 ml; 5 min) increased gastroduodenal bicarbonate secretion (p ... markedly inhibited both basal and stimulated gastric and duodenal mucosal bicarbonate secretion, and this reduction was similar to the degree of cyclooxygenase inhibition estimated by the luminal release of PGE2 (p

Oral cryotherapy reduced oral mucositis in patients having cancer treatments.

Science.gov (United States)

Spivakovsky, Sylvia

2016-09-01

Data sourcesCochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CANCERLIT, CINAHL, the US National Institutes of Health Trials Registry and the WHO Clinical Trials Registry Platform.Study selectionRandomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment compared to usual care, no treatment or other interventions to prevent mucositis. The primary outcome was incidence of mucositis and its severity.Data extraction and synthesisTwo reviewers carried out study assessment and data extraction independently. Treatment effect for continuous data was calculated using mean values and standard deviations and expressed as mean difference (MD) and 95% confidence interval. Risk ratio (RR) was calculated for dichotomous data. Meta-analysis was performed.ResultsFourteen studies with 1280 participants were included. Subgroup analysis was undertaken according to the main cancer treatment type. Cryotherapy reduced the risk of developing mucositis by 39% (RR = 0.61; 95%CI, 0.52 to 0.72) on patients treated with fluorouracil (5FU). For melphalan-based treatment the risk of developing mucositis was reduced by 41% (RR =0.59; 95%CI, 0.35 to 1.01). Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies.ConclusionsThere is confidence that oral cryotherapy leads to a large reduction in oral mucositis in adults treated with 5FU. Although there is less certainty on the size of the reduction on patients treated with melphalan, it is certain there is reduction of severe mucositis.

Single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent H5N1, H3N2 and H1N1 viruses.

Directory of Open Access Journals (Sweden)

Graeme E Price

2010-10-01

Full Text Available The sudden emergence of novel influenza viruses is a global public health concern. Conventional influenza vaccines targeting the highly variable surface glycoproteins hemagglutinin and neuraminidase must antigenically match the emerging strain to be effective. In contrast, "universal" vaccines targeting conserved viral components could be used regardless of viral strain or subtype. Previous approaches to universal vaccination have required protracted multi-dose immunizations. Here we evaluate a single dose universal vaccine strategy using recombinant adenoviruses (rAd expressing the conserved influenza virus antigens matrix 2 and nucleoprotein.In BALB/c mice, administration of rAd via the intranasal route was superior to intramuscular immunization for induction of mucosal responses and for protection against highly virulent H1N1, H3N2, or H5N1 influenza virus challenge. Mucosally vaccinated mice not only survived, but had little morbidity and reduced lung virus titers. Protection was observed as early as 2 weeks post-immunization, and lasted at least 10 months, as did antibodies and lung T cells with activated phenotypes. Virus-specific IgA correlated with but was not essential for protection, as demonstrated in studies with IgA-deficient animals.Mucosal administration of NP and M2-expressing rAd vectors provided rapid and lasting protection from influenza viruses in a subtype-independent manner. Such vaccines could be used in the interval between emergence of a new virus strain and availability of strain-matched vaccines against it. This strikingly effective single-dose vaccination thus represents a candidate off-the-shelf vaccine for emergency use during an influenza pandemic.

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

Science.gov (United States)

Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-07-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients

NARCIS (Netherlands)

Saunders, Deborah P.; Epstein, Joel B.; Elad, Sharon; Allemano, Justin; Bossi, Paolo; van de Wetering, Marianne D.; Rao, Nikhil G.; Potting, Carin; Cheng, Karis K.; Freidank, Annette; Brennan, Michael T.; Bowen, Joanne; Dennis, Kristopher; Lalla, Rajesh V.

2013-01-01

The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. A systematic review of the available literature was conducted. The body

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients.

NARCIS (Netherlands)

Saunders, D.P.; Epstein, J.B.; Elad, S.; Allemano, J.; Bossi, P.; Wetering, M.D. van de; Rao, N.G.; Potting, C.M.J.; Cheng, K.K.; Freidank, A.; Brennan, M.T.; Bowen, J.; Dennis, K.; Lalla, R.V.

2013-01-01

PURPOSE: The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. METHODS: A systematic review of the available literature was

Transgenic Killer Commensal Bacteria as Mucosal Protectants

Directory of Open Access Journals (Sweden)

Luciano Polonelli

2001-01-01

Full Text Available As first line of defense against the majority of infections and primary site for their transmission, mucosal surfaces of the oral cavity and genitourinary, gastrointestinal, and respiratory tracts represent the most suitable sites to deliver protective agents for the prevention of infectious diseases. Mucosal protection is important not only for life threatening diseases but also for opportunistic infections which currently represent a serious burden in terms of morbidity, mortality, and cost of cures. Candida albicans is among the most prevalent causes of mucosal infections not only in immuno- compromised patients, such as HIV-infected subjects who are frequently affected by oral and esophageal candidiasis, but also in otherwise healthy individuals, as in the case of acute vaginitis. Unfortunately, current strategies for mucosal protection against candidiasis are severely limited by the lack of effective vaccines and the relative paucity and toxicity of commercially available antifungal drugs. An additional option has been reported in a recent

Microneedle and mucosal delivery of influenza vaccines

Science.gov (United States)

Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

2017-01-01

In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

Psittacid herpesviruses associated with mucosal papillomas in neotropical parrots

International Nuclear Information System (INIS)

Styles, Darrel K.; Tomaszewski, Elizabeth K.; Jaeger, Laurie A.; Phalen, David N.

2004-01-01

Mucosal papillomas are relatively common lesions in several species of captive neotropical parrots. They cause considerable morbidity and in some cases, result in mortality. Previous efforts to identify papillomavirus DNA and proteins in these lesions have been largely unsuccessful. In contrast, increasing evidence suggests that mucosal papillomas may contain psittacid herpesviruses (PsHVs). In this study, 41 papillomas from 30 neotropical parrots were examined by PCR with PsHV-specific primers. All 41 papillomas were found to contain PsHV DNA. This 100% prevalence of PsHV infection in the papilloma population was found to be significantly higher than PsHV infection prevalence observed in other surveys of captive parrots. PsHV genotypes 1, 2, and 3, but not 4 were found in these lesions. Psittacus erithacus papillomavirus DNA and finch papillomavirus DNA were not found in the papillomas. A papilloma from a hyacinth macaw (Anodorhynchus hyacinthinus) was found to contain cells that had immunoreactivity to antiserum made to the common antigenic region of human papillomavirus (HPV) L1 major capsid protein. However, four other mucosal papillomas were negative for this immunoreactivity, and negative control tissues from a parrot embryo showed a similar staining pattern to that seen in the cloaca papilloma of the hyacinth macaw, strongly suggesting that the staining seen in hyacinth macaw papilloma was nonspecific. Based on these findings, it was concluded that specific genotypes of PsHV play a direct role in the development of mucosal papillomas of neotropical parrots and there is no evidence to suggest the concurrent presence of a papillomavirus in these lesions

1st Applied Electromagnetic International Conference

CERN Document Server

Othman, Mohd; Aziz, Mohamad; Malek, Mohd

2015-01-01

In this book, experts from academia and industry present the latest advances in scientific theory relating to applied electromagnetics and examine current and emerging applications particularly within the fields of electronics, communications, and computer technology. The book is based on presentations delivered at APPEIC 2014, the 1st Applied Electromagnetic International Conference, held in Bandung, Indonesia in December 2014. The conference provided an ideal platform for researchers and specialists to deliver both theoretically and practically oriented contributions on a wide range of topics relevant to the theme of nurturing applied electromagnetics for human technology. Many novel aspects were addressed, and the contributions selected for this book highlight the relevance of advances in applied electromagnetics to a variety of industrial engineering problems and identify exciting future directions for research.

Investigation of how to prevent mucositis induced by chemoradiotherapy

International Nuclear Information System (INIS)

Tosaka, Chihiro; Tajima, Hakuju; Inoue, Tadao

2011-01-01

Chemoradiotherapy for head and neck cancer is associated with a high incidence of severe oral mucositis; an adverse, painful event. Oral mucositis also causes nutritional deficiency by making oral feeding difficult. This may lead to prolongation of hospitalization due to complications caused by malnutrition. However, an effective way to prevent oral mucositis completely, remains to be found. In this study, we evaluated the occurrence of oral mucositis, and nutritional conditions such as hypoalbuminemia, reduction of body weight, and length of hospital stay (days) when the mouth was rinsed using rebamipide solution (R solution), or Poraprezinc-alginate sodium solution (P-A solution) (both considered to be effective for oral mucositis). A mouth rinsed with sodium azulene sulfonate (S solution) was used as a control. The mouth was rinsed out six times per day continuously during chemoradiotherapy. In the study, 31 patients were assigned to rinse their mouths using R solution, 11 patients using P-A solution, and 15 patients using S solution (reduction rate of body weight in 14 patients). For the evaluation, the criteria for adverse drug reactions CTCAE (v3.0) were used. Grade 1 and over, oral mucositis occurred in 48% of the R solution group, 36% of the P-A solution group, and 80% of the S solution group, indicating that the P-A solution group significantly prevented the occurrence of oral mucositis as opposed to the S solution group. A reduction in body weight was observed in 81% of the R solution group, 82% of the P-A solution group, and 79% of the S solution group, indicating a similar weight reduction rate among individual solution groups. Hypoalbuminemia equal to grade 2 or higher occurred in 3% of the R solution group, 18% of the P-A solution group, and 29% of the S solution group, indicating that the R group significantly prevented the occurrence of hypoalbuminemia compared to the S solution group. In addition, the length of hospital stays were 44±8.0 days for

Digital gastrointestinal imaging: Effect of pixel size of subtle mucosal abnormalities on observer performance

International Nuclear Information System (INIS)

Kastan, D.J.; Ackerman, L.V.; Feczko, P.J.

1986-01-01

Radiographs from double-contrast colon examinations demonstrating subtle mucosal changes of inflammatory bowel disease and radiographs showing normal colon were digitized (0.1-mm, 0.2-mm, 0.4-mm and 0.8-mm pixel sizes). Ten radiologists interpreted the laser-printed images. Receiver operating characteristic analysis was performed. The results indicated that (1) the sensitivity of radiography in detecting subtle mucosal abnormalities improved as resolution improved; (2) more experience readers performed remarkably well even at the poorer levels of resolution; (3) the resolution necessary for evaluating the colonic mucosa was less than expected; and (4) at low noise levels, conventional television fluoroscopy may have sufficient resolution for mucosal evaluation

CRP-ductin, the mouse homologue of gp-340/deleted in malignant brain tumors 1 (DMBT1), binds gram-positive and gram-negative bacteria and interacts with lung surfactant protein D

DEFF Research Database (Denmark)

Madsen, Jens; Tornøe, Ida; Nielsen, Ole

2003-01-01

CRP-ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP-ductin is the mouse homologue of human gp-340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein-D (SP-D). Here we report...... that purified CRP-ductin binds human SP-D in a calcium-dependent manner and that the binding is not inhibited by maltose. The same properties have previously been observed for gp-340 binding of SP-D. CRP-ductin also showed calcium-dependent binding to both gram-positive and -negative bacteria. A polyclonal...... antibody raised against gp-340 reacted specifically with CRP-ductin in Western blots. Immunoreactivity to CRP-ductin was found in the exocrine pancreas, in epithelial cells throughout the gastrointestinal tract and in the parotid ducts. A panel of RNA preparations from mouse tissues was screened for CRP...

Vaccination against Salmonella Infection: the Mucosal Way.

Science.gov (United States)

Gayet, Rémi; Bioley, Gilles; Rochereau, Nicolas; Paul, Stéphane; Corthésy, Blaise

2017-09-01

Salmonella enterica subspecies enterica includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti- Salmonella vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy. Copyright © 2017 American Society for Microbiology.

Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles

International Nuclear Information System (INIS)

Guo Lizheng; Lu Xiaoyan; Kang, S.-M.; Chen Changyi; Compans, Richard W.; Yao Qizhi

2003-01-01

To enhance mucosal immune responses using simian/human immunodeficiency virus-like particles (SHIV VLPs), we have produced novel phenotypically mixed chimeric influenza HA/SHIV VLPs and used them to immunize C57BL/6J mice intranasally. Antibody and cytotoxic T-cell (CTL) responses as well as cytokine production in both systemic and mucosal sites were compared after immunization with SHIV VLPs or chimeric HA/SHIV VLPs. By using enzyme-linked immunosorbent assay (ELISA), the levels of serum IgG and mucosal IgA to the HIV envelope protein (Env) were found to be highest in the group immunized with chimeric HA/SHIV VLPs. Furthermore, the highest titer of serum neutralizing antibody against HIV Env was found with the group immunized with chimeric HA/SHIV VLPs. Analysis of the IgG1/IgG2a ratio indicated that a T H 1-oriented immune response resulted from these VLP immunizations. HA/SHIV VLP-immunized mice also showed significantly higher CTL responses than those observed in SHIV VLP-immunized mice. Moreover, a MHC class I restricted T-cell activation ELISPOT assay showed a mixed type of T H 1/T H 2 cytokines in the HA/SHIV VLP-immunized mice, indicating that the chimeric VLPs can enhance both humoral and cellular immune responses to the HIV Env protein at multiple mucosal and systemic sites. The results indicate that incorporation of influenza HA into heterotypic VLPs may be highly effective for targeting vaccines to mucosal surfaces

Characterising the mucosal and systemic immune responses to experimental human hookworm infection.

Directory of Open Access Journals (Sweden)

Soraya Gaze

2012-02-01

Full Text Available The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13 and regulatory (IL-10 and TGF-β response, with some evidence of a Th1 (IFN-γ and IL-2 response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17 response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.

Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection against Naegleria fowleri Meningoencephalitis

Science.gov (United States)

Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A.; López-Revilla, Rubén; Reséndiz-Albor, Aldo A.; Moreno-Fierros, Leticia

2004-01-01

Cry1Ac protoxin has potent mucosal and systemic adjuvant effects on antibody responses to proteins or polysaccharides. In this work, we examined whether Cry1Ac increased protective immunity against fatal Naegleria fowleri infection in mice, which resembles human primary amoebic meningoencephalitis. Higher immunoglobulin G (IgG) than IgA anti-N. fowleri responses were elicited in the serum and tracheopulmonary fluids of mice immunized by the intranasal or intraperitoneal route with N. fowleri lysates either alone or with Cry1Ac or cholera toxin. Superior protection against a lethal challenge with 5 × 104 live N. fowleri trophozoites was achieved for immunization by the intranasal route. Intranasal immunization of N. fowleri lysates coadministered with Cry1Ac increased survival to 100%; interestingly, immunization with Cry1Ac alone conferred similar protection to that achieved with amoebal lysates alone (60%). When mice intranasally immunized with Cry1Ac plus lysates were challenged with amoebae, both IgG and IgA mucosal responses were rapidly increased, but only the increased IgG response persisted until day 60 in surviving mice. The brief rise in the level of specific mucosal IgA does not exclude the role that this isotype may play in the early defense against this parasite, since higher IgA responses were detected in nasal fluids of mice intranasally immunized with lysates plus either Cry1Ac or cholera toxin, which, indeed, were the treatments that provided the major protection levels. In contrast, serum antibody responses do not seem to be related to the protection level achieved. Both acquired and innate immune systems seem to play a role in host defense against N. fowleri infection, but further studies are required to elucidate the mechanisms involved in protective effects conferred by Cry1Ac, which may be a valuable tool to improve mucosal vaccines. PMID:15271892

Clinical effectiveness of Ancer 20 injection for prevention of radiation-induced oral mucositis

International Nuclear Information System (INIS)

Suzuki, Tsubura; Shimoyama, Tetsuo; Nasu, Daisuke; Kaneko, Takahiro; Horie, Norio

2000-01-01

Although radiotherapy is very useful for treatment of oral cancer, it can cause radiation-induced oral mucositis as a troublesome side effect. Ancer 20 injection is useful for enhancing macrophage function, and apart from its inductive effect on IL-3, it also enhances G-CSF production. Therefore, Ancer 20 injection might also prevent mucositis. This effect was tested by administering the drug to prevent oral mucositis during radiotherapy. Eleven patients (5 males and 6 females, aged 39 to 84 yr, mean 64.5 yr) with squamous cell carcinoma were examined. Radiation was applied externally with a linear accelerator up to a total dose of 20-70 Gy, mean 38.2 Gy. All patients received a small dose of cisplatin concomitantly. Ancer 20 injection 1 ml twice weekly was administered subcutaneously. There was almost no objective or subjective abnormality up to a dose of 30 Gy, and at doses higher than that, the symptoms were mild in comparison with general mucosal reactions. This showed that Ancer 20 injection is useful for prevention of radiation-induced oral mucositis during radiotherapy of oral cancer. (author)

Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Bossi, Paolo, E-mail: Paolo.bossi@istitutotumori.mi.it [Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Bergamini, Cristiana [Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Miceli, Rosalba [Clinical Epidemiology and Trial Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Cova, Agata [Unity of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Orlandi, Ester [Radiotherapy 2 Unity, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Resteghini, Carlo; Locati, Laura; Alfieri, Salvatore; Imbimbo, Martina; Granata, Roberta [Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Mariani, Luigi [Clinical Epidemiology and Trial Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Iacovelli, Nicola Alessandro [Radiotherapy 2 Unity, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Huber, Veronica [Unity of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Cavallo, Anna [Department of Physics and Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Licitra, Lisa [Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Rivoltini, Licia [Unity of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy)

2016-12-01

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, especially 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.

Isthmin 1 Is a Secreted Protein Expressed in Skin, Mucosal Tissues, and NK, NKT, and Th17 Cells

OpenAIRE

Valle-Rios, Ricardo; Maravillas-Montero, José L.; Burkhardt, Amanda M.; Martinez, Cynthia; Buhren, Bettina Alexandra; Homey, Bernhard; Gerber, Peter Arne; Robinson, Octavio; Hevezi, Peter; Zlotnik, Albert

2014-01-01

Using a comprehensive microarray database of human gene expression, we identified that in mammals, a secreted protein known as isthmin 1 (ISM1) is expressed in skin, mucosal tissues, and selected lymphocyte populations. ISM1 was originally identified in Xenopus brain during development, and it encodes a predicted ∼50-kDa protein containing a signal peptide, a thrombospondin domain, and an adhesion-associated domain. We confirmed the pattern of expression of ISM1 in both human and mouse tissue...

Oral Candida as an aggravating factor of mucositis Induced by radiotherapy

International Nuclear Information System (INIS)

Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia

2011-01-01

Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

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

Science.gov (United States)

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.

Chitosan-Based Nanoparticles for Mucosal Delivery of RNAi Therapeutics

DEFF Research Database (Denmark)

Martirosyan, Alina; Olesen, Morten Jarlstad; Howard, Kenneth A.

2014-01-01

of the polysaccharide chitosan have been used to facilitate delivery of siRNA across mucosal surfaces following local administration. This chapter describes the mucosal barriers that need to be addressed in order to design an effective mucosal delivery strategy and the utilization of the mucoadhesive properties...... of chitosan. Focus is given to preparation methods and the preclinical application of chitosan nanoparticles for respiratory and oral delivery of siRNA....

Omalizumab reduces bronchial mucosal IgE and improves lung function in non-atopic asthma.

Science.gov (United States)

Pillai, Prathap; Chan, Yih-Chih; Wu, Shih-Ying; Ohm-Laursen, Line; Thomas, Clare; Durham, Stephen R; Menzies-Gow, Andrew; Rajakulasingam, Raj K; Ying, Sun; Gould, Hannah J; Corrigan, Chris J

2016-12-01

Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE and inflammation and preserves/improves lung function when disease is destabilised by staged withdrawal of therapy.18 symptomatic, non-atopic asthmatics were randomised (1:1) to receive omalizumab or identical placebo treatment in addition to existing therapy for 20 weeks. Bronchial biopsies were collected before and after 12-14 weeks of treatment, then the patients destabilised by substantial, supervised reduction of their regular therapy. Primary outcome measures were changes in bronchial mucosal IgE + cells at 12-14 weeks, prior to regular therapy reduction, and changes in lung function (forced expiratory volume in 1 s) after destabilisation at 20 weeks. Quality of life was also monitored.Omalizumab but not placebo therapy significantly reduced median total bronchial mucosal IgE + cells (pomalizumab treated patients, with significant differences in absolute (p=0.04) and % predicted forced expiratory volume in 1 s (p=0.015).Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE + mast cells and improves lung function despite withdrawal of conventional therapy. Copyright ©ERS 2016.

1st Central and Eastern European Proteomic Conference and 3rd Czech Proteomic Conference

Czech Academy of Sciences Publication Activity Database

Kovářová, Hana; Gadher, S. J.; Archakov, A.

2008-01-01

Roč. 5, č. 1 (2008), s. 25-28 ISSN 1478-9450 Institutional research plan: CEZ:AV0Z50450515 Keywords : proteomic conference Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.848, year: 2008

TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1

OpenAIRE

Allam, Atef; Majji, Sai; Peachman, Kristina; Jagodzinski, Linda; Kim, Jiae; Ratto-Kim, Silvia; Wijayalath, Wathsala; Merbah, Melanie; Kim, Jerome H.; Michael, Nelson L.; Alving, Carl R.; Casares, Sofia; Rao, Mangala

2015-01-01

CD4+ T follicular helper cells (TFH) in germinal centers are required for maturation of B-cells. While the role of TFH-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of TFH (CXCR5+PD-1++) and precursor-TFH (CXCR5+PD-1+) cells. The majority of TFH-cells expressed CCR...

Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1.

Science.gov (United States)

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.

Traffic-days at Aalborg University 1996. Conference report 1

International Nuclear Information System (INIS)

Lahrmann, H.; Hald Pedersen, L.

1996-01-01

Volume 1 (of two volumes) of the report on the conference 'Traffic days '96' held at Aalborg University (Denmark) on August 19-20, 1996, contains the papers presented at the conference under the general headings of the role of the car in the transport system of the future, traffic models, urban planning and traffic, traffic control, traffic and the urban environment, traffic and emissions, freight transport and railways. (EG)

The salivary scavenger and agglutinin (SALSA binds MBL and regulates the lectin pathway of complement in solution and on surfaces

Directory of Open Access Journals (Sweden)

Martin eParnov Reichhardt

2012-07-01

Full Text Available The scavenger receptor cysteine-rich (SRCR protein SALSA, also known as gp340, salivary agglutinin (SAG and deleted in malignant brain tumor 1 (DMBT1, is a 340 kDa glycoprotein expressed on mucosal surfaces and secreted into several body fluids. SALSA binds to a broad variety of microbes and endogenous ligands, such as complement factor C1q, surfactant proteins D and A (SP-D and SP-A and IgA. Our search for novel ligands of SALSA by direct protein-interaction studies led to the identification of mannan binding lectin (MBL as a new binding partner. We observed that surface-associated SALSA activates complement via binding of MBL. On the other hand, soluble SALSA was found to inhibit C. albicans-induced complement activation. Thus, SALSA has a dual complement regulatory function. It activates the lectin pathway when bound to a surface and inhibits it when free in the fluid-phase. These activities are mediated via a direct interaction with MBL.

Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer.

Science.gov (United States)

Guney, Yildiz; Ozel Turkcu, Ummuhani; Hicsonmez, Ayse; Nalca Andrieu, Meltem; Kurtman, Cengiz

2007-01-01

Body weight loss is common in cancer patients, and is often associated with poor prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is used in head and neck cancers (HNC) either as a primary treatment or as an adjuvant therapy to surgery. Patients with HNC are most susceptible to malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have been all associated with the development of both anorexia and oral mucositis. Radiation-induced mucositis occurs in almost all patients, who are treated for HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide, which up-regulates body weight through appetite control, increase food intake, down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which may cause oral mucositis and aneroxia, which are the results of weight loss. Thus weight loss during RT is an early indicator of nutritional decline, we propose that recombinant ghrelin used prophylactically could be useful as an appetite stimulant; and preventive of mucositis because of its anti-inflammatory effect, it might help patients maintain weight over the course of curative RT of the HNC and can improve specific aspects of QOL. This issue warrants further studies.

41 CFR 301-74.1 - What policies must we follow in planning a conference?

Science.gov (United States)

2010-07-01

...-CONFERENCE PLANNING Agency Responsibilities § 301-74.1 What policies must we follow in planning a conference... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false What policies must we follow in planning a conference? 301-74.1 Section 301-74.1 Public Contracts and Property Management...

Acute mucosal radiation reactions in patients with head and neck cancer. Patterns of mucosal healing on the basis of daily examinations

Energy Technology Data Exchange (ETDEWEB)

Wygoda, A.; Skladowski, K.; Rutkowski, T.; Hutnik, M.; Golen, M.; Pilecki, B.; Przeorek, W.; Lukaszczyk-Widel, B. [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice (Poland). 1st Dept. of Radiation Oncology

2012-08-15

Purpose: The goal of this research was to evaluate the healing processes of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer. Materials and methods: In 46 patients with oral and oropharyngeal cancer patients irradiated with conventional (n = 25) and accelerated (n = 21) dose fractionation AMRR was evaluated daily during and after radiotherapy. Complex of morphological and functional symptoms according to the Dische score were collected daily until complete healing. Results: Duration of healing after the end of radiotherapy ranged widely (12-70 days). It was on the average 8 days longer for accelerated than for conventional radiotherapy (p = 0.016). Duration of dysphagia was also longer for accelerated irradiation (11 days, p = 0.027). Three types of morphological symptoms were observed as the last symptom at the end of AMRR healing: spotted and confluent mucositis, erythema, and edema. Only a slight correlation between healing duration and area of irradiation fields (r = 0.23) was noted. In patients with confluent mucositis, two morphological forms of mucosal healing were observed, i.e., marginal and spotted. The spotted form was noted in 71% of patients undergoing conventional radiotherapy and in 38% of patients undergoing accelerated radiotherapy. The symptoms of mucosal healing were observed in 40% patients during radiotherapy. Conclusion: The wide range of AMRR healing reflects individual potential of mucosa recovery with longer duration for accelerated radiotherapy. Two morphological forms of confluent mucositis healing were present: marginal and spotted. Healing of AMRR during radiotherapy can be observed in a significant proportion of patients. (orig.)

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

Science.gov (United States)

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 Saccharomyces boulardii did not reverse this effect (p > 0.05). Mucositis induced an increase in intestinal permeability and intestinal inflammation (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.

Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination.

Science.gov (United States)

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.

7 CFR 1.421 - Prehearing conferences and procedures.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Prehearing conferences and procedures. 1.421 Section 1.421 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Rules of Practice...; (iii) The legal theories upon which the party will rely; (iv) Copies of or a list of documents which...

Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

Science.gov (United States)

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.

1st International Conference on Advancements of Medical Electronics

CERN Document Server

Bag, Sandip; Ganguly, Karabi; Sarkar, Indranath; Biswas, Papun

2015-01-01

The book is a collection of peer-reviewed scientific papers submitted by active researchers in the 1st International Conference on Advancements of Medical Electronics (ICAME2015). The conference is organized jointly by the Department of Biomedical Engineering and Electronics and Communication Engineering, JIS College of Engineering, West Bengal, India. The primary objective of the conference is to strengthen interdisciplinary research and its applications for the welfare of humanity. A galaxy of academicians, professionals, scientists, statesman and researchers from different parts of the country and abroad got together and shared their knowledge. The book presents research articles of medical image processing & analysis, biomedical instrumentation & measurements, DSP & clinical applications, embedded systems & its applications in healthcare. The book can be referred as a tool for further research.

The prevalence of oral mucosal lesions in patients visiting a dental school in Southern India

Directory of Open Access Journals (Sweden)

Mathew Anuna

2008-01-01

Full Text Available The purpose of the present study was to evaluate the prevalence of oral mucosal lesions in Manipal, Karnataka State, India. A total of 1190 subjects who visited the department of oral medicine and radiology for diagnosis of various oral complaints over a period of 3 months were interviewed and clinically examined for oral mucosal lesions. The result showed the presence of one or more mucosal lesions in (41.2% of the population. Fordyce′s condition was observed most frequently (6.55% followed by frictional keratosis (5.79%, fissured tongue (5.71%, leukoedema (3.78%, smoker′s palate (2.77%, recurrent aphthae, oral submucous fibrosis (2.01%, oral malignancies (1.76%, leukoplakia (1.59%, median rhomboid glossitis (1.50%, candidiasis (1.3%, lichen planus (1.20%, varices (1.17%, traumatic ulcer and oral hairy leukoplakia (1.008%, denture stomatitis, geographic tongue, betel chewer′s mucosa and irritational fibroma (0.84%, herpes labialis, angular cheilitis (0.58%, and mucocele (0.16%. Mucosal lesions like tobacco-related lesions (leukoplakia, smoker′s palate, oral submucous fibrosis, and oral malignancies were more prevalent among men than among women. Denture stomatitis, herpes labialis, and angular cheilitis occurred more frequently in the female population.

Successful BNCT for patients with cutaneous and mucosal melanomas. Report of 4 cases

International Nuclear Information System (INIS)

Morita, Norimasa; Hiratsuka, Junichi; Kuwabara, Chiaki; Aihara, Teruhito; Harada, Tamotsu; Imajo, Yoshinari; Ono, Koji; Fukuda, Hiroshi; Kumada, Hiroaki

2006-01-01

Since 2003 we have conducted BNCT clinical trials on melanomas at the Kyoto University Research Reactor (KUR) and Japan Research Reactor No.4 (JRR-4). We report 4 patients given BNCT for malignant melanomas: 2 with superficial spreading types on the heel, 1 with mucosal melanoma in the nasal cavity, and 1 with a melanoma on the vulva and in the vagina. The two cutaneous melanomas and the nasal cavity mucosal melanoma showed a complete response (CR) by 6 months after BNCT. The residual melanoma showed a partial response (PR) by 3 months after treatment and no regrowth since then. Although two patients experienced normal-tissue damage that exceeded the tolerance level, all the participants were cured within a few months of treatment. BNCT was shown to be a promising treatment for mucosal, as well as for cutaneous, melanomas. (author)

Biochemical Evaluation of the Therapeutic Effectiveness of Honey in Oral Mucosal Ulcers

Directory of Open Access Journals (Sweden)

Nergiz Yılmaz

2009-11-01

Full Text Available The aim of this study was to describe and quantify the therapeutic value of honey in oral mucosal ulcers healing in comparison with Glyceroloxytriester (TGO. We also aimed to biochemically evaluate the healing effects of honey which had been collected from the Blacksea region flora on mucosal ulcers resulting in material loss.Thirty wistar rats (240±30 g were enrolled in this study. Excisional wounds were performed in all rats for animal oral mucosal ulcer model. They were randomly allocated to three groups: group 1 was treated with Apitherapeutic agent or honey (0,1 ml, 2x1, group 2 was treated with TGO (0,1ml, 2x1 locally, Group 3 served as the control group.Following the surgical procedure on day 7, biopsy specimens were taken from right buccal mucosa and on day 14 biopsy specimens were taken from left bucal mucosa in all rats. Afterwards, hydroxy pyroline levels were measured. Data were analyzed statisticallyThere was no statistically significant difference between Group 1 and 2, and also between Group 2 and 3, but there was statistically significant difference between Group 1 and 3 on day 7. There was no statistically significant difference between Group 1, 2 and 3 on day 14.

Measurement of Mucosal Thickness in Denture-bearing Area of Edentulous Mandible

Directory of Open Access Journals (Sweden)

Jian Dong

2015-01-01

Full Text Available Background: The thickness of the alveolar mucosa influences the probability of the occurrence of denture-induced irritations. Thick denture-supporting tissues offer relief from mucosal tenderness and ulcers; however, the uniformity of the thickness across the entire mandibular alveolar mucosa cannot be accurately determined in edentulous patients. This study aimed to assess the mucosal thickness of the denture-bearing area in the edentulous mandible. Methods: Twenty-seven edentulous patients underwent cone-beam computed tomography scanning, wherein the patients wore a record base to retract soft tissues away from the alveolar mucosa. The measured regions were the central incisor (IC, lateral incisor (IL, canine (Ca, first premolar (P1, second premolar (P2, first molar (M1, and second molar (M2 regions. The thickness was measured in the alveolar ridge crest (T, buccal (B1-B4, and lingual (L1-L4 alveolar ridge mucosa. The average thickness of the mucosa at buccal sides (B and lingual sides (L were also assessed. Results: The differences in the mucosal thickness between the left and right sides were not significant. In the Ca-M2 regions, T was the thickest, and L3 was the thinnest of all the measured points in the same regions. L was significantly less than B in posterior regions (P < 0.01. On the other hand, M2 at L4 was thinnest of all the measured regions from Ca to M2 (P < 0.01, and was thicker than IC, IL, P1, and P2 at B2. Conclusions: Since the mucosal thickness of denture-bearing area in the edentulous mandible is not uniform; the tissue surface of the denture base or custom tray should be selectively relieved, which may reduce the risk of denture-induced irritations.

[White House Conference on Aging, 1981: Reports of the Mini-Conferences, MCR 1-42.

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White House Conference on Aging, Washington, DC.

This document contains the 42 reports from mini-conferences held in various nationwide locations prior to the 1981 White House Conference on Aging. Each report presents an overview of the topic, descriptions of particular problems, and statements of recommendations, based on the views of mini-conference participants, and made available to the…

Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

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Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

2013-01-01

Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

Alpha-Toxin Promotes Mucosal Biofilm Formation by Staphylococcus aureus

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Michele J Anderson

2012-05-01

Full Text Available Staphylococcus aureus causes numerous diseases in humans ranging from the mild skin infections to serious, life-threatening, superantigen-mediated Toxic Shock Syndrome (TSS. S. aureus may also be asymptomatically carried in the anterior nares, vagina or on the skin, which serve as reservoirs for infection. Pulsed-field gel electrophoresis clonal type USA200 is the most widely disseminated colonizer and a major cause of TSS. Our prior studies indicated that α-toxin was a major epithelial proinflammatory exotoxin produced by TSS S. aureus USA200 isolates. It also facilitated the penetration of TSS Toxin-1 (TSST-1 across vaginal mucosa. However, the majority of menstrual TSS isolates produce low α-toxin due to a nonsense point mutation at codon 113, designated hly, suggesting mucosal adaptation. The aim of this study was to characterize the differences between TSS USA200 strains [high (hla+ and low (hly+ α-toxin producers] in their abilities to infect and disrupt vaginal mucosal tissue. A mucosal model was developed using ex vivo porcine vaginal mucosa, LIVE/DEAD® staining and confocal microscropy to characterize biofilm formation and tissue viability of TSS USA 200 isolates CDC587 and MN8, which contain the α-toxin pseudogene (hly, MNPE (hla+ and MNPE isogenic hla knockout (hlaKO. All TSS strains grew to similar bacterial densities (1-5 x 108 CFU on the mucosa and were proinflammatory over 3 days. However, MNPE formed biofilms with significant reductions in the mucosal viability whereas neither CDC587, MN8 (hly+, or MNPE hlaKO, formed biofilms and were less cytotoxic. The addition of exogenous, purified α-toxin to MNPE hlaKO restored the biofilm phenotype. Our studies suggest α-toxin affects S. aureus phenotypic growth on vaginal mucosa, by promoting tissue disruption and biofilm formation; and α–toxin mutants (hly are not benign colonizers, but rather form a different type of infection, which we have termed high density pathogenic

Co-administration of Bacillus subtilis RJGP16 and Lactobacillus salivarius B1 strongly enhances the intestinal mucosal immunity of piglets.

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Deng, Jun; Li, Yunfeng; Zhang, Jinhua; Yang, Qian

2013-02-01

Probiotics, including Bacillus spp. and Lactobacillus, are potential replacements for low dose in-feed antibiotics for pig. This study aimed to evaluate the effect of the co-administration of Bacillus subtilis RJGP16 and Lactobacillus salivarius B1 as potential probiotics to stimulate local immune responses. Thirty two newborn piglets were divided into four groups and orally administrated with different combination of probiotics (none; RJGP16; B1; RJGP16 and B1) at the age of 0, 7 and 11 days. We analysed the parameters of the mucosal immunity of piglets a week after weaning. Our results showed that the gene expression of interleukin (IL)-6 in the duodenum and ileum, porcine beta-defensins (pBD)-2 in the duodenum were significantly increased (p<0.01) with co-administration of the RJGP16 and B1. Also the expression and release of TLR-2 and the number of immunoglobulin (Ig) A producing cells were increased (p<0.01). The results demonstrate that the co-administration of the two bacteria stimulate a more intense mucosal immunity than the administration of each bacterium alone. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mucosal immunity and B cells in teleosts: effect of vaccination and stress.

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David eParra

2015-07-01

Full Text Available Fish are subjected to several insults from the environment, which may endanger animal survival. Mucosal surfaces are the first line of defense against those threats and they act as a physical barrier to protect the animal but also function as immunologically active tissues. Thus, four mucosal-associated lymphoid tissues have been described in fish, which lead the immune responses in gut, skin, gills and nose. Humoral and cellular immunity, as well as its regulation and the factors that influence the response in these mucosal lymphoid tissues is still not well known in most of fish species. Mucosal B-lymphocytes and immunoglobulins (Igs are one of the key players in the immune response after vaccination. Recent findings about IgT in trout have delimited the compartmentalization of immune response in systemic and mucosal. The existence of IgT as a specialized mucosa Ig gives us the opportunity of measuring mucosal specific responses after vaccination, a fact that was not possible until recently in most of the fish species. Vaccination process is influenced by several factors, being stress one of the main stimuli determining the success of the vaccine. Thus, one of the major goals in a vaccination process is to avoid possible situations of stress, which might interfere with fish immune performance. However, the interaction between immune and neuroendocrine systems at mucosal tissues is still unknown. In this review we will summarized the latest findings about B-lymphocytes and immunoglobulins in mucosal immunity and the effect of stress and vaccines on B cell response at mucosal sites. It is important to point out that a small number of studies have been published regarding mucosal stress and very few about the influence of stress over mucosal B-lymphocytes.

Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

International Nuclear Information System (INIS)

Fukuyama, Yoshiko; Tokuhara, Daisuke; Sekine, Shinichi; Kataoka, Kosuke; Markham, Jonathan D.; Irwin, Allyson R.; Moon, Grace H.; Tokuhara, Yuka; Fujihashi, Keiko; Davydova, Julia; Yamamoto, Masato; Gilbert, Rebekah S.; Fujihashi, Kohtaro

2012-01-01

Highlights: ► Nasal Ad-FL effectively up-regulates APC function by CD11c + DCs in mucosal tissues. ► Nasal Ad-FL induces Notch ligand (L)-expressing CD11c + DCs. ► Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c + dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c + DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FL activated CD11c + DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c + DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4 + T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-γ, IL-2 and IL-4 producing CD4 + T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch–Notch-L pathway. These results show that Ad-FL induces CD11c + DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.

C-kit expression in canine mucosal melanomas.

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Newman, S J; Jankovsky, J M; Rohrbach, B W; LeBlanc, A K

2012-09-01

The c-kit receptor is responsible for transmission of promigration signals to melanocytes; its downregulation may be involved in malignant progression of human melanocytic neoplasms. Expression of this receptor has not been examined in normal or neoplastic melanocytes from dogs. In this study, 14 benign dermal and 61 malignant mucosal melanocytic tumors were examined for c-kit (KIT) expression. Sites of the mucosal melanomas were gingiva (not further specified; n = 30), buccal gingiva (n = 6), soft palate (n = 4), hard palate (n = 5), tongue (n = 7), lip (n = 6), and conjunctiva (n = 3). Melan A was expressed in all 14 dermal melanocytomas and in 59 of 61 (96.7%) tumors from oral or conjunctival mucosa, confirming melanocytic origin. C-kit receptor expression was strong and diffuse throughout the cytoplasm in all 14 dermal melanocytomas and was identified in basilar mucosal melanocytes over submucosal neoplasms (27 of 61, 44.3%), junctional (neoplastic) melanocytes (17 of 61, 27.9%), and, less commonly, neoplastic melanocytes of the subepithelial tumors (6 of 61, 9.8%). KIT expression anywhere within the resected melanomas correlated with significantly longer survival. These results suggest that c-kit receptor expression may be altered in canine melanomas and may have potential as a prognostic indicator for mucosal melanomas.

Mucosal versus muscle pain sensitivity in provoked vestibulodynia

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Witzeman K

2015-08-01

Full Text Available Kathryn Witzeman,1 Ruby HN Nguyen,2 Alisa Eanes,3 Sawsan As-Sanie,4 Denniz Zolnoun51Department of Obstetrics and Gynecology, Denver Health Medical Center, Denver, CO, 2Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 3Pelvic Pain Research Unit, Division of Advanced Laparoscopy and Pelvic Pain, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC, 4Department of Obstetrics and Gynecology, Division of Minimally Invasive Gynecologic Surgery, University of Michigan, Ann Arbor, MI, 5Department of Obstetrics and Gynecology and Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC, USABackground: An estimated 8.3%–16% of women experience vulvovaginal discomfort during their lifetime. Frequently these patients report provoked pain on contact or with attempted intercourse, commonly referred to as provoked vestibulodynia (PVD. Despite the burden of this condition, little is known about its potential etiologies including pelvic floor muscular dysfunction and mucosal components. This knowledge would be beneficial in developing targeted therapies including physical therapy.Objective: To explore the relative contribution of mucosal versus muscle pain sensitivity on pain report from intercourse among women with PVD.Design: In this proof of concept study, 54 women with PVD underwent a structured examination assessing mucosal and pelvic muscle sensitivity.Methods: We examined three mucosal sites in the upper and lower vestibule. Patients were asked to rate their pain on cotton swab palpation of the mucosa using a 10-point visual analog scale. Muscle pain was assessed using transvaginal application of pressure on right and left puborectalis, and the perineal muscle complex. The Gracely pain scale (0–100 was used to assess the severity of pain with intercourse, with women rating the lowest, average, and highest pain levels; a 100 rating the

Inmunización intranasal con AFCo1 induce respuesta inmune de memoria, sistemica y mucosal en ratones neonatal

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Julio A. Balboa

2009-08-01

Full Text Available Neonates have a poorly developed immune system. Respiratory pathogens cause disease during early periods of live. Consequently, it is important to develop protective vaccines that induce immunity and immunological memory against respiratory pathogens early in life. Intranasal (i.n. route could be an effective via for immunization. Therefore, we explored the effectiveness of AF (Adjuvant Finlay PL1 (Proteoliposome from Neisseria meningitidis serogroup B and its derivate Cochleate (AFCo1 by nasal route in neonatal mice. They were immunized i.n. 3 times 7 days apart and anti PL systemic and mucosal antibody response were measured by ELISA. In addition, a prime-boost strategy was used to evaluate the humoral immune response in neonate mice. The 3 doses of AFPL1 or AFCo1 induced significant levels of anti PL IgG antibodies in comparison whit control, but AFCo1 (2017 U/mL was significantly higher than AFPL1 (1107 U/mL. AFCo1 and AFPL1 induced a predominant Th1 pattern with IgG2a/IgG1 >1 by i.n. immunization and AFCo1 induced a high anti PL IgA saliva response in saliva. Interestingly, one nasally prime at 7 days of born and a memory one boost i.n. dose 9 weeks later with AFCo1 or AFPL1 showed similar specific IgG levels and IgG2a/IgG1 relation than 3 i.n. doses in adult mice. In conclusion, these results represent the first report of neonatal intranasal vaccination using AFCo1 capable to induce systemic and mucosal immunity and priming for memory.

Human colorectal mucosal microbiota correlates with its host niche physiology revealed by endomicroscopy.

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Wang, Ai-Hua; Li, Ming; Li, Chang-Qing; Kou, Guan-Jun; Zuo, Xiu-Li; Li, Yan-Qing

2016-02-26

The human gut microbiota plays a pivotal role in the maintenance of health, but how the microbiota interacts with the host at the colorectal mucosa is poorly understood. We proposed that confocal laser endomicroscopy (CLE) might help to untangle this relationship by providing in vivo physiological information of the mucosa. We used CLE to evaluate the in vivo physiology of human colorectal mucosa, and the mucosal microbiota was quantified using 16 s rDNA pyrosequencing. The human mucosal microbiota agglomerated to three major clusters dominated by Prevotella, Bacteroides and Lactococcus. The mucosal microbiota clusters did not significantly correlate with the disease status or biopsy sites but closely correlated with the mucosal niche physiology, which was non-invasively revealed by CLE. Inflammation tilted two subnetworks within the mucosal microbiota. Infiltration of inflammatory cells significantly correlated with multiple components in the predicted metagenome, such as the VirD2 component of the type IV secretory pathway. Our data suggest that a close correlation exists between the mucosal microbiota and the colorectal mucosal physiology, and CLE is a clinically available tool that can be used to facilitate the study of the in vivo correlation between colorectal mucosal physiology and the mucosal microbiota.

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

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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).

Pilot study of ice-ball cryotherapy for radiation-induced oral mucositis

International Nuclear Information System (INIS)

Ohyama, Waichiro; Ebihara, Satoshi

1996-01-01

Oral mucositis caused by radiotherapy is intractable and may worsen the patient's nutritional condition and interrupt treatment. To reduce the incidence and severity of oral mucositis induced by cancer therapy and promote early improvement of its symptoms, we devised cryotherapy by ice balls using Elase (fibrinolysin and deoxyribonuclease, combined). The therapeutic effect of ice-ball cryotherapy was evaluated in 10 patients with carcinoma of the oral cavity and pharynx who were undergoing radiotherapy. Cryotherapy was continued from the development of oral mucositis until its disappearance. The severity of various symptoms of mucositis were reduced by cryotherapy. Healing required 3 to 16 days (median, 7 days) after the end of radiotherapy. Radiotherapy was not interrupted in any cases. This preliminary report suggests that ice-ball cryotherapy is an effective treatment for radiation-induced oral mucositis. (author)

Mucosal serpin A1 and A3 levels in HIV highly exposed sero-negative women are affected by the menstrual cycle and hormonal contraceptives but are independent of epidemiological confounders.

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Rahman, Syeda; Rabbani, Rasheda; Wachihi, Charles; Kimani, Joshua; Plummer, Francis A; Ball, Terry B; Burgener, Adam

2013-01-01

Serpins (serine protease inhibitors) are associated with protection against HIV infection. Here, we characterized mucosal serpin expression in the genital tract of HIV highly exposed sero-negative (HESN) women meeting our epidemiological definition of HIV resistance in relation to epidemiological variables. Cervicovaginal lavage (CVL) fluid and plasma were collected from 84 HIV-resistant, 54 HIV-uninfected, and 66 HIV-infected female commercial sex workers. Serpin A1 and A3 concentrations were measured by ELISA and compared with clinical information. Mucosal serpin A1 was elevated during proliferative phase over secretory phase (P = 0.017*), while A3 remained similar (P = 0.25). Plasma and mucosal serpin A1/A3 levels were not associated with each other and appeared compartment specific (r = 0.21, r = 0.056). Serpin A1/A3 expression did not associate with age (r = 0.009, r = -0.06), duration of sex work (r = 0.13, r = -0.10), clients per day (r = -0.11, r = -0.02), concurrent STIs (P = 0.36, P = 0.15), but was lower in women using hormonal contraceptives (P = 0.034, P = 0.008). Mucosal serpin A1/A3 levels in HIV-infected individuals were not significantly different with disease status as determined by plasma CD4(+) T-cell counts (P = 0.94, P = 0.30). This study shows the relationship of serpins to the menstrual cycle and hormonal contraceptives, as well as their independence to epidemiological sexual confounders. This information provides a broader understanding of innate components of the mucosal immune system in women. © 2012 John Wiley & Sons A/S.

The Mucosal Adjuvant Cholera Toxin B Instructs Non-Mucosal Dendritic Cells to Promote IgA Production Via Retinoic Acid and TGF-β

NARCIS (Netherlands)

A.K. Gloudemans (Anouk); M. Plantinga (Maud); M. Guilliams (Martin); M.A. Willart (Monique); A. Ozir-Fazalalikhan (Arifa); A. van der Ham (Alwin); L. Boon (Louis); N.L. Harris (Nicola); H. Hammad (Hamida); H.C. Hoogsteden (Henk); M. Yazdanbakhsh (Maria); R.W. Hendriks (Rudi); B.N.M. Lambrecht (Bart); H.H. Smits (Hermelijn)

2013-01-01

textabstractIt is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing

Effectiveness of triclosan in the management of radiation-induced oral mucositis: A randomized clinical trial

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Satheeshkumar P

2010-01-01

Full Text Available Introduction: Oral care in cancer patients is an important aspect in the quality of life of patients undergoing cancer therpay. Mucositis, trismus, salivary gland dysfunction are the main complications of the cancer therapy, which lead to long-term comlications such as radiation caries, poor oral hygiene and osteoradionecrosis. A timely oral evaluation and intervention in these patients can reduce the severity of the potential complications. Triclosan is an antibacterial agent widely used in periodontal therapy, the effectiveness of triclosan in the management of radiation induced oral mucositis is evaluated here. Aims: 1 To determine the effectiveness of triclosan in the management of radiation-induced oral mucositis. 2 To compare the effectiveness of triclosan mouth rinse with conventional sodium bicarbonate mouth rinse. Materials and Methods: Twenty-four patients who underwent radiation therapy for oral cancer and subsequently developed oral mucositis were included in the study. They were randomly allocated into two groups on noticing grade I mucositis (erythema. The study group was advised to use triclosan mouthwash containing triclosan 0.03% W/V and sodium bicarbonate 2 mg mouth wash for the control group. A weekly follow-up evaluation of body weight, food intake, pain and grading of mucositis were made during the radiation treatment period and post radiation treatment period. Results: Both the groups were statistically identical. All the 24 patients in both the groups passed through grade 3 mucositis on the last day of radiotherapy. However, 10 patients in the control group and only one patient in the study group entered to grade 4 mucositis. A definite change was noticed in the severity of the mucositis, food intake and weight loss. The control group took more than 45 days to resolve while the study group took only less than 28 days. Discussion: The results of the study were evaluated and tried to formulate a hypothesis so as to explain

Short bowel mucosal morphology, proliferation and inflammation at first and repeat STEP procedures.

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Mutanen, Annika; Barrett, Meredith; Feng, Yongjia; Lohi, Jouko; Rabah, Raja; Teitelbaum, Daniel H; Pakarinen, Mikko P

2018-04-17

Although serial transverse enteroplasty (STEP) improves function of dilated short bowel, a significant proportion of patients require repeat surgery. To address underlying reasons for unsuccessful STEP, we compared small intestinal mucosal characteristics between initial and repeat STEP procedures in children with short bowel syndrome (SBS). Fifteen SBS children, who underwent 13 first and 7 repeat STEP procedures with full thickness small bowel samples at median age 1.5 years (IQR 0.7-3.7) were included. The specimens were analyzed histologically for mucosal morphology, inflammation and muscular thickness. Mucosal proliferation and apoptosis was analyzed with MIB1 and Tunel immunohistochemistry. Median small bowel length increased 42% by initial STEP and 13% by repeat STEP (p=0.05), while enteral caloric intake increased from 6% to 36% (p=0.07) during 14 (12-42) months between the procedures. Abnormal mucosal inflammation was frequently observed both at initial (69%) and additional STEP (86%, p=0.52) surgery. Villus height, crypt depth, enterocyte proliferation and apoptosis as well as muscular thickness were comparable at first and repeat STEP (p>0.05 for all). Patients, who required repeat STEP tended to be younger (p=0.057) with less apoptotic crypt cells (p=0.031) at first STEP. Absence of ileocecal valve associated with increased intraepithelial leukocyte count and reduced crypt cell proliferation index (pSTEP. Persistent inflammation and lacking mucosal growth may contribute to continuing bowel dysfunction in SBS children, who require repeat STEP procedure, especially after removal of the ileocecal valve. Level IV, retrospective study. Copyright © 2018 Elsevier Inc. All rights reserved.

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

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Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-01-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reactio...

Mucosal Immune Regulation in Early Infancy: Monitoring and Intervention

NARCIS (Netherlands)

J. Hol (Jeroen)

2011-01-01

textabstractThe mucosal immune system of infants is dependent on the maintenance of mucosal homeostasis. Homeostasis results from the interaction between the mucosa and exogenous factors such as dietar and microbial agents. Induction and maintenance of homeostasis is a highly regluated system that

Microscopic Colitis Evolved Into Inflammatory Bowel Diseases Is Characterized by Increased Th1/Tc1 Cells in Colonic Mucosal Lamina Propria.

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Li, Ji; Yan, Yuchu; Meng, Ziran; Liu, Shuhong; Beck, Paul L; Ghosh, Subrata; Qian, Jiaming; Gui, Xianyong

2017-10-01

An association between microscopic colitis (MC), i.e., lymphocytic colitis (LC) and collagenous colitis (CC), and inflammatory bowel diseases (IBD) has been noticed. A subset of MC cases may evolve into IBD, and IBD in remission may present as MC in a histologic pattern. Moreover, MC and IBD may coexist in different regions of the bowel. A link between MC and IBD in their pathogenesis is, therefore, suggested. Abnormal mucosal immunity is likely the key. We reviewed 2324 MC cases in Calgary over 14 years and identified 20 cases evolved into IBD (IBD transformers). 13 of them were further investigated for colonic mucosal lamina propria mononuclear cells (LPMNCs), as opposed to 22 cases whose MC resolved. On their index colonic biopsy immunohistochemistry was performed to detect major T cell subsets characterized by key cytokines and master transcription factors (IFNγ and T-bet for Th1/Tc1, GATA-3 for Th2/Tc2, IL-17 and RORc for Th17/Tc17, FoxP3 for Treg/Tcreg) as well as TNFα + cells (partly representing Th1). LPMNCs positive for each marker were counted (average number per high-power field). IBD transformers had increased IFNγ + , T-bet + , TNF-α + , and GATA-3 + LPMNCs compared to the MC-resolved cases. The LC-to-IBD subgroup had increased IFNγ + and GATA-3 + cells compared to the LC-resolved subgroup. The CC-to-IBD subgroup had increased T-bet + , TNF-α + , and GATA-3 + cells compared to the CC-resolved subgroup. Among MC-resolved patients, more TNF-α + and RORc + cells were seen in LC than in CC. Th1/Tc1- and TNFα-producing cells, and likely a subset of Th2/Tc2 cells as well, may be involved in the MC-to-IBD transformation.

Pilot study of ice-ball cryotherapy for radiation-induced oral mucositis

Energy Technology Data Exchange (ETDEWEB)

Ohyama, Waichiro; Ebihara, Satoshi [National Cancer Center Hospital, Tokyo (Japan)

1996-02-01

Oral mucositis caused by radiotherapy is intractable and may worsen the patient`s nutritional condition and interrupt treatment. To reduce the incidence and severity of oral mucositis induced by cancer therapy and promote early improvement of its symptoms, we devised cryotherapy by ice balls using Elase (fibrinolysin and deoxyribonuclease, combined). The therapeutic effect of ice-ball cryotherapy was evaluated in 10 patients with carcinoma of the oral cavity and pharynx who were undergoing radiotherapy. Cryotherapy was continued from the development of oral mucositis until its disappearance. The severity of various symptoms of mucositis were reduced by cryotherapy. Healing required 3 to 16 days (median, 7 days) after the end of radiotherapy. Radiotherapy was not interrupted in any cases. This preliminary report suggests that ice-ball cryotherapy is an effective treatment for radiation-induced oral mucositis. (author).

Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

International Nuclear Information System (INIS)

Narayan, Samir; Lehmann, Joerg; Coleman, Matthew A.; Vaughan, Andrew; Yang, Claus Chunli; Enepekides, Danny; Farwell, Gregory; Purdy, James A.; Laredo, Grace; Nolan, Kerry A.S.; Pearson, Francesca S.; Vijayakumar, Srinivasan

2008-01-01

Purpose: We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. Methods and Materials: Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. Results: Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade ≤ 1) and short duration (≤1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. Conclusions: In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction

Primary prevention of peri-implantitis: managing peri-implant mucositis.

Science.gov (United States)

Jepsen, Søren; Berglundh, Tord; Genco, Robert; Aass, Anne Merete; Demirel, Korkud; Derks, Jan; Figuero, Elena; Giovannoli, Jean Louis; Goldstein, Moshe; Lambert, France; Ortiz-Vigon, Alberto; Polyzois, Ioannis; Salvi, Giovanni E; Schwarz, Frank; Serino, Giovanni; Tomasi, Cristiano; Zitzmann, Nicola U

2015-04-01

Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are--in contrast to periodontitis--at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis. Discussions were informed by four systematic reviews on the current epidemiology of peri-implant diseases, on potential risks contributing to the development of peri-implant mucositis, and on the effect of patient and of professionally administered measures to manage peri-implant mucositis. This consensus report is based on the outcomes of these systematic reviews and on the expert opinion of the participants. Key findings included: (i) meta-analysis estimated a weighted mean prevalence for peri-implant mucositis of 43% (CI: 32-54%) and for peri-implantitis of 22% (CI: 14-30%); (ii) bleeding on probing is considered as key clinical measure to distinguish between peri-implant health and disease; (iii) lack of regular supportive therapy in patients with peri-implant mucositis was associated with increased risk for onset of peri-implantitis; (iv) whereas plaque accumulation has been established as aetiological factor, smoking was identified as modifiable patient-related and excess cement as local risk indicator for the development of peri-implant mucositis; (v) patient-administered mechanical plaque control (with manual or powered toothbrushes) has been shown to be an effective preventive measure; (vi) professional intervention

Abnormalities of magnesium homeostasis in patients with chemotherapy-induced alimentary tract mucositis

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Neven Baršić

2016-03-01

Full Text Available Purpose: Hypomagnesemia contributes to morbidity in a significant proportion of hospitalized and severely ill patients, but it could also have beneficial anticancer effects. Alimentary tract mucositis is a frequent complication of cytotoxic chemotherapy. The aim of this study was to determine frequency and severity of hypomagnesemia in patients with different grades of chemotherapy-induced alimentary tract mucositis and to assess its clinical manifestations. Methods: Multicentric observational study included 226 adult patients with alimentary mucositis treated at 3 different institutions. Patients were evaluated for severity of mucositis and the presence of hypomagnesemia, symptoms associated with hypomagnesemia, hypocalcemia, ECG changes and granulocytopenia. Subgroup analysis related to mucositis severity and presence of hypomagnesemia was performed. Results: Patients with grade 3 or 4 alimentary mucositis expectedly had more frequent and more severe granulocytopenia than patients with milder mucositis (49.6% vs. 35.4%, P = 0.043, but there were no differences in rate of hypomagnesemia (24.8% vs. 26.5%. When compared to patients with normal magnesium levels, patients with hypomagnesemia had higher rates of hypocalcemia (50.0% vs. 32.7%, P = 0.026, QTc prolongation (15.5% vs. 3.0%, P = 0.002 and granulocytopenia (77.6% vs. 39.9%, P < 0.001, while there was no difference in symptoms or other ECG features among these subgroups. Conclusions: Hypomagnesaemia is not associated with the severity of chemotherapy-induced mucositis. However, hypomagnesaemia was associated with higher rates of granulocytopenia and hypocalcemia. Our study failed to identify the link between hypomagnesaemia and chemotherapy-induced mucositis.

Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response.

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Yu, Xiao-Yu; Fu, Fei; Kong, Wen-Na; Xuan, Qian-Kun; Wen, Dong-Hua; Chen, Xiao-Qing; He, Yong-Ming; He, Li-Hua; Guo, Jian; Zhou, Ai-Ping; Xi, Yang-Hong; Ni, Li-Jun; Yao, Yu-Feng; Wu, Wen-Juan

2018-01-01

Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans , and that EFG1 -Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae , while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1 -Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans .

The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β.

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Anouk K Gloudemans

Full Text Available It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA, and how T cell-dependent (TD or -independent (TI pathways might be involved. Mucosal dendritic cells (DCs are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL, B cell activating factor (BAFF, Retinoic Acid (RA, TGF-β or nitric oxide (NO. We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.

The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β.

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Gloudemans, Anouk K; Plantinga, Maud; Guilliams, Martin; Willart, Monique A; Ozir-Fazalalikhan, Arifa; van der Ham, Alwin; Boon, Louis; Harris, Nicola L; Hammad, Hamida; Hoogsteden, Henk C; Yazdanbakhsh, Maria; Hendriks, Rudi W; Lambrecht, Bart N; Smits, Hermelijn H

2013-01-01

It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.

The role of sucralfate oral suspension in prevention of radiation induced mucositis

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Hamid Emami

2008-12-01

Full Text Available

• BACKGROUND: Mucositis is one of the most common complications of radiotherapy in head and neck cancers. The aim of this study was to evaluate sucralfate mouthwash in prevention of radiation induced mucositis.
• METHODS: A clinical randomized trial performed on 52 patients with head and neck cancers in Sayyed-Al-Shohada Hospital of Isfahan University of Medical Sciences. These patients randomly assigned in 2 groups of 26 patients. Placebo and sucralfate was used for control and experimental patients respectiv ly, from the beginning of radiotherapy. Patients were visited weekly until the end of treatment. Grade of the mucositis was evaluated according to WHO grading scale.
• RESULTS: Sucralfate significantly reduced the mean grade of mucositis in weeks one to four (with P-values of 0.02, 0.02, 0.001 and 0.004, respectively. Development of grade3 mucositis was also lower in sucralfate group (P-value = 0.0001. But, time interval between radiotherapy and appearance of mucositis was not statistically different in the two groups (P-value = 0.9
• CONCLUSIONS: This study indicated that using oral suspension of sucralfate reduced the grade of radiation-induced mucositis, but did not prevent or delay it.
• KEYWORDS: Mucositis, radiotherapy, sucralfate, head and neck cancers.

Commensal microbiota and NKT cells in the control of inflammatory diseases at mucosal surfaces.

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Zeissig, Sebastian; Blumberg, Richard S

2013-12-01

Natural Killer T (NKT) cells are a phenotypically and functionally diverse subset of T cells, which recognizes self- and microbial lipids in the context of the atypical MHC class I molecule CD1d. NKT cells exhibit potent effector functions and play critical roles in antimicrobial defense, cancer immunosurveillance and the modulation of immune-mediated disorders. Recent evidence has revealed extensive cross-regulation between the mucosal microbiota and CD1d as well as NKT cells. Microbial exposure at mucosal surfaces, particularly during early postnatal development, regulates NKT cell trafficking and function in the intestine and the lung and determines the susceptibility to NKT cell-mediated inflammatory disorders. Conversely, CD1d controls the composition of the intestinal microbiota; perhaps through the regulation of Paneth cell function. Here, we provide an overview of recent findings on the crosstalk between the microbiota and NKT cells and discuss the implication for mucosal homeostasis and its dysregulation in inflammatory disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

Voice disorders in mucosal leishmaniasis.

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Ana Cristina Nunes Ruas

Full Text Available INTRODUCTION: Leishmaniasis is considered as one of the six most important infectious diseases because of its high detection coefficient and ability to produce deformities. In most cases, mucosal leishmaniasis (ML occurs as a consequence of cutaneous leishmaniasis. If left untreated, mucosal lesions can leave sequelae, interfering in the swallowing, breathing, voice and speech processes and requiring rehabilitation. OBJECTIVE: To describe the anatomical characteristics and voice quality of ML patients. MATERIALS AND METHODS: A descriptive transversal study was conducted in a cohort of ML patients treated at the Laboratory for Leishmaniasis Surveillance of the Evandro Chagas National Institute of Infectious Diseases-Fiocruz, between 2010 and 2013. The patients were submitted to otorhinolaryngologic clinical examination by endoscopy of the upper airways and digestive tract and to speech-language assessment through directed anamnesis, auditory perception, phonation times and vocal acoustic analysis. The variables of interest were epidemiologic (sex and age and clinic (lesion location, associated symptoms and voice quality. RESULTS: 26 patients under ML treatment and monitored by speech therapists were studied. 21 (81% were male and five (19% female, with ages ranging from 15 to 78 years (54.5+15.0 years. The lesions were distributed in the following structures 88.5% nasal, 38.5% oral, 34.6% pharyngeal and 19.2% laryngeal, with some patients presenting lesions in more than one anatomic site. The main complaint was nasal obstruction (73.1%, followed by dysphonia (38.5%, odynophagia (30.8% and dysphagia (26.9%. 23 patients (84.6% presented voice quality perturbations. Dysphonia was significantly associated to lesions in the larynx, pharynx and oral cavity. CONCLUSION: We observed that vocal quality perturbations are frequent in patients with mucosal leishmaniasis, even without laryngeal lesions; they are probably associated to disorders of some

Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

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Chentoufi, Aziz Alami; BenMohamed, Lbachir

2012-01-01

Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed. PMID:23320014

Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

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Aziz Alami Chentoufi

2012-01-01

Full Text Available Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2 are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed.

76 FR 64083 - Reliability Technical Conference; Notice of Technical Conference

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2011-10-17

... Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, November 29, 2011, from 1 p.m. to 5 p.m. and... reliability that were identified in earlier Commission technical conferences. The conference also will discuss...

The 3rd international conference on reproductive immunology in Shanghai: September 27-29, 2013. Shanghai, China.

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Du, MeiRong; Piao, HaiLan; Li, DaJin

2014-03-01

After the first and second international conferences on reproductive immunology held by Dr. DaJin Li in Shanghai, the related investigators all over the world hope to get together to share their latest findings with each other. Drs. DaJin Li and MeiRong Du sponsored and organized the third international conference on reproductive immunology at the Obstetrics and Gynecology Hospital affiliated with Fudan University, Shanghai, China, in the autumn of 2013. This congress brought together more than 100 International and National investigators representing a wide range of scientific disciplines. All the investigators actively work on reproductive immunology using human or large and small animal models. A range of reproductive immunological topics including the maternal-fetal immune regulation, reproductive tract mucosal immunology, immunocontraception, and pregnancy complications were highlighted and discussed in this conference. This conference supplied a good platform for the international reproductive immunologists to exchange their latest study progression and discuss the development direction of reproductive immunology in the near future. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mucosal Healing and Risk of Lymphoproliferative Malignancy in Celiac Disease

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Lebwohl, Benjamin; Granath, Fredrik; Ekbom, Anders; Smedby, Karin Ekström; Murray, Joseph A.; Neugut, Alfred I.; Green, Peter HR; Ludvigsson, Jonas F.

2013-01-01

Background Celiac disease (CD) is associated with an increased risk of lymphoproliferative malignancy (LPM). It is unknown whether this risk is affected by the results of the follow-up intestinal biopsy, performed to document mucosal healing. Objective To examine the association between mucosal healing in CD and later LPM. Design Population-based cohort study Setting We identified patients with CD from all of Sweden’s 28 pathology departments. Patients Individuals with CD who had a follow-up biopsy after initial diagnosis. Measurements We compared the risk of LPM to that of the general population using expected rates; and through Cox regression we compared the rate of LPM in those with persistent villous atrophy to those with mucosal healing. Results Among 7,625 patients with CD and a follow-up biopsy, persistent villous atrophy was present in 3,308 (43%). The overall risk of LPM was increased compared to the general population (Standardized incidence ratio, SIR 2.81; 95%CI 2.10–3.67), but this increase was greater among those with persistent villous atrophy (SIR 3.78; 95%CI 2.71–5.12) as compared to those with mucosal healing (SIR 1.50; 95%CI 0.77–2.62). Persistent villous atrophy compared to mucosal healing was associated with an increased risk of LPM (Hazard ratio, HR 2.26; 95%CI 1.18–4.34). We found an increased risk of T cell lymphoma (HR 3.51; 95%CI 0.75–16.34), but no excess risk of B cell lymphoma (HR 0.97; 95%CI 0.21–4.49). Limitation We had no data on dietary compliance. Conclusions The increased LPM risk in CD is associated with the results of the follow-up biopsy, with a higher risk among those with persistent villous atrophy. Follow-up biopsy may be a means to effectively stratify CD patients regarding subsequent LPM risk. Primary funding source the National Center for Advancing Translational Sciences, National Institutes of Health, The American Scandinavian Foundation, the Celiac Sprue Association, Örebro University Hospital, Karolinska

Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

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Wang, Hanru; Brook, Caitlin L; Whittaker, Alexandra L; Lawrence, Andrew; Yazbeck, Roger; Howarth, Gordon S

2013-08-01

Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. Body weight was significantly decreased by doxorubicin compared with normal controls (p TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

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Fukuyama, Yoshiko; Tokuhara, Daisuke [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Sekine, Shinichi [Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University, Osaka 565-0871 (Japan); Kataoka, Kosuke [Department of Preventive Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Markham, Jonathan D.; Irwin, Allyson R.; Moon, Grace H.; Tokuhara, Yuka; Fujihashi, Keiko [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Davydova, Julia; Yamamoto, Masato [Department of Surgery, University of Minnesota, Minneapolis, MN 55455 (United States); Gilbert, Rebekah S. [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States); Fujihashi, Kohtaro, E-mail: kohtarof@uab.edu [Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The Institute of Oral Health Research, The University of Alabama at Birmingham, Birmingham, AL 35294-0007 (United States)

2012-02-03

Highlights: Black-Right-Pointing-Pointer Nasal Ad-FL effectively up-regulates APC function by CD11c{sup +} DCs in mucosal tissues. Black-Right-Pointing-Pointer Nasal Ad-FL induces Notch ligand (L)-expressing CD11c{sup +} DCs. Black-Right-Pointing-Pointer Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c{sup +} dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c{sup +} DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FL activated CD11c{sup +} DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c{sup +} DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4{sup +} T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-{gamma}, IL-2 and IL-4 producing CD4{sup +} T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch-Notch-L pathway. These results show that Ad-FL induces CD11c{sup +} DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.

How to prevent ripening blockage in 1-MCP-treated 'Conference' pears.

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Chiriboga, Maria-Angeles; Schotsmans, Wendy C; Larrigaudière, Christian; Dupille, Eve; Recasens, Inmaculada

2011-08-15

Some European pear varieties treated with 1-methylcyclopropene (1-MCP) often remain 'evergreen', meaning that their ripening process is blocked and does not resume after removal from cold storage. In this work this was confirmed also to be the case in 'Conference' pears. To reverse the blockage of ripening 1-MCP treatments combined with external exogenous ethylene were tested. 1-MCP treatment of 'Conference' pears is very effective in delaying ripening and, more specifically, softening. The same 1-MCP concentration in different experimental years caused a different response. The higher dose of 1-MCP (600 nL L⁻¹) always resulted in irreversible blockage of ripening, whereas the behaviour of fruit receiving a lower dose (300 nL L⁻¹) depended on the year, and this did not depend on maturity at harvest or on storage conditions. Simultaneous exposure to 1-MCP and exogenous ethylene significantly affected fruit ripening, allowing significant softening to occur but at a lower rate compared with control fruit. The application of exogenous ethylene and 1-MCP simultaneously after harvest permitted restoration of the ripening process after storage in 'Conference' pears, extending the possibility of marketing and consumption. Copyright © 2011 Society of Chemical Industry.

Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

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Watkins, E.B.; Findlay, P.; Gelmann, E.; Lane, H.C.; Zabell, A.

1987-09-01

The oropharynx and hypopharynx are common sites of involvement in AIDS patients with mucocutaneous Kaposi's sarcoma. The radiotherapist is often asked to intervene with these patients due to problems with pain, difficulty in swallowing, or impending airway obstruction. We have noted an unexpected decrease in normal tissue tolerance of the oropharyngeal mucosa to irradiation in AIDS patients treated in our department. Data on 12 patients with AIDS and Kaposi's sarcoma receiving oropharyngeal irradiation are presented here. Doses ranged from 1000 cGy to 1800 cGy delivered in 150-300 cGy fractions. Seven of eight patients receiving doses of 1200 cGy or more developed some degree of mucositis, four of these developed mucositis severe enough to require termination of treatment. All patients in this study received some form of systemic therapy during the course of their disease, but no influence on mucosal response to irradiation was noted. Four patients received total body skin electron treatments, but no effect on degree of mucositis was seen. Presence or absence of oral candidiasis was not an obvious factor in the radiation response of the oral mucosa in these patients. T4 counts were done on 9 of the 12 patients. Although the timing of the T4 counts was quite variable, no correlation with immune status and degree of mucositis was found. The degree of mucositis seen in these patients occurred at doses much lower than expected based on normal tissue tolerances seen in other patient populations receiving head and neck irradiations. We believe that the ability of the oral mucosa to repair radiation damage is somehow altered in patients with AIDS.

Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

International Nuclear Information System (INIS)

Watkins, E.B.; Findlay, P.; Gelmann, E.; Lane, H.C.; Zabell, A.

1987-01-01

The oropharynx and hypopharynx are common sites of involvement in AIDS patients with mucocutaneous Kaposi's sarcoma. The radiotherapist is often asked to intervene with these patients due to problems with pain, difficulty in swallowing, or impending airway obstruction. We have noted an unexpected decrease in normal tissue tolerance of the oropharyngeal mucosa to irradiation in AIDS patients treated in our department. Data on 12 patients with AIDS and Kaposi's sarcoma receiving oropharyngeal irradiation are presented here. Doses ranged from 1000 cGy to 1800 cGy delivered in 150-300 cGy fractions. Seven of eight patients receiving doses of 1200 cGy or more developed some degree of mucositis, four of these developed mucositis severe enough to require termination of treatment. All patients in this study received some form of systemic therapy during the course of their disease, but no influence on mucosal response to irradiation was noted. Four patients received total body skin electron treatments, but no effect on degree of mucositis was seen. Presence or absence of oral candidiasis was not an obvious factor in the radiation response of the oral mucosa in these patients. T4 counts were done on 9 of the 12 patients. Although the timing of the T4 counts was quite variable, no correlation with immune status and degree of mucositis was found. The degree of mucositis seen in these patients occurred at doses much lower than expected based on normal tissue tolerances seen in other patient populations receiving head and neck irradiations. We believe that the ability of the oral mucosa to repair radiation damage is somehow altered in patients with AIDS

Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

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Savannah E. Howe

2016-10-01

Full Text Available Nanoparticles (NPs are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n. priming followed by i.n. or subcutaneous (s.c. boosting immunization affects the humoral immune response to chicken ovalbumin (Ova and Ova conjugated to 20 nm NPs (NP-Ova. We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA. In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.

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

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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.

Oral and intestinal mucositis - causes and possible treatments.

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Duncan, M; Grant, G

2003-11-01

Chemotherapy and radiotherapy, whilst highly effective in the treatment of neoplasia, can also cause damage to healthy tissue. In particular, the alimentary tract may be badly affected. Severe inflammation, lesioning and ulceration can occur. Patients may experience intense pain, nausea and gastro-enteritis. They are also highly susceptible to infection. The disorder (mucositis) is a dose-limiting toxicity of therapy and affects around 500 000 patients world-wide annually. Oral and intestinal mucositis is multi-factorial in nature. The disruption or loss of rapidly dividing epithelial progenitor cells is a trigger for the onset of the disorder. However, the actual dysfunction that manifests and its severity and duration are greatly influenced by changes in other cell populations, immune responses and the effects of oral/gut flora. This complexity has hampered the development of effective palliative or preventative measures. Recent studies have concentrated on the use of bioactive/growth factors, hormones or interleukins to modify epithelial metabolism and reduce the susceptibility of the tract to mucositis. Some of these treatments appear to have considerable potential and are at present under clinical evaluation. This overview deals with the cellular changes and host responses that may lead to the development of mucositis of the oral cavity and gastrointestinal tract, and the potential of existing and novel palliative measures to limit or prevent the disorder. Presently available treatments do not prevent mucositis, but can limit its severity if used in combination. Poor oral health and existing epithelial damage predispose patients to mucositis. The elimination of dental problems or the minimization of existing damage to the alimentary tract, prior to the commencement of therapy, lowers their susceptibility. Measures that reduce the flora of the tract, before therapy, can also be helpful. Increased production of free radicals and the induction of inflammation are

Peptic ulcer pathophysiology: acid, bicarbonate, and mucosal function

DEFF Research Database (Denmark)

Højgaard, L; Mertz Nielsen, A; Rune, S J

1996-01-01

The previously accepted role of gastric acid hypersecretion in peptic ulcer disease has been modified by studies showing no correlation between acid output and clinical outcome of ulcer disease, or between ulcer recurrence rate after vagotomy and preoperative acid secretion. At the same time......, studies have been unable to demonstrate increased acidity in the duodenal bulb in patients with duodenal ulcer, and consequently more emphasis has been given to the mucosal protecting mechanisms. The existence of an active gastric and duodenal mucosal bicarbonate secretion creates a pH gradient from...... cell removal and repair regulated by epidermal growth factor. Sufficient mucosal blood flow, including a normal acid/base balance, is important for subepithelial protection. In today's model of ulcer pathogenesis, gastric acid and H. pylori work in concert as aggressive factors, with the open question...

1988 DOE model conference proceedings: Volume 1

International Nuclear Information System (INIS)

1988-01-01

These Proceedings of the October 3-7, 1988, DOE Model Conference are a compilation of the papers that were presented in the technical or poster sessions at the conference. Papers and posters not submitted for publication are not included in the Proceedings. The Table of Contents lists the titles of papers as well as the names of the presenters. These individuals are not, in all cases, the primary authors of the papers published. The actual title pages, appearing later with the papers, show the primary author(s) and all co-authors. The papers in all three volumes of the Proceedings appear as they were originally submitted for publication and have not been edited or changed in any way. Topics included in Volume 1 are Environmental Data Management, Site characterization technology, Wastewater treatment, Waste management in foreign countries, Transuranic waste management, and Groundwater characterization and treatment

1988 DOE model conference proceedings: Volume 1

Energy Technology Data Exchange (ETDEWEB)

1988-01-01

These Proceedings of the October 3-7, 1988, DOE Model Conference are a compilation of the papers that were presented in the technical or poster sessions at the conference. Papers and posters not submitted for publication are not included in the Proceedings. The Table of Contents lists the titles of papers as well as the names of the presenters. These individuals are not, in all cases, the primary authors of the papers published. The actual title pages, appearing later with the papers, show the primary author(s) and all co-authors. The papers in all three volumes of the Proceedings appear as they were originally submitted for publication and have not been edited or changed in any way. Topics included in Volume 1 are Environmental Data Management, Site characterization technology, Wastewater treatment, Waste management in foreign countries, Transuranic waste management, and Groundwater characterization and treatment.

Low-level laser therapy in the prevention of radiotherapy-induced xerostomia and oral mucositis

International Nuclear Information System (INIS)

Lopes, Carlos de Oliveira; Mas, Josepa Rigau I.; Zangaro, Renato Amaro

2006-01-01

Objective: to verify if the use of InGaAIP laser with 685 nm wave length can reduce the xerostomy incidence, the oral mucositis severity and the pain related to mucositis in patients with head and neck cancer submitted to radiotherapy. Objective: sixty patients presenting head and neck carcinoma were submitted to radiotherapy with daily doses of 1.8 to 2.0 Gy and a final dose of 45 to 72 Gy. The salivary volume was evaluated in the first and fifteenth days, at the end of the treatment and after 15 and 30 days. The oral mucositis was evaluated on a weekly basis. Twenty-nine patients were submitted to radiotherapy without laser and 31 were submitted to radiotherapy and laser with daily doses of 2 joules/cm 2 in predetermined areas of the oral mucosa and the parotid and submandibular glands. Results: in the group submitted to radiotherapy and laser the incidence of mucositis (p < 0.001) and pain (p < 0.016) was significantly lower and the salivary volume (p < 0.001) was kept higher during and after the treatment. Conclusion: the group of patients submitted to radiotherapy and laser had lower incidence of xerostomy, oral mucositis and pain when compared to the group treated with radiotherapy without laser, producing statistically significant results. (author)

Sucralfate for radiation mucositis: results of a double-blind randomized trial

International Nuclear Information System (INIS)

Meredith, R.; Salter, M.; Kim, R.; Spencer, S.; Weppelmann, B.; Rodu, B.; Smith, J.; Lee, J.

1995-01-01

Purpose: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of Maalox, diphenhyrdramine and viscous lidocaine alone. Methods: A double-blind study was conducted in which nurses/pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of Maalox, diphenhydramime and viscous lidocaine verses the same solution plus sucralfate. Eligible patients were those receiving > 40 Gy at 1.8 Gy/fraction, 1 fraction/day, 5 fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. Baseline information regarding use of tobacco, alcohol, and food intake was obtained prior to symptomatic mucositis. This was compared with similar information obtained weekly once symptoms occurred. The patients subjected evaluation of throat soreness and relief with medication was elicited as well as physician observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective non-study agents was not allowed. Subjective soreness was graded on a scale of 0-20 with 0 indicating no soreness and 20 designating severe soreness that compromised ability to swallow secretions. The ability to eat various consistency of foods was graded 0-5 with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + S.D. for food and soreness scores, paired t-test and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. Results: Over 2 years, 110 patients were entered. Since some withdrew and others did not require medication, results are presented for

Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

Directory of Open Access Journals (Sweden)

Daryan A Kaveh

Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

Acceptability and feasibility of repeated mucosal specimen collection in clinical trial participants in Kenya.

Directory of Open Access Journals (Sweden)

Gloria Omosa-Manyonyi

Full Text Available Mucosal specimens are essential to evaluate compartmentalized immune responses to HIV vaccine candidates and other mucosally targeted investigational products. We studied the acceptability and feasibility of repeated mucosal sampling in East African clinical trial participants at low risk of HIV and other sexually transmitted infections.The Kenya AIDS Vaccine Initiative (KAVI enrolled participants into three Phase 1 trials of preventive HIV candidate vaccines in 2011-2012 at two clinical research centers in Nairobi. After informed consent to a mucosal sub-study, participants were asked to undergo collection of mucosal secretions (saliva, oral fluids, semen, cervico-vaginal and rectal, but could opt out of any collection at any visit. Specimens were collected at baseline and two additional time points. A tolerability questionnaire was administered at the final sub-study visit. Of 105 trial participants, 27 of 34 women (79% and 62 of 71 men (87% enrolled in the mucosal sub-study. Nearly all sub-study participants gave saliva and oral fluids at all visits. Semen was collected from about half the participating men (47-48% at all visits. Cervico-vaginal secretions were collected by Softcup from about two thirds of women (63% at baseline, increasing to 78% at the following visits, with similar numbers for cervical secretion collection by Merocel sponge; about half of women (52% gave cervico-vaginal samples at all visits. Rectal secretions were collected with Merocel sponge from about a quarter of both men and women (24% at all 3 visits, with 16% of men and 19% of women giving rectal samples at all visits.Repeated mucosal sampling in clinical trial participants in Kenya is feasible, with a good proportion of participants consenting to most sampling methods with the exception of rectal samples. Experienced staff members of both sexes and trained counselors with standardized messaging may improve acceptance of rectal sampling.

[Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

Science.gov (United States)

Mu, F H; Hu, F L; Wei, H; Zhang, Y Y; Yang, G B; Lei, X Y; Yang, Y P; Sun, W N; Cui, M H

2016-02-01

To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all Pcompound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, Pcompound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, PCompound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

Intravenous glutamine does not modify leucocyte count but shortens duration of mucositis after bone marrow transplant

Directory of Open Access Journals (Sweden)

María Belén Andrade Hernández

2018-04-01

Full Text Available Rationale: Intravenous administration of Glutamine dipeptides (Gln has been proposed as treatment of oral mucositis following a bone marrow transplant (BMT. Objective: To establish the effects of intravenous Gln supplementation upon the severity of oral mucositis after BMT. Study design: Retrospective, analytical. Study serie: Records from 25 patients (Males: 56.0%; BMT cause: Leukemia: 64.0% who developed oral mucositis (Grades III – IV: 48.0% after BMT (Autologous: 44.0% at the "Juan Tanca Marengo" Hospital (Guayaquil, Ecuador between 2009 – 2017. Glutamine source: Dipeptiven©®: 13 grams of Gln suspended in 100 milliliters of a 20% solution of the alanine-glutamine dipeptide (Fresenius-Kabi©®, Germany. Materials and Methods: Gln-treated patients received 3(4.0% of the treatment leg, 5 (20.0%; 6 (12.0%; 7 (48.0%; or 10 (16.0% doses of the dipeptide until resolution of the symptoms. Impact of Gln was estimated from changes observed in the severity and duration of mucositis, white blood cell counts, and body weight regarding 25 non-Gln treated patients (Males: 68.0%; Leukemias: 32.0%; Autologous graft: 68.0%; Grade III – IV mucositis: 48.0%. Results: Intravenously-administered Gln shortened duration of oral mucositis: Gln-Treated: 12.5 ± 5.1 days vs. Non-Gln Treated: 21.3 ± 17.8 days (p < 0.05. Also, intravenous Gln marginally ameliorated loss of body weight: Gln-Treated -4.5 ± 5.5% vs. Non-Gln Treated: -7.5 ± 5.7% (p = 0.07. Conclusions: Intravenous Gln administration shortens duration of oral mucositis following BMT. Gln effect might be translated to a lesser weight loss in patients with oral mucositis.

Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation.

Science.gov (United States)

Kurashima, Yosuke; Goto, Yoshiyuki; Kiyono, Hiroshi

2013-12-01

Continuous exposure of intestinal mucosal surfaces to diverse microorganisms and their metabolites reflects the biological necessity for a multifaceted, integrated epithelial and immune cell-mediated regulatory system. The development and function of the host cells responsible for the barrier function of the intestinal surface (e.g., M cells, Paneth cells, goblet cells, and columnar epithelial cells) are strictly regulated through both positive and negative stimulation by the luminal microbiota. Stimulation by damage-associated molecular patterns and commensal bacteria-derived microbe-associated molecular patterns provokes the assembly of inflammasomes, which are involved in maintaining the integrity of the intestinal epithelium. Mucosal immune cells located beneath the epithelium play critical roles in regulating both the mucosal barrier and the relative composition of the luminal microbiota. Innate lymphoid cells and mast cells, in particular, orchestrate the mucosal regulatory system to create a mutually beneficial environment for both the host and the microbiota. Disruption of mucosal homeostasis causes intestinal inflammation such as that seen in inflammatory bowel disease. Here, we review the recent research on the biological interplay among the luminal microbiota, epithelial cells, and mucosal innate immune cells in both healthy and pathological conditions. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative analysis of differentially expressed saliva proteins in human immunodeficiency virus type 1 (HIV-1) infected individuals

International Nuclear Information System (INIS)

Zhang, Nawei; Zhang, Zhenyu; Feng, Shan; Wang, Qingtao; Malamud, Daniel; Deng, Haiteng

2013-01-01

Highlights: ► A high-throughput method for profiling and quantification of the differentially expressed proteins in saliva samples was developed. ► Identified that DMBT1, S100A7, S100A8, S100A9 and alpha defensin were up-regulated in saliva from HIV-1 seropositive patients. ► Established analytical strategies are translatable to the clinical setting. -- Abstract: In the present study, we have established a new methodology to analyze saliva proteins from HIV-1-seropositive patients before highly active antiretroviral therapy (HAART) and seronegative controls. A total of 593 and 601 proteins were identified in the pooled saliva samples from 5 HIV-1 subjects and 5 controls, respectively. Forty-one proteins were found to be differentially expressed. Bioinformatic analysis of differentially expressed salivary proteins showed an increase of antimicrobial proteins and decrease of protease inhibitors upon HIV-1 infection. To validate some of these differentially expressed proteins, a high-throughput quantitation method was established to determine concentrations of 10 salivary proteins in 40 individual saliva samples from 20 seropositive patients before HAART and 20 seronegative subjects. This method was based on limited protein separation within the zone of the stacking gel of the 1D SDS PAGE and using isotope-coded synthetic peptides as internal standards. The results demonstrated that a combination of protein profiling and targeted quantitation is an efficient method to identify and validate differentially expressed salivary proteins. Expression levels of members of the calcium-binding S100 protein family and deleted in malignant brain tumors 1 protein (DMBT1) were up-regulated while that of Mucin 5B was down-regulated in HIV-1 seropositive saliva samples, which may provide new perspectives for monitoring HIV-infection and understanding the mechanism of HIV-1 infectivity

Quantitative analysis of differentially expressed saliva proteins in human immunodeficiency virus type 1 (HIV-1) infected individuals

Energy Technology Data Exchange (ETDEWEB)

Zhang, Nawei; Zhang, Zhenyu [Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing (China); Feng, Shan [MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing (China); Wang, Qingtao [Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing (China); Malamud, Daniel [NYU College of Dentistry, 345 East 24th Street, New York, NY 10010 (United States); Deng, Haiteng, E-mail: dht@mail.tsinghua.edu.cn [MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing (China)

2013-04-24

Highlights: ► A high-throughput method for profiling and quantification of the differentially expressed proteins in saliva samples was developed. ► Identified that DMBT1, S100A7, S100A8, S100A9 and alpha defensin were up-regulated in saliva from HIV-1 seropositive patients. ► Established analytical strategies are translatable to the clinical setting. -- Abstract: In the present study, we have established a new methodology to analyze saliva proteins from HIV-1-seropositive patients before highly active antiretroviral therapy (HAART) and seronegative controls. A total of 593 and 601 proteins were identified in the pooled saliva samples from 5 HIV-1 subjects and 5 controls, respectively. Forty-one proteins were found to be differentially expressed. Bioinformatic analysis of differentially expressed salivary proteins showed an increase of antimicrobial proteins and decrease of protease inhibitors upon HIV-1 infection. To validate some of these differentially expressed proteins, a high-throughput quantitation method was established to determine concentrations of 10 salivary proteins in 40 individual saliva samples from 20 seropositive patients before HAART and 20 seronegative subjects. This method was based on limited protein separation within the zone of the stacking gel of the 1D SDS PAGE and using isotope-coded synthetic peptides as internal standards. The results demonstrated that a combination of protein profiling and targeted quantitation is an efficient method to identify and validate differentially expressed salivary proteins. Expression levels of members of the calcium-binding S100 protein family and deleted in malignant brain tumors 1 protein (DMBT1) were up-regulated while that of Mucin 5B was down-regulated in HIV-1 seropositive saliva samples, which may provide new perspectives for monitoring HIV-infection and understanding the mechanism of HIV-1 infectivity.

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

Science.gov (United States)

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.

Trophic factors in the treatment and prevention of alimentary tract mucositis

DEFF Research Database (Denmark)

Rathe, Mathias; Shen, Rene L; Sangild, Per T

2018-01-01

PURPOSE OF REVIEW: Mucositis is a common adverse effect of cytotoxic anticancer treatment with serious implications for the quality of life, morbidity and mortality of cancers patients. Although, evidence supporting the use of certain treatments exists there is no gold standard for preventing...... clinical trials and uniform reporting of mucositis, are important elements to help establish new standard interventions that can be included into the continuously updated clinical recommendations for treatment of mucositis....

M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

Science.gov (United States)

Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

2014-07-31

Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dual oxidase in mucosal immunity and host-microbe homeostasis.

Science.gov (United States)

Bae, Yun Soo; Choi, Myoung Kwon; Lee, Won-Jae

2010-07-01

Mucosal epithelia are in direct contact with microbes, which range from beneficial symbionts to pathogens. Accordingly, hosts must have a conflicting strategy to combat pathogens efficiently while tolerating symbionts. Recent progress has revealed that dual oxidase (DUOX) plays a key role in mucosal immunity in organisms that range from flies to humans. Information from the genetic model of Drosophila has advanced our understanding of the regulatory mechanism of DUOX and its role in mucosal immunity. Further investigations of DUOX regulation in response to symbiotic or non-symbiotic bacteria and the in vivo consequences in host physiology will give a novel insight into the microbe-controlling system of the mucosa. Copyright 2010 Elsevier Ltd. All rights reserved.

Proceedings of the 1. Arabic conference on chemical applications (Chemia 2). Vol. 1

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-11-01

The 1. Arabic conference on chemical applications was held on 1-5 Nov 1997 in Cairo. The specialists discussed the chemical applications for environmental service. This first volume covers papers presented on the subjects environmental protection of pollution, nuclear materials and environment, nuclear materials and industry.

Proceedings of the 1. Arabic conference on chemical applications (Chemia 2). Vol. 1

International Nuclear Information System (INIS)

1997-11-01

The 1. Arabic conference on chemical applications was held on 1-5 Nov 1997 in Cairo. The specialists discussed the chemical applications for environmental service. This first volume covers papers presented on the subjects environmental protection of pollution, nuclear materials and environment, nuclear materials and industry

Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness.

Directory of Open Access Journals (Sweden)

Jaideep Dhariwal

Full Text Available Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF.We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 per protocol. Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM, a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1 was quantified from nasal epithelial curettage samples taken before and after challenge.Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8 and CCL3 (MIP-1α (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS. At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05. Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS.Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.Ultrapure LPS was used

EVALUATING THE EFFICACY OF PRESERVING THE MUCOSAL FLAP IN ENDONASAL DCR

Directory of Open Access Journals (Sweden)

Koteswar

2015-11-01

Full Text Available INTRODUCTION Endoscopic DCR is routinely performed by otolaryngologists for the treatment of chronic dacryocystitis. However, postoperative stenosis and failure rates are common. OBJECTIVE The objective of our study is to evaluate the role of preserving the mucosal flap in maintaining the patency of neo ostium. The surgical technique involved the creation of nasal mucosal and large posterior lacrimal flaps at the medial lacrimal sac wall and the two flaps were placed in close apposition. Success was defined as complete resolution of epiphora and a patent lacrimal system, evaluated by lacrimal irrigation and endoscopy followed upto 1 year postoperatively. MATERIALS AND METHODS A prosective study was conducted in 60 patients and followed for a duration of 1 year in ENT department,KMC,Guntur RESULTS In our study, Symptomatic and anatomic success was seen in 59 out of 60 operations that is 98% success in syringing patency was seen with this technique, which is comparable to external DCR and better than other endoscopic techniques. CONCLUSION Mucosal flap preservation appears to be the single most important innovation in endoscopic DCR surgery, which makes it comfortable for both the surgeon and patient, apart from providing a 98% success rate in our study.

Cryopreservation of Human Mucosal Leukocytes.

Directory of Open Access Journals (Sweden)

Sean M Hughes

Full Text Available 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.

Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh.

Science.gov (United States)

Charles, Richelle C; Nakajima, Rie; Liang, Li; Jasinskas, Al; Berger, Amanda; Leung, Daniel T; Kelly, Meagan; Xu, Peng; Kovác, Pavol; Giffen, Samantha R; Harbison, James D; Chowdhury, Fahima; Khan, Ashraful I; Calderwood, Stephen B; Bhuiyan, Taufiqur Rahman; Harris, Jason B; Felgner, Philip L; Qadri, Firdausi; Ryan, Edward T

2017-07-01

Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera. We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V. cholerae O1 in Bangladesh and age-, sex-, and ABO-matched Bangladeshi controls. We validated a subset of identified antigens using enzyme-linked immunosorbent assay. Overall, we identified 608 immunoreactive V. cholerae antigens in our screening, 59 of which had higher immunoreactivity in convalescent compared with acute-stage or healthy control samples (34 in plasma, 39 in mucosal ALS; 13 in both sample sets). Identified antigens included cholera toxin B and A subunits, V. cholerae O-specific polysaccharide and lipopolysaccharide, toxin coregulated pilus A, sialidase, hemolysin A, flagellins (FlaB, FlaC, and FlaD), phosphoenolpyruvate-protein phosphotransferase, and diaminobutyrate-2-oxoglutarate aminotransferase. This study is the first antibody profiling of the mucosal and systemic antibody responses to the nearly complete V. cholerae O1 protein immunome; it has identified antigens that may aid in the development of an improved cholera vaccine. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Proceedings IEEE Visualization Conference and IEEE Information Visualization Conference (VIS'07 and INFOVIS'07, Sacramento CA, USA, October 28-November 1, 2007)

NARCIS (Netherlands)

Chen, M.; Hansen, C.; North, C.; Pang, A.; Wijk, van J.J.

2007-01-01

These are the proceedings of the IEEE Visualization Conference 2007 (Vis 2007) and the IEEE Information Visualization Conference 2007 (InfoVis 2007) held during October 28 to November 1, 2007 in Sacramento, California. The power of using computing technology to create useful, effective imagery for

Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response

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Xiao-Yu Yu

2018-02-01

Full Text Available Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans, and that EFG1-Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC, the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae, while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1-Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans.

Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells.

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Jason A Neidleman

2017-02-01

Full Text Available Understanding early events of HIV transmission within mucosal tissues is vital for developing effective prevention strategies. Here, we report that primary stromal fibroblasts isolated from endometrium, cervix, foreskin, male urethra, and intestines significantly increase HIV infection of CD4+ T cells-by up to 37-fold for R5-tropic HIV and 100-fold for X4-tropic HIV-without themselves becoming infected. Fibroblasts were more efficient than dendritic cells at trans-infection and mediate this response in the absence of the DC-SIGN and Siglec-1 receptors. In comparison, mucosal epithelial cells secrete antivirals and inhibit HIV infection. These data suggest that breaches in the epithelium allow external or luminal HIV to escape an antiviral environment to access the infection-favorable environment of the stromal fibroblasts, and suggest that resident fibroblasts have a central, but previously unrecognized, role in HIV acquisition at mucosal sites. Inhibiting fibroblast-mediated enhancement of HIV infection should be considered as a novel prevention strategy.

1st National Conference on Sensors

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D’Amico, Arnaldo; Natale, Corrado; Siciliano, Pietro; Seeber, Renato; Stefano, Luca; Bizzarri, Ranieri; Andò, Bruno

2014-01-01

This book contains a selection of papers presented at the First National Conference on Sensors held in Rome 15-17 February 2011. The conference highlighted state-of-the-art results from both theoretical and applied research in the field of sensors and related technologies. This book presents material in an interdisciplinary approach, covering many aspects of the disciplines related to sensors, including physics, chemistry, materials science, biology and applications.   ·         Provides a selection of the best papers from the First Italian National Conference on Sensors; ·         Covers a broad range of topics relating to sensors and microsystems, including physics, chemistry, materials science, biology and applications;       ·        Offers interdisciplinary coverage, aimed at defining a common ground for sensors beyond the specific differences among the different particular implementation of sensors.

The efficacy of a steroid mixture for chemoradiotherapy-induced acute mucositis

International Nuclear Information System (INIS)

Tamamura, Hiroyasu; Ohoguchi, Manabu; Ichioka, Kazuhiro; Ohta, Kiyotaka; Higashi, Kotarou; Tonami, Hisao

2005-01-01

Radiotherapy is an important therapeutic tool for malignant tumors in the head and neck and thoracic region. However, radiotherapy has also been known to cause acute mucositis and esophagitis during the early phase of treatment, for which there is no cure to date. A mixture of mucosal protective steroids has been shown to be beneficial in patients with these symptoms receiving radiotherapy alone. The purpose of this study was to examine the efficacy of this agent to treat the mucositis that accompanies chemoradiotherapy. Moreover, the differences between the curative effects were examined retrospectively, according to the region irradiated. Radiotherapy was administered to the head and neck, and thoracic region, and the steroid mixture was prescribed for patients in the radiotherapy alone and chemoradiotherapy groups that exhibited acute radiation-induced mucositis symptoms. We then evaluated daily food consumption, total serum-protein value, serum-albumin value and body weight of the radiation-induced mucositis patients that were treated with the mixture. Moreover, we also examined the efficacy in patients undergoing irradiation of the oral cavity, and of the esophagus (which did not entail irradiation of the oral cavity). Two hundred and fourteen patients treated with the steroid mixture in this study had no treatment-related adverse events. In comparison between the radiotherapy alone and chemoradiotherapy groups, no significant differences were observed for daily food consumption. However, differences were observed for daily food consumption between the groups undergoing irradiation of the oral cavity and irradiation of the esophagus (p=0.0008). In the group experiencing irradiation of the mouth, decreased ability to swallow and digest food associated with the primary disease was also observed. Total serum-protein values, serum-albumin values and body weight exhibited a slight decrease despite the onset of radiation-induced mucositis, compared with the values

Absorption of iron in the aged; investigation of mucosal-uptake, mucosal-transfer and retention of a physiological dose of inorganic iron

International Nuclear Information System (INIS)

Marx, J.J.M.

1976-01-01

Iron (II) and iron (III) uptake by the mucosal cells, the retention in the body, and the mucosal-transport fraction were studied in 40 healthy people over 65 years old, in 30 young adults and in 20 patients with iron-deficiency. The study was performed with 59 Fe as a tracer and 51 Cr as an inert indicator. The radioactivity was measured with a whole body scanner 24 hours and 24 days after ingestion

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

Science.gov (United States)

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.

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

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Chung-Hsien Li

2015-06-01

Full Text Available 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 2nd 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.

A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

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Bryan Oronsky

2018-06-01

Full Text Available The first tenet of medicine, “primum non nocere” or “first, do no harm”, is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM, which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.

Assessment of intestinal permeability and bacterial translocation employing nuclear methods in murine mucositis

International Nuclear Information System (INIS)

Pessoa, Rafaela M.; Takenaka, Isabella K.T.M.; Barros, Patricia A.V.; Moura, Livia P.; Contarini, Sara M.L.; Amorim, Juliana M.; Castilho, Raquel O.; Leite, Camila M.A.; Cardoso, Valbert N.; Diniz, Simone Odilia F.

2017-01-01

Full text: Introduction: Mucositis affects approximately 80% of patients who receive chemotherapy combinations. The lesions are painful, restrict food intake and make patients more susceptible to systemic infections. Some agents and strategies are being studied for controlling mucositis, none of them is used in clinical practice. In Minas Gerais, many studies have addressed the popular use of the plant Arrabidaea chica in the form of tea, to treat intestinal cramps and diarrhea, the main symptoms of mucositis. Objective: To evaluate the potential of Arrabidaea chica extract in the management of the integrity of the intestinal mucosa, using the experimental model of gut mucositis induced by 5-Fluorouracila (5-FU). Methods: The UFMG Ethics Committee for Animal Experimentation (CETEA/UFMG) approved this study (nº 411/2015). Male BALB/c mice between 6-8 weeks of age were randomly divided into four groups (n=9) as follows: 1. Control (CTL) - oral administration of saline solution (10 days); 2. A. chica (AC) - oral administration of A. chica extract (10 days); 3. Mucositis (MUC) - underwent mucositis (5-FU) (10 days); 4. Mucositis + A. chica (MUC+ AC) - underwent mucositis and received oral administration of A. chica extract (10 days). At the 7 th day, mice in the MUC and MUC + AC groups received an intraperitoneal (IP) injection containing 300 mg/kg 5-FU, whereas the animals of the CTL and AC groups received a saline IP injection. After 72 hours (10 th experimental day), intestinal permeability was determined by measuring the radioactivity diffusion in the blood after oral administration of diethylenetriaminepentaacetic acid (DTPA) labelled with technetium-99m ( 99m Tc) and bacterial translocation was determined by measuring the radioactivity diffusion in the blood after oral administration of E. coli labelled with technetium-99m ( 99m Tc). After 4 hours, the mice were euthanized and assessed for intestinal permeability, bacterial translocation and intestinal histology

Assessment of intestinal permeability and bacterial translocation employing nuclear methods in murine mucositis

Energy Technology Data Exchange (ETDEWEB)

Pessoa, Rafaela M.; Takenaka, Isabella K.T.M.; Barros, Patricia A.V.; Moura, Livia P.; Contarini, Sara M.L.; Amorim, Juliana M.; Castilho, Raquel O.; Leite, Camila M.A.; Cardoso, Valbert N.; Diniz, Simone Odilia F. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Mg (Brazil)

2017-07-01

Full text: Introduction: Mucositis affects approximately 80% of patients who receive chemotherapy combinations. The lesions are painful, restrict food intake and make patients more susceptible to systemic infections. Some agents and strategies are being studied for controlling mucositis, none of them is used in clinical practice. In Minas Gerais, many studies have addressed the popular use of the plant Arrabidaea chica in the form of tea, to treat intestinal cramps and diarrhea, the main symptoms of mucositis. Objective: To evaluate the potential of Arrabidaea chica extract in the management of the integrity of the intestinal mucosa, using the experimental model of gut mucositis induced by 5-Fluorouracila (5-FU). Methods: The UFMG Ethics Committee for Animal Experimentation (CETEA/UFMG) approved this study (nº 411/2015). Male BALB/c mice between 6-8 weeks of age were randomly divided into four groups (n=9) as follows: 1. Control (CTL) - oral administration of saline solution (10 days); 2. A. chica (AC) - oral administration of A. chica extract (10 days); 3. Mucositis (MUC) - underwent mucositis (5-FU) (10 days); 4. Mucositis + A. chica (MUC+ AC) - underwent mucositis and received oral administration of A. chica extract (10 days). At the 7{sup th} day, mice in the MUC and MUC + AC groups received an intraperitoneal (IP) injection containing 300 mg/kg 5-FU, whereas the animals of the CTL and AC groups received a saline IP injection. After 72 hours (10{sup th} experimental day), intestinal permeability was determined by measuring the radioactivity diffusion in the blood after oral administration of diethylenetriaminepentaacetic acid (DTPA) labelled with technetium-99m ({sup 99m}Tc) and bacterial translocation was determined by measuring the radioactivity diffusion in the blood after oral administration of E. coli labelled with technetium-99m ({sup 99m}Tc). After 4 hours, the mice were euthanized and assessed for intestinal permeability, bacterial translocation and

Comparison of Mucosal, Subcutaneous and Intraperitoneal Routes of Rat Leptospira Infection

Science.gov (United States)

Zilber, Anne-Laure; Belli, Patrick; Grezel, Delphine; Artois, Marc; Kodjo, Angeli; Djelouadji, Zoheira

2016-01-01

Leptospirosis is a zoonosis found worldwide that is caused by a spirochete. The main reservoirs of Leptospira, which presents an asymptomatic infection, are wild rodents, including the brown rat (Rattus norvegicus). Experimental studies of the mechanisms of its renal colonization in rats have previously used an intraperitoneal inoculation route. However, knowledge of rat-rat transmission requires the use of a natural route of inoculation, such as a mucosal or subcutaneous route. We investigated for the first time the effects of subcutaneous and mucosal inoculation routes compared to the reference intraperitoneal route during Leptospira infection in adult rats. Infection characteristics were studied using Leptospira renal isolation, serology, and molecular and histological analyses. Leptospira infection was asymptomatic using each inoculation route, and caused similar antibody production regardless of renal colonization. The observed renal colonization rates were 8 out of 8 rats, 5 out of 8 rats and 1 out of 8 rats for the intraperitoneal, mucosal and subcutaneous inoculation routes, respectively. Thus, among the natural infection routes studied, mucosal inoculation was more efficient for renal colonization associated with urinary excretion than the subcutaneous route and induced a slower-progressing infection than the intraperitoneal route. These results can facilitate understanding of the infection modalities in rats, unlike the epidemiological studies conducted in wild rats. Future studies of other natural inoculation routes in rat models will increase our knowledge of rat-rat disease transmission and allow the investigation of infection kinetics. PMID:27031867

Characteristic patients with oral mucositis receiving 5-FU chemotherapy at Hasan Sadikin Hospital Bandung

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Syarifah Fatimah

2016-11-01

Full Text Available Introduction: Oral mucositis is an inflammatory reaction of oral mucous membrane that often appears in cancer patients due to the chemotherapeutic agents, such as 5-fluorouracil (5-FU. The aim of this study was to describe the characteristic patients who receive 5-FU and had oral mucositis. Methods: This study was conducted on 41 patients with cancer receiving 5-FU chemotherapy at Dr Hasan Sadikin Hospital Bandung. The data was retrieved through interviews to find out patient’s characteristic; nutritional status examination by using body mass index measurement; and oral examination. Severity level was determined by using National Cancer Institute’s Common Toxicity Criteria scale, and the level of pain was measured by Numeric Pain Intensity Rating scale. Results: This research have shown 60,98% patient with cancer had received 5-FU chemotherapy treatment, and 44% with poor nutritional status (underweight. Oral mucositis was only found at non-keratinised mucous. The finding of this study was patients that receiving 5-FU chemotherapy treatment diagnosed with oral mucositis was on the 1st stadium (52% and the 2nd stadium (44% with the level of pain was on the mild level (48% and moderate level (32%.Conclusion: Oral mucositis was found on patients with cancer that received 5-FU chemotherapy with a variety of characteristics, nutritional statuses, locations, levels of severity and pain.

PREFACE: 1st International Conference on Mechanical Engineering Research 2011 (ICMER2011)

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Abu Bakar, Rosli

2012-09-01

The year 2010 represented a significant milestone in the history of the Mechanical Engineering community with the organization of the first and second national level conferences (National Conference in Mechanical Engineering for Research, 1st and 2nd NCMER) at Universiti Malaysia Pahang on 26-27 May and 3-4 December 2010. The conferences attracted a large number of delegates from different premier academic and research institutions in the country to participate and share their research experiences at the conference. The International Conference on Mechanical Engineering Research (ICMER 2011) followed on from the first and second conferences due to good support from researchers. The ICMER 2011 is a good platform for researchers and postgraduate students to present their latest finding in research. The conference covers a wide range of topics including the internal combustion engine, machining processes, heat and mass transfer, fuel, biomechanical analysis, aerodynamic analysis, thermal comfort, computational techniques, design and simulation, automotive transmission, optimization techniques, hybrid electric vehicles, engine vibration, heat exchangers, finite element analysis, computational fluid dynamics, green energy, vehicle dynamics renewable energy, combustion, design, product development, advanced experimentation techniques, to name but a few. The international conference has helped to bridge the gap between researchers working at different institutions and in different countries to share their knowledge and has helped to motivate young scientists with their research. This has also given some clear direction for further research from the deliberations of the conference. Several people have contributed in different ways to the success of the conference. We thank the keynote speakers and all authors of the contributed papers, for the cooperation rendered to us in the publication of the CD conference proceedings. In particular, we would like to place on record our

20th Annual Systems Engineering Conference. Volume 1, Monday-Tuesday

Science.gov (United States)

2017-10-26

20th Annual Systems Engineering Conference October 23-26, 2017 | Waterford at Springfield | Springfield, VA NDIA.org/systemsengineering...Conference Program SYSTEMS ENGINEERING CONFERENCE 2 Welcome to the NDIA Systems Engineering Conference On behalf of the National Defense Industrial...Association’s Systems Engineering Division, I would like to extend a very warm welcome to the 20th Annual Systems Engineering Conference. Yes, the 20th Annual

A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia.

Science.gov (United States)

Oosterom, N; Dirks, N F; Heil, S G; de Jonge, R; Tissing, W J E; Pieters, R; van den Heuvel-Eibrink, M M; Heijboer, A C; Pluijm, S M F

2018-06-19

Children with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that low vitamin D levels were associated with an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and studied the association between vitamin D levels and methotrexate (MTX)-induced oral mucositis in pediatric ALL. We assessed 25-hydroxyvitamin D (25(OH)D 3 ) and 24,25-dihydroxyvitamin D (24,25(OH) 2 D 3 ) levels in 99 children with ALL before the start of 4 × 5 g/m 2 high-dose methotrexate (HD-MTX) (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cutoff values for vitamin D deficiency exist: 25(OH)D 3 levels D deficiency occurred in respectively 8% ( 4 years of age as compared to children between 1 and 4 years of age. A decrease in 25(OH)D 3 levels during HD-MTX therapy was associated with developing severe oral mucositis (OR 1.6; 95% CI [1.1-2.4]). 25(OH)D 3 and 24,25(OH) 2 D 3 levels at T0 and the change in 24,25(OH) 2 D 3 levels during therapy were not associated with the development of severe oral mucositis. This study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4 years. A decrease in 25(OH)D 3 levels during MTX therapy was observed in children with ALL that developed severe oral mucositis.

Risk, Outcomes, and Costs of Radiation-Induced Oral Mucositis Among Patients With Head-and-Neck Malignancies

International Nuclear Information System (INIS)

Elting, Linda S.; Cooksley, Catherine D.; Chambers, Mark S.; Garden, Adam S.

2007-01-01

Purpose: To study the risk, outcomes, and costs of radiation-induced oral mucositis (OM) among patients receiving radiotherapy (RT) to head and neck primary cancers. Methods and Materials: A retrospective cohort consisting of 204 consecutive head-and-neck cancer patients who received RT with or without chemotherapy during 2002 was formed; their records were reviewed for clinical and resource use information. Patients who had received prior therapy, had second primary cancers, or received palliative radiation therapy were excluded. The risk of OM was analyzed by multiple variable logistic regression. The cost of care was computed from the provider's perspective in 2006 U.S. dollars and compared among patients with and without OM. Results: Oral mucositis occurred in 91% of patients; in 66% it was severe (Grade 3-4). Oral mucositis was more common among patients with oral cavity or oropharynx primaries (odds ratio [OR], 44.5; 95% confidence interval [CI], 5.2 to >100; p < 0.001), those who received chemotherapy (OR = 7.8; 95% CI, 1.5-41.6; p 0.02), and those who were treated with altered fractionation schedules (OR 6.3; 95% CI, 1.1-35.1; p = 0.03). Patients with OM were significantly more likely to have severe pain (54% vs. 6%; p < 0.001) and a weight loss of ≥5% (60% vs. 17%; p < 0.001). Oral mucositis was associated with an incremental cost of $1700-$6000, depending on the grade. Conclusions: Head-and-neck RT causes OM in virtually all patients. Oral mucositis is associated with severe pain, significant weight loss, increased resource use, and excess cost. Preventive strategies are needed

Multiplex immunoassay of lower genital tract mucosal fluid from women attending an urban STD clinic shows broadly increased IL1ß and lactoferrin.

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Gregory T Spear

Full Text Available BACKGROUND: More than one million new cases of sexually transmitted diseases (STDs occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects. METHODOLOGY/PRINCIPAL FINDINGS: 32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1ß, VEGF, angiogenin, IL-8, ß2Defensin and ß3Defensin were detected in all subjects, Interferon-α was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-α and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-α, IL-1ß and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1ß, lactoferrin and myeloperoxidase. IL-1ß and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis. CONCLUSIONS/SIGNIFICANCE: These studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1ß and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site.

Mucosal T cells in gut homeostasis and inflammation

OpenAIRE

van Wijk, Femke; Cheroutre, Hilde

2010-01-01

The antigen-rich environment of the gut interacts with a highly integrated and specialized mucosal immune system that has the challenging task of preventing invasion and the systemic spread of microbes, while avoiding excessive or unnecessary immune responses to innocuous antigens. Disruption of the mucosal barrier and/or defects in gut immune regulatory networks may lead to chronic intestinal inflammation as seen in inflammatory bowel disease. The T-cell populations of the intestine play a c...

Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis

DEFF Research Database (Denmark)

D'Angelo, Sandra P; Larkin, James; Sosman, Jeffrey A

2017-01-01

Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported...... in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined...... with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response...

Oral mucositis: recent perspectives on prevention and treatment

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Paulo Sérgio da Silva Santos

2009-10-01

Full Text Available Oral mucositis is a result of toxicity and one of the most common side effects of radiotherapy and chemotherapy in cancer treatment and in hematopoietic stem cell transplantation. Clinically these changes are characterized by epithelial atrophy, edema, erythema and the appearance of ulcerations that can affect the entire oral mucosa, causing pain and discomfort, impairing speech, and swallowing food. In addition to the major symptoms, the ulcers increase the risk of local and systemic infection, compromising function and interfering with oral antineoplastic treatment and may lead to it being discontinued. The diagnosis, prevention and therapeutic strategies in providing support in cases of oral mucositis are the dentist’s responsibility. Through critical analysis of literature, the aim of this article is to present oral mucositis, its pathogenesis, clinical features and treatments offered today to address or control the condition, highlighting the importance of dentists’ role in its management.

Colonization and effector functions of innate lymphoid cells in mucosal tissues

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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

The effect of mucosal cuff shrinkage around dental implants during healing abutment replacement.

Science.gov (United States)

Nissan, J; Zenziper, E; Rosner, O; Kolerman, R; Chaushu, L; Chaushu, G

2015-10-01

Soft tissue shrinkage during the course of restoring dental implants may result in biological and prosthodontic difficulties. This study was conducted to measure the continuous shrinkage of the mucosal cuff around dental implants following the removal of the healing abutment up to 60 s. Individuals treated with implant-supported fixed partial dentures were included. Implant data--location, type, length, diameter and healing abutments' dimensions--were recorded. Mucosal cuff shrinkage, following removal of the healing abutments, was measured in bucco-lingual direction at four time points--immediately after 20, 40 and 60 s. anova was used to for statistical analysis. Eighty-seven patients (49 women and 38 men) with a total of 311 implants were evaluated (120 maxilla; 191 mandible; 291 posterior segments; 20 anterior segments). Two-hundred and five (66%) implants displayed thick and 106 (34%) thin gingival biotype. Time was the sole statistically significant parameter affecting mucosal cuff shrinkage around dental implants (P < 0.001). From time 0 to 20, 40 and 60 s, the mean diameter changed from 4.1 to 4.07, 3.4 and 2.81 mm, respectively. The shrinkage was 1%, 17% and 31%, respectively. The gingival biotype had no statistically significant influence on mucosal cuff shrinkage (P = 0.672). Time required replacing a healing abutment with a prosthetic element should be minimised (up to 20/40 s), to avoid pain, discomfort and misfit. © 2015 John Wiley & Sons Ltd.

Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

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Logan Richard M

2010-03-01

Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy.

Science.gov (United States)

Riley, Philip; Glenny, Anne-Marie; Worthington, Helen V; Littlewood, Anne; Clarkson, Jan E; McCabe, Martin G

2015-12-23

where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format. We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancersOral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5).The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6).Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3

A pilot study of rebamipide-gargle for chemoradiotherapy-induced mucositis in oral cancer patients

International Nuclear Information System (INIS)

Yasuda, Takashi; Chiba, Hiroshige; Satomi, Takafumi; Matsuo, Akira; Kaneko, Tadayoshi; Miyamatsu, Hironobu

2008-01-01

Mucositis induced by chemoradiotherapy is one of the serious side effects of cancer therapy for oral cancer. It is caused by toxic free radicals (activated oxygen) produced by these therapeutic modalities. Rebamipide is a novel anti-ulcer drug which possesses various cytoprotective activities such as free radical scavenging, induction of prostaglandin-E and acceleration of ulcer healing. We report the results of a pilot study on rebamipide-gargle for inhibition of mucositis induced by chemo-radiotherapy. The present study was conducted on 13 patients (7 men and 6 women; age range 53-88) with oral cancer. They received radiotherapy (30-60 Gy) for the oro-facial area and chemotherapy (docetaxel: 11 cases; tegafur-uracil (UFT): 1 case; radiotherapy alone: 1 case) with simultaneous addition of 1% rebamipide-gargle treatment (10-15 times/day) to prevent the onset of mucositis. Informed consent was obtained prior to entry. Nine cases had grade 1-2 according to the World Health Organization (WHO) criteria, and 4 patients were classified as grade 3-4. No adverse reactions that could be caused by the rebamipide gargle were observed. These results suggested that rebamipide gargle could inhibit the occurrence of stomatitis induced by chemoradiotherapy. (author)

Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients.

Science.gov (United States)

Silkoff, Philip E; Laviolette, Michel; Singh, Dave; FitzGerald, J Mark; Kelsen, Steven; Backer, Vibeke; Porsbjerg, Celeste M; Girodet, Pierre-Olivier; Berger, Patrick; Kline, Joel N; Chupp, Geoffrey; Susulic, Vedrana S; Barnathan, Elliot S; Baribaud, Frédéric; Loza, Matthew J

2017-09-01

The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled patients with mild, moderate, and severe asthma and nonatopic healthy control subjects. We explored this data set to define type 2 inflammation based on airway mucosal IL-13-driven gene expression and how this related to clinically accessible biomarkers. IL-13-driven gene expression was evaluated in several human cell lines. We then defined type 2 status in 25 healthy subjects, 28 patients with mild asthma, 29 patients with moderate asthma, and 26 patients with severe asthma based on airway mucosal expression of (1) CCL26 (the most differentially expressed gene), (2) periostin, or (3) a multigene IL-13 in vitro signature (IVS). Clinically accessible biomarkers included fraction of exhaled nitric oxide (Feno) values, blood eosinophil (bEOS) counts, serum CCL26 expression, and serum CCL17 expression. Expression of airway mucosal CCL26, periostin, and IL-13-IVS all facilitated segregation of subjects into type 2-high and type 2-low asthmatic groups, but in the ADEPT study population CCL26 expression was optimal. All subjects with high airway mucosal CCL26 expression and moderate-to-severe asthma had Feno values (≥35 ppb) and/or high bEOS counts (≥300 cells/mm 3 ) compared with a minority (36%) of subjects with low airway mucosal CCL26 expression. A combination of Feno values, bEOS counts, and serum CCL17 and CCL26 expression had 100% positive predictive value and 87% negative predictive value for airway mucosal CCL26-high status. Clinical variables did not differ between subjects with type 2-high and type 2-low status. Eosinophilic inflammation was associated with but not limited to airway mucosal type 2 gene expression. A panel of clinical biomarkers accurately classified type 2 status based on airway mucosal CCL26, periostin, or IL-13-IVS gene expression. Use of Feno values, bEOS counts, and serum marker levels (eg, CCL26 and CCL17) in combination might allow patient

Direction-Modulated Brachytherapy for High-Dose-Rate Treatment of Cervical Cancer. I: Theoretical Design

International Nuclear Information System (INIS)

Han, Dae Yup; Webster, Matthew J.; Scanderbeg, Daniel J.; Yashar, Catheryn; Choi, Dongju; Song, Bongyong; Devic, Slobodan; Ravi, Ananth; Song, William Y.

2014-01-01

Purpose: To demonstrate that utilization of the direction-modulated brachytherapy (DMBT) concept can significantly improve treatment plan quality in the setting of high-dose-rate (HDR) brachytherapy for cervical cancer. Methods and Materials: The new, MRI-compatible, tandem design has 6 peripheral holes of 1.3-mm diameter, grooved along a nonmagnetic tungsten-alloy rod (ρ = 18.0 g/cm 3 ), enclosed in Delrin tubing (polyoxymethylene, ρ = 1.41 g/cm 3 ), with a total thickness of 6.4 mm. The Monte Carlo N-Particle code was used to calculate the anisotropic 192 Ir dose distributions. An in-house-developed inverse planning platform, geared with simulated annealing and constrained-gradient optimization algorithms, was used to replan 15 patient cases (total 75 plans) treated with a conventional tandem and ovoids (T and O) applicator. Prescription dose was 6 Gy. For replanning, we replaced the conventional tandem with that of the new DMBT tandem for optimization but left the ovoids in place and kept the dwell positions as originally planned. All DMBT plans were normalized to match the high-risk clinical target volume V100 coverage of the T and O plans. Results: In general there were marked improvements in plan quality for the DMBT plans. On average, D2cc for the bladder, rectum, and sigmoid were reduced by 0.59 ± 0.87 Gy (8.5% ± 28.7%), 0.48 ± 0.55 Gy (21.1% ± 27.2%), and 0.10 ± 0.38 Gy (40.6% ± 214.9%) among the 75 plans, with best single-plan reductions of 3.20 Gy (40.8%), 2.38 Gy (40.07%), and 1.26 Gy (27.5%), respectively. The high-risk clinical target volume D90 was similar, with 6.55 ± 0.96 Gy and 6.59 ± 1.06 Gy for T and O and DMBT, respectively. Conclusions: Application of the DMBT concept to cervical cancer allowed for improved organ at risk sparing while achieving similar target coverage on a sizeable patient population, as intended, by maximally utilizing the anatomic information contained in 3-dimensional imaging. A

Mucosal Immunogenicity of Genetically Modified Lactobacillus acidophilus Expressing an HIV-1 Epitope within the Surface Layer Protein.

Directory of Open Access Journals (Sweden)

Akinobu Kajikawa

Full Text Available Surface layer proteins of probiotic lactobacilli are theoretically efficient epitope-displaying scaffolds for oral vaccine delivery due to their high expression levels and surface localization. In this study, we constructed genetically modified Lactobacillus acidophilus strains expressing the membrane proximal external region (MPER from human immunodeficiency virus type 1 (HIV-1 within the context of the major S-layer protein, SlpA. Intragastric immunization of mice with the recombinants induced MPER-specific and S-layer protein-specific antibodies in serum and mucosal secretions. Moreover, analysis of systemic SlpA-specific cytokines revealed that the responses appeared to be Th1 and Th17 dominant. These findings demonstrated the potential use of the Lactobacillus S-layer protein for development of oral vaccines targeting specific peptides.

Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

International Nuclear Information System (INIS)

Schmidt, M.; Haagen, J.; Noack, R.; Siegemund, A.; Gabriel, P.; Doerr, W.

2014-01-01

Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation. Daily fractionated irradiation (5 x 3 Gy/week) was given over 1 (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose-effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols. Transplantation of 6 x 10 6 , but not of 3 x 10 6 bone marrow stem cells on day -1, +4, +8, +11 or +15 significantly increased the ED 50 values (dose, at which an ulcer is expected in 50% of the mice); transplantation on day +2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day -1, 2 or +8 significantly, and on day +4 marginally increased the ED 50 values. Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation. (orig.)

Sucralfate for radiation mucositis: results of a double-blind randomized trial

International Nuclear Information System (INIS)

Meredith, Ruby; Salter, Merle; Kim, Robert; Spencer, Sharon; Weppelmann, Burkhard; Rodu, Brad; Smith, Judy; Lee, Jeanette

1997-01-01

Purpose: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of antacid, diphenhydramine, and viscous lidocaine alone. Methods and Materials: A double-blind study was conducted in which nurses and pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of antacid, diphenhydramine, and viscous lidocaine vs. the same solution plus sucralfate. Eligible patients were those receiving >40 Gy at 1.8 Gy/fraction, one fraction/day, five fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. The observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective nonstudy agents was not allowed. The ability to eat various consistency of foods was graded 0-5, with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + SD for food and soreness scores, paired t-test, and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. Results: Over 2 years, 111 patients were entered. Because some withdrew and others did not require medication, results are presented for evaluable patients in each category. Mild adverse effects from the medication solution (usually mouth discomfort) were reported by <10% of patients in each treatment group among 106 patients evaluable for toxicity. There was a comparable incidence of mild-moderate mucositis for the two treatment groups. Severe mucositis was noted in two patients of the standard medication group and none among patients receiving sucralfate. The groups were comparable

Low energy laser in prevention of oral mucositis in patients receiving radiotherapy and/or chemotherapy in Pernambuco Cancer Hospital

International Nuclear Information System (INIS)

Kelner, Natalie; Castro, Jurema Freire Lisboa de

2007-01-01

Oral mucositis induced by antineoplastic therapy causes wide-range pain and discomfort resulting in decreased quality of life. The present study evaluated the benefits of low intensity laser and 0.12% chlorhexidine gluconate in the prevention of oral mucositis induced by radiation, associated or not with chemotherapy, and considered degrees/severity, time of appearance of the lesions and functional loss. Eighty-four outpatients were considered and 49 were included in this study and divided into two groups: Group 1 received laser treatments in three stages, starting three days before treatment until the end of therapy. Group 2 was instructed to do daily mouth rinses with chlorhexidine gluconate. The prevalence of clinical mucositis was 49%, and of functional mucositis, 28.6%, when the two groups were considered together. This percentage was smaller in the laser group, 44% for the clinical mucositis group and 24% for the functional. The two protocols were well tolerated and showed benefits, mainly from the point of view of functionality, and delayed the onset and development of mucositis. (author)

Low energy laser in prevention of oral mucositis in patients receiving radiotherapy and/or chemotherapy in Pernambuco Cancer Hospital

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Kelner, Natalie; Castro, Jurema Freire Lisboa de [Federal University of Pernambuco, Recife (Brazil). Dept. of Clinics and Preventive Dentistry. Discipline of Oral Pathology]. E-mail: jlisboa72@hotmail.com

2007-07-01

Oral mucositis induced by antineoplastic therapy causes wide-range pain and discomfort resulting in decreased quality of life. The present study evaluated the benefits of low intensity laser and 0.12% chlorhexidine gluconate in the prevention of oral mucositis induced by radiation, associated or not with chemotherapy, and considered degrees/severity, time of appearance of the lesions and functional loss. Eighty-four outpatients were considered and 49 were included in this study and divided into two groups: Group 1 received laser treatments in three stages, starting three days before treatment until the end of therapy. Group 2 was instructed to do daily mouth rinses with chlorhexidine gluconate. The prevalence of clinical mucositis was 49%, and of functional mucositis, 28.6%, when the two groups were considered together. This percentage was smaller in the laser group, 44% for the clinical mucositis group and 24% for the functional. The two protocols were well tolerated and showed benefits, mainly from the point of view of functionality, and delayed the onset and development of mucositis. (author)

1st Large Hadron Collider Physics Conference

CERN Document Server

Juste, A; Martínez, M; Riu, I; Sorin, V

2013-01-01

The conference is the result of merging two series of international conferences, "Physics at Large Hadron Collider" (PLHC2012) and "Hadron Collider Physics Symposium" (HCP2012). With a program devoted to topics such as the Standard Model and Beyond, the Higgs Boson, Supersymmetry, Beauty and Heavy Ion Physics, the conference aims at providing a lively forum for discussion between experimenters and theorists of the latest results and of new ideas. LHCP 2013 will be hosted by IFAE (Institut de Fisica d'Altes Energies) in Barcelona (Spain), and will take place from May 13 to 18, 2013. The venue will be the Hotel Catalonia Plaza, Plaza España (Barcelona). More information will be posted soon. For questions, please contact lhcp2013@ifae.es.

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

Science.gov (United States)

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.

Clinical, Immune, and Microbiome Traits of Gingivitis and Peri-implant Mucositis.

Science.gov (United States)

Schincaglia, G P; Hong, B Y; Rosania, A; Barasz, J; Thompson, A; Sobue, T; Panagakos, F; Burleson, J A; Dongari-Bagtzoglou, A; Diaz, P I

2017-01-01

Tissues surrounding dental implants and teeth develop clinical inflammation in response to microbial stimuli. However, the literature suggests that differences exist in the microbial insult and inflammatory responses leading to gingivitis and peri-implant mucositis. In this pilot study, the authors use for the first time a systems biology approach to comprehensively evaluate clinical parameters, selected inflammatory markers, and the microbiome of subject-matched tooth and implant sites during native inflammation and in response to experimental plaque accumulation. Fifteen subjects with 2 posterior implants and corresponding contralateral teeth were examined at enrollment; at day 0, after reinstitution of gingival/mucosal health; at days 7, 14, and 21, during stent-mediated oral hygiene (OH) abstention; and at day 42, after resumption of OH. The subgingival microbiome was evaluated via 16S rRNA gene sequencing and 8 selected inflammatory markers measured in crevicular fluid. Comparison of teeth and implants via general linear models based on orthogonal polynomials showed similar responses in clinical parameters, inflammatory mediators, and proportions of individual microbial taxa during OH abstention. Implants, however, accumulated less plaque and underwent more heterogeneous shifts in microbiome structure. A multilevel, within-group, sparse partial least squares analysis of covariation of microbial, inflammatory, and clinical parameters throughout all study visits found inflammation around teeth and implants positively correlated with IL-1 alpha and IL-1 beta and with the proportions of Selenomonas, Prevotella, and 5 species-level phylotypes. Gingivitis, however, showed a stronger positive correlation with lactoferrin and IL-1ra and a stronger negative correlation with Rothia. Peri-implant mucositis, on the contrary, correlated positively with certain microbial taxa not associated with gingivitis by a previous study or the current one. In summary, differences

1st European-Middle Asian Conference on Computer Modelling 2015

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Kolosov, Dmitrii; Snášel, Václav; Karakeyev, Taalaybek; Abraham, Ajith

2016-01-01

This volume of Advances in Intelligent Systems and Computing contains papers presented at the 1st European-Middle Asian Conference on Computer Modelling, EMACOM 2015. This international conference was conceived as a brand new scientific and social event of mutual collaboration between the VSB - Technical University of Ostrava (Ostrava, Czech Republic) and the Kyrgyz National University named after J. Balasagyn (Bishkek, Kyrgyz Republic). The aim of EMACOM 2015 was to present the latest development in the field of computer-aided modelling as an essential aspect of research and development of innovative systems and their applications. The conference showed that together with simulations, various modeling techniques, enabled and encouraged by the rapid development of high-performance computing platforms, are crucial for cost-efficient design, verification, and prototyping of solutions in many diverse industrial fields spanning the whole range from manufacturing, mining, machinery, and automotive industries to in...

2010 ELECTRODEPOSITION GORDON RESEARCH CONFERENCE, AUGUST 1-6, 2010

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Peter Searson

2010-08-06

The 2010 Gordon Conference on Electrodeposition will present cutting-edge research on electrodeposition with emphasis on (i) advances in basic science, (ii) developments in next-generation technologies, and (iii) new and emerging areas. The Conference will feature a wide range of topics, from atomic scale processes, nucleation and growth, thin film deposition, and electrocrystallization, to applications of electrodeposition in devices including microelectronics, solar energy, and power sources. The Conference will bring together investigators from a wide range of scientific disciplines, including chemical engineering, materials science and engineering, physics, and chemistry. The Conference will feature invited speakers at the forefront of the field, and a late-breaking news session that will provide the opportunity for graduate students, post-docs, and junior faculty to participate. The collegial atmosphere of this Conference, with scientific talks and poster sessions, as well as opportunities for informal gatherings in the afternoons and evenings, provides an avenue for scientists from different disciplines to discuss current issues and promotes cross-disciplinary collaborations in the various research areas represented. The Conference will be held at Colby-Sawyer College, located in the Mt. Kearsarge-Lake Sunapee Region of New Hampshire. The surrounding mountains, forests, and lakes provide a beautiful setting for this conference. The attendance is limited so early application is strongly advised.

Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation

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Bélin Poletto Mezzomo

2015-12-01

Full Text Available In addition to their applicability as biopesticides, Bacillus thuringiensis (Bt Cry1Ac spore-crystals are being researched in the immunology field for their potential as adjuvants in mucosal and parenteral immunizations. We aimed to investigate the hematotoxicity and genotoxicity of Bt spore-crystals genetically modified to express Cry1Ac individually, administered orally (p.o. or with a single intraperitoneal (i.p. injection 24 h before euthanasia, to simulate the routes of mucosal and parenteral immunizations in Swiss mice. Blood samples were used to perform hemogram, and bone marrow was used for the micronucleus test. Cry1Ac presented cytotoxic effects on erythroid lineage in both routes, being more severe in the i.p. route, which also showed genotoxic effects. The greater severity noted in this route, mainly at 6.75 mg/kg, as well as the intermediate effects at 13.5 mg/kg, and the very low hematotoxicity at 27 mg/kg, suggested a possible inverse agonism. The higher immunogenicity for the p.o. route, particularly at 27 mg/kg, suggested that at this dose, Cry 1Ac could potentially be used as a mucosal adjuvant (but not in parenteral immunizations, due to the genotoxic effects observed. This potential should be investigated further, including making an evaluation of the proposed inverse agonism and carrying out cytokine profiling.

Proceedings of the 29th annual conference of the Canadian Nuclear Association and 10th annual conference of the Canadian Nuclear Society. V. 1-3

Energy Technology Data Exchange (ETDEWEB)

Harvey, M; Fehrenbach, P J [eds.

1990-12-31

The symposium was designed to highlight how the technical information for nuclear energy came to Canada, the effect this information had in Canada in the fields of Physics, Chemistry, Medicine and Nuclear Power. Volume 1 is the combined proceedings of the Canadian Nuclear Association twenty-ninth annual conference and the Canadian Nuclear Society tenth annual conference. Volume 2 is the proceedings of the Canadian Nuclear Association twenty-ninth annual conference, and volume 3 is the proceedings of the Canadian Nuclear Society tenth annual conference.

Proceedings of the 29th annual conference of the Canadian Nuclear Association and 10th annual conference of the Canadian Nuclear Society. V. 1-3

International Nuclear Information System (INIS)

Harvey, M.; Fehrenbach, P.J.

1989-01-01

The symposium was designed to highlight how the technical information for nuclear energy came to Canada, the effect this information had in Canada in the fields of Physics, Chemistry, Medicine and Nuclear Power. Volume 1 is the combined proceedings of the Canadian Nuclear Association twenty-ninth annual conference and the Canadian Nuclear Society tenth annual conference. Volume 2 is the proceedings of the Canadian Nuclear Association twenty-ninth annual conference, and volume 3 is the proceedings of the Canadian Nuclear Society tenth annual conference

Risk assessment, session 1-4. International conference 1992. Part 1

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NONE

1992-07-01

The international conference on Risk Assessment, 5-9 October 1992, London was organised by the Health and Safety Commission of the UK and co-sponsored by a number of regional and international organizations namely: the European Commission, the ILO, the OECD and WHO. The main sessions of the conference cover what risk assessment means, the role of risk assessment in devising policies and regulations; and risk assessment in practice.

Risk assessment, session 1-4. International conference 1992. Part 1

International Nuclear Information System (INIS)

1992-01-01

The international conference on Risk Assessment, 5-9 October 1992, London was organised by the Health and Safety Commission of the UK and co-sponsored by a number of regional and international organizations namely: the European Commission, the ILO, the OECD and WHO. The main sessions of the conference cover what risk assessment means, the role of risk assessment in devising policies and regulations; and risk assessment in practice

Hericium erinaceus polysaccharide facilitates restoration of injured intestinal mucosal immunity in Muscovy duck reovirus-infected Muscovy ducklings.

Science.gov (United States)

Wu, Yijian; Jiang, Huihui; Zhu, Erpeng; Li, Jian; Wang, Quanxi; Zhou, Wuduo; Qin, Tao; Wu, Xiaoping; Wu, Baocheng; Huang, Yifan

2018-02-01

To elucidate the effect of Hericium erinaceus polysaccharide (HEP) on the intestinal mucosal immunity in normal and Muscovy duck reovirus (MDRV)-infected Muscovy ducklings, 1-day-old healthy Muscovy ducklings were pretreated with 0.2g/L HEP and/or following by MDRV infection in this study, duodenal samples were respectively collected at 1, 3, 6, 10, 15 and 21day post-infection, tissue sections were prepared for observation of morphological structure and determination of intestinal parameters (villus height/crypt depth ratio, villus surface area) as well as counts of intraepithelial lymphocytes (IELs), goblet cells, mast cells. Additionally, dynamics of secretory immunoglobin A (sIgA), interferon-γ (IFN-γ) and interleukin-4 (IL-4) productions in intestinal mucosa were measured with radioimmunoassay. Results showed that HEP significantly improved intestinal morphological structure and related indexes, and significantly inhibited the reduction of intestinal mucosal IELs, goblet cells and mast cells caused by MDRV infection. Furthermore, HEP significantly increased the secretion of sIgA, IFN-γ and IL-4 to enhance intestinal mucosal immune functions. Our findings indicate that HEP treatment can effectively repair MDRV-caused injures of small intestinal mucosal immune barrier, and improve mucosal immune function in sick Muscovy ducklings, which will provide valuable help for further application of HEP in prevention and treatment of MDRV infection. Copyright © 2017. Published by Elsevier B.V.

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

Science.gov (United States)

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.

Protein energy malnutrition alters mucosal IgA responses and reduces mucosal vaccine efficacy in mice.

Science.gov (United States)

Rho, Semi; Kim, Heejoo; Shim, Seung Hyun; Lee, Seung Young; Kim, Min Jung; Yang, Bo-Gie; Jang, Myoung Ho; Han, Byung Woo; Song, Man Ki; Czerkinsky, Cecil; Kim, Jae-Ouk

2017-10-01

Oral vaccine responsiveness is often lower in children from less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purified isocaloric diets containing low protein (1/10 the protein of the control diet) were used to determine the effect of PEM. PEM increased both nonspecific total IgA and oral antigen-specific IgA in serum without alteration of gut permeability. However, PEM decreased oral antigen-specific IgA in feces, which is consistent with decreased expression of polymeric Immunoglobulin receptor (pIgR) in the small intestine. Of note, polymeric IgA was predominant in serum under PEM. In addition, PEM altered B cell development status in the bone marrow and increased the frequency of IgA-secreting B cells, as well as IgA secretion by long-lived plasma cells in the small intestinal lamina propria. Moreover, PEM reduced the protective efficacy of the mucosally administered cholera vaccine and recombinant attenuated Salmonella enterica serovar Typhimurium vaccine in a mouse model. Our results suggest that PEM can impair mucosal immunity where IgA plays an important role in host protection and may partly explain the reduced efficacy of oral vaccines in malnourished subjects. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Identification of risk factors for mucosal injury during laparoscopic Heller myotomy for achalasia.

Science.gov (United States)

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.

The Design of New Adjuvants for Mucosal Immunity to Neisseria meningitidis B in Nasally Primed Neonatal Mice for Adult Immune Response

Directory of Open Access Journals (Sweden)

Tatiane Ferreira

2012-01-01

Full Text Available The aim of this study was to determine the value of detoxified Shiga toxins Stx1 and Stx2 (toxoids of Escherichia coli as mucosal adjuvants in neonatal mice for immunogenicity against the outer membrane proteins (OMPs of Neisseria meningitidis B. Mucosal immunization has been shown to be effective for the induction of antigen-specific immune responses in both the systemic and mucosal compartments. Systemic antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, and IgA and mucosal IgM and IgA were measured by ELISA using an N. meningitidis as an antigen. In addition, IFN-γ and IL-6 production were measured after stimulated proliferation of immune cells. Intranasal administration elicited a higher anti-OMP IgA response in both saliva and vaginal fluids. Our results suggest that both Stx1 and Stx2 toxoids are effective mucosal adjuvants for the induction of Ag-specific IgG, IgM, and IgA antibodies. The toxoids significantly enhanced the IgG and IgM response against OMPs with a potency equivalent to CT, with the response being characterized by both IgG1 and IgG2a isotypes, and increased IFN-gamma production. Additionally, bactericidal activity was induced with IgG and IgM antibodies of high avidity. These results support the use of the new toxoids as potent inducing adjuvants that are particularly suitable for mucosal immunization.

Gastric mucosal defence mechanism during stress of pyloric obstruction in albino rats.

Science.gov (United States)

Somasundaram, K; Ganguly, A K

1987-04-01

1. The integrity of the gastric mucosa and its ability to secrete mucus are believed to be essential for protection of gastric mucosa against ulceration induced by aggressive factors active in any stress situation. This study involves a three-compartmental analysis of gastric mucosal barrier in pylorus-ligated albino rats. 2. Quantitative analyses of histologically identifiable gastric mucosal epithelial neutral glycoproteins and gastric adherent mucus from oxyntic and pyloric gland areas, and components of non-dialysable mucosubstances in gastric secretion were made under stress of pyloric obstruction for 4, 8, and 16 h durations. Epithelial mucin was identified by periodic acid-Schiff (PAS) staining technique and assessed from the ratio of gastric mucosal thickness to the depth of PAS positive materials in it. The remaining visible mucus adhered to the gastric mucosa was estimated by Alcian blue binding technique. The results were compared with that of identical control groups. 3. A significant reduction in mucosal epithelial PAS positive materials after 8 or 16 h of pylorus ligation was observed. 4. The Alcian blue binding capacity of the pyloric gland area was increased significantly after 4 h of pylorus ligation, while after 8 or 16 h it was reduced in both oxyntic and pyloric gland areas. 5. Significant reductions in the rate of gastric secretion and volume, as well as concentration of the components of non-dialysable mucosubstances, were observed, indicating decreased synthesis of mucus glycoproteins. 6. Disruption of the mucosal barrier may have occurred due to decreased mucus synthesis and acid-pepsin accumulation; both could be due to stress associated with gastric distension. 7. The present findings confirm the role of mucus in protecting the underlying gastric epithelium during stress. The adherent mucus offers a first line of defence and epithelial mucus a second line of defence.

Eosinophils in mucosal immune responses

Science.gov (United States)

Travers, J; Rothenberg, M E

2015-01-01

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

International Nuclear Information System (INIS)

Epstein, J.B.; Wong, F.L.W.

1994-01-01

The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed using a quantitative scale and symptoms were assessed using visual analogue scales. The statistical model was developed to detect a 40% reduction in mucositis. No statistically significant reduction in mucositis was seen. Early during radiation therapy less oral pain was reported in the sucralfate group, but as treatment progressed all patients experienced pain. Patients in the sucralfate group were prescribed topical and systemic analgesics later in the course of radiation therapy. Prophylactic oral rinsing with sucralfate did not prevent oral ulcerative mucositis. Sucralfate may reduce the experience of pain during radiation therapy. 32 refs., 3 tabs

The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Epstein, J.B.; Wong, F.L.W. (British Columbia Cancer Agency, Vancouver (Canada))

1994-02-01

The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed using a quantitative scale and symptoms were assessed using visual analogue scales. The statistical model was developed to detect a 40% reduction in mucositis. No statistically significant reduction in mucositis was seen. Early during radiation therapy less oral pain was reported in the sucralfate group, but as treatment progressed all patients experienced pain. Patients in the sucralfate group were prescribed topical and systemic analgesics later in the course of radiation therapy. Prophylactic oral rinsing with sucralfate did not prevent oral ulcerative mucositis. Sucralfate may reduce the experience of pain during radiation therapy. 32 refs., 3 tabs.

Endoscopic mucosal resection for early gastric cancer. A case report.

Science.gov (United States)

Gheorghe, Cristian; Sporea, Ioan; Becheanu, Gabriel; Gheorghe, Liana

2002-03-01

European experience in endoscopic mucosal resection (EMR) for early gastric cancer is still relatively low, since early stomach cancer is diagnosed at a much lower rate in Europe than in Japan and generally operable patients are referred to surgery for radical resection. Endoscopic mucosal resection or mucosectomy was developed as a promising technology to diagnose and treat mucosal lesions in the esophagus, stomach and colon. In contrast to surgical resection, EMR allows "early cancers" to be removed with a minimal cost, morbidity and mortality. We present the case of a patient with hepatic cirrhosis incidentally diagnosed with an elevated-type IIa early gastric cancer. Echoendoscopy was performed in order to assess the depth of invasion into the gastric wall confirming the only mucosal involvement. We performed an EMR using "cup and suction" method. After the procedure, the patient experienced an acute upper gastrointestinal bleeding from the ulcer bed requiring argon plasma coagulation. The histopathological examination confirmed an early cancer, without involvement of muscularis mucosae. The patient has had an uneventful evolution being well at six months after the procedure

Effects of LEDs on oral mucositis prevention in a patient with classic Hodgkin's lymphoma - a case report

International Nuclear Information System (INIS)

Bicudo, Leticia Lang

2004-01-01

The purpose of this case report was to evaluate the efficacy of therapy using LEDs (light-emitting diodes), at a wavelength of 880 nm, in the prevention of oral mucositis in a patient with Hodgkin's disease treated with ABVD regimen. Mucositis is a dose limiting complication of cancer treatment, of high incidence, which severity can lead to alterations of treatment planning or even to suspension of cancer therapy, with serious consequences in tumor response and even survival. Lesions develop most commonly on the nonkeratinized mucosa and present symptoms that begin like mild burning and evolve to severe pain. For this reason, low power laser and, recently, LEDs have been considered for preventing and management of oral mucositis, with great results. In this study, a 34-year-old male received intraoral irradiations with an infrared LEDs array (3,6 J/cm 2 , 74 mW), for five consecutive days, starting on the day of chemotherapy. In each chemotherapy cycle, he received ABVD protocol on day 1 and day 15, and received LEDs treatment during five days on each ABVD infusion. To analyze results, the WHO (World Health Organization) scale was used for grading of mucositis and VAS (Visual Analogue Scale) for pain evaluation, on days 1, 3, 7, 10 and 13 post-chemotherapy. The results obtained showed the patient did not develop oral mucositis, during the five chemotherapy cycles and did not present any pain symptom. Therapy with LEDs was a safe and effective method for the prevention of oral mucositis in this case report. However, new studies are needed in order to prove the efficacy of this methodology with more patients, increasing their quality of life. (author)

Chemotherapy: the effect of oral cryotherapy on the development of mucositis.

Science.gov (United States)

Karagözoğlu, Serife; Filiz Ulusoy, Mehlika

2005-07-01

The aim of this study is to investigate the effect of oral cryotherapy on the development of chemotherapy-induced mucositis in patients administered combined chemotherapy. Mucositis has been of interest to scientists for more than 20 years. Unfortunately, this has not resulted in the development of standard procedures for prevention and management. To cope with this side-effect and to prevent opportunistic infections that may emerge during treatment, attempts are taken to provide preventative and comfort measures. In this context, cryotherapy (oral cooling) has become popular as a cheap and readily applicable method in preventing the developing due the rapid infusion of chemotherapy agents, or decreasing its severity. Study involved 60 patients, 30 of whom were in the study group and 30 in the control group. Ice cubes at a size that can be moved easily in the mouth and whose corners have been smoothed in order that they will not cause irritation in the mouth has been used in oral cryotherapy in the study group. Oral chemotherapy was initiated five minutes before chemotherapy and maintained during venous infusions of etoposide (Vepesid), platinol (Cisplatin), mitomycin (Mitomycin-C) and vinblastin (Velbe) depending on the chemotherapy course. According to Patient-Judged Mucositis Grading, the rate of mucositis is 36.7% in study group and 90.0% in control group, the difference between two groups being statistically significant (P cryotherapy makes an important contribution to the protection of oral health by reducing the mucositis score according to patient- and physician-judged mucositis score and by increasing oral pH values. Aggressive cancer therapy places patients at greater risk for oral complications and treatment-related consequences. Unfortunately, prevention and/or treatment of such oral sequelae have often become overlooked as priorities of the treatment team. Effective approaches for the prevention or treatment of oral mucositis have not been standardized

Clinical assessment of oral mucositis and candidiasis compare to chemotherapic nadir in transplanted patients.

Science.gov (United States)

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.

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

Science.gov (United States)

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 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). 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.

Treatment of Helicobacter pylori infection favourably affects gastric mucosal superoxide dismutases

NARCIS (Netherlands)

Götz, J. M.; Thio, J. L.; Verspaget, H. W.; Offerhaus, G. J.; Biemond, I.; Lamers, C. B.; Veenendaal, R. A.

1997-01-01

Excessive production of reactive oxygen metabolites (ROMs) by phagocytic cells is thought to contribute to the mucosal pathology of Helicobacter pylori infection. Previously, H pylori infection was shown to have a differential effect on some gastric mucosal scavenger enzymes of ROMs-namely,

Neonatal Cytokine Profile in the Airway Mucosal Lining Fluid Is Skewed by Maternal Atopy

DEFF Research Database (Denmark)

Folsgaard, Nilofar V.; Chawes, Bo L.; Rasmussen, Morten A.

2012-01-01

on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. Objectives: To study parental atopic imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. Methods: Eighteen cytokines and chemokines were quantified in nasal mucosal...

Rectal dexmedetomidine in rats: evaluation of sedative and mucosal effects

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Volkan Hanci

2015-02-01

Full Text Available BACKGROUND AND OBJECTIVES: In this study, we investigated the anesthetic and mucosal effects of the rectal application of dexmedetomidine to rats. METHODS: Male Wistar albino rats weighing 250-300 g were divided into four groups: Group S (n = 8 was a sham group that served as a baseline for the normal basal values; Group C (n = 8 consisted of rats that received the rectal application of saline alone; Group IPDex (n = 8 included rats that received the intraperitoneal application of dexmedetomidine (100 µg kg-1; and Group RecDex (n = 8 included rats that received the rectal application of dexmedetomidine (100 µg kg-1. For the rectal drug administration, we used 22 G intravenous cannulas with the stylets removed. We administered the drugs by advancing the cannula 1 cm into the rectum, and the rectal administration volume was 1 mL for all the rats. The latency and anesthesia time (min were measured. Two hours after rectal administration, 75 mg kg-1 ketamine was administered for intraperitoneal anesthesia in all the groups, followed by the removal of the rats' rectums to a distal distance of 3 cm via an abdominoperineal surgical procedure. We histopathologically examined and scored the rectums. RESULTS: Anesthesia was achieved in all the rats in the Group RecDex following the administration of dexmedetomidine. The onset of anesthesia in the Group RecDex was significantly later and of a shorter duration than in the Group IPDEx (p < 0.05. In the Group RecDex, the administration of dexmedetomidine induced mild-moderate losses of mucosal architecture in the colon and rectum, 2 h after rectal inoculation. CONCLUSION: Although 100 µg kg-1 dexmedetomidine administered rectally to rats achieved a significantly longer duration of anesthesia compared with the rectal administration of saline, our histopathological evaluations showed that the rectal administration of 100 µg kg-1 dexmedetomidine led to mild-moderate damage to the mucosal structure of the

Use of serological and mucosal immune responses to Mycoplasma hyopneumoniae antigens P97R1, P46 and P36 in the diagnosis of infection.

Science.gov (United States)

Feng, Zhi-Xin; Bai, Yun; Yao, Jing-Ting; Pharr, G Todd; Wan, Xiu-Feng; Xiao, Shao-Bo; Chi, Ling-Zhi; Gan, Yuan; Wang, Hai-Yan; Wei, Yan-Na; Liu, Mao-Jun; Xiong, Qi-Yan; Bai, Fang-Fang; Li, Bin; Wu, Xu-Su; Shao, Guo-Qing

2014-10-01

Currently available ELISAs used to diagnose Mycoplasma hyopneumoniae infection in pigs have high specificity but low sensitivity. To develop more sensitive assays, the kinetics of specific serum IgG and respiratory mucosal sIgA responses against three M. hyopneumoniae antigens, namely, P97R1 (an adhesin protein), P46 (a membrane protein), and P36 (a cytosolic protein), were characterised over 133 days following experimental infection. Immunoglobulin G against the three proteins remained at high concentrations from 28 to 133 days post-infection (dpi), although IgG against P97R1 was detected earlier and was more reactive than the other two antigens under assessment. Mucosal sIgA appeared earlier than serum IgG but did not persist as long; sIgA concentrations against P97R1 were the highest. Seroconversion was detected 2 weeks earlier with the P97R1-based ELISA than with a commercially available ELISA. On analysis of serum samples from five pig farms that did not use a M. hyopneumoniae vaccine, the P97R1-based IgG ELISA demonstrated a 73.6% coincidence rate with the commercial kit. Moreover, this more specific P97R1-based ELISA detected more positive samples than the commercial kit (52.8% vs. 39.2%). It was concluded that the systemic immune response to M. hyopneumoniae infection in pigs was delayed in onset but persistent whereas the mucosal response developed more rapidly but was less sustained. The P97R1 antigen was identified as a suitable serological marker for diagnosing M. hyopneumoniae infection in pigs, particularly early stage infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

Mucosal Immune Regulation in Early Infancy: Monitoring and Intervention

OpenAIRE

Hol, Jeroen

2011-01-01

textabstractThe mucosal immune system of infants is dependent on the maintenance of mucosal homeostasis. Homeostasis results from the interaction between the mucosa and exogenous factors such as dietar and microbial agents. Induction and maintenance of homeostasis is a highly regluated system that involves different cell types. If homeostasis is lost this may lead to disease, including allergy and chronic intestinal inflammation. In this thesis we observed whether loss of homeostasis leading ...

Preliminary study on radio-chemo-induced oral mucositis and low level laser therapy

Science.gov (United States)

Merigo, Elisabetta; Fontana, Matteo; Fornaini, Carlo; Clini, Fabio; Cella, Luigi; Vescovi, Paolo; Oppici, Aldo

2012-09-01

Background: Oral mucositis remains one of the most common and troubling side effects of antineoplastic radiation and drug therapy: its incidence in onco-hematological radio-chemotreated patients is variable between 50 and 100% and its impact on this populations is directly linked with the experience of intense pain causing reduction and modification of therapy regimens, decreased survival rates and increased cost of care. Purpose: Aim of this study is the preliminary evaluation of a Low Level Laser therapy (LLLT) protocol on healing process of oral mucositis and on pain and quality of life of patients experiencing this dramatic side-effect. Materials and methods: Patients were evaluated and treated at the Unita` Operativa Semplice Dipartimentale di Odontostomatologia e Chirurgia Maxillo-Facciale of the Hospital of Piacenza were they were treated for primary disease with protocols of chemotherapy and/or radiotherapy. LLLT protocol was performed with a diode laser (808 nm -XD Smile - Fotona -Slovenia) on a two weeks-6 treatments schedule with power of 0.5 W and application of 30 seconds. Mucositis grading was scored on the basis of WHO classification by two blind operators at each treatment and at 1 and 2 weeks after treatment. Pain and capability of deglutition were described by patients by means questionnaires based on Visual Analogue Scale, Numerical Rating Scale and Quality of Life. Results: A relevant improvement of healing of oral mucositis, in terms of reduction of grading score, and of pain, swallowing discomfort and quality of life was recorded. Discussion and conclusion: Results of this preliminary study are encouraging for the realization of larger studies focused on the application of LLLT protocols in management of radio-chemotreated patients with oral mucositis.

Mucosal safety of PHI-443 and stampidine as a combination microbicide to prevent genital transmission of HIV-1.

Science.gov (United States)

D'Cruz, Osmond J; Uckun, Fatih M

2007-10-01

To investigate the in vitro and in vivo mucosal safety of a nonnucleoside reverse transcriptase (RT) inhibitor (PHI-443) and a nucleoside analogue RT inhibitor (stampidine)-based anti-HIV microbicide either alone or in combination. In vitro and in vivo studies using three-dimensional vaginal epithelia integrating Langerhans cells and 16 New Zealand White rabbits, respectively. Research laboratory. Rabbits in groups of four were exposed intravaginally to a gel with and without 1% PHI-443, 1% stampidine, or 1% PHI-443 plus 1% stampidine for 14 days. Cytokine/chemokine release by three-dimensional co-cultures in the presence and absence of PHI-443 or stampidine. Histologic scoring of vaginal tissue for mucosal toxicity at 24 hours after dosing. Simultaneous evaluation of levels of 10 cytokines (granulocyte-macrophage colony-stimulating factor, interleukin-1 alpha, interleukin-13, macrophage inflammatory protein-1 beta, granulocyte colony-stimulating factor, interleukin-18, tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta, and interferon-gamma) and 6 chemokines (epithelial neutrophil-activating peptide-78, interleukin-8, monocyte/macrophage chemoattractant protein-1, macrophage inflammatory protein-3 alpha, interferon-inducible protein-10, and regulated upon activation of normal T-cell expressed and secreted) in culture media by a multiplexed chemiluminescence-based immunoassay. In the rabbit model, repeated intravaginal administration of PHI-443 plus stampidine via a gel formulation at concentrations nearly 2,000 and 10,000 times higher than their respective in vitro anti-HIV IC(50) values did not result in vaginal irritation. The levels of proinflammatory cytokines/chemokines secreted by multilayered human genital epithelia integrating Langerhans cells were unaffected by prolonged exposure to PHI-443 or stampidine. The combination of PHI-443 and stampidine was noncytotoxic to vaginal epithelial cells, nonirritating to vaginal mucosa, and did not induce

Airway mucosal permeability in chronic bronchitics and bronchial asthmatics with hypersecretion

International Nuclear Information System (INIS)

Honda, I.; Shimura, S.; Sasaki, T.; Sasaki, H.; Takishima, T.; Nakamura, M.

1988-01-01

To determine airway mucosal permeability, radiolabeled albumin in sputum was examined on the basis of a 2-h period of sputum collection for as long as 8h after intravenous administration of 131 I-labeled human serum albumin. This technique was applied to 12 patients with bronchial asthma associated with hypersecretion or chronic bronchitis. Group A consisted of 6 asthmatics (2 females and 4 males, 56.0 +/- 6.4 yr of age, mean +/- SEM); Group B consisted of 6 bronchitics (3 females and 3 males, 53.8 +/- 6.5 yr of age). Between Groups A and B, there was no significant difference in sputum volume per day or in obstructive impairment. Radiolabeled albumin concentration (cpm/ml) was obtained from radiocount of each sputum sample and then divided by serum concentration at the time of each sampling (2, 4, 6, and 8 h after administration). Group B showed large values compared with those in Group A. In Group A, the ratios were 2.0 +/- 0.8, 2.5 +/- 0.5, 2.2 +/- 0.2, and 1.5 +/- 0.4% (mean +/- SEM) at 2, 4, 6, and 8 h after the administration, respectively, whereas in Group B, the ratios were 3.0 +/- 0.6, 7.0 +/- 1.8, 7.2 +/- 1.8, and 7.4 +/- 2.4%, respectively. The differences between Groups A and B were statistically significant (two-way analysis of variance). These findings suggest that an increase in airway mucosal permeability is due to mucosal epithelial damage by chronic inflammation in bronchitics and not to the underlying abnormality of asthma

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

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Ivana Škrnjug

Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

Science.gov (United States)

Škrnjug, Ivana; Guzmán, Carlos Alberto; Rueckert, Christine; Ruecker, Christine

2014-01-01

The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients.

Science.gov (United States)

Vanstraelen, Kim; Prattes, Juergen; Maertens, Johan; Lagrou, Katrien; Schoemans, Hélène; Peersman, Nele; Vermeersch, Pieter; Theunissen, Koen; Mols, Raf; Augustijns, Patrick; Annaert, Pieter; Hoenigl, Martin; Spriet, Isabel

2016-08-01

Low posaconazole plasma concentrations (PPCs) are frequently encountered in allogeneic hematopoietic stem cell transplant (HSCT) patients, due to variable gastrointestinal absorption. In this study, the impact of intestinal mucositis on posaconazole exposure is investigated. A prospective pharmacokinetic study was performed including allogeneic HSCT patients receiving posaconazole prophylaxis with the oral suspension or tablets. Steady state PPCs were determined using high-performance liquid chromatography-fluorescence detection at the day of transplantation (=day 0), day +7, and +14. Citrulline was measured using liquid chromatography-tandem mass spectrometry to evaluate severity of mucositis, at baseline (day -7 or -6), and at day 0, +7 and +14. Additionally, citrulline plasma concentrations and steady state trough PPCs were determined in hematological patients without HSCT or mucositis. Thirty-four HSCT patients received posaconazole oral suspension together with 25 cL of Coca Cola, 6 HSCT patients received posaconazole tablets and 33 hematological patients not receiving HSCT received posaconazole oral suspension. The median (interquartile range) average PPC was 0.26 mg/L (0.17-0.43), 0.67 mg/L (0.27-1.38), and 1.08 mg/L (0.96-1.38), with suspension in HSCT patients, suspension in hematological patients and tablets in HSCT patients, respectively. A higher trough PPC was encountered with the oral suspension when citrulline plasma concentrations were above 10 μmol/L compared to values below 10 μmol/L (p < 0.001), whereas for tablets, average PPCs remained high with citrulline plasma concentrations below or above 10 μmol/L (p = 0.64). Posaconazole tablets should be preferred to suspension in HSCT patients immediately after transplantation to prevent insufficient plasma exposure due to intestinal mucositis.

Chemotherapy-Induced and/or Radiation Therapy-Induced Oral Mucositis-Complicating the Treatment of Cancer

Directory of Open Access Journals (Sweden)

Maddireddy Umameshwar Rao Naidu

2004-09-01

Full Text Available 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 (Sphase-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

Proceedings of the 1st International Operational Modal Analysis Conference, April 26-27, 2005, Copenhagen, Denmark

DEFF Research Database (Denmark)

These proceedings contain approximately 100 papers presented at the 1st International Operational Modal Conference, Copenhagen, Denmark, April 26 - 27, 2005. The conference is jointly organised by Structural Vibration Systems (SVS), Aalborg, Brüel & Kjær Sound and Vibration Measurement A/S and th......These proceedings contain approximately 100 papers presented at the 1st International Operational Modal Conference, Copenhagen, Denmark, April 26 - 27, 2005. The conference is jointly organised by Structural Vibration Systems (SVS), Aalborg, Brüel & Kjær Sound and Vibration Measurement A....../S and the Department of Building Technology and Structural Engineering at Aalborg University. It is the first conference ever to focus solely on experimental modal analysis for cases where only the responses are measured. It was decided to hold the conference to generate interest in operational modal analysis (also...... effort and higher versatility. However, because the mathematical background was initially weak, computer power was insufficient and the equipment not sensitive enough for this kind of testing, the technology has only become popular during the last 3 - 4 years. For this reason, the first conference...

Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

Directory of Open Access Journals (Sweden)

Yun Wu

2016-01-01

Full Text Available Background: Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions. Methods: We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated. Results: Among 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115-16.592, dual anti-platelet medication (OR = 3.443, 95% CI: 1.154-10.271, current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870, male gender (OR = 2.211, 95% CI: 1.027-4.760, GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278, and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016-4.669 were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding. Conclusions: Peptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in

Adrenergic influence on gastric mucosal blood flow in gastric fistula dogs

DEFF Research Database (Denmark)

Hovendal, C P; Bech, K; Gottrup, F

1984-01-01

micrograms/kg/min) induced an increase in mucosal blood flow and a similar increase in acid secretion. If the dopamine infusion was preceded by alpha-receptor blockade, a pronounced increase in mucosal blood flow was observed without a similar increase in acid secretion. beta-adrenergic stimulation...

Substitution urethroplasty for anterior urethral strictures: buccal versus lingual mucosal graft.

Science.gov (United States)

Kumar, Abhay; Das, Suren K; Trivedi, Sameer; Dwivedi, Udai S; Singh, Pratap B

2010-01-01

To compare the results of substitution urethroplasty and donor site morbidity between buccal mucosal graft (BMG) and lingual mucosal graft (LMG). Patients who underwent single-stage dorsal onlay free oral mucosal graft substitution urethroplasty by Barbagli's technique between January 2004 and August 2008 were included in this study. Patients who underwent buccal (cheek, lip) mucosal graft urethroplasty were included in group I and those who underwent LMG urethroplasty (tongue) were included in group II. All patients underwent complete evaluation of the stricture including inspection of the oral cavity. Exclusion criteria were stricture length speech complications was seen in group II, but not in group I. The long-term complications of persistent oral discomfort, perioral numbness and tightness of the mouth were seen only in group I. LMG urethroplasty is a good substitute for BMG urethroplasty with equally good results of urethroplasty with lower donor site morbidity. Copyright 2010 S. Karger AG, Basel.

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

Science.gov (United States)

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.

Endomicroscopy for assessing mucosal healing in patients with ulcerative colitis.

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Gheorghe, Cristian; Cotruta, Bogdan; Iacob, Razvan; Becheanu, Gabriel; Dumbrava, Mona; Gheorghe, Liana

2011-12-01

The assessment of tissue healing has emerged as an important treatment goal in patients with inflammatory bowel disease. In patients with ulcerative colitis (UC), mucosal healing may represent the ultimate therapeutic goal due to the fact that the inflammation is limited to the mucosal layer. Mucosal and histological healing may indicate a subset of UC patients in long-term clinical, endoscopic and histological remission in whom immunomodulators, biologics, and even aminosalicylates may be withdrawn. Confocal laser endomicroscopy allows the assessment of residual cellular inflammation, crypt and vessel architecture distortion during ongoing endoscopy, and therefore permits a real-time evaluation of histological healing in patients with ulcerative proctitis. Images of conventional optical microscopy and confocal laser endomicroscopy in patients with ulcerative proctitis in remission are presented.

Epithelium-innate immune cell axis in mucosal responses to SIV.

Science.gov (United States)

Shang, L; Duan, L; Perkey, K E; Wietgrefe, S; Zupancic, M; Smith, A J; Southern, P J; Johnson, R P; Haase, A T

2017-03-01

In the SIV (simian immunodeficiency virus)-rhesus macaque model of HIV-1 (human immunodeficiency virus type I) transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T-cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T-cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T-cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment, and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.

1st Iberian Robotics Conference

CERN Document Server

Sanfeliu, Alberto; Ferre, Manuel; ROBOT2013; Advances in robotics

2014-01-01

This book contains the proceedings of the ROBOT 2013: FIRST IBERIAN ROBOTICS CONFERENCE and it can be said that included both state of the art and more practical presentations dealing with implementation problems, support technologies and future applications. A growing interest in Assistive Robotics, Agricultural Robotics, Field Robotics, Grasping and Dexterous Manipulation, Humanoid Robots, Intelligent Systems and Robotics, Marine Robotics, has been demonstrated by the very relevant number of contributions. Moreover, ROBOT2013 incorporates a special session on Legal and Ethical Aspects in Robotics that is becoming a topic of key relevance. This Conference was held in Madrid (28-29 November 2013), organised by the Sociedad Española para la Investigación y Desarrollo en Robótica (SEIDROB) and by the Centre for Automation and Robotics - CAR (Universidad Politécnica de Madrid (UPM) and Consejo Superior de Investigaciones Científicas (CSIC)), along with the co-operation of Grupo Temático de Robótica CEA-GT...

Mucosal healing and deep remission: What does it mean?

Science.gov (United States)

Rogler, Gerhard; Vavricka, Stephan; Schoepfer, Alain; Lakatos, Peter L

2013-01-01

The use of specific terms under different meanings and varying definitions has always been a source of confusion in science. When we point our efforts towards an evidence based medicine for inflammatory bowel diseases (IBD) the same is true: Terms such as “mucosal healing” or “deep remission” as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are altered. It appears to be useful to first have a look at the development of terms and their definitions, to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and trials. The purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the terms. It may also lead to a better defined use of those terms for future studies. The terms “mucosal healing” and “deep remission” have been introduced in recent years as new therapeutic targets in the treatment of IBD patients. Several clinical trials, cohort studies or inception cohorts provided data that the long term disease course is better, when mucosal healing is achieved. However, it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical remission. Clinical trials are under way to answer this question. Attention should be paid to clearly address what levels of IBD activity are looked at. In the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists. PMID:24282345

Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine

NARCIS (Netherlands)

Bartlett, Jeremy A.; Maarschalk, Kees van der Voort

2012-01-01

Absorption of drugs from the oral cavity into the mucosal tissues is typically a fast event. Dissolved drugs partition into the mucosal membranes and within minutes will reach equilibrium with drug in solution in the oral cavity. However, this does not always equate to rapid drug appearance in the

Bladder Mucosal Graft Vaginoplasty: A Case Report.

Science.gov (United States)

Chiaramonte, Cinzia; Vestri, Elettra; Tripi, Flavia; Giannone, Antonino Giulio; Cimador, Marcello; Cataliotti, Ferdinando

2018-06-18

Female vaginoplasty reconstruction, by choice, is usually performed with adjacent tissue. However in some clinical conditions such as high urogenital confluence sinus, cloacal malformation with extreme vaginal hypoplasia, local tissue may not be available. When vaginal replacement is performed in pediatric patients intestinal segments is preferred to non-operative procedures that require continuative dilations. However mucus production, malignant transformation risk and diversion colitis are important side effects. We present a nouvel technique for vaginoplasty in a female child presenting with an isolated urogenital sinus malformation without virilization. The patient at 20 months underwent vaginoplasty using tubularized bladder mucosal graft. Surgical procedure was devoid of complications. Pubertal development occurred at age of 15. She underwent regular follow up until 18 years of age. At this age we performed clinical evaluation: absence of vaginal introitus stenosis and good cosmetic results were observed. Then she underwent vaginoscopy with multiple biopsies. Pathology examination of the bladder mucosal graft evidenced a normal structure of the mucosa, with a stratified squamous epithelium. Different techniques are taken into account for vaginal reconstruction according to the severity and to the type of malformation. We describe the use of bladder mucosal graft with favorable results after long term follow-up. Copyright © 2018. Published by Elsevier Inc.

Conference proceedings of the 4. international conference on CANDU fuel. V. 1,2

International Nuclear Information System (INIS)

1995-01-01

These proceedings contain the full texts of all 65 papers presented at the 4th International Conference on CANDU fuel. As such, they represent an update on the state-of-the-art in such important CANDU fuel topics as International Development Programs and Operating Experience with CANDU fuel, Performance Assessments and Fuel Behavior Modeling, Fuel Properties, Licensing and Accident Analyses for CANDU fuel, Design, Testing and Manufacturing, and Advanced Fuel Designs. The large number of papers required the use of parallel sessions for the first time at a CANDU Fuel Conference

Conference proceedings of the 4. international conference on CANDU fuel. V. 1,2

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-12-31

These proceedings contain the full texts of all 65 papers presented at the 4th International Conference on CANDU fuel. As such, they represent an update on the state-of-the-art in such important CANDU fuel topics as International Development Programs and Operating Experience with CANDU fuel, Performance Assessments and Fuel Behavior Modeling, Fuel Properties, Licensing and Accident Analyses for CANDU fuel, Design, Testing and Manufacturing, and Advanced Fuel Designs. The large number of papers required the use of parallel sessions for the first time at a CANDU Fuel Conference.

1st Fire Behavior and Fuels Conference: Fuels Management-How to Measure Success

Science.gov (United States)

Patricia L. Andrews

2006-01-01

The 1st Fire Behavior and Fuels Conference: Fuels Management -- How to Measure Success was held in Portland, Oregon, March 28-30, 2006. The International Association of Wildland Fire (IAWF) initiated a conference on this timely topic primarily in response to the needs of the U.S. National Interagency Fuels Coordinating Group (http://www.nifc.gov/).

Sage tea-thyme-peppermint hydrosol oral rinse reduces chemotherapy-induced oral mucositis: A randomized controlled pilot study.

Science.gov (United States)

Mutluay Yayla, Ezgi; Izgu, Nur; Ozdemir, Leyla; Aslan Erdem, Sinem; Kartal, Murat

2016-08-01

This pilot study aimed to investigate the preventive effect of sage tea-thyme-peppermint hydrosol oral rinse used in conjunction with basic oral care on chemotherapy-induced oral mucositis. An open-label randomized controlled study. Two oncology hospitals in Ankara, Turkey. Patients receiving 5-fluorouracil-based chemotherapy regimens were divided into the intervention group (N=30) and control group (N=30). Basic oral care was prescribed to the control group, while the intervention group was prescribed sage tea-thyme-peppermint hydrosol in addition to basic oral care. All patients were called to assess their compliance with the study instructions on day 5 and 14. Oral mucositis was evaluated using an inspection method or by assessing oral cavity photos based on the World Health Organization oral toxicity scale on day 5 and 14. Most of the patients in the intervention group did not develop oral mucositis on day 5. In addition, the incidence of grade 1 oral mucositis was statistically lower in the intervention group (10%) than the control group (53.3%) on day 5. By day 14, the majority of patients in both the groups had grade 0 oral mucositis. Sage tea-thyme-peppermint hydrosol oral rinse has promising results in alleviating oral mucositis. This hydrosol can be recommended for clinical use as it is well tolerated and cost-effective. However, further randomized controlled trials are needed to support the study. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Mucosal Immune System and Its Regulation by Autophagy.

Science.gov (United States)

Kabat, Agnieszka M; Pott, Johanna; Maloy, Kevin J

2016-01-01

The gastrointestinal tract presents a unique challenge to the mucosal immune system, which has to constantly monitor the vast surface for the presence of pathogens, while at the same time maintaining tolerance to beneficial or innocuous antigens. In the intestinal mucosa, specialized innate and adaptive immune components participate in directing appropriate immune responses toward these diverse challenges. Recent studies provide compelling evidence that the process of autophagy influences several aspects of mucosal immune responses. Initially described as a "self-eating" survival pathway that enables nutrient recycling during starvation, autophagy has now been connected to multiple cellular responses, including several aspects of immunity. Initial links between autophagy and host immunity came from the observations that autophagy can target intracellular bacteria for degradation. However, subsequent studies indicated that autophagy plays a much broader role in immune responses, as it can impact antigen processing, thymic selection, lymphocyte homeostasis, and the regulation of immunoglobulin and cytokine secretion. In this review, we provide a comprehensive overview of mucosal immune cells and discuss how autophagy influences many aspects of their physiology and function. We focus on cell type-specific roles of autophagy in the gut, with a particular emphasis on the effects of autophagy on the intestinal T cell compartment. We also provide a perspective on how manipulation of autophagy may potentially be used to treat mucosal inflammatory disorders.

Pharmacological Protection From Radiation ± Cisplatin-Induced Oral Mucositis

International Nuclear Information System (INIS)

Cotrim, Ana P.; Yoshikawa, Masanobu; Sunshine, Abraham N.; Zheng Changyu; Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B.; Baum, Bruce J.

2012-01-01

Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation ± cisplatin. Methods and Materials: Female C3H mice, ∼8 weeks old, were irradiated with five fractionated doses ± cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 × 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

Mucosal expression of basic fibroblastic growth factor, Syndecan 1 and tumor necrosis factor-alpha in diverticular disease of the colon: a case-control study.

Science.gov (United States)

Tursi, A; Elisei, W; Brandimarte, G; Giorgetti, G M; Inchingolo, C D; Nenna, R; Picchio, M; Giorgio, F; Ierardi, E

2012-09-01

Inflammation may be detected in diverticular disease (DD), and fibrosis may also develop. We assessed the mucosal expression of bFGF, SD1, and TNF-α in DD according to the severity of the disease. Moreover, we assessed the response to therapy of these cytokines in acute uncomplicated diverticulitis (AUD). Fifteen patients affected by AUD and seven patients affected by symptomatic uncomplicated diverticular disease (SUDD) were enrolled. Patients with asymptomatic diverticulosis (AD), segmental colitis associated with diverticulosis (SCAD), ulcerative colitis (UC), and healthy subjects (HC) served as control groups. The expression of bFGF, SD1, and TNF-α was significantly higher in diverticulitis than in healthy controls, in diverticulosis, and in uncomplicated diverticular disease. Cytokines were significantly higher in uncomplicated diverticular disease than in healthy controls. Cytokine expression in diverticulitis did not differ significantly from that of ulcerative colitis. After treatment, TNF-α expression dropped significantly. Mucosal TNF-α is overexpressed only in symptomatic DD, while SD1 and bFGF are already overexpressed in AD. Finally, TNF-α but not SD1 or bFGF expression seems to be influenced by the treatment in AUD. © 2012 Blackwell Publishing Ltd.

Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma

DEFF Research Database (Denmark)

Chaiyarit, Ponlatham; Utrawichian, Akasith; Leelayuwat, Chanvit

2012-01-01

Objectives The aims of our study were to determine levels of trefoil factor (TFF) peptides in saliva and oral mucosal tissues from patients with oral squamous cell carcinoma (OSCC), and to evaluate whether individual members of TFFs (TFF1, TFF2, and TFF3) might act as biomarkers of disease....... Materials and methods Saliva samples were from 23 healthy subjects and 23 OSCC patients. Tissue samples were collected from 32 normal oral mucosa (NOM) and 32 OSCC biopsy specimens. ELISA and immunohistochemical methods were used to evaluate the expression of TFF1, TFF2, and TFF3 in saliva and oral mucosal...... tissues, respectively. Results Expression of TFF2 and TFF3 in oral mucosal tissues of OSCC patients was strongly downregulated when compared to healthy subjects (p 

Mucus reduction promotes acetyl salicylic acid-induced small intestinal mucosal injury in rats.

Science.gov (United States)

Suyama, Yosuke; Handa, Osamu; Naito, Yuji; Takayama, Shun; Mukai, Rieko; Ushiroda, Chihiro; Majima, Atsushi; Yasuda-Onozawa, Yuriko; Higashimura, Yasuki; Fukui, Akifumi; Dohi, Osamu; Okayama, Tetsuya; Yoshida, Naohisa; Katada, Kazuhiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Konishi, Hideyuki; Itoh, Yoshito

2018-03-25

Acetyl salicylic acid (ASA) is a useful drug for the secondary prevention of cerebro-cardiovascular diseases, but it has adverse effects on the small intestinal mucosa. The pathogenesis and prophylaxis of ASA-induced small intestinal injury remain unclear. In this study, we focused on the intestinal mucus, as the gastrointestinal tract is covered by mucus, which exhibits protective effects against various gastrointestinal diseases. ASA was injected into the duodenum of rats, and small intestinal mucosal injury was evaluated using Evans blue dye. To investigate the importance of mucus, Polysorbate 80 (P80), an emulsifier, was used before ASA injection. In addition, rebamipide, a mucus secretion inducer in the small intestine, was used to suppress mucus reduction in the small intestine of P80-administered rats. The addition of P80 reduced the mucus and exacerbated the ASA-induced small intestinal mucosal injury. Rebamipide significantly suppressed P80-reduced small intestinal mucus and P80-increased intestinal mucosal lesions in ASA-injected rats, demonstrating that mucus is important for the protection against ASA-induced small intestinal mucosal injury. These results provide new insight into the mechanism of ASA-induced small intestinal mucosal injury. Mucus secretion-increasing therapy might be useful in preventing ASA-induced small intestinal mucosal injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of 60Co panoramic source in the induction of oral mucositis in rats

International Nuclear Information System (INIS)

Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M.; Correa, Luciana

2013-01-01

Oral Mucositis is a well-known side effect of chemo-radiotherapy in cancer patients or transplant recipients that could induce hospitalization or impairs therapy in different levels of severity. This study is devoted to define the first steps in the research of low level laser treatments in oral mucositis, proposing a 60 Co radiation to experimentally induce oral mucositis in rats using Panoramic gamma irradiator, simulating usual radiotherapy of head and neck cancer. Fifteen male Wistar rats, above 250g, were irradiated at Centro de Tecnologia das Radiacoes (IPEN - CNEN/SP) and divided in three experimental groups, with different single doses of radiation (30 Gy, 25 Gy and 20 Gy). The animals were observed for a 20 days period. Animals that received 30 Gy and 25 Gy developed greater severity of mucositis and premature euthanasia was performed in these groups on the 7th and 11th day after the irradiation, respectively. The 20 Gy group developed oral mucositis grading from moderated to severe between the days 7 and 11 after irradiation, with progressive body mass loss and decrease in the intake of food and water. These animals recovered from oral mucositis around the 18th day and clinical remission at the 20th day. The single dose of 20 Gy Gamma radiation proved to be efficient way for inducing oral mucositis in rats, allowing the establishment of an experimental model for oral mucositis in rats for future use on interventions of this serious aspect of radiation therapy, such as laser therapy using different wave lengths and power densities. (author)

PREFACE: 1st International Conference on Rheology and Modeling of Materials

Science.gov (United States)

Gömze, László A.

2015-04-01

Understanding the rheological properties of materials and their rheological behaviors during their manufacturing processes and in their applications in many cases can help to increase the efficiency and competitiveness not only of the finished goods and products but the organizations and societies also. The more scientific supported and prepared organizations develop more competitive products with better thermal, mechanical, physical, chemical and biological properties and the leading companies apply more competitive knowledge, materials, equipment and technology processes. The idea to organize in Hungary the 1st International Conference on Rheology and Modeling of Materials we have received from prospective scientists, physicists, chemists, mathematicians and engineers from Asia, Europe, North and South America including India, Korea, Russia, Turkey, Estonia, France, Italy, United Kingdom, Chile, Mexico and USA. The goals of ic-rmm1 the 1st International Conference on Rheology and Modeling of Materials are the following: • Promote new methods and results of scientific research in the fields of modeling and measurements of rheological properties and behavior of materials under processing and applications. • Change information between the theoretical and applied sciences as well as technical and technological implantations. • Promote the communication between the scientists of different disciplines, nations, countries and continents. The international conference ic-rmm1 provides a platform among the leading international scientists, researchers, PhD students and engineers for discussing recent achievements in measurement, modeling and application of rheology in materials technology and materials science of liquids, melts, solids, crystals and amorphous structures. Among the major fields of interest are the influences of material structures, mechanical stresses temperature and deformation speeds on rheological and physical properties, phase transformation of

Superfund 16: Conference and exhibition proceedings. Volume 1

International Nuclear Information System (INIS)

Anon.

1995-01-01

This conference was held November 6--8, 1995 in Washington, D.C. The purpose of the conference was to provide a multidisciplinary forum dealing with state-of-the-art methods and site characterization technologies for environmental monitoring and remedial action planning of hazardous wastes. Individual papers have been processed separately for inclusion in the appropriate data bases

Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Yangkun Luo

2016-01-01

Full Text Available 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.

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

Science.gov (United States)

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.

Efficacy and safety of granulocyte macrophage-colony stimulating factor (GM-CSF) on the frequency and severity of radiation mucositis in patients with head and neck carcinoma

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Kannan, V.; Bapsy, Poonamallee P.; Anantha, Naranappa; Doval, Dinesh Chandra; Vaithianathan, Hema; Banumathy, G.; Reddy, Krishnamurthy B.; Kumaraswamy, Saklaspur Veerappaiah; Shenoy, Ashok Mohan

1997-01-01

Purpose: Based on the clinical evidence of mucosal protection by GM-CSF during cytotoxic chemotherapy, a pilot study was undertaken to determine the safety and mucosal reaction of patients receiving GM-CSF while undergoing definitive conventional fractionated radiotherapy in head and neck carcinoma. Methods and Materials: Patients were considered eligible if buccal mucosa and oropharynx were included in the teleradiation field. Ten adult patients with squamous cell carcinoma of head and neck (buccal mucosa--8 and posterior (1(3)) tongue--2) were entered into the trial. Radiation therapy was delivered with telecobalt machine at conventional 2 Gy fraction and 5 fractions/week. The radiation portals consisted of two parallel opposing lateral fields. GM-CSF was given subcutaneously at a dose of 1 μg/kg body weight, daily, after 20 Gy until the completion of radiation therapy. Patients were evaluated daily for mucosal reaction, pain, and functional impairment. Results: The median radiation dose was 66 Gy. Eight patients received ≥60 Gy. The tolerance to GM-CSF was good. All 10 patients completed the planned daily dose of GM-CSF without interruption. Mucosal toxicity was Grade I in four patients till the completion of radiotherapy (dose range 50-66 Gy). Six patients developed Grade II reaction, fibrinous mucosal lesions of maximum size 1.0-1.5 cm, during radiotherapy. None developed Grade III mucositis. The maximum mucosal pain was Grade I during GM-CSF therapy. In two patients after starting GM-CSF the pain reduced in intensity. Functional impairment was mild to moderate. All patients were able to maintain adequate oral intake during the treatment period. Total regression of mucosal reaction occurred within 8 days following completion of radiotherapy. Conclusions: GM-CSF administration concurrently with conventional fractionated radiotherapy was feasible without significant toxicity. The acute side effects of radiotherapy namely mucositis, pain, and functional

Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats

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Egan Erin A

2010-01-01

Full Text Available Abstract Background The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL, therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses. Results Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL. Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia. Conclusions Our results indicate

Esophageal mucosal breaks in gastroesophageal reflux disease partially responsive to proton pump inhibitor therapy.

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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.

Close association between oral Candida species and oral mucosal disorders in patients with xerostomia.

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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.

Oral mucosal lesions in denture wearers.

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Jainkittivong, Aree; Aneksuk, Vilaiwan; Langlais, Robert P

2010-03-01

To determine the prevalence of oral mucosal lesions (OMLs) and denture-related mucosal lesions (DMLs) in denture wearers and to co-relate the prevalence with age, gender, type of denture and any systemic conditions. Dental records of 380 denture wearers were retrospectively reviewed for OMLs and DMLs. We found 45% of the denture wearers had DMLs and 60.8% had OMLs not related to denture wearing. Although the prevalence of DMLs was higher in complete denture wearers than in partial denture wearers (49% vs. 42.2%), this difference was not significant. The most common DMLs were traumatic ulcer (19.5%) and denture-induced stomatitis (18.1%). When analysed by type, traumatic ulcer, denture hyperplasia, frictional keratosis and candidiasis were more common in complete denture wearers, whereas denture-induced stomatitis was more common in partial denture wearers. Frictional keratosis was more common in men than in women. The prevalence of OMLs not related to denture wearing was higher in complete denture wearers than in partial denture wearers, and the most common OML was fissured tongue (27.6%). No association between DMLs and systemic conditions or xerostomic drugs was noted. No differences in the prevalence of DMLs in association with denture type were found. The prevalence of OMLs not related to denture wearing was higher in complete denture wearers than in partial denture wearers. This difference was affected by age, and the data were similar to the findings observed in the elderly.

Radioprotective agents to reduce BNCT (Boron Neutron Capture Therapy) induced mucositis in the hamster cheek pouch

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Monti Hughes, A.; Pozzi, E.C.C.; Thorp, S.

2013-01-01

Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of BNCT mediated by boronophenylalanine (BPA) in the hamster cheek pouch oral cancer and pre cancer model. Despite therapeutic efficacy, mucositis induced in premalignant tissue was dose limiting and favored, in some cases, tumor development. In a clinical scenario, oral mucositis limits the dose administered to head and neck tumors. Aim: Our aim was to evaluate the effect of the administration of different radioprotective agents, seeking to reduce BNCT-induced mucositis to acceptable levels in dose-limiting premalignant tissue; without compromising therapeutic effect evaluated as inhibition on tumor development in premalignant tissue; without systemic or local side effects; and without negative effects on the biodistribution of the boron compound used for treatment. Materials and methods: Cancerized hamsters with DMBA (dimethylbenzanthracene) were treated with BPA-BNCT 5 Gy total absorbed dose to premalignant tissue, at the RA-3 Nuclear Reactor, divided into different groups: 1-treated with FLUNIXIN; 2- ATORVASTATIN; 3-THALIDOMIDE; 4-HISTAMINE (two concentrations: Low -1 mg/ml- and High -5 mg/ml-); 5-JNJ7777120; 6-JNJ10191584; 7-SALINE (vehicle). Cancerized animals without any treatment (neither BNCT nor radioprotective therapy) were also analyzed. We followed the animals during one month and evaluated the percentage of animals with unacceptable/severe mucositis, clinical status and percentage of animals with new tumors post treatment. We also performed a preliminary biodistribution study of BPA + Histamine “low” concentration to evaluate the potential effect of the radioprotector on BPA biodistribution. Results: Histamine �

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.

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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.

Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

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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 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.

The Molecular Immunology of Mucositis: Implications for Evidence-Based Research in Alternative and Complementary Palliative Treatments

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Francesco Chiappelli

2005-01-01

Full Text Available The terms ‘mucositis’ and ‘stomatitis’ are often used interchangeably. Mucositis, however, pertains to pharyngeal-esophago-gastrointestinal inflammation that manifests as red, burn-like sores or ulcerations throughout the mouth. Stomatitis is an inflammation of the oral tissues proper, which can present with or without sores, and is made worse by poor dental hygiene. Mucositis is observed in a variety of immunosuppressed patients, but is most often consequential to cancer therapy. It appears as early as the third day of intervention, and is usually established by Day 7 of treatment. Mucositis increases mortality and morbidity and contributes to rising health care costs. The precise immune components involved in the etiology of mucositis are unclear, but evidence-based research (EBR data has shown that applications of granulocyte–macrophage-colony stimulating factor prevent the onset or the exacerbation of oropharyngeal mucositis. The molecular implications of this observation are discussed from the perspective of future developments of complementary and alternative treatments for this condition. It must be emphasized that this article is meant to be neither a review on mucositis and the various treatments for it, nor a discussion paper on its underlying molecular immunology. It is a statement of the implications of EBR for CAM-based interventions for mucositis. It explores and discusses the specific domain of molecular immunology in the context of mucositis and its direct implications for EBR research in CAM-based treatments for mucositis.

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

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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.

1st International Conference of IFToMM Italy

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Gasparetto, Alessandro

2017-01-01

This volume contains the Proceedings of the First International Conference of IFToMM Italy (IFIT2016), held at the University of Padova, Vicenza, Italy, on December 1-2, 2016. The book contains contributions on the latest advances on Mechanism and Machine Science. The fifty-nine papers deal with such topics as biomechanical engineering, history of mechanism and machine science, linkages and mechanical controls, multi-body dynamics, reliability, robotics and mechatronics, transportation machinery, tribology, and vibrations.

HIV enteropathy and aging: gastrointestinal immunity, mucosal epithelial barrier, and microbial translocation.

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Wang, Hongyin; Kotler, Donald P

2014-07-01

Despite decreases in morbidity and mortality as a result of antiretroviral therapy, gastrointestinal dysfunction remains common in HIV infection. Treated patients are at risk for complications of 'premature' aging, such as cardiovascular disease, osteopenia, neurocognitive decline, malignancies, and frailty. This review summarizes recent observations in this field. Mucosal CD4 lymphocytes, especially Th17 cells, are depleted in acute HIV and simian immune deficiency virus (SIV) infections, although other cell types also are affected. Reconstitution during therapy often is incomplete, especially in mucosa. Mucosal barrier function is affected by both HIV infection and aging and includes paracellular transport via tight junctions and uptake through areas of apoptosis; other factors may affect systemic antigen exposure. The resultant microbial translocation is associated with systemic immune activation in HIV and SIV infections. There is evidence of immune activation and microbial translocation in the elderly. The immune phenotypes of immunosenescence in HIV infection and aging appear similar. There are several targets for intervention; blockage of residual mucosal virus replication, preventing antigen uptake, modulating the microbiome, improving T cell recovery, combining therapies aimed at mucosal integrity, augmenting mucosal immunity, and managing traditional risk factors for premature aging in the general population. Aging may interact with HIV enteropathy to enhance microbial translocation and immune activation.

Minocycline down-regulates topical mucosal inflammation during the application of microbicide candidates.

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Liangzhu Li

Full Text Available An effective anti-human immunodeficiency virus-1 (HIV-1 microbicide should exert its action in the absence of causing aberrant activation of topical immunity that will increase the risk of HIV acquisition. In the present study, we demonstrated that the vaginal application of cellulose sulfate (CS gel induced topical mucosal inflammatory responses; the addition of minocycline to CS gel could significantly attenuate the inflammation in a mice model. The combined gel of CS plus minocycline not only reduced the production of inflammatory cytokines in cervicovaginal lavages (CVLs, also down-regulated the activation of CD4+ T cells and the recruitment of other immune cells including HIV target cells into vaginal tissues. Furthermore, an In vitro HIV-1 pseudovirus infection inhibition assay showed that the combined gel decreased the infection efficacy of different subtypes of HIV-1 pseudoviruses compared with that of CS gel alone. These results implicate that minocycline could be integrated into microbicide formulation to suppress the aberrant activation of topical mucosal immunity and enhance the safety profile during the application of microbicides.

Oral Mucositis Prevention By Low-Level Laser Therapy in Head-and-Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy: A Phase III Randomized Study

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Gouvea de Lima, Aline [Departamento de Radiologia, Disciplina de Oncologia, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil); Villar, Rosangela Correa [Instituto de Radiologia, Servico de Radioterapia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil); Castro, Gilberto de, E-mail: gilberto.castro@usp.br [Department of Clinical Oncology, Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, SP (Brazil); Antequera, Reynaldo [Divisao de Odontologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil); Gil, Erlon; Rosalmeida, Mauro Cabral [Instituto de Radiologia, Servico de Radioterapia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil); Federico, Miriam Hatsue Honda; Snitcovsky, Igor Moises Longo [Departamento de Radiologia, Disciplina de Oncologia, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP (Brazil)

2012-01-01

Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm{sup 2} or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might

Frequency of fungal infection in biopsies of oral mucosal lesions: A prospective hospital-based study

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Thimmarasa Venkappa Bhovi

2015-01-01

Full Text Available Aims and Objectives: To determine the frequency and common site of fungal infection in biopsies of oral mucosal lesions and also to detect the lesions most likely to be infected with fungal infection. Materials and Methods: A total of 100 patients with oral mucosal lesions were advised routine hematological examination followed by incisional biopsy under local anesthesia. The specimen were fixed in 10% neutral buffered formalin and processed. One section from the specimen was stained with hematoxylin and eosin staining for histopathological diagnosis of the lesion and a second section was stained with Periodic acid-Schiff (PAS stain for detection of fungal infection. Results: Out of the 100 patients, the most common mucosal lesion encountered was carcinoma (56% followed by lesions with dysplastic changes (28%, benign lesions (9%, squamous papilloma (2% and oral submucous fibrosis (5%. The most common anatomic location affected by the mucosal lesions were buccal mucosa, followed by the tongue, gingiva, maxillary tuberosity and floor of the mouth with values of 73%, 16%, 6%, 4% and 1%, respectively. Squamous papilloma had the highest positive association with fungal infection (100% followed by lesions with dysplastic changes (17.9% and carcinoma (8.9%. The maximum fungal positive association was encountered in the mucosal lesions over the tongue (18.7% followed by the buccal mucosa (12.3%. Conclusion: There is statistically significant association of fungal infection with dysplastic lesions and papilloma with the tongue and buccal mucosa as the most common sites. Hence a PAS stain should be performed whenever epithelial dysplasia on the tongue and buccal mucosa is diagnosed.

Intestinal dendritic cells in the regulation of mucosal immunity

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Bekiaris, Vasileios; Persson, Emma K.; Agace, William Winston

2014-01-01

immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive....... The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality...

The etiological structure, biological properties of causative agents of peri-implant mucositis

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M. O. Faustova

2017-10-01

Full Text Available The purpose was to examine the peri-implant mucositis microflora and sensitivity of dominant pathogens to antibiotics and antiseptics. Materials and methods. The study involved 43 patients with peri-implant mucositis. During the study 162 clinical strains of microorganisms were isolated and identified. Cultivation of clinical isolates was performed by the standard method, final identification was carried out with using bacteriological automatic analyzer Vitec – 2compact bioMérieux (France. Determination of sensitivity to antibiotics of pathogens was carried with disc-diffusion method; the study of sensitivity to antiseptics was carried by means of double serial dilutions method by the standard procedure approved by the Order № 167 of the Ministry of Public Health of Ukraine on “On Approval of Training Guidance “Assessment of the sensitivity of microorganisms to antibiotics”, dated by April, 5, 2007. Results. It is The microflora of peri-implant area of patients with mucositis was revealed to consist of opportunistic species. Representatives of Streptococcus spp. and Staphylococcus spp. were dominating among them, although Kocuria spp., Enterobacter spp. and yeast-like fungi Candida spp. were detected quite common. Investigated clinical strains of microorganisms had different sensitivity to antibiotics. All cultures were sensitive to fluoroquinolones, but very significant number of them showed resistance to penicillins, macrolides and lincosamides. In turn, horosten, dekasan and chlorhexidine had powerful antimicrobial effect on dominant pathogens of periimplant mucositis in patients. Moreover, the effect of decametoxine-based antiseptics on some of them significantly exceeded the activity of chlorhexidine. Conclusions. Microflora from peri-implant area of patients with peri-implant mucositis consists mainly of aerobic and facultative anaerobic microorganisms, belonging to normal oral microflora. Most of pathogens of mucositis obtaine

Efficacy of Sucralfate Mouth Wash in Prevention of 5-fluorouracil Induced Oral Mucositis: A Prospective, Randomized, Double-Blind, Controlled Trial.

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Ala, Shahram; Saeedi, Majid; Janbabai, Ghasem; Ganji, Reza; Azhdari, Elham; Shiva, Afshin

2016-01-01

Sucralfate has been used for the prevention and treatment of radiotherapy- and chemotherapy-induced stomatitis and mucositis in a number of studies, but the results are contradictory. To answer such discrepancies, the present study was designed to evaluate the efficacy of sucralfate mouthwash in prevention of 5-fluorouracil (5-FU)-induced oral mucositis in patients with gastrointestinal malignancies. Patients with gastrointestinal cancers receiving 5-FU-based chemotherapy regimens were included in this randomized, blinded, controlled trial and were randomly allocated to either sucralfate mouthwash (every 6 h) or placebo. The patients were visited at fifth and tenth day of trial; the presence and severity of oral mucositis and the intensity of pain were assessed. The patients receiving sucralfate experienced lower frequency and severity of mucositis (76% vs. 38.5%, P = 0.005 and 84 vs. 38.5%, P < 0.001, respectively) and less intense pain (2.5 ± 2.2 vs. 5.08 ± 3.82, P = 0.004 and 1.33 ± 0.86 vs. 4.12 ± 3.5, P = 0.001, respectively) compared with the placebo group both at day 5 and day 10. Within the sucralfate group, a decrease in frequency and severity of mucositis was observed throughout the trial period, while in the placebo group no such effect was observed. Sucralfate mouthwash reduced the frequency and severity of 5-FU-induced oral mucositis in patients with gastrointestinal malignancies compared with placebo, indicating its efficacy in the prevention of chemotherapy-induced mucositis.

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

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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.

TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1

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Allam, Atef; Majji, Sai; Peachman, Kristina; Jagodzinski, Linda; Kim, Jiae; Ratto-Kim, Silvia; Wijayalath, Wathsala; Merbah, Melanie; Kim, Jerome H.; Michael, Nelson L.; Alving, Carl R.; Casares, Sofia; Rao, Mangala

2015-01-01

CD4+ T follicular helper cells (TFH) in germinal centers are required for maturation of B-cells. While the role of TFH-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of TFH (CXCR5+PD-1++) and precursor-TFH (CXCR5+PD-1+) cells. The majority of TFH-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of TFH-cells mainly in the Peyer’s patches and FRT. The novel finding of TFH-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study TFH-cells and to evaluate HIV-1 vaccines. PMID:26034905

Oral mucosal lesions and immune status in HIV-infected Indian children.

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Subramaniam, Priya; Kumar, Krishna

2015-04-01

Pediatric HIV is growing at an alarming rate in developing countries. Due to their compromised immune status, children infected with HIV are prone to a number of opportunistic infections. Oral manifestations are the first signs of the disease in many of them. To assess the oral mucosal status of Indian children with HIV, based on their CD4 cell counts. Two hundred and twenty one HIV infected children aged 6-18 years from various HIV centers, were divided into three groups, based on their CD4 cell counts; Group 1: ≥500, Group 2: 201-499 and Group 3: ≤200 cells. The children in each group were further considered as 'prior to antiretroviral treatment (ART)' and 'on ART'. Oral mucosal examination was done based on presumptive criteria given by Ramos-Gomez for diagnosis of oro-facial lesions commonly associated with HIV infection in children. Data obtained was subjected to statistical analysis. Angular cheilitis and pseudomembranous candidiasis were the frequently seen oral lesions. Children with CD4 cell count ≥500 had significantly fewer oral lesions each. A high percentage of HIV-infected children were affected with oral mucosal lesions. There was a significant association between immune status and frequency of oral lesions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Duodenal mucosal protein kinase C-δ regulates glucose production in rats.

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Kokorovic, Andrea; Cheung, Grace W C; Breen, Danna M; Chari, Madhu; Lam, Carol K L; Lam, Tony K T

2011-11-01

Activation of protein kinase C (PKC) enzymes in liver and brain alters hepatic glucose metabolism, but little is known about their role in glucose regulation in the gastrointestinal tract. We investigated whether activation of PKC-δ in the duodenum is sufficient and necessary for duodenal nutrient sensing and regulates hepatic glucose production through a neuronal network in rats. In rats, we inhibited duodenal PKC and evaluated whether nutrient-sensing mechanisms, activated by refeeding, have disruptions in glucose regulation. We then performed gain- and loss-of-function pharmacologic and molecular experiments to target duodenal PKC-δ; we evaluated the impact on glucose production regulation during the pancreatic clamping, while basal levels of insulin were maintained. PKC-δ was detected in the mucosal layer of the duodenum; intraduodenal infusion of PKC inhibitors disrupted glucose homeostasis during refeeding, indicating that duodenal activation of PKC-δ is necessary and sufficient to regulate glucose homeostasis. Intraduodenal infusion of the PKC activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) specifically activated duodenal mucosal PKC-δ and a gut-brain-liver neuronal pathway to reduce glucose production. Molecular and pharmacologic inhibition of duodenal mucosal PKC-δ negated the ability of duodenal OAG and lipids to reduce glucose production. In the duodenal mucosa, PKC-δ regulates glucose homeostasis. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Use of {sup 60}Co panoramic source in the induction of oral mucositis in rats

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Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M., E-mail: mairandrade@yahoo.com, E-mail: zezell@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Correa, Luciana, E-mail: lcorrea@usp.br [Universidade de Sao Paulo (FO/USP), Sao Paulo, SP (Brazil). Fac. de Odontologia

2013-07-01

Oral Mucositis is a well-known side effect of chemo-radiotherapy in cancer patients or transplant recipients that could induce hospitalization or impairs therapy in different levels of severity. This study is devoted to define the first steps in the research of low level laser treatments in oral mucositis, proposing a {sup 60}Co radiation to experimentally induce oral mucositis in rats using Panoramic gamma irradiator, simulating usual radiotherapy of head and neck cancer. Fifteen male Wistar rats, above 250g, were irradiated at Centro de Tecnologia das Radiacoes (IPEN - CNEN/SP) and divided in three experimental groups, with different single doses of radiation (30 Gy, 25 Gy and 20 Gy). The animals were observed for a 20 days period. Animals that received 30 Gy and 25 Gy developed greater severity of mucositis and premature euthanasia was performed in these groups on the 7th and 11th day after the irradiation, respectively. The 20 Gy group developed oral mucositis grading from moderated to severe between the days 7 and 11 after irradiation, with progressive body mass loss and decrease in the intake of food and water. These animals recovered from oral mucositis around the 18th day and clinical remission at the 20th day. The single dose of 20 Gy Gamma radiation proved to be efficient way for inducing oral mucositis in rats, allowing the establishment of an experimental model for oral mucositis in rats for future use on interventions of this serious aspect of radiation therapy, such as laser therapy using different wave lengths and power densities. (author)

A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans.

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Jeffrey Tomalka

2011-12-01

Full Text Available Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1β production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell recruitment to infected tissues, as well as protects against systemic dissemination of infection. Deficiency in either NLRC4 or NLRP3 results in severely attenuated pro-inflammatory and antimicrobial peptide responses in the oral cavity. Using bone marrow chimeric mouse models, we show that, in contrast to NLRP3 which limits the severity of infection when present in either the hematopoietic or stromal compartments, NLRC4 plays an important role in limiting mucosal candidiasis when functioning at the level of the mucosal stroma. Collectively, these studies reveal the tissue specific roles of the NLRP3 and NLRC4 inflammasome in innate immune responses against mucosal Candida infection.

Radio and chemioinduced oral mucositis treatment: comparison between conventional drug protocol and treatments with low intensity lasers

International Nuclear Information System (INIS)

Alencar, Anelise Ribeiro Peixoto

2011-01-01

In this clinical study verified the effects of low intensity laser in the prevention and treatment of oral mucositis radio and/or chemical induced. Thirty one patients with head and neck cancer were selected before being submitted to cancer exclusive radiotherapy or radio and associated chemotherapy. The patients were distributed into three randomly groups as follows: group 1- (control) conventional medicine treatment; group 2 - conventional medicine treatment and daily laser therapy as soon as grade two oral mucositis appeared; group 3 - conventional medicine treatment and daily laser therapy to be initiated immediately before radiotherapy sessions.The irradiation parameters were: wavelength of 660nm, potency of 100mW, continuous mode, punctual application, 2J energy on thirty pre-determined 30 points, with 20s of exposure per point. The control group received medical treatment which consisted in using a set of preventive and therapeutic approach for acute radiation-induced adverse effects. Results were evaluated observing occurrence and grade of oral mucositis, score of pain, loss of body mass, use of nasogastric sound line, internment and interruption of oncologic treatment due to oral mucositis. The results showed that the preventive protocol as used was the most effective in prevention and treatment of oral mucositis and that its daily application contributed in relieving the painful symptomatology so collaborating to maintain and/or bettering the life quality of oncologic patients. (author)

Eosinophils express muscarinic receptors and corticotropin-releasing factor to disrupt the mucosal barrier in ulcerative colitis.

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Wallon, Conny; Persborn, Mats; Jönsson, Maria; Wang, Arthur; Phan, Van; Lampinen, Maria; Vicario, Maria; Santos, Javier; Sherman, Philip M; Carlson, Marie; Ericson, Ann-Charlott; McKay, Derek M; Söderholm, Johan D

2011-05-01

Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropin-releasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers ((51)Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), α-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Summary report of the 20th IAEA fusion energy conference (November 1-6, 2004, Vilamoura, Portugal)

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NONE

2005-09-01

Fusion Energy Conference has been held aiming to report and exchange the information concerning the nuclear fusion research every two years since 1961 by IAEA. The conference has authorities most in the field of the fusion research. The 20th Fusion Energy Conference was held at Vilamoura in Portugal on November 1st through 6th in 2004, and 700 researchers or more participated in the conference from 35 countries. This report is a summary of the conference that the JAERI researchers who participated in this conference (35 persons in total) have seen presentations of each contributed papers at the conference room and have understood from each point of view. The contents of this report are very comprehensible, because those are written from the viewpoint of each researchers of JAERI. The purpose of this report is to provide the information which is useful for many researchers to understand the latest study results over a wide field of fusion research. (author)

Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

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Blandizzi, Corrado; Fornai, Matteo; Colucci, Rocchina; Natale, Gianfranco; Lubrano, Valter; Vassalle, Cristina; Antonioli, Luca; Lazzeri, Gloria; Tacca, Mario Del

2005-01-01

AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 µmol/kg), diclofenac (60 µmol/kg), piroxicam (150 µmol/kg) or ketoprofen (150 µmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 µmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 µmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 µmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 µmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 µmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID

Mucosal immunization with live attenuated Francisella novicida U112ΔiglB protects against pulmonary F. tularensis SCHU S4 in the Fischer 344 rat model.

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Aimee L Signarovitz

Full Text Available The need for an efficacious vaccine against Francisella tularensis is a consequence of its low infectious dose and high mortality rate if left untreated. This study sought to characterize a live attenuated subspecies novicida-based vaccine strain (U112ΔiglB in an established second rodent model of pulmonary tularemia, namely the Fischer 344 rat using two distinct routes of vaccination (intratracheal [i.t.] and oral. Attenuation was verified by comparing replication of U112ΔiglB with wild type parental strain U112 in F344 primary alveolar macrophages. U112ΔiglB exhibited an LD(50>10(7 CFU compared to the wild type (LD(50 = 5 × 10(6 CFU i.t.. Immunization with 10(7 CFU U112ΔiglB by i.t. and oral routes induced antigen-specific IFN-γ and potent humoral responses both systemically (IgG2a>IgG1 in serum and at the site of mucosal vaccination (respiratory/intestinal compartment. Importantly, vaccination with U112ΔiglB by either i.t. or oral routes provided equivalent levels of protection (50% survival in F344 rats against a subsequent pulmonary challenge with ~25 LD(50 (1.25 × 10(4 CFU of the highly human virulent strain SCHU S4. Collectively, these results provide further evidence on the utility of a mucosal vaccination platform with a defined subsp. novicida U112ΔiglB vaccine strain in conferring protective immunity against pulmonary tularemia.

Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene