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Sample records for rat oral mucosa

  1. The effect of cola consumption on oral mucosa in rats.

    PubMed

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

    2000-01-01

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

  2. Biomechanics of oral mucosa

    PubMed Central

    Chen, Junning; Ahmad, Rohana; Li, Wei; Swain, Michael; Li, Qing

    2015-01-01

    The prevalence of prosthodontic treatment has been well recognized, and the need is continuously increasing with the ageing population. While the oral mucosa plays a critical role in the treatment outcome, the associated biomechanics is not yet fully understood. Using the literature available, this paper provides a critical review on four aspects of mucosal biomechanics, including static, dynamic, volumetric and interactive responses, which are interpreted by its elasticity, viscosity/permeability, apparent Poisson's ratio and friction coefficient, respectively. Both empirical studies and numerical models are analysed and compared to gain anatomical and physiological insights. Furthermore, the clinical applications of such biomechanical knowledge on the mucosa are explored to address some critical concerns, including stimuli for tissue remodelling (interstitial hydrostatic pressure), pressure–pain thresholds, tissue displaceability and residual bone resorption. Through this review, the state of the art in mucosal biomechanics and their clinical implications are discussed for future research interests, including clinical applications, computational modelling, design optimization and prosthetic fabrication. PMID:26224566

  3. Dynamic changes in cell-surface expression of mannose in the oral epithelium during the development of graft-versus-host disease of the oral mucosa in rats

    PubMed Central

    2014-01-01

    Background The role of cell-surface glycoconjugates in oral mucosal graft-versus-host disease (GVHD) is still unclear, even though molecular changes in the oral epithelium are essential for the pathogenesis of these lesions. In this study, we investigated changes in the binding of mannose (Man)-specific Lens culinaris lectin (LCA) in the oral mucosa of rats with GVHD. Methods Lewis rat spleen cells were injected into (Lewis x Brown Norway) F1 rats to induce systemic GVHD, including oral mucosal lesions. Tongue and spleen samples were evaluated using lectin histochemistry, immunohistochemistry, Western blotting, transwell migration assays and Stamper-Woodruff binding assays. Results Binding of Man-specific LCA expanded to the epithelial layers of the tongue in GVHD-rats. An expansion of LCA binding was related to the increased expression of mannosyltransferase in the oral mucosa. CD8+ cells, effector cells of oral mucosal GVHD, expressed mannose-binding protein (MBP) and migrated to the medium containing Man in the transwell migration assay. Adherence of CD8+ cells to the oral epithelium could be inhibited by pretreating CD8+ cells with MBP antibody and/or by pretreating sections with Man-specific LCA. Conclusions Increased expression of Man on keratinocytes leads to the migration and/or adhesion of CD8+ cells in the surface epithelium, which is mediated in part by the MBP/Man-binding pathway during the development of oral mucosal GVHD. PMID:24433462

  4. Hyperplasia of gastric mucosa in donor rats orally infected with Taenia taeniaeformis eggs and in recipient rats surgically implanted with the larvae in the abdominal cavity.

    PubMed

    Konno, K; Oku, Y; Nonaka, N; Kamiya, M

    1999-06-01

    Rats heavily infected with Taenia taeniaeformis larvae in the liver show a remarkable increase in their stomach weight, hyperplasia, and hypergastrinemia. However, it is unknown what causes these phenomena. Hence, as a preliminary study to investigate the importance of larval parasitism in the liver, two experiments were done. In the first experiment, 14 donor rats were orally inoculated with 3,000 T. taeniaeformis eggs. In the second experiment, 136-300 of the larvae obtained from the rats were surgically implanted into the abdominal cavity of 7 recipient rats. Gastrin levels and histopathological changes in the gastric mucosa were investigated. In all, 11 donor rats showed hypergastrinemia and hyperplasia, 5 recipient rats showed gastric mucosal hyperplasia accompanied by excessive mucous cell proliferation, and 2 recipient rats showed hypergastrinemia. These results suggest that parasitism of the liver by the larvae is not essential for the development of hyperplasia and that factors from the larvae might cause these phenomena.

  5. Genotoxic effect of chronic exposure to DDT on lymphocytes, oral mucosa and breast cells of female rats.

    PubMed

    Canales-Aguirre, Alejandro; Padilla-Camberos, Eduardo; Gómez-Pinedo, Ulises; Salado-Ponce, Hugo; Feria-Velasco, Alfredo; De Celis, Ruth

    2011-02-01

    The genotoxicity of some environmental contaminants may affect human health directly by damaging genetic material and thus plays an important role in cancer development. Xenoestrogens are one kind of environmental pollutants that may alter hormonal routes or directly affect DNA. The number of available biomarkers used to assess genetic risk and cancer is very extensive. The present study evaluated genotoxicity produced by the pesticide DDT on systemic and mammary gland cells obtained from adult female Wistar rats. Oral mucosa cells micronuclei were assessed; the comet assay in peripheral blood-isolated lymphocytes and mammary epithelial cells was also carried out. Additionally, oxidative stress was studied in mammary tissue through a lipid peroxidation assay. Our data showed an increase in lipid peroxidation, product of an increase in free oxygen radical levels, which leads to an oxidative stress status. Our results suggest that DDT is genotoxic, not only for lymphocytes but also to mammary epithelial cells.

  6. Precancerous lesions of oral mucosa

    PubMed Central

    Yardimci, Gurkan; Kutlubay, Zekayi; Engin, Burhan; Tuzun, Yalcin

    2014-01-01

    Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaque-like, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary. The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used. PMID:25516862

  7. [Infections of the oral mucosa].

    PubMed

    Reibel, Jesper; Kragelund, Camilla

    2010-11-01

    The most common infections of the oral mucosa are those caused by Candida albicans and herpes simplex virus (HSV). Candidosis occurs as pseudomembraneous, erythematous and hyperplastic types with varying symptoms from no to a burning sensation. Treatment most importantly includes elimination of any predisposing factors such as smoking, sub-optimal denture hygiene and hyposalivation. A primary HSV infection results in a life-long latent infection recurring in some infected persons either intraorally or on the lip. If treatment is indicated, topical or systemic aciclovir and related drugs can be used.

  8. Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.

    PubMed

    Ribeiro, Daniel Araki; Fávero Salvadori, Daisy Maria; da Silva, Renata Nunes; Ribeiro Darros, Bruno; Alencar Marques, Mariangela Esther

    2004-10-01

    4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the level of DNA damage induced by 4NQO in oral mucosa cells by the single cell gel (comet) assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Statistically significant increase of DNA damage was observed in non-neoplastic oral cells at four weeks of 4NQO administration when compared with control (P < 0.05). The level of DNA damage was directly associated with the severity of histological changes. The results suggest that histologically normal tissue is able to harbor genetically unstable cells contributing to the initiation of oral carcinogenesis. Genomic instability appears to be associated with the risk and progression of oral cancer.

  9. Diseases of the Oral Mucosa

    PubMed Central

    Bradley, G.

    1988-01-01

    This article provides a clinical approach to the more common oral mucosal lesions. Histologic diagnoses are not included, apart from their use in diagnosis and management. In a small number of oral mucosal lesions, clinical appearance is sufficiently distinctive to permit accurate diagnosis, but a biopsy is usually necessary. Clinical appearance is important in directing further investigations such as culture and serologic testing. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:21253207

  10. [Bullous autoimmune diseases of the oral mucosa].

    PubMed

    Vaillant, L

    1999-10-01

    Autoimmune bullous diseases (AIBD) are characterized by autoantibodies targeted against adhesion molecules, impairing their formation. According to localization criteria, pemphigus (intraepidermal blister and desmosomal involvement) and pemphigoid (subepidermal blister and dermoepidermal junction involvement) can be distinguished. In two-thirds of the cases, pemphigus vulgaris begins with oral lesions (mainly the buccal mucosa and palate, rarely the gingiva). Skin lesions are usual. Excepting paraneoplastic pemphigus (a recently individualized entity), oral lesions are uncommon in other types of pemphigus. Cicatricial pemphigoid mainly involves oral mucosa, frequently other mucous membranes, and rarely the skin. Gingival involvement is frequent. In case of desquamative gingivitis, the clip sign gives the diagnosis of cicatricial pemphigoid. Ocular involvement is frequent and causes blindness. Epidermolysis bullosa acquisita and IgA linear dermatosis are rare. Bullous pemphigoid and bullous lupus rarely involve the oral mucosa. Diagnosis of AIBD requires a biopsy within the mucosal membrane lesion for pathology examination and another biopsy in a lesion-free area for direct immunofluorescence detection of antibody fixation. Immunoelectron microscopy or immunoblast transfer may be needed for positive diagnosis. Corticosteroids are used to treat pemphigus and dapsone is used for cicatricial pemphigoid. Immunosuppressive therapy is rarely needed.

  11. A disguised tuberculosis in oral buccal mucosa.

    PubMed

    Nanda, Kanwar Deep Singh; Mehta, Anurag; Marwaha, Mohita; Kalra, Manpreet; Nanda, Jasmine

    2011-01-01

    Tuberculosis is a major cause of morbidity and mortality worldwide. It is a chronic granulomatous disease that can affect any part of the body, including the oral cavity. Oral lesions of tuberculosis, though uncommon, are seen in both the primary and secondary stages of the disease. This article presents a case of tuberculosis of the buccal mucosa, manifesting as non-healing, non-painful ulcer. The diagnosis was confirmed based on histopathology, sputum examination and immunological investigation. The patient underwent anti-tuberculosis therapy and her oral and systemic conditions improved rapidly. Although oral manifestations of tuberculosis are rare, clinicians should include them in the differential diagnosis of various types of oral ulcers. An early diagnosis with prompt treatment can prevent complications and potential contaminations.

  12. Assessment of the mutagenic potential of Cr(VI) in the oral mucosa of Big Blue® transgenic F344 rats.

    PubMed

    Thompson, Chad M; Young, Robert R; Suh, Mina; Dinesdurage, Harshini R; Elbekai, Reem H; Harris, Mark A; Rohr, Annette C; Proctor, Deborah M

    2015-08-01

    Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water was associated with an increased incidence of oral tumors in F344 rats in a 2-year cancer bioassay conducted by the National Toxicology Program. These tumors primarily occurred at 180 ppm Cr(VI) and appeared to originate from the gingival mucosa surrounding the upper molar teeth. To investigate whether these tumors could have resulted from a mutagenic mode of action (MOA), a transgenic mutation assay based on OECD Test Guideline 488 was conducted in Big Blue(®) TgF344 rats. The mutagenic oral carcinogen 4-nitroquinoline-1-oxide (4-NQO) served as a positive control. Mutant frequency was measured in the inner gingiva with adjacent palate, and outer gingiva with adjacent buccal tissue. Exposure to 10 ppm 4-NQO in drinking water for 28 days increased mutant frequency in the cII transgene significantly, from 39.1 ± 7.5 × 10(-6) to 688 ± 250 × 10(-6) in the gingival/buccal region, and from 49.8 ± 17.8 × 10(-6) to 1818 ± 362 × 10(-6) in the gingival/palate region. Exposure to 180 ppm Cr(VI) in drinking water for 28 days did not significantly increase the mutant frequency in the gingival/buccal (44.4 ± 25.4 × 10(-6)) or the gingival/palate (57.8 ± 9.1 × 10(-6)) regions relative to controls. These data indicate that high (∼180,000 times expected human exposure), tumorigenic concentrations of Cr(VI) did not significantly increase mutations in the gingival epithelium, and suggest that Cr(VI) does not act by a mutagenic MOA in the rat oral cavity.

  13. [Optimizing biopsies of the oral mucosa].

    PubMed

    Raybaud, H; Voha, C; Cardot-Leccia, N; Monteil, R A

    2012-11-01

    We had for aim to describe and illustrate the artefacts observed in biopsies of the oral mucosa, as well as the impact of sending non-representative histological material to a laboratory. This article was based on an international literature review, as well as on our experience. We analysed the problems raised, for the pathologists and the histology lab-technicians, by these artefacts as well as their impact on the pathology report patient management. We suggest simple solutions.

  14. [Oral medicine 8. Leukoplakia of the oral mucosa].

    PubMed

    Schepman, K P; van der Meij, E H; de Visscher, J G A M

    2013-01-01

    Leukoplakia of the oral mucosa is a potentially malignant disorder, which means that there is an elevated risk oftransformation into a squamous cell carcinoma. The term oral leukoplakia is a clinical diagnosis for a predominantly white lesion which is not immediately recognizable as another well definable lesion which is white in appearance. Oral leukoplakia is generally an asymptomatic disorder of the mucosa with a prevalence of less than 2 per cent in the adult population. Tobacco usage is considered to be the most important etiological factor. Malignant transformation into a squamous cell carcinoma occurs in about I per cent per year. A patient with oral leukoplakia is generally referred to an oral and maxillofacial surgeon, who takes a biopsy for a definitive histopathological diagnosis. The outcome of the histopathological study, which may vary from hyperkeratosis to invasive squamous cell carcinoma, will determine the treatment. It is preferable that every leukoplakia is removed to reduce the risk of malignant transformation. Long term follow-up is indicated. Follow-up may in some cases be performed by the general dental practitioner.

  15. A standard picture of healthy oral mucosae by direct oral microscopy

    PubMed Central

    Drogoszewska, Barbara; Michcik, Adam; Polcyn, Adam

    2013-01-01

    Introduction Direct oral microscopy constitutes a novel technique of in vivo oral mucosae examination. The basic principles of this method derive from colposcopy and dermoscopy. The main goal of direct oral microscopy is the earliest possible detection of oral precancerous lesions in order to implement their treatment as quickly as possible and prevent malignant transformation. Aim To establish a standard picture of healthy oral mucosae with direct oral microscopy applying standard colposcopic criteria in order to create a reference point for further diagnosis of precancerous lesions. Material and methods Thirty patients of both genders with clinically unaltered oral mucosae were examined. For every individual, clinical examination with the naked eye was performed, followed by direct oral microscopy with colposcopic assessment criteria. Oral mucosae at various sites (lip, cheek, floor of mouth, ventral and lateral sides of the tongue, alveolar ridge and soft palate) were examined. Results Subepithelial blood vessel patterns, mucosal surface, colour tone and transparency were described for healthy oral mucosae. Moreover, cases with clinically unaltered oral mucosae where direct oral microscopy revealed subclinical alterations were described. Conclusions Direct oral microscopy with colposcopic assessment criteria enables establishment of a repeated picture of unaltered oral mucosae. The standard picture of healthy oral mucosae is an essential reference point for application of this technique to early diagnose potentially malignant oral mucosal lesions as well as apply their early treatment. PMID:24278068

  16. Optical detection of (pre-)malignant lesions of the oral mucosa: autofluorescence characteristics of healthy mucosa

    NASA Astrophysics Data System (ADS)

    de Veld, Diana C. G.; Witjes, Max; Roodenburg, Jan L.; Star, Willem M.; Sterenborg, Hericus J. C. M.

    2001-10-01

    Previous clinical results demonstrate the potential of in vivo autofluorescence spectroscopy for early detection of (pre-)malignant lesions of the oral mucosa. For reliable diagnosis, it is necessary to study autofluorescence spectra of healthy mucosa first. We measured excitation-emission maps in healthy subjects and subjects with a history of cancer in the head -neck region. Our results show that different anatomical locations produce distinct autofluorescence spectra. Influences of, among others, smoking and drinking habits require further investigation.

  17. Lichen sclerosus of the oral mucosa: a case report.

    PubMed

    Jiménez, Yolanda; Gavaldá, Carmen; Carbonell, Enrique; Margaix, María; Sarrión, Gracia

    2008-07-01

    Lichen sclerosus or lichen sclerosus et atrophicus is a chronic inflammatory disease predominantly affecting the genital mucosa and skin. Clinically, it is characterized by white atrophic plaques in the anogenital region. The lesions are generally asymptomatic, but may cause discomfort with itching and pain. Extragenital mucosal involvement is very unusual, and lesions limited to the oral mucosa are even less frequent. Knowledge of such lesions is important in order to establish a differential diagnosis with other white oral lesions, and histological confirmation is required. We present the case of a 31-year-old woman with a well delimited, pearly white lesion located in the upper gingival mucosa, lip mucosa and adjacent skin. The lesion had led to loss of periodontal attachment of the affected tooth, causing pain in response to tooth brushing. The biopsy confirmed lichen sclerosus, and treatment was provided in the form of intralesional corticoid injections, followed by improvement of the mucosal lesion, though without recovery of the periodontal loss.

  18. Oral lining mucosa development depends on mesenchymal microRNAs.

    PubMed

    Otsuka-Tanaka, Y; Oommen, S; Kawasaki, M; Kawasaki, K; Imam, N; Jalani-Ghazani, F; Hindges, R; Sharpe, P T; Ohazama, A

    2013-03-01

    The oral mucosa plays critical roles in protection, sensation, and secretion and can be classified into masticatory, lining, and specialized mucosa that are known to be functionally, histologically, and clinically distinct. Each type of oral mucosa is believed to develop through discrete molecular mechanisms, which remain unclear. MicroRNAs (miRNAs) are 19 to 25nt non-coding small single-stranded RNAs that negatively regulate gene expression by binding target mRNAs. miRNAs are crucial for fine-tuning of molecular mechanisms. To investigate the role of miRNAs in oral mucosa development, we examined mice with mesenchymal (Wnt1Cre;Dicer(fl/fl)) conditional deletion of Dicer. Wnt1Cre;Dicer(fl/fl) mice showed trans-differentiation of lining mucosa into an epithelium with masticatory mucosa/ skin-specific characteristics. Up-regulation of Fgf signaling was found in mutant lining mucosal epithelium that was accompanied by an increase in Fgf7 expression in mutant mesenchyme. Mesenchyme miRNAs thus have an indirect effect on lining mucosal epithelial cell growth/differentiation.

  19. Nested PCR for detection of HSV-1 in oral mucosa

    PubMed Central

    Jalouli, Miranda-Masoumeh; Jalouli, Jamshid; Hasséus, Bengt; Öhman, Jenny; Hirsch, Jan-Michaél

    2015-01-01

    Background It has been estimated that 15%-20% of human tumours are driven by infection and inflammation, and viral infections play an important role in malignant transformation. The evidence that herpes simplex virus type 1 (HSV-1) could be involved in the aetiology of oral cancer varies from weak to persuasive. This study aimed to investigate by nested PCR (NPCR) the prevalence of HSV-1 in samples from normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma (OSCC). Material and Methods We investigated the prevalence of HSV-1 in biopsies obtained from 26 fresh, normal oral mucosa from healthy volunteers as well as 53 oral leukoplakia and 27 OSCC paraffin-embedded samples. DNA was extracted from the specimens and investigated for the presence of HSV-1 by nested polymerase chain reaction (NPCR) and DNA sequencing. Results HSV-1 was detected in 14 (54%) of the healthy samples, in 19 (36%) of the oral leukoplakia samples, and in 14 (52%) of the OSCC samples. The differences were not statistically significant. Conclusions We observed a high incidence of HSV-1 in healthy oral mucosa, oral leukoplakia, and OSCC tissues. Thus, no connection between OSCC development and presence of HSV-1 was detected. Key words:HSV-1, nested PCR, PCR. PMID:26449432

  20. [Oral mucosa reaction in patients adapting to removable dentures].

    PubMed

    Iordanishvili, A K; Soldatova, L N; Pikhur, O L; Mikhailova, E S; Peremyshlenko, A S; Soldatov, V S

    2016-01-01

    Oral mucosa reaction of prosthetic bed to the removable acrylic dentures was evaluated in 43 patients (12 male and 31 female) aged 56-69 years with partial and full teeth loss in one or both jaws. Patients of the first (control) group (17 patients) were not using additional tools improving fixation of the removable dentures during adaptation period, while patients of the second (main) group (26 patients) used Corega cream for dentures fixation for 30 days follow-up. Oral mucosa assessment was carried out on 3-4 and 28-30 day of dentures use by 3 end points: pain syndrome, moisture level, inflammation of a prosthetic bed. The results proved Corega cream to improve prosthetic bed mucosa condition reducing inflammatory response to polymeric materials of removable dentures basis.

  1. Immunohistochemistry of lymphocytes in benign lymphoadenosis of oral mucosa.

    PubMed

    Li, S-X; Li, Q; Yang, Y-Q; Jin, L-J; Sun, Z; Yu, S-F

    2015-06-29

    Benign lymphoadenosis of oral mucosa (BLOM) is a common oral mucosa disease and may be regarded as a precancerous lesion. However, the association between its biological behavior and lymphocyte distribution remains unclear. Therefore, to investigate the characteristics of BLOM, we studied the infiltration of lymphocytes associated with it. The expression levels of CD74, CD20, CD3, and CD45RO were evaluated by immunohistochemical staining in 14 sam-ples from BLOM, 9 samples from BLOM with atypia hyperplasia, 11 samples from BLOM with canceration, and 10 samples from normal oral mucosa tissues. The results were analyzed by two-sample t-test using SPSS 10.0 for Windows, and P < 0.05 was considered to be sig-nificant. In normal oral mucosa, positive expression levels of CD3 and CD45RO were presented in the extra-lymphoid follicle, and the expres-sion levels of CD74 and CD20 were negative. In all BLOM groups, the expression level of CD20 was positive except for one case of BLOM with canceration; the expression levels of CD74 were all positive. Posi-tive expression levels of CD3 and CD45RO could be found not only in extra-lymphoid follicles but also in inner-lymphoid follicles in the BLOM groups. The expression levels of CD74 and CD20 in extra-lym-phoid follicles, and CD3 and CD45RO in inner-lymphoid follicles in BLOM were significantly higher than in BLOM with canceration. The infiltrated lymphocytes in BLOM comprise T- and B-cells. This indi-cates that the lymphoid tissue in BLOM is mucosa-associated lymphoid tissue and BLOM is a proliferative lesion.

  2. Raman microspectroscopic study of oral buccal mucosa

    NASA Astrophysics Data System (ADS)

    Behl, Isha; Mamgain, Hitesh; Deshmukh, Atul; Kukreja, Lekha; Hole, Arti R.; Krishna, C. Murali

    2014-03-01

    Oral cancer is the most common cancer among Indian males, with 5-year- survival-rates of less than 50%. Efficacy of Raman spectroscopic methods in non-invasive and objective diagnosis of oral cancers and confounding factors has already been demonstrated. The present Raman microspectroscopic study was undertaken for in-depth and site-specific analysis of normal and tumor tissues. 10 normal and 10 tumors unstained sections from 20 tissues were accrued. Raman data of 160 x 60 μm and 140 x 140 μm in normal and tumor sections, respectively, were acquired using WITec alpha 300R equipped with 532 nm laser, 50X objective and 600 gr/mm grating. Spectral data were corrected for CCDresponse, background. First-derivitized and vector-normalized data were then subjected to K-mean cluster analysis to generate Raman maps and correlated with their respective histopathology. In normal sections, stratification among epithelial layers i.e. basal, intermediate, superficial was observed. Tumor, stromal and inflammatory regions were identified in case of tumor section. Extracted spectra of the pathologically annotated regions were subjected to Principal component analysis. Findings suggest that all three layers of normal epithelium can be differentiated against tumor cells. In epithelium, basal and superficial layers can be separated while intermediate layer show misclassifications. In tumors, discrimination of inflammatory regions from tumor cells and tumor-stroma regions were observed. Finding of the study indicate Raman mapping can lead to molecular level insights of normal and pathological states.

  3. [Oral medicine 9. Lichen planus and lichenoid lesions of the oral mucosa].

    PubMed

    van der Meij, E H; Schepman, K P; de Visscher, J G A M

    2013-09-01

    The general dentist is sometimes confronted with white lesions of the oral mucosa. Oral lichen planus is the most common oral white lesion. The diagnosis can usually be made on the basis of the clinical aspect, but is sometimes made more difficult by certain abnormalities in the oral mucosa which clinically resemble oral lichen planus or by abnormalities which cannot be distinguished from oral lichen planus but have a different origin. Those lesions are classified as oral lichenoid lesions. Malignant deterioration has been described in allforms of oral lichen planus lesions and oral lichenoid lesions. There is no known method to predict or prevent malignant transformation. Nor are there any studies examining the efficacy of frequent follow-up visits. It seems sensible, in keeping with the tendency in recent literature, to schedule annual check-ups for patients to be on the safe side. These follow-up visits may reasonably be performed in a general dental practice.

  4. Epithelial-mesenchymal interactions as a working concept for oral mucosa regeneration.

    PubMed

    Liu, Jiarong; Mao, Jeremy J; Chen, Lili

    2011-02-01

    Oral mucosa consists of two tissue layers, the superficial epithelium and the underlying lamina propria. Together, oral mucosa functions as a barrier against exogenous substances and pathogens. In development, interactions of stem/progenitor cells of the epithelium and mesenchyme are crucial to the morphogenesis of oral mucosa. Previous work in oral mucosa regeneration has yielded important clues for several meritorious proof-of-concept approaches. Tissue engineering offers a broad array of novel tools for oral mucosa regeneration with reduced donor site trauma and accelerated clinical translation. However, the developmental concept of epithelial-mesenchymal interactions (EMIs) is rarely considered in oral mucosa regeneration. EMIs in postnatal oral mucosa regeneration likely will not be a simple recapitulation of prenatal oral mucosa development. Biomaterial scaffolds play an indispensible role for oral mucosa regeneration and should provide a conducive environment for pivotal EMIs. Autocrine and paracrine factors, either exogenously delivered or innately produced, have rarely been and should be harnessed to promote oral mucosa regeneration. This review focuses on a working concept of epithelial and mesenchymal interactions in oral mucosa regeneration.

  5. [Tobacco-associated lesions of the oral mucosa].

    PubMed

    Bornstein, Michael M; Klingler, Karl; Saxer, Ulrich P; Walter, Clemens; Ramseier, Christoph A

    2006-01-01

    Consumption of tobacco can result not only in a multitude of different general health problems like carcinoma of the lung, ischaemic cardiac diseases, peripheral vascular diseases, stroke, chronic-obstructive pulmonary diseases or peptic ulcers, but also in pathologic lesions of the oral mucosa. Benign oral lesions from smoking or consumption of smokeless tobacco are the so-called smoker's palate and smoker's melanosis. On the other hand, tobacco-associated lesions like oral leukoplakia or oral squamous cell carcinoma are already potentially life-threatening diseases that in general require active treatment. The following review article will present and discuss the typical lesions of the oral mucosa that result from chronic tobacco consumption. The aim of this article is to demonstrate dental health care providers the needs and benefits of tobacco use cessation in a dental setting, especially regarding stomatologic sequelae and consequences. The present article is the first in a series of articles from the Swiss task force "Smoking - Intervention in the private dental office" on the topic "tobacco use and dental medicine".

  6. Comparative proteomics of paired vocal fold and oral mucosa fibroblasts

    PubMed Central

    Karbiener, Michael; Darnhofer, Barbara; Frisch, Marie-Therese; Rinner, Beate; Birner-Gruenberger, Ruth; Gugatschka, Markus

    2017-01-01

    Injuries of the vocal folds frequently heal with scar formation, which can have lifelong detrimental impact on voice quality. Current treatments to prevent or resolve scars of the vocal fold mucosa are highly unsatisfactory. In contrast, the adjacent oral mucosa is mostly resistant to scarring. These differences in healing tendency might relate to distinct properties of the fibroblasts populating oral and vocal fold mucosae. We thus established the in vitro cultivation of paired, near-primary vocal fold fibroblasts (VFF) and oral mucosa fibroblasts (OMF) to perform a basic cellular characterization and comparative cellular proteomics. VFF were significantly larger than OMF, proliferated more slowly, and exhibited a sustained TGF-β1-induced elevation of pro-fibrotic interleukin 6. Cluster analysis of the proteomic data revealed distinct protein repertoires specific for VFF and OMF. Further, VFF displayed a broader protein spectrum, particularly a more sophisticated array of factors constituting and modifying the extracellular matrix. Conversely, subsets of OMF-enriched proteins were linked to cellular proliferation, nuclear events, and protection against oxidative stress. Altogether, this study supports the notion that fibroblasts sensitively adapt to the functional peculiarities of their respective anatomical location and presents several molecular targets for further investigation in the context of vocal fold wound healing. Biological significance Mammalian vocal folds are a unique but delicate tissue. A considerable fraction of people is affected by voice problems, yet many of the underlying vocal fold pathologies are sparsely understood at the molecular level. One such pathology is vocal fold scarring - the tendency of vocal fold injuries to heal with scar formation -, which represents a clinical problem with highly suboptimal treatment modalities. This study employed proteomics to obtain comprehensive insight into the protein repertoire of vocal fold

  7. Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis.

    PubMed

    Yadev, Nishant P; Murdoch, Craig; Saville, Stephen P; Thornhill, Martin H

    2011-06-01

    Candida albicans is a commensal organism that can be isolated from the majority of healthy individuals. However, in certain susceptible individuals C. albicans can become pathogenic leading to the mucocutaneous infection; oral candidiasis. Murine models and in vitro monolayer cultures have generated some data on the likely virulence and host factors that contribute to oral candidiasis but these models have limitations. Recently, tissue engineered oral mucosal models have been developed to mimic the normal oral mucosa but little information is available on their true representation. In this study, we assessed the histological features of three different tissue engineered oral mucosal models compared to the normal oral mucosa and analysed both cell damage and cytokine release following infection with C. albicans. Models comprised of normal oral keratinocytes and a fibroblast-containing matrix displayed more similar immunohistological and proliferation characteristics to normal mucosa, compared to models composed of an oral carcinoma cell line. Although all models were invaded and damaged by C. albicans in a similar manner, the cytokine response was much more pronounced in models containing normal keratinocytes. These data suggest that models based on normal keratinocytes atop a fibroblast-containing connective tissue will significantly aid in dissecting the molecular pathogenesis of oral candidiasis.

  8. Phenotype and Tissue Residency of Lymphocytes in the Murine Oral Mucosa

    PubMed Central

    Park, Joo-Young; Chung, Hyunsoo; Choi, Youngnim; Park, Jung-Hyun

    2017-01-01

    The oral mucosa is a critical barrier tissue that harbors a series of distinct immune cell subsets. Immune surveillance in the oral mucosa is important for both local and systemic immunity because the oral cavity is a heavily utilized route of pathogen entry and also serves as site of pathogen propagation. Nonetheless, composition and phenotype of the lymphocyte pool in the oral mucosa have remained poorly characterized. Utilizing a newly established protocol for mucosal immune cell isolation, here, we report that the oral mucosa features a unique cellular composition of immune cells, which differed not only from secondary lymphoid organs but also from mucosal tissues in the gut and lung. We observed profound accumulation of CD11b+Ly6Clo monocytes in the oral mucosa that were maintained independently of T- and B-lymphocytes. Unlike the gut mucosa, the oral mucosa neither contained CD8αα T cells nor was it enriched for CD103+CD69+ tissue-resident memory CD8 T cells. In fact, a major fraction of T cells circulated and trafficked through the mucosa as revealed by treatment with the S1P1 receptor antagonist, FTY720, a potent inhibitor of lymphocyte migration. Collectively, these results provide a comprehensive picture of immune cells in the oral mucosa as an active site of lymphocyte recruitment and surveillance. PMID:28337201

  9. Epidemiology of oral HPV in the oral mucosa in women without signs of oral disease from Yucatan, Mexico

    PubMed Central

    Gonzalez-Losa, María del Refugio; Barrera, Ernesto Soria; Herrera-Pech, Verónica; Conde-Ferráez, Laura; Puerto-Solís, Marylin; Ayora-Talavera, Guadalupe

    2015-01-01

    High-risk human papillomaviruses (HR-HPV) are considered necessary for the development of cervical cancer. Furthermore, there is no doubt that some types of oral squamous cell carcinoma are associated with HR-HPV. The epidemiology of oral HPV infections in healthy subjects remains unclear due to a lack of knowledge. The objective of this study was to investigate the epidemiology of human papillomavirus infections of the oral mucosa without pathology. A cross-sectional study was performed; samples from 390 women seeking prenatal care, Pap smears, family planning or gynecological diseases were studied. Oral cells were collected by direct swab sampling. Information regarding sociodemographic status, sexual behavior, infectious diseases, contraceptive history and tobacco and alcohol consumption were obtained through direct interviews. HPV and genotypes were detected by type-specific polymerase chain reaction. Our results revealed that 14% of the women studied had an oral HPV infection. Women ≤ 20 years of age had the highest HPV prevalence (24.5%). In total, seven genotypes were identified, including the high-risk genotypes 16, 18, 58 and 59 and the low-risk genotypes 6, 81 and 13, the latter of which is a type exclusive to oral mucosa. Sexual behavior was not associated with the presence of genital HPV types in the oral mucosa. Genital HPV types were present in the oral mucosa of women without associated clinical manifestations; however, sexual behavior was not associated with infection, and therefore others routes of transmission should be explored. PMID:26221121

  10. Epidemiology of oral HPV in the oral mucosa in women without signs of oral disease from Yucatan, Mexico.

    PubMed

    Gonzalez-Losa, María Del Refugio; Barrera, Ernesto Soria; Herrera-Pech, Verónica; Conde-Ferráez, Laura; Puerto-Solís, Marylin; Ayora-Talavera, Guadalupe

    2015-03-01

    High-risk human papillomaviruses (HR-HPV) are considered necessary for the development of cervical cancer. Furthermore, there is no doubt that some types of oral squamous cell carcinoma are associated with HR-HPV. The epidemiology of oral HPV infections in healthy subjects remains unclear due to a lack of knowledge. The objective of this study was to investigate the epidemiology of human papillomavirus infections of the oral mucosa without pathology. A cross-sectional study was performed; samples from 390 women seeking prenatal care, Pap smears, family planning or gynecological diseases were studied. Oral cells were collected by direct swab sampling. Information regarding sociodemographic status, sexual behavior, infectious diseases, contraceptive history and tobacco and alcohol consumption were obtained through direct interviews. HPV and genotypes were detected by type-specific polymerase chain reaction. Our results revealed that 14% of the women studied had an oral HPV infection. Women ≤ 20 years of age had the highest HPV prevalence (24.5%). In total, seven genotypes were identified, including the high-risk genotypes 16, 18, 58 and 59 and the low-risk genotypes 6, 81 and 13, the latter of which is a type exclusive to oral mucosa. Sexual behavior was not associated with the presence of genital HPV types in the oral mucosa. Genital HPV types were present in the oral mucosa of women without associated clinical manifestations; however, sexual behavior was not associated with infection, and therefore others routes of transmission should be explored.

  11. [Pathology of the oral mucosa in patients with type I diabetes mellitus: study of 44 cases].

    PubMed

    Bagan Sebastian, J V; Gisbert Selles, C; Milian Masanet, A

    1988-01-01

    We study the pathology of the oral mucosa in a group of type I diabetics. The most common disease was oral candidiasis (9.09%), whereas the other pathologies encountered showed no significant differences with the controls.

  12. Raman mapping of oral buccal mucosa: a spectral histopathology approach

    NASA Astrophysics Data System (ADS)

    Behl, Isha; Kukreja, Lekha; Deshmukh, Atul; Singh, S. P.; Mamgain, Hitesh; Hole, Arti R.; Krishna, C. Murali

    2014-12-01

    Oral cancer is one of the most common cancers worldwide. One-fifth of the world's oral cancer subjects are from India and other South Asian countries. The present Raman mapping study was carried out to understand biochemical variations in normal and malignant oral buccal mucosa. Data were acquired using WITec alpha 300R instrument from 10 normal and 10 tumors unstained tissue sections. Raman maps of normal sections could resolve the layers of epithelium, i.e. basal, intermediate, and superficial. Inflammatory, tumor, and stromal regions are distinctly depicted on Raman maps of tumor sections. Mean and difference spectra of basal and inflammatory cells suggest abundance of DNA and carotenoids features. Strong cytochrome bands are observed in intermediate layers of normal and stromal regions of tumor. Epithelium and stromal regions of normal cells are classified by principal component analysis. Classification among cellular components of normal and tumor sections is also observed. Thus, the findings of the study further support the applicability of Raman mapping for providing molecular level insights in normal and malignant conditions.

  13. Sulglycotide displays cytoprotective activity in rat gastric mucosa.

    PubMed

    Niada, R; Mantovani, M; Prino, G; Omini, C; Berti, F

    1983-01-01

    Sulglycotide, a well known antisecretory and antiulcer compound, has been further investigated for its ability to protect rat gastric mucosa against extensive necrosis induced by absolute ethanol, NaOH (0.2N) and NaCl (30%). Sulglycotide, which has been compared with cimetidine, displays a dose-dependent cytoprotective activity against the above necrotizing agents. The results obtained indicate that Sulglycotide requires a normal prostaglandin biosynthetic process in order to manifest its antiulcer activity. In fact gastric mucosa from animals treated with Sulglycotide releases in vitro a greater amount of PGl2-like activity; and furthermore no protection was observed against gastric lesions induced by indomethacin. As far as the mode of action of Sulglycotide is concerned it is tempting to speculate that the compound may interfere with prostaglandin degradation or it may trigger an adaptive cytoprotection which is important in maintaining the cellular integrity of rat gastric mucosa.

  14. Oral bacteria as potential probiotics for the pharyngeal mucosa.

    PubMed

    Guglielmetti, Simone; Taverniti, Valentina; Minuzzo, Mario; Arioli, Stefania; Stuknyte, Milda; Karp, Matti; Mora, Diego

    2010-06-01

    The research described here was aimed at the selection of oral bacteria that displayed properties compatible with their potential use as probiotics for the pharyngeal mucosa. We included in the study 56 bacteria newly isolated from the pharynges of healthy donors, which were identified at the intraspecies level and characterized in vitro for their probiotic potential. The experiments led us to select two potential probiotic bacterial strains (Streptococcus salivarius RS1 and ST3) and to compare them with the prototype oral probiotic S. salivarius strain K12. All three strains efficiently bound to FaDu human epithelial pharyngeal cells and thereby antagonized Streptococcus pyogenes adhesion and growth. All were sensitive to a variety of antibiotics routinely used for the control of upper respiratory tract infections. Immunological in vitro testing on a FaDu layer revealed different responses to RS1, ST3, and K12. RS1 and ST3 modulated NF-kappaB activation and biased proinflammatory cytokines at baseline and after interleukin-1beta (IL-1beta) induction. In conclusion, we suggest that the selected commensal streptococci represent potential pharyngeal probiotic candidates. They could display a good degree of adaptation to the host and possess potential immunomodulatory and anti-inflammatory properties.

  15. Integrating-Sphere Measurements for Determining Optical Properties of Tissue-Engineered Oral Mucosa

    NASA Astrophysics Data System (ADS)

    Ionescu, A. M.; Cardona, J. C.; Garzón, I.; Oliveira, A. C.; Ghinea, R.; Alaminos, M.; Pérez, M. M.

    2015-02-01

    Surgical procedures carried out in the oral and maxillofacial region can result in large tissue defects. Accounting for the shortage of oral mucosa to replace the excised tissues, different models of an organotypic substitute of the oral mucosa generated by tissue engineering have recently been proposed. In this work, the propagation of light radiation through artificial human oral mucosa substitutes based on fibrin-agarose scaffolds (fibrin, fibrin-0.1% agarose, fibrin-0.2%agarose) is investigated, and their optical properties are determined using the inverse adding-doubling (IAD) method based on integrating-sphere measurements. Similar values for the absorption and scattering coefficients between the fibrin and fibrin-0.1% agarose bioengineered tissues and the native oral mucosa were found. These results suggest the adequacy of these biomaterials for potential clinical use in human oral mucosa applications. These optical properties represent useful references and data for applications requiring the knowledge of the light transport through this type of tissues, applications used in clinical practice. It also provides a new method of information analysis for the quality control of the development of the artificial nanostructured oral mucosa substitutes and its comparison with native oral mucosa tissues.

  16. The Oral Mucosa Immune Environment and Oral Transmission of HIV/SIV

    PubMed Central

    Wood, Lianna F.; Chahroudi, Ann; Chen, Hui-Ling; Jaspan, Heather B.; Sodora, Donald L.

    2013-01-01

    Summary The global spread of human immunodeficiency virus (HIV) is dependent on the ability of this virus to efficiently cross from one host to the next by traversing a mucosal membrane. Unraveling how mucosal exposure of HIV results in systemic infection is critical for the development of effective therapeutic strategies. This review focuses on understanding the immune events associated with the oral route of transmission (via breastfeeding or sexual oral intercourse), which occurs across the oral and/or gastrointestinal mucosa. Studies in both humans and simian immunodeficiency virus (SIV) monkey models have identified viral changes and immune events associated with oral HIV/SIV exposure. This review covers our current knowledge of HIV oral transmission in both infants and adults, the use of SIV models in understanding early immune events, oral immune factors that modulate HIV/SIV susceptibility (including mucosal inflammation), and interventions that may impact oral HIV transmission rates. Understanding the factors that influence oral HIV transmission will provide the foundation for developing immune therapeutic and vaccine strategies that can protect both infants and adults from oral HIV transmission. PMID:23772613

  17. Adherence of Entamoeba histolytica trophozoites to rat and human colonic mucosa.

    PubMed Central

    Ravdin, J I; John, J E; Johnston, L I; Innes, D J; Guerrant, R L

    1985-01-01

    We studied the adherence of [3H]thymidine-labeled axenic Entamoeba histolytica (strain HM1-IMSS) to in vitro preparations of rat and human colonic mucosa. Studies were performed with fixed or unfixed rat colonic mucosa, unfixed rat mucosa exposed to trypsin, unfixed rat submucosa, and fixed human colonic mucosa. Twenty percent of the amebae adhered to fixed rat colonic mucosa; adherence was specifically inhibited by N-acetyl-D-galactosamine (GalNAc), galactose, and asialofetuin. The adherence of amebae to fixed human colonic mucosa was also GalNAc inhibitable. Greater adherence was found with unfixed rat colonic mucosa (40.9%) and was not GalNAc inhibitable unless the tissue was first exposed to trypsin. However, GalNAc did inhibit the adherence of amebae to unfixed rat submucosa. Glutaraldehyde fixation of amebae inactivates known amebic adhesion proteins; there was a markedly decreased adherence of fixed amebae to trypsin-exposed mucosa or fixed rat colonic mucosa. However, fixed or viable amebae had equal levels of adherence to unfixed rat colonic mucosa, suggesting the presence of a host adhesion protein that binds to receptors on amebae. Human (10%) and rabbit (5%) immune sera reduced the adherence of viable amebae to fixed rat colonic mucosa. We concluded that the GalNAc-inhibitable adhesion protein on the surface of E. histolytica trophozoites mediated adherence to fixed rat mucosa, fixed human colonic mucosa, trypsin-exposed unfixed rat mucosa, and unfixed rat submucosa. The surface of unfixed rat colonic mucosa contained a glutaraldehyde- and trypsin-sensitive host adhesion protein, perhaps in the overlying mucus blanket, which bound viable or fixed E. histolytica trophozoites. Images PMID:2580787

  18. Expression of E-cadherin in normal oral mucosa, in oral precancerous lesions and in oral carcinomas

    PubMed Central

    Sridevi, Ugrappa; Jain, Ajay; Nagalaxmi, Velpula; Kumar, Ugrappa Vijay; Goyal, Stuti

    2015-01-01

    Objective: The aim of the present study was to assess the expression of E-cad in oral precancerous lesions and conditions and oral carcinomas in comparison with normal mucosa. Materials and Methods: Total of 50 samples were selected for the study and were categorized into five groups and 10 samples in each group as Group I-oral leukoplakia (OL), Group II-oral lichen planus (OLP), Group III-oral submucous fibrosis (OSMF), Group IV-oral squamous cell carcinoma (OSCC) and Group V-normal oral mucosa (NOM) as control group. All the samples were assessed for the expression of E-cad by immunohistochemical study. Results: Upon assessing the expression of E-cad in OL, OSMF, OLP and OSCC, as majority of the samples with OSCC (90%), OL (80%), OLP (70%) and OSMF (60%) showed mild to moderate expression of E-cad staining, which was suggestive of reduction in dysplastic cells on comparison to NOM cells. This difference in expression and variation of E-cad upon comparison with normal mucosa was statistically significant (P < 0.001). Conclusion: There is significant (P < 0.001) variation of expression of E-cad with the histopathological dysplasia of the oral precancerous lesions and conditions, and the tumor differentiation of the oral cancers. However, there was no correlation of the degree of loss of expression of E-cad with the degree of dysplasia or the tumor differentiation of oral cancers. We conclude with our study that, there is a variation in the expression of E-cad but its value as a prognostic marker is questionable. PMID:26430364

  19. Regional quantitative histological variations in human oral mucosa.

    PubMed

    Ciano, Joseph; Beatty, Brian Lee

    2015-03-01

    Oral mucosa demonstrates regional variations that reflect contact with food during mastication. Though known qualitatively, our aim was to quantitatively assess regions to establish a measurable baseline from which one could compare in pathological and comparative studies, in which the abrasiveness of diets may differ. We assessed variations in the epithelial-connective tissue junction (rete ridges counts), collagen organization within the lamina propria, and elastin composition of the lamina propria of 15 regions of the labial (buccal) gingiva, lingual gingiva, vestibule, and palate. All characteristics varied more between regions within the same individual than between individuals. Lingual gingiva had high rete ridges counts, high level of collagen organization, and moderate elastin composition compared to other regions. The labial gingiva had few rete ridges, high collagen organization, and low elastin. The vestibule had the fewest average of rete ridges, least organized collagen, and high elastin. The hard palate had the highest average of rete ridges, high collagen organization, and the lowest elastin content. The soft palate conversely had the smallest average of rete ridges, moderate collagen organization, and the highest elastin composition. Our results indicate that comparison of these quantitative histological differences is warranted only for collagen organization and elastin composition. Differences in rete ridges counts were not statistically significant. Most histological characteristics observed were not significantly different between dentulous and edentulous cadavers, and the group containing all individuals. An exception was the level of collagen fiber organization within the lamina propria, which was higher in most regions when teeth were present.

  20. Phase 2 Clinical Trial of Intraoral Grafting of Human Tissue-Engineered Oral Mucosa

    DTIC Science & Technology

    2013-10-01

    differences in the primary efficacy measure of increased keratinized mucosa; secondary measures of graft contracture and Wound Healing Index; and...per treatment group, will be randomized to receive either the experimental treatment , EVPOME (Group 1), or standard of care, the palatal oral mucosa...Keratinized mucosa, graft contracture 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE

  1. Cytoprotective activity of deboxamet: a possible interference with prostaglandin and prostacyclin metabolism in rat gastric mucosa.

    PubMed

    Franzone, J S; Cirillo, R; Cravanzola, C

    1988-01-01

    Deboxamet (5-methoxy-2-methyl-3-indolyl-acetohydroxamic acid) is a new synthetic drug with anti-ulcer and anti-secretory activity. The authors evaluated the ability of deboxamet to protect the rat gastric mucosa against the intensive necroses induced experimentally by absolute ethanol, NaCl (25%), HCl (0.6 N), acetylsalicylic acid plus HCl, and sodium taurocholate plus HCl. Deboxamet, as compared with pirenzepine, sulglycotide and PGE2, displayed a cytoprotective activity against these necrotizing agents. The involvement of deboxamet with prostacyclin metabolism was also investigated. In order to assess the presence of PGI2-like substances, extracts of mucosa from rats treated orally with deboxamet and sulglycotide were assayed i) on isolated rabbit mesenteric artery, ii) for hypotensive effect in anaesthetized rat, and iii) for anti-platelet activity. Deboxamet, like sulglycotide, was able to raise the availability of prostacyclins in the rat gastric mucosa, which is an important action in maintaining its cellular integrity. However, our results cannot determine whether this activity is due to an enhanced biosynthesis or a decreased degradation of prostacyclins.

  2. [Focal epithelial hyperplasia of the oral mucosa. A unique manifestation of human papillomavirus].

    PubMed

    van der Voort, E A M; Arani, S Fallah; Hegt, V Noordhoek; van Praag, M C G

    2009-03-01

    A 34-year old Creole woman appeared at the dermatology department with white-pink spots on the oral mucosa, which had been there for some time. Histology showed lesions characteristic of focal epithelial hyperplasia. The patient was treated with a CO2 laser. Focal epithelial hyperplasia is a rare benign lesion and is caused by human papillomavirus subtypes 13 or 32; it only appears on the oral mucosa.

  3. Human Papillomavirus in the Lesions of the Oral Mucosa According to Topography

    PubMed Central

    Mravak-Stipetić, Marinka; Sabol, Ivan; Kranjčić, Josip; Knežević, Marjana; Grce, Magdalena

    2013-01-01

    Background The association between human papillomavirus (HPV) types and oral lesions has been shown in many studies. Considering the significance that HPV has in the development of malignant and potentially malignant disorders of the oral mucosa, the purpose of this study was to investigate the prevalence of HPV DNA in different oral lesions. In addition, we wanted to elucidate whether the HPV infection is associated predominantly with either the lesion or a particular anatomic site of the oral cavity. Methodology/Principal Findings The study included 246 subjects with different oral lesions, and 73 subjects with apparently healthy oral mucosa (controls). The oral lesions were classified according to their surface morphology and clinical diagnosis. The epithelial cells were collected with a cytobrush from different topographic sites in the oral cavity of the oral lesions and controls. The presence of HPV DNA was evaluated by consensus and type-specific primer-directed polymerase chain reaction. The HPV positivity was detected in 17.7% of oral lesions, significantly more than in apparently healthy mucosa (6.8%), with a higher presence in benign proliferative mucosal lesions (18.6%). High-risk HPV types were predominantly found in potentially malignant oral disorders (HPV16 in 4.3% and HPV31 in 3.4%), while benign proliferative lesions as well as healthy oral mucosa contained mainly undetermined HPV type (13.6 and 6.8%, respectively). Conclusions/Significance The distribution of positive HPV findings on the oral mucosa seems to be more associated with a particular anatomical site than the diagnosis itself. Samples taken from the vermilion border, labial commissures, and hard palate were most often HPV positive. Thus, topography plays a role in HPV prevalence findings in oral lesions. Because of the higher prevalence of the high-risk HPV types in potentially malignant oral disorders, these lesions need to be continuously controlled and treated. PMID:23922786

  4. Lichen sclerosus in the oral mucosa: a rare form of presentation.

    PubMed

    Louvain, Dailana; Moura Jacques, Claudio; Fernandes Ferreira, Adriana; Hoehl Carneiro, Leonardo; Quintela, Leonardo; Cuzzi, Tullia; Soares de Azevedo, Lucia; Moritz Trope, Beatriz; Ramos-e-Silva, Marcia

    2012-01-01

    Lichen sclerosus is a chronic inflammatory disease of unknown origin, which affects mostly women in the fifth and sixth decades of life, but can also occur in men and children. The involvement of the oral mucosa alone or together with other forms of presentation is extremely rare, requiring a differential diagnosis with other diseases of the oral cavity, particularly lichen planus. There are less than 30 cases of lichen sclerosus in the oral mucosa described in the literature and there are no reports on malignant transformation so far. We describe a patient with skin, oral and genital lesions of lichen sclerosus.

  5. [Generation of a substitute for human oral mucosa and verification of its viability by tissue-engineering].

    PubMed

    Marañés Gálvez, C; Liceras Liceras, E; Alaminos, M; Fernández Valadés, R; Ruiz Montes, A M; Garzón, I; Sánchez-Quevedo, M C; Campos, A

    2011-01-01

    Reconstruction of large oral mucosa defects is often challenging, since the shortage of healthy oral mucosa to replace the excised tissues. This way, tissue ingineering techniques may provide a source of autologous tissues available for transplant in these patients. In this work, we have developed a new model for artificial oral mucosa generated by tissue engineering using a fibrin-agarosa scaffold. For that purpose, we have generated primary cultures of human oral mucosa fibroblasts and keratinocytes from small biopsies of normal mucosa oral using enzymatic treatments. Then, we have determined the viability of cultured cells by electron probe quantitative X-ray microanalysis, and we have demonstrated that most of the cells in the primary cultures were alive and hd high K/Na ratios. Once cell viability was determined, we used cultured fibroblasts and keratinocytes to develop an artificial oral mucosa construct by using a fibrin-agarosa extracellular matrix and a sequential culture technique using porous culture inserts. Histological analysis of the artificial tissues showed high similarities with normal oral mucosa controls. The epithelium of the oral substitutes had several layers, with desmosomes and apical microvilli and microplicae. Both the controls and de oral mucosa substitutes showed high suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All these results suggest that our model of oral mucosa using fibrin-agarose scaffolds show several similarities with native human oral mucosa.

  6. Collagen fibril arrangement and size distribution in monkey oral mucosa

    PubMed Central

    OTTANI, V.; FRANCHI, M.; DE PASQUALE, V.; LEONARDI, L.; MOROCUTTI, M.; RUGGERI, A.

    1998-01-01

    Collagen fibre organisation and fibril size were studied in the buccal gingival and hard palate mucosa of Macacus rhesus monkey. Light and electron microscopy analysis showed connective papillae exhibiting a similar inner structure in the different areas examined, but varying in distribution, shape and size. Moving from the deep to surface layers of the buccal gingival mucosa (free and attached portions), large collagen fibril bundles became smaller and progressively more wavy with decreasing collagen fibril diameter. This gradual diameter decrease did not occur in the hard palate mucosa (free portion, rugae and interrugal regions) where the fibril diameter remained constant. A link between collagen fibril diameter and mechanical function is discussed. PMID:9688498

  7. Micronuclei in nasal mucosa, oral mucosa and lymphocytes in students exposed to formaldehyde vapor in anatomy class.

    PubMed

    Ying, C J; Yan, W S; Zhao, M Y; Ye, X L; Xie, H; Yin, S Y; Zhu, X S

    1997-12-01

    The frequency of micronuclei (MN) in cells of the nasal mucosa, oral mucosa and in lymphocytes was evaluated for 25 students in anatomy classes exposed to formaldehyde (FA) over an 8-week period. Each student served as his or her own control. The time-weighted average concentration (TWA) of formaldehyde in anatomical laboratories and in students' dormitories was 0.508 +/- 0.299 mg/m3 and 0.012 +/- 0.0025 mg/m3, respectively. A higher frequency of micronuclei was observed in nasal and oral exfoliative cells after formaldehyde exposure (3.85 +/- 1.48 vs 1.20 +/- 0.676 and 0.857 +/- 0.558 vs 0.568 +/- 0.317, paired-t test: P < 0.001 and P < 0.01, respectively). No significant increase in the frequency of lymphocyte micronuclei was found after formaldehyde exposure (P > 0.05). The present study shows that nasal mucosa cells exposed through respiration are the chief target of FA-induced genotoxic effects.

  8. Ex Vivo Produced Oral Mucosa Equivalent by Using the Direct Explant Cell Culture Technique

    PubMed Central

    Bayar, Gürkan Raşit; Aydıntuğ, Yavuz Sinan; Günhan, Ömer; Öztürk, Kamile; Gülses, Aydın

    2012-01-01

    Objective: The aim of this study is the histological and immunohistochemical evaluation of ex vivo produced oral mucosal equivalents using keratinocytes cultured by direct explant technique. Material and Methods: Oral mucosa tissue samples were obtained from the keratinized gingival tissues of 14 healthy human subjects. Human oral mucosa keratinocytes from an oral mucosa biopsy specimen were dissociated by the explant technique. Once a sufficient population of keratinocytes was reached, they were seeded onto the type IV collagen coated “AlloDerm” and taken for histological and immunohistochemical examinations at 11 days postseeding of the keratinocytes on the cadaveric human dermal matrix. Results: Histopathologically and immunohistochemically, 12 out of 14 successful ex vivo produced oral mucosa equivalents (EVPOME) that consisted of a stratified epidermis on a dermal matrix have been developed with keratinocytes cultured by the explant technique. Conclusion: The technical handling involved in the direct explant method at the beginning of the process has fewer steps than the enzymatic method and use of the direct explant technique protocol for culturing of human oral mucosa keratinocyte may be more adequate for EVPOME production. PMID:25207018

  9. [Role of keratinocytes in preservation of oral mucosa epithelium integrity. Part I].

    PubMed

    Zapała, Jan; Zarzecka, Joanna; Drukała, Justyna

    2005-01-01

    Functions of oral mucosa epithelium in preservation of homeostasis have been presented. Characteristic features that distinguish epithelial cells from the other somatic cells influencing mechanical resistance of oral epithelium and creating selective chemical barrier have been described. The participation of keratinocytes in selected phases of wound healing process has been analyzed.

  10. Paracoccidioides brasiliensis interacts with dermal dendritic cells and keratinocytes in human skin and oral mucosa lesions.

    PubMed

    Silva, Wellington Luiz Ferreira da; Pagliari, Carla; Duarte, Maria Irma Seixas; Sotto, Mirian N

    2016-05-01

    Paracoccidioidomycosis (PCM) is a systemic disease caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. In PCM the skin and oral mucosa are often affected. Dendritic cells and keratinocytes of the integument play a role in innate and adaptive immune response against pathogens, due to their function as antigen presenting cells. Aiming to verify the interaction of P. brasiliensis with these cell populations, we studied 52 skin and 47 oral mucosa samples taken from patients with proven diagnosis of PCM. The biopsies were subjected to immunohistochemical and/or immunofluorescence staining with anti-factor XIIIa (marker of dermal dendrocytes), anti-CD207 (marker of mature Langerhans cells), anti-pan cytokeratins (AE1-AE3) and anti-P. brasiliensis antibodies. Analyses with confocal laser microscopy were also performed for better visualization of the interaction between keratinocytes and the fungi. In sum, 42% of oral mucosa samples displayed yeast forms in Factor XIIIa dermal dendrocytes cytoplasm. Langerhans cells in skin and oral mucosa samples did not show yeast cells in their cytoplasm. In sum, 54% of skin and 60% of mucosal samples displayed yeast cells in the cytoplasm of keratinocytes. The parasitism of keratinocytes may represent a possible mechanism of evasion of the fungus to local immune mechanisms. Factor XIIIa dendrocytes and keratinocytes may be acting as antigen-presenting cells to fulfill the probably impaired function of Langerhans cells in skin and oral mucosa of human PCM.

  11. Measuring the impact of oral mucosa disease on quality of life.

    PubMed

    López-Jornet, Pía; Camacho-Alonso, Fabio; Lucero Berdugo, Mayra

    2009-01-01

    Our objective was to study the quality of life in patients with oral mucosa disease. Two hundred sixteen consecutive patients with oral pathology were studied at the Department of Oral Medicine, University of Murcia (Spain). Sixty patients had burning mouth syndrome, 100 oral lichen planus, 41 recurrent aphthous stomatitis and 15 had and other oral mucosa disorders. The instruments applied were the Spanish version of the SF-36, used to evaluate general quality of life, and the OHIP-49, Spanish version, to measure oral health-related quality of life. With respect to oral quality of life (OHIP-49 all items), the worst scores were found for burning mouth syndrome. The group formed by other mucosal lesions presented the lowest scores for the domains role physical and general health in the SF-36. Oral mucosa diseases have a negative impact on health and quality of life. Administration of specific and generic questionnaires provides a detailed picture of the impact of oral diseases on patients, which adds information that may be useful in clinical practice.

  12. HIV infection induces morphometrical changes on the oral (buccal mucosa and tongue) epithelial cells.

    PubMed

    Pompermayer, Adriane Bastos; Gil, Francisca Berenice Dias; França, Beatriz Helena Sottile; Machado, Maria Ângela Naval; Trevilatto, Paula Cristina; Fernandes, Angela; de Lima, Antônio Adilson Soares

    2011-01-01

    The aim of this study was to assess morphological and morphometrical alterations of oral squamous epithelial cells in type 1 HIV infected individuals. Oral smears were collected from tongue and buccal mucosa of 30 HIV infected (experimental) and 30 non-infected (control) individuals by liquid-based exfoliative cytology. The cells were morphologically analyzed and the nuclear area (NA), the cytoplasmic area (CA) and the nucleus-to-cytoplasm area ratio (NA/CA) were calculated. No morphological differences were found between the groups. The mean values of CA were decreased in tongue (P=.00006) and buccal mucosa (P=.00242) in HIV infected individual, while mean values of NA were increased (P=.00308 and .00095, respectively) in the same group. NA/CA ratio for experimental group was increased in both collected places, with P=.00001 (tongue) and P=.00000 (buccal mucosa). This study revealed that HIV infection was able to induce morphometrical changes on the oral epithelial cells.

  13. Cultivated Oral Mucosa Epithelium in Ocular Surface Reconstruction in Aniridia Patients

    PubMed Central

    Dobrowolski, Dariusz; Orzechowska-Wylegala, Boguslawa; Wowra, Bogumil; Wroblewska-Czajka, Ewa; Grolik, Maria; Szczubialka, Krzysztof; Nowakowska, Maria; Puzzolo, Domenico; Wylegala, Edward A.; Micali, Antonio; Aragona, Pasquale

    2015-01-01

    Purpose. Efficacy of cultivated oral mucosa epithelial transplantation (COMET) procedure in corneal epithelium restoration of aniridia patients. Methods. Study subjects were aniridia patients (13 patients; 17 eyes) with irregular, vascular conjunctival pannus involving visual axis who underwent autologous transplantation of cultivated epithelium. For the procedure oral mucosa epithelial cells were obtained from buccal mucosa with further enzymatic treatment. Suspension of single cells was seeded on previously prepared denuded amniotic membrane. Cultures were carried on culture dishes inserts in the presence of the inactivated with Mitomycin C monolayer of 3T3 fibroblasts. Cultures were carried for seven days. Stratified oral mucosa epithelium with its amniotic membrane carrier was transplanted on the surgically denuded corneal surface of aniridia patients with total or subtotal limbal stem cell deficiency. Outcome Measures. Corneal surface, epithelial regularity, and visual acuity improvement were evaluated. Results. At the end of the observation period, 76.4% of the eyes had regular transparent epithelium and 23.5% had developed epithelial defects or central corneal haze; in 88.2% of cases visual acuity had increased. VA range was from HM 0.05 before the surgery to HM up to 0.1 after surgery. Conclusion. Application of cultivated oral mucosa epithelium restores regular epithelium on the corneal surface with moderate improvement in quality of vision. PMID:26451366

  14. Low prevalence of high risk human papillomavirus in normal oral mucosa by hybrid capture 2

    PubMed Central

    González-Losa, Maria del Refugio; Manzano-Cabrera, Luis; Rueda-Gordillo, Florencio; Hernández-Solís, Sandra E.; Puerto-Solís, Luis

    2008-01-01

    High risk human papillomavirus (HR-HPV) are recognized as a necessary factor to development cervical cancer. During the last decade many studies have found HR-HPV in oral squamous cell carcinoma (OSCC) and normal oral mucosa, however the association between HR-HPV and OSCC is still uncertain. The aim of the study was to determine DNA HR-HPV in normal oral cavity of healthy adults. A cross-sectional study was performed; samples from 77 patients with normal oral cavity were collected at the Dentistry school, Autonomous University of Yucatan, Merida, Yucatan, México. HR-HPV was detected by hybrid capture 2. One sample out of 77(1.2%) was positive for HR-PVH. It was from a man of 50 years old. HRHPV is present in low rate among healthy oral mucosa. Hybrid capture 2 could be a good methodology for large epidemiology studies. PMID:24031173

  15. Oral Mucocele of Unusual Size on the Buccal Mucosa: Clinical Presentation and Surgical Approach

    PubMed Central

    Seo, Juliana; Bruno, Ingrid; Artico, Gabriela; Vechio, Aluana dal; Migliari, Dante A

    2012-01-01

    Oral mucoceles are small-size, benign minor salivary gland pathologies. The most frequent localizations of these lesions are the lower lip mucosa. However, in some cases, they grow to an unusual size and hinder the preliminary diagnosis of mucocele. The purpose of this article is to report a case of a large oral mucocele with a diameter of 3.5 cm on the buccal mucosa of a 43-years-old male patient. The surgical procedure was carried out for a complete removal of the lesion. PMID:22550550

  16. The microbiome of the oral mucosa in irritable bowel syndrome.

    PubMed

    Fourie, Nicolaas H; Wang, Dan; Abey, Sarah K; Sherwin, LeeAnne B; Joseph, Paule V; Rahim-Williams, Bridgett; Ferguson, Eric G; Henderson, Wendy A

    2016-07-03

    Irritable bowel syndrome (IBS) is a poorly understood disorder characterized by persistent symptoms, including visceral pain. Studies have demonstrated oral microbiome differences in inflammatory bowel diseases suggesting the potential of the oral microbiome in the study of non-oral conditions. In this exploratory study we examine whether differences exist in the oral microbiome of IBS participants and healthy controls, and whether the oral microbiome relates to symptom severity. The oral buccal mucosal microbiome of 38 participants was characterized using PhyloChip microarrays. The severity of visceral pain was assessed by orally administering a gastrointestinal test solution. Participants self-reported their induced visceral pain. Pain severity was highest in IBS participants (P = 0.0002), particularly IBS-overweight participants (P = 0.02), and was robustly correlated to the abundance of 60 OTUs, 4 genera, 5 families and 4 orders of bacteria (r(2) > 0.4, P < 0.001). IBS-overweight participants showed decreased richness in the phylum Bacteroidetes (P = 0.007) and the genus Bacillus (P = 0.008). Analysis of β-diversity found significant separation of the IBS-overweight group (P < 0.05). Our oral microbial results are concordant with described fecal and colonic microbiome-IBS and -weight associations. Having IBS and being overweight, rather than IBS-subtypes, was the most important factor in describing the severity of visceral pain and variation in the microbiome. Pain severity was strongly correlated to the abundance of many taxa, suggesting the potential of the oral microbiome in diagnosis and patient phenotyping. The oral microbiome has potential as a source of microbial information in IBS.

  17. The microbiome of the oral mucosa in irritable bowel syndrome

    PubMed Central

    Fourie, Nicolaas H.; Wang, Dan; Abey, Sarah K.; Sherwin, LeeAnne B.; Joseph, Paule V.; Rahim-Williams, Bridgett; Ferguson, Eric G.; Henderson, Wendy A.

    2016-01-01

    abstract Irritable bowel syndrome (IBS) is a poorly understood disorder characterized by persistent symptoms, including visceral pain. Studies have demonstrated oral microbiome differences in inflammatory bowel diseases suggesting the potential of the oral microbiome in the study of non-oral conditions. In this exploratory study we examine whether differences exist in the oral microbiome of IBS participants and healthy controls, and whether the oral microbiome relates to symptom severity. The oral buccal mucosal microbiome of 38 participants was characterized using PhyloChip microarrays. The severity of visceral pain was assessed by orally administering a gastrointestinal test solution. Participants self-reported their induced visceral pain. Pain severity was highest in IBS participants (P = 0.0002), particularly IBS-overweight participants (P = 0.02), and was robustly correlated to the abundance of 60 OTUs, 4 genera, 5 families and 4 orders of bacteria (r2 > 0.4, P < 0.001). IBS-overweight participants showed decreased richness in the phylum Bacteroidetes (P = 0.007) and the genus Bacillus (P = 0.008). Analysis of β-diversity found significant separation of the IBS-overweight group (P < 0.05). Our oral microbial results are concordant with described fecal and colonic microbiome-IBS and -weight associations. Having IBS and being overweight, rather than IBS-subtypes, was the most important factor in describing the severity of visceral pain and variation in the microbiome. Pain severity was strongly correlated to the abundance of many taxa, suggesting the potential of the oral microbiome in diagnosis and patient phenotyping. The oral microbiome has potential as a source of microbial information in IBS. PMID:26963804

  18. Elastofibromatous Changes and Hyperelastosis of the Oral Mucosa

    PubMed Central

    Tosios, Konstantinos I.; Economou, Ioanna; Vasilopoulos, Nektarios-Nikolaos

    2009-01-01

    Three cases of abnormalities of elastic fibers, two of them on the floor of the mouth and one on the lingual alveolar mucosa, close to the floor of the mouth, in a patient with history of homolateral squamous cell carcinoma of the floor of the mouth, are presented. Comparison with elastofibromatous changes and elastofibromas are made and their possible pathogenesis is discussed. It is suggested that increased awareness may facilitate recognition of such lesions as they can be easily overlooked, especially when they do not present as discrete tumors or they are associated with other “more significant” pathologic processes. PMID:20237986

  19. Cytogenetic biomonitoring of peripheral blood and oral mucosa cells from car painters.

    PubMed

    Pereira da Silva, Victor Hugo; Gomes de Moura, Carolina Foot; Spadari-Bratfisch, Regina Célia; Araki Ribeiro, Daniel

    2012-09-01

    The aim of the present study was to comparatively evaluate genomic damage and cellular death in exfoliated oral mucosa cells and peripheral blood from car painters. A total of 24 car painters and 19 healthy controls (non-exposed individuals) were included in this setting. Individuals had epithelial cells from cheek mucosa (left and right side) mechanically exfoliated, placed in fixative and dropped in clean slides which were checked for the specific nuclear phenotypes. A total of 5 μL from peripheral blood was collected for the single cell gel (comet) assay. The results pointed out statistically significant differences (p < 0.05) of micronucleated oral mucosa cells from car painters. In addition, DNA damage was detected in peripheral blood cells by single cell gel (comet) assay. Nevertheless, exposure to car paints did not cause increases other nuclear alterations closely related to cytotoxicity such as karrhyorexis, pyknosis and karyolysis in buccal mucosa cells. In summary, the results of the present study suggest that car painters comprise a high risk group since paints can induce genotoxic and mutagenic effects in peripheral blood and oral mucosa cells, respectively.

  20. The lupus band test in oral mucosa, conjunctiva and skin.

    PubMed

    Burge, S M; Frith, P A; Millard, P R; Wojnarowska, F

    1989-12-01

    The prevalence and clinical significance of subepithelial immunoglobulin and complement deposition (the lupus band) were examined in the uninvolved sun-protected skin of the forearm, the uninvolved sun-protected lip mucosa and sun-protected bulbar conjunctival mucosa in systemic lupus erythematosus (SLE) and chronic cutaneous lupus erythematosus (CCLE). In SLE, linear deposition of an immunoreactant at the BMZ was detected in 32% (6/19) of skin biopsies; 21% (4/19) of lip mucosal biopsies and 42% (5/12) of conjunctival biopsies. There was no significant difference in the sensitivity of the test at different sites in SLE and no correlation between a positive test in skin, lip or conjunctiva and clinical mucosal involvement. In CCLE, linear deposition of an immunoreactant at the BMZ was found in 3% (1/32) of skin biopsies; 3% (1/29) of lip mucosal biopsies and 50% (10/20) of conjunctiva and clinical mucosal involvement. In the conjunctiva, IgG was present in all but one of the biopsies and was the only immunoreactant in 90% (9/10) of positive CCLE biopsies and 60% (3/5) of positive SLE biopsies. In lupus erythematosus immunoreactants may be deposited in the basement membrane zone beneath non-keratinizing mucosal surfaces of the lip and the eye as well as the skin. In CCLE, the test may be positive in conjunctiva when skin and lip are negative.

  1. Cellular death but not genetic damage in oral mucosa cells after exposure to digital lateral radiography.

    PubMed

    Ribeiro, Daniel A; Sannomiya, Eduardo K; Pozzi, Renan; Miranda, Sandra R; Angelieri, Fernanda

    2011-06-01

    The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis, and karyorrhexis) in exfoliated buccal mucosa cells from individuals following digital lateral radiography. A total of 30 healthy patients (15 men and 15 women) indicated to the orthodontic therapy were submitted to digital lateral X-ray. Exfoliated oral mucosa cells were collected immediately before the X-ray exposure and after 10 days. The results pointed out no significant statistically differences (p > 0.05) of micronucleated oral mucosa cells. On the other hand, X-ray was able to increase other nuclear alterations closely related to cytotoxicity such as karyorrhexis, pyknosis, and karyolysis. In summary, these data indicate that exposure to digital lateral radiography may not be a factor that induced chromosomal damage, but it is able to promote cytotoxicity.

  2. Impact of oral mucosa lesions on the quality of life related to oral health. An etiopathogenic study

    PubMed Central

    Villanueva-Vilchis, María-del-Carmen; López-Ríos, Patricia; García, Ixchel-Maya

    2016-01-01

    Background To assess the impact of oral mucosa lesions on quality of life related to oral health (QLROH) and additionally to establish whether the etiopathogenicy of oral lesion is associated to the degree of QLROH impact. Material and Methods In this cross-sectional study performed on a non-probability sample of 247 consecutively patients attending the oral medicine and pathology clinic the Spanish version of Oral Health Impact Profile-49 questionnaire (OHIP-49-mx) was applied. Responses were recorded on Likert-type scale whose values ranged from 0 (never) to 4 (always). Values greater than the 50 percentile (median) were considered as indicative of poor quality of life. All patients were orally examined and diagnosed. In accordance to their etiopathogenicy 6 study groups were formed: 4 corresponded to MIND classification for diseases (Metabolic, Inflammatory, Neoplastic, and Development groups), with ≥2 diseases and no-lesion group. To identify possible differences of OHIP-49 values between study groups an ANOVA (one factor) parametric and a chi square tests were performed (SPSS®20.0). Results The OHIP-49-mx values were higher than the 50 percentile (established at 39) in metabolic, inflammatory, development, and ≥2 diseases groups, suggesting that this type of oral lesions negatively impact the quality of life. ≥2 diseasesgroup followed by metabolic and inflammatory diseases group (p 0.001) depicted worst quality of life. Functional limitation (p 0.003), pain, physical inability (p 0.001) and psychological disabilities dimensions exhibited greater values in all groups. Conclusions Injured oral mucosa negatively impacts quality of life, specifically functional limitation, physical inability and psychological disabilities could lead to social isolation.To our knowledge, this is the first time that an association between QLROH and the etiopathogenicy of oral mucosal diseases is established. Key words:Quality of life, quality of life related to oral health

  3. Mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients.

    PubMed

    Morgado de Abreu, M A M; Roselino, A M; Enokihara, M; Nonogaki, S; Prestes-Carneiro, L E; Weckx, L L M; Alchorne, M M A

    2014-01-01

    In leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus Mycobacterium leprae. The objective of this study was to identify M. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (PB) and 29 multibacillary (MB) patients, using immunohistochemistry (IHC), with antibodies against bacillus Calmette-Guérin (BCG) and phenolic glycolipid antigen-1 (PGL-1), and polymerase chain reaction (PCR), with MntH-specific primers for M. leprae, and to compare the results. The material was represented by 163 paraffin blocks containing biopsy samples obtained from clinically normal sites (including the tongue, buccal mucosa and soft palate) and visible lesions anywhere in the oral mucosa. All patients and 158 available samples were included for IHC study. Among the 161 available samples for PCR, 110 had viable DNA. There was viable DNA in at least one area of the oral mucosa for 47 patients. M. leprae was detected in 70% and 78% of patients using IHC and PCR, respectively, and in 94% of the patients by at least one of the two diagnostic methods. There were no differences in detection of M. leprae between MB and PB patients. Similar results were obtained using anti-BCG and anti-PGL-1 antibodies, and immunoreactivity occurred predominantly on free-living bacteria on the epithelial surface, with a predilection for the tongue. Conversely, there was no area of predilection according to the PCR results. M. leprae is present in the oral mucosa at a high frequency, implicating this site as a potential means of leprosy transmission.

  4. Quantitative comparison of the expression of antimicrobial peptides in the oral mucosa and extraoral skin.

    PubMed

    Kesting, Marco R; Mueller, Christian; Wagenpfeil, Stefan; Stoeckelhuber, Mechthild; Steiner, Timm; Bauer, Florian; Teichmann, Jan; Baumann, Claudia M; Barthel, Leopold C; Satanovskij, Robin M; Mücke, Thomas; Schulte, Matthias; Schütz, Katrin; Wolff, Klaus-D; Rohleder, Nils H

    2012-07-01

    Antimicrobial peptides (AMP) defend epithelial surfaces against pathological micro-organisms. We know of no comparison of their expression between the oral mucosa and extraoral epithelium, but knowledge of differences in their quantities is of interest, possibly as a starting point for new treatments. Expression of AMP human beta-defensin (hBD)-1/-2/-3 and psoriasin in the oral mucosa and extraoral epithelium of the head and neck were measured by real-time polymerase chain reaction (RT-PCR) (n=14), immunohistochemistry (n=6), and western blot (n=8). RT-PCR showed that all the genes investigated were expressed significantly more in the oral mucosa than in the skin (hBD-1: p=0.002; hBD-2: p=0.006; hBD-3: p=0.035; psoriasin: p=0.02). Immunohistochemistry and western blot showed differential concentrations of proteins: hBD-2 (p=0.021) and hBD-3 (p=0.043) were pronounced in the oral mucosa, whereas psoriasin was raised in the extraoral skin (p=0.021). There was no difference in protein concentrations for hBD-1 (p=0.08). The observed differences in the expression of AMP may be important for new treatments such as topical application of AMP derivatives.

  5. Lichen planus pigmentosus of the oral mucosa: a rare clinical variety.

    PubMed

    Laskaris, G C; Papavasiliou, S S; Bovopoulou, O D; Nicolis, G D

    1981-01-01

    In this paper, we describe a case of lichen planus of the mouth with intense melanosis, in a middle-aged white male. Due to its unusual clinical characteristics, we believe that this case represents a rare variant of lichen planus of the oral mucosa. The histopathologic findings, differential diagnosis and its possible connection with lichen planus pigmentosus of the skin are discussed.

  6. [Lesions of the oral mucosa. Epidemiological study of 7,297 patients].

    PubMed

    Díaz-Guzmán, L; Castellanos, J L

    1991-01-01

    To our Knowledge, this is the first work in a number population (higher than 500 sample WHO) that is carried out in our country about lesions in the Oral Mucosa. The advantages in this Kind of studies are recognized particularly in the fields of academic, research and services. This work presents the first view of a permanent research project of Oral Mucosa Lesions at the admission clinic, School of Dentistry, Universidad del Bajío. The findings are from the evaluation of 7,297 patients, 15 years or older, that seek dental services between January 1982 and June 1989 (7.5 years). The lack of national data and the oldest population samples in other countries studies stopped wider evaluations, even though the study purpose was not affected, it was possible to offer qualitative data in the respect of prevalecence, variety and etiopathogenesis of those type of pathosis in the Oral Mucosa. The general prevalecence in the group was approximately 13%, identifying lesions more frequently in males, but higher variety in females. Report on 40 different entities, presented in general according to a descent order of prevalencece and reagrouped by sex and pathology. In half the lesions was possible to identify as the cause, acute and cronic traumatic agents; The infectious associations were also very frequent. Those last observations are of high relevance concerning the prevention of Oral Mucosa lesions.

  7. Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Kong, Chee Kwan; Alizan, Abdul Khalil; Ramanujam, Tindivanam Muthurangam; Wong, Kum Thong

    2017-03-21

    Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion.

  8. Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa

    PubMed Central

    Phyu, Win Kyaw; Ong, Kien Chai; Kong, Chee Kwan; Alizan, Abdul Khalil; Ramanujam, Tindivanam Muthurangam; Wong, Kum Thong

    2017-01-01

    Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion. PMID:28322333

  9. Esomeprazole immediate release tablets: Gastric mucosa ex vivo permeation, absorption and antisecretory activity in conscious rats.

    PubMed

    Benetti, Camillo; Flammini, Lisa; Vivo, Valentina; Colombo, Paolo; Colombo, Gaia; Elviri, Lisa; Scarpignato, Carmelo; Buttini, Francesca; Bettini, Ruggero; Barocelli, Elisabetta; Rossi, Alessandra

    2016-10-10

    The aim of this work was to study the esomeprazole activity on the control of gastric secretion after administration of a novel immediate release tablet. The ex vivo permeation of esomeprazole across porcine gastric mucosa from immediate release tablets, containing sodium carbonate or magnesium oxide as alkalinizing agents, was firstly assessed. Pharmacokinetics and pharmacodynamics studies in conscious rats following the administration of immediate release tablets with sodium carbonate, in comparison with delayed-release tablets having the same formula, were also conducted. The results showed an important effect of sodium carbonate and magnesium oxide on the drug release, on the ex vivo trans-mucosal transport and the stability in acid environment. In particular, the presence of sodium carbonate in esomeprazole tablet formulation provided the maximum increase of the drug in vitro transport across the mucosa. Then, the absorption and the antisecretory activity of this proton pump inhibitor orally administered in rats as immediate release tablets containing Na2CO3, was superior but not significantly different compared to delayed-release tablets having the same formula. In the adopted animal model, an activity of esomeprazole from immediate release alkaline formulation was seen also in presence of partial gastric absorption allowing inhibition of proton pumps reached via systemic circulation. This esomeprazole immediate release formulation could be used for the on-demand treatment of acid-related disorders such as gastro-esophageal reflux disease.

  10. Differentiation of oral precancerous stages with optical coherence tomography based on the evaluation of optical scattering properties of oral mucosae

    NASA Astrophysics Data System (ADS)

    Tsai, M. T.; Lee, J. D.; Lee, Y. J.; Lee, C. K.; Jin, H. L.; Chang, F. Y.; Hu, K. Y.; Wu, C. P.; Chiang, C. P.; Yang, C. C.

    2013-04-01

    Optical coherence tomography (OCT) has been demonstrated to be a powerful tool for noninvasive, real-time oral cancer diagnosis. However, in previous reports, OCT has still been found to be difficult to use in the diagnosis of oral precancerous stages, including mild dysplasia and moderate dysplasia. In clinical applications, early diagnosis and treatment of oral cancer can greatly improve the survival rate. Therefore, in this study, we propose a new approach to differentiate the oral precancerous stages based on the evaluation of the optical scattering properties of the epithelial layer, which is where the dysplastic cells start to develop in the precancerous stages. Instead of using exponential decay fitting to evaluate the scattering properties of mucosal tissues based on the Beer-Lambert law, linear fitting of the OCT depth intensity is used to evaluate the scattering properties of normal and dysplastic cells. From the statistical results of the linear fitting, the slope, a, can be an effective indicator to discriminate healthy mucosa and moderate dysplasia when an a value equal to zero is the threshold value, and the intercept, b, can be used to differentiate healthy and dysplastic mucosae, as well as mild and moderate dysplasia, when b values of 0.15 and 0.18 are used as the threshold values, respectively. Furthermore, this approach is also applied to the determination of the safe margin between normal and abnormal mucosae, making it possible to provide real-time, in vivo inspection during oral maxillofacial surgery.

  11. Analysis of immune cells within the healthy oral mucosa of specific pathogen-free cats.

    PubMed

    Arzi, B; Murphy, B; Baumgarth, N; Vapniarsky, N; Nemec, A; Naydan, D K; Cox, D P; Verstraete, F J M

    2011-02-01

    The oral mucosa is an important interface for host-environment interactions. Based on previous studies, it is generally accepted that the cellular compartments of the oral immune system comprise organized mucosal-associated lymphoid tissues as well as diffusely and focally distributed T- and to lesser extent B-lymphocytes, oral mucosal Langerhans cells (OMLC), macrophages and mast cells. However, a comprehensive quantification of the cellular elements in the oral mucous membranes of the cat has not been reported. The aim of this study was to provide a comprehensive analysis of the immune cell compartments in the oral mucous membranes and anatomically related tissues of healthy cats. Multiple biopsies of the oral mucous membranes and related tissues were obtained from four specific pathogen-free cats for histological and immunohistochemical assessment of lymphocyte subsets, OMLC, macrophages and mast cells. T-lymphocyte subsets, OMLC, mast cells and macrophages were present in varying frequencies among the tissue compartments of the feline oral cavity. B-lymphocytes were not identified in any of the examined tissues except the tonsils and mandibular lymph nodes. Lymphocytic aggregates (follicles) were found in the palatoglossal folds and the gingiva. We describe the topographical distribution of various leucocyte subsets in the normal healthy feline oral mucosa, and demonstrate regional differences in the distribution of these cells.

  12. Comparative evaluation of eosinophils in normal mucosa, dysplastic mucosa and oral squamous cell carcinoma with hematoxylin-eosin, Congo red, and EMR1 immunohistochemical staining techniques

    PubMed Central

    kargahi, Neda; Razavi, Sayyed Mohammad; Deyhimi, Parviz; Homayouni, Solmaz

    2015-01-01

    Background: Oral squamous cell carcinoma is the most common malignant lesion of the oral cavity, and it involves various molecular mechanisms. The development of oral squamous cell carcinoma is influenced by the host immune cells, such as eosinophils. The present study was conducted to compare the presence of eosinophils in normal mucosa, dysplastic mucosa, and oral squamous cell carcinoma by -hematoxylin- eosin staining, Congo red staining, and epidermal growth factor-like (EGF-like) module containing a mucin–like hormone receptor1 (EMR1) immunohistochemical marker. Methods: In this cross-sectional study, 60 paraffinized samples were selected, consisting of 20 normal mucosae, 20 dysplastic mucosae, and 20 squamous cell carcinoma samples. After confirmation of the diagnosis, the mean number of eosinophils was evaluated by hematoxylin-eosin, Congo red, and immunohystochemical staining techniques. The data were analyzed by SPSS-10 software using the Kruskal-Wallis and Friedman tests. Results: The results showed that the number of eosinophils in dysplastic mucosa was significantly higher than the number in normal mucosa, and the number of eosinophils in squamous cell carcinoma was significantly higher than the number in dysplastic mucosa in all staining techniques (p<0.001). Moreover, the comparison of staining techniques showed a significantly higher number of eosinophils in EMR1immunohistochemicalmarker than were observed when Congo red and hematoxylin - eosin (H&E) staining techniques were used (p<0.001). Conclusion: It can be argued that eosinophil contributes to the identification of lesions that have a higher potential of malignant transformation. Moreover, eosinophil can be suggested as an indicator in the differentiation of oral lesions in cases with borderline diagnosis and in targeted molecular therapy. PMID:26120409

  13. The dynamic structure of a flat small intestinal mucosa studied on the explanted rat jejunum.

    PubMed

    Loehry, C A; Grace, R

    1974-04-01

    Small pieces of jejunum with an intact blood supply were explanted to the anterior abdominal wall in rats. Six weeks after explantation the mucosa appeared totally flat in many areas, both histologically and under the dissecting microscope. The structure of the flattened mucosa was shown to be identical to that in coeliac disease with hypertrophied intervillous ridges. A dynamic study with tritium-labelled thymidine demonstrated a considerably increased turnover in the flat mucosa with some disorganization of cell production and migration.

  14. Papillomavirus infections in the oral and genital mucosa of asymptomatic women.

    PubMed

    Oliveira, Ledy Horto Santos; Santos, Larissa Silva; Silva, Carolina Oliveira; Augusto, Everton Faccini; Neves, Felipe Piedade Gonçalves

    Human papillomavirus (HPV) has been found in several regions of the body, including the oral cavity. Recently, this virus has been associated with oropharyngeal cancer, but little is known about HPV transmission to the oral cavity. We carried out a study to investigate concurrent oral and cervical infections in 76 asymptomatic women attending a healthcare program. Demographic and behavior data were obtained through a structured questionnaire. Oral and cervical mucosa scrapings were collected and stored for DNA extraction. HPV DNA amplification was performed by polymerase chain reaction assay (PCR) using both primers My09/My11 and FAP59/64, followed by HPV typing with restriction fragment length polymorphism analysis (RFLP) and sequencing. The data collected revealed no risk factors for HPV infection in these 76 women. HPV prevalence of 9.2 and 5.3% was found in cervical and oral mucosa, respectively. Concurrent infections by discordant types were detected in one case only. Sequencing procedures allowed us to detect a new putative HPV 17 subtype from the Betapapillomavirus genus. Our results support the view that cervical and oral HPV infections are independent events. The observed low prevalence of both oral and cervical HPV infections could be associated with attendance in a healthcare program.

  15. Two-photon autofluorescence spectroscopy of oral mucosa tissue

    NASA Astrophysics Data System (ADS)

    Edward, Kert; Shilagard, Tuya; Qiu, Suimin; Vargas, Gracie

    2011-03-01

    The survival rate for individuals diagnosed with oral cancer is correlated with the stage of detection. Thus the development of novel techniques for the earliest possible detection of malignancies is of critical importance. Single photon (1P) autofluorescence spectroscopy has proven to be a powerful diagnostic tool in this regard, but 2P (two photon) spectroscopy remains essentially unexplored. In this investigation, a spectroscopic system was incorporated into a custom-built 2P laser scanning microscope. Oral cancer was induced in the buccal pouch of Syrian Golden hamsters by tri-weekly topical application of 9,10-dimethyl-1,2-benzanthracene (DMBA).Three separated sites where investigated in each hamster at four excitation wavelengths from 780 nm to 890 nm. A Total of 8 hamsters were investigated (4 normal and 4 DMBA treated). All investigated sites were imaged via 2p imaging, marked for biopsy, processed for histology and H&E staining, and graded by a pathologist. The in vivo emission spectrum for normal, mild/high grade dysplasia and squamous cell carcinoma is presented. It is shown that the hamsters with various stages of dysplasia are characterized by spectral differences as a function of depth and excitation wavelength, compared to normal hamsters.

  16. Oral mucosa alterations in chronic hepatitis and cirrhosis due to HBV or HCV infection.

    PubMed

    Sulka, Agnieszka; Simon, Krzysztof; Piszko, Paweł; Kalecińska, Ewa; Dominiak, Marzena

    2006-03-01

    The aim of the study was to evaluate the character of lesions within oral mucosa in patients suffering from chronic hepatitis and cirrhosis of the liver due to either HBV or HCV infection. A total of 74 patients treated at the Clinic of Infectious Diseases in Wrocław for chronic hepatitis B (20 patients, group I) and for chronic hepatitis C (23 patients group III) and cirrhosis of the liver due to HBV (15 patients , group II) and HCV (16 patients, group IV) infection. The control group comprised 29 healthy subjects. Lesions within the oral mucosa found on clinical examinations were confirmed with a histopathological evaluation. Patients suffering from chronic hepatitis B revealed leukoplakia (1/20), melanoplakia (1/20), petechiae (1/20), 17 patients from this group did not show any changes. Patients suffering from chronic hepatitis C revealed leukoplakia (6/23), Delbanco's disease (2/23), melanoplakia (1/23), lichen planus (1/23), petechiae (1/23), 12 patients from this group did not show any changes. Patients suffering from cirrhosis of the liver due of HBV infection revealed leukoplakia (3/15) petechiae (2/15), Delbanco's disease (1/15), angular cheilitis (1/15), aphthae (1/15), 7 patients from this group did not reveal any changes. Patients suffering from cirrhosis of the liver due of HCV infection revealed petechiae (2/16), melanoplakia (1/16), candidosis (1/16), labial herpes (1/16), 11 patients from this group did not reveal any changes. In control group we observed leukoplakia (3/29), Delbanco's disease (1/29), labial herpes (1/29), petechiae (1/29), and 23 subjects did not present pathological lesions within the oral mucosa. Results indicate the lack of connection between chronic HBV and HCV infection as well as the stage of the disease with the incidence and character of oral lesions in oral mucosa.

  17. Astrocyte-Like Cells Derived From Human Oral Mucosa Stem Cells Provide Neuroprotection In Vitro and In Vivo

    PubMed Central

    Ganz, Javier; Arie, Ina; Ben-Zur, Tali; Dadon-Nachum, Michal; Pour, Sammy; Araidy, Shareef; Offen, Daniel

    2014-01-01

    Human oral mucosa stem cells (hOMSC) are a recently described neural crest-derived stem cell population. Therapeutic quantities of potent hOMSC can be generated from small biopsies obtained by minimally invasive procedures. Our objective was to evaluate the potential of hOMSC to differentiate into astrocyte-like cells and provide peripheral neuroprotection. We induced hOMSC differentiation into cells showing an astrocyte-like morphology that expressed characteristic astrocyte markers as glial fibrillary acidic protein, S100β, and the excitatory amino acid transporter 1 and secreted neurotrophic factors (NTF) such as brain-derived neurotrophic factor, vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor 1. Conditioned medium of the induced cells rescued motor neurons from hypoxia or oxidative stress in vitro, suggesting a neuroprotective effect mediated by soluble factors. Given the neuronal support (NS) ability of the cells, the differentiated cells were termed hOMSC-NS. Rats subjected to sciatic nerve injury and transplanted with hOMSC-NS showed improved motor function after transplantation. At the graft site we found the transplanted cells, increased levels of NTF, and a significant preservation of functional neuromuscular junctions, as evidenced by colocalization of α-bungarotoxin and synaptophysin. Our findings show for the first time that hOMSC-NS generated from oral mucosa exhibit neuroprotective effects in vitro and in vivo and point to their future therapeutic use in neural disorders. PMID:24477074

  18. Melanoma of the oral mucosa. Clinical cases and review of the literature.

    PubMed

    González-García, Raúl; Naval-Gías, Luis; Martos, Pedro L; Nam-Cha, Syong Hyun; Rodríguez-Campo, Francisco J; Muñoz-Guerra, Mario F; Sastre-Pérez, Jesús

    2005-01-01

    The appearance of primary melanomas of the oral mucosa is uncommon. The aggressiveness of this entity and the absence of any standardized treatment protocol make the prognostic unfortunate. The difficulty to obtain free surgical margins, the elevated tendency to invade in depth and the early haematogenous metastasis have been referred as features which may explain its bad prognosis, even in comparison with cutaneous melanoma. However, no large clinical series exist and actually, clinical cases are the main source of information. Due to the absence of any treatment modality which may substantially increase long-term survival, we suggest the use of resective surgery with wide margins and early diagnosis by means of biopsy for suspicious melanotic-pigmented lesions. In this work we present 2 new cases of primary melanoma of the oral mucosa, with a follow-up period of 72 and 12 months respectively, and we make a review of the literature in relation with this rare entity.

  19. Lesions of the oral mucosa in cocaine users who apply the drug topically.

    PubMed

    Gandara-Rey, J M; Diniz-Freitas, M; Gandara-Vila, P; Blanco-Carrion, A; Garcia-Garcia, A

    2002-01-01

    The use and abuse of cocaine is increasingly frequent in many countries, and the associated problems are increasingly evident. The effects of cocaine in the oral cavity vary depending on the form used and the route of self-administration. In the present study we describe the lesions observed in four patients with a history of topical self-application of cocaine to the oral and/or nasal mucosa, with the aim of relieving pain produced by cocaine-induced cluster headache. In three of the four patients this practice has led to erythematous lesions, while the remaining patient showed gingival recession and bone sequestration. These lesions can probably be attributed to the vasoconstrictor activity of cocaine, and to its caustic effects on the mucosa.

  20. Bacterial-killing effect of atmospheric pressure non-equilibrium plasma jet and oral mucosa response.

    PubMed

    Liu, Dexi; Xiong, Zilan; Du, Tianfeng; Zhou, Xincai; Cao, Yingguang; Lu, Xinpei

    2011-12-01

    Recently, plasma sterilization has attracted increasing attention in dental community for the atmospheric pressure non-equilibrium plasma jet (APNPs), which is driven by a kilohertz pulsed DC power, may be applied to the dental and oral diseases. However, it is still in doubt whether APNPs can effectively kill pathogenic bacteria in the oral cavity and produce no harmful effects on normal oral tissues, especially on normal mucosa. The aim of this study was to evaluate the bacterial-killing effect of APNPs in the biofilms containing a single breed of bacteria (Porphyromonas gingivalis, P.g.), and the pathological changes of the oral mucosa after treatment by APNPs. P.g. was incubated to form the biofilms in vitro, and the samples were divided into three groups randomly: group A (blank control); group B in which the biofilms were treated by APNPs (the setting of the equipment: 10 kHz, 1600 ns and 8 kV); group C in which the biofilms were exposed only to a gas jet without ignition of the plasma. Each group had three samples and each sample was processed for up to 5 min. The biofilms were then fluorescently stained, observed and photographed under a laser scanning confocal microscope. In the animal experiment, six male Japanese white rabbits were divided into two groups randomly (n=3 in each group) in terms of the different post-treatment time (1-day group and 5-day group). The buccal mucosa of the left side and the mucosa of the ventral surface of the tongue were treated by APNPs for 10 min in the same way as the bacterial biofilm experiment in each rabbit, and the corresponding mucosa of the other sides served as normal control. The clinical manifestations of the oral mucosa were observed and recorded every day. The rabbits were sacrificed one or five day(s) after APNPs treatment. The oral mucosa were harvested and prepared to haematoxylin and eosin-stained sections. Clinical observation and histopathological scores were used to assess mucosal changes. The results

  1. Rheological characterization of human fibrin and fibrin-agarose oral mucosa substitutes generated by tissue engineering.

    PubMed

    Rodríguez, I A; López-López, M T; Oliveira, A C X; Sánchez-Quevedo, M C; Campos, A; Alaminos, M; Durán, J D G

    2012-08-01

    In regenerative medicine, the generation of biocompatible substitutes of tissues by in vitro tissue engineering must fulfil certain requirements. In the case of human oral mucosa, the rheological properties of tissues deserve special attention because of their influence in the acoustics and biomechanics of voice production. This work is devoted to the rheological characterization of substitutes of the connective tissue of the human oral mucosa. Two substitutes, composed of fibrin and fibrin-agarose, were prepared in cell culture for periods in the range 1-21 days. The time evolution of the rheological properties of both substitutes was studied by two different experimental procedures: steady-state and oscillatory measurements. The former allows the plastic behaviour of the substitutes to be characterized by estimating their yield stress; the latter is employed to quantify their viscoelastic responses by obtaining the elastic (G') and viscous (G'') moduli. The results demonstrate that both substitutes are characterized by a predominant elastic response, in which G' (order 100 Pa) is roughly one order of magnitude larger than G'' (order 10 Pa). But the most relevant insight is the stability, throughout the 21 days of culture time, of the rheological quantities in the case of fibrin-agarose, whereas the fibrin substitute shows a significant hardening. This result provides evidence that the addition to fibrin of a small amount of agarose allows the rheological stability of the oral mucosa substitute to be maintained. This feature, together with its viscoelastic similitude with native tissues, makes this biomaterial appropriate for potential use as a scaffold in regenerative therapies of human oral mucosa.

  2. Reflectance confocal endomicroscope with optical axial scanning for in vivo imaging of the oral mucosa

    PubMed Central

    Jabbour, Joey M.; Bentley, Julie L.; Malik, Bilal H.; Nemechek, John; Warda, John; Cuenca, Rodrigo; Cheng, Shuna; Jo, Javier A.; Maitland, Kristen C.

    2014-01-01

    This paper presents the design and evaluation of a reflectance confocal laser endomicroscope using a miniature objective lens within a rigid probe in conjunction with an electrically tunable lens for axial scanning. The miniature lens was characterized alone as well as in the endoscope across a 200 µm axial scan range using the tunable lens. The ability of the confocal endoscope to probe the human oral cavity is demonstrated by imaging of the oral mucosa in vivo. The results indicate that reflectance confocal endomicroscopy has the potential to be used in a clinical setting and guide diagnostic evaluation of biological tissue. PMID:25426310

  3. Reflectance confocal endomicroscope with optical axial scanning for in vivo imaging of the oral mucosa.

    PubMed

    Jabbour, Joey M; Bentley, Julie L; Malik, Bilal H; Nemechek, John; Warda, John; Cuenca, Rodrigo; Cheng, Shuna; Jo, Javier A; Maitland, Kristen C

    2014-11-01

    This paper presents the design and evaluation of a reflectance confocal laser endomicroscope using a miniature objective lens within a rigid probe in conjunction with an electrically tunable lens for axial scanning. The miniature lens was characterized alone as well as in the endoscope across a 200 µm axial scan range using the tunable lens. The ability of the confocal endoscope to probe the human oral cavity is demonstrated by imaging of the oral mucosa in vivo. The results indicate that reflectance confocal endomicroscopy has the potential to be used in a clinical setting and guide diagnostic evaluation of biological tissue.

  4. Potential applications of oral brush cytology with liquid-based technology: results from a cohort of normal oral mucosa.

    PubMed

    Kujan, Omar; Desai, Mina; Sargent, Alexandra; Bailey, Andrew; Turner, Andrew; Sloan, Philip

    2006-09-01

    Fifty healthy volunteers were studied to assess the potential applications of oral brush sampling using liquid-based cytology. Three specimens from the buccal mucosa and lateral border of tongue were collected from each subject by using cervical brushes and brooms. The brush was immersed in a preservative fluid. The sample in the preservative fluid was processed according to the manufacturer's directions (SurePath, UK). Slides were stained by the Papanicolaou method and assessed for squamous cell adequacy by the same criteria used for cervical cytology screening. Immunocytochemical staining for FHIT (Fragile Histidine Triad) was applied in liquid-based preparations following the streptavidin-biotin-peroxidase method. Human papillomavirus (HPV) detection was performed using the Hybrid Capture 2 assay (Digene) and the PCR-based Roche AMPLICOR HPV Test. LBC preparation slides showed good sample preservation, specimen adequacy and visualization of cell morphology. Interestingly, nine cases showed borderline cytological abnormalities from apparently normal oral mucosa. All cases showed good quality positive FHIT immunoreactivity staining. All studied cases were high-risk HPV negative using HC2 assay method. However, the AMPLICOR Roche Test detected four samples with positive results for high-risk HPVs. Liquid-based cytology has potential as a screening tool for oral cancer and precancer. The method may also have applications for research and practice in the field of oral cancer and precancer. However a special custom-designed oral cytobrush is required.

  5. A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa.

    PubMed

    Mohanty, Tirthankar; Sjögren, Jonathan; Kahn, Fredrik; Abu-Humaidan, Anas H A; Fisker, Niels; Assing, Kristian; Mörgelin, Matthias; Bengtsson, Anders A; Borregaard, Niels; Sørensen, Ole E

    2015-10-29

    Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins to l-selectin on neutrophils. This led to rapid loss of nuclear membrane and intracellular release of granule proteins with subsequent neutrophil extracellular trap (NET) release independent of elastase and reduced NAD phosphate-oxidase activation. The saliva-induced NETs were more DNase-resistant and had higher capacity to bind and kill bacteria than NETs induced by bacteria or by phorbol-myristate acetate. Furthermore, saliva/sialyl Lewis(X) mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet disease prone to oral ulcers failed to induce NETosis, but for different reasons it demonstrated that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis.

  6. Overgrowth of oral mucosa and facial skin, a novel feature of aspartylglucosaminuria

    PubMed Central

    Arvio, P.; Arvio, M.; Kero, M.; Pirinen, S.; Lukinmaa, P.

    1999-01-01

    Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by deficiency of aspartylglucosaminidase (AGA). The main symptom is progressive mental retardation. A spectrum of different mutations has been reported in this disease, one missense mutation (Cys163Ser) being responsible for the majority of Finnish cases. We were able to examine 66 Finnish AGU patients for changes in the oral mucosa and 44 of these for changes in facial skin. Biopsy specimens of 16 oral lesions, 12 of them associated with the teeth, plus two facial lesions were studied histologically. Immunohistochemical staining for AGA was performed on 15 oral specimens.
  Skin was seborrhoeic in adolescent and adult patients, with erythema of the facial skin already common in childhood. Of 44 patients, nine (20%) had facial angiofibromas, tumours primarily occurring in association with tuberous sclerosis. Oedemic buccal mucosa (leucoedema) and gingival overgrowths were more frequent in AGU patients than in controls (p<0.001).
  Of 16 oral mucosal lesions studied histologically, 15 represented fibroepithelial or epithelial hyperplasias and were reactive in nature. Cytoplasmic vacuolisation was evident in four. Immunohistochemically, expression of AGA in AGU patients' mucosal lesions did not differ from that seen in corresponding lesions of normal subjects. Thus, the high frequency of mucosal overgrowth in AGU patients does not appear to be directly associated with lysosomal storage or with alterations in the level of AGA expression.


Keywords: aspartylglucosaminidase; lysosomal storage disease; oral mucosa; skin tumours PMID:10353787

  7. Texture analysis of CT images in the characterization of oral cancers involving buccal mucosa

    PubMed Central

    Raja, JV; Khan, M; Ramachandra, VK; Al-Kadi, O

    2012-01-01

    Objective The aim of this study was to investigate the usefulness of texture analysis in the characterization of oral cancers involving the buccal mucosa and to assess its effectiveness in differentiating between the various grades of the tumour. Methods Contrast enhanced CT examination was carried out in 21 patients with carcinoma of the buccal mucosa who had consented to retrospective analysis during a research study that was approved by the institutional review board. Two regions of interest (ROIs) were created, one at the site of the lesion and the other at the contralateral normal side. Texture analysis measures of fractal dimension (FD), lacunarity and grey level co-occurrence matrix (GLCM) were computed for each ROI. The numeric data from the two ROIs were compared and were correlated with the tumour grade as confirmed by biopsy. Results The difference between the mean FD and GLCM parameters of the lesion vs the normal ROI were statistically significant (p < 0.05); no significant difference was observed between the three grades of tumour for any of the parameters (p > 0.05). Conclusion Texture analysis on CT images is a potential method in the characterization of oral cancers involving the buccal mucosa and deserves further investigation as a predictor of tumour aggression. PMID:22241875

  8. Th1/Th2 balance in mouse delayed-type hypersensitivity model with mercuric chloride via skin and oral mucosa.

    PubMed

    Ukichi, Kenichirou; Okamura, Taito; Fukushima, Daihei; Morimoto, Mitsuaki; Yamane, Gen-Yuki; Takahashi, Shinichi

    2011-01-01

    In order to compare delayed-type hypersensitivity (DTH) among different exposure sites, we evaluated the sensitization potency of mercuric chloride (HgCl(2)) via exposure to the skin, or oral or esophageal mucosa using the mouse ear swelling test. Furthermore, we investigated in vitro splenocyte proliferation reaction and cytokine profile in HgCl(2)-exposed and control mice. Sensitization with HgCl(2) was established via the skin and oral mucosa but not via the esophageal mucosa. The splenocyte proliferation reaction was significantly enhanced to a similar degree in skin and oral mucosa-sensitized mice compared with in the control mice. IL-10 levels from cultured splenocytes were significantly increased in skin and oral mucosa-sensitized mice compared with those in control mice, whilst IFN-γ significantly increased only in splenocytes from skin-sensitized mice. These results suggest that exposure of the skin or oral mucosa to HgCl(2) can induce DTH, but that Th1/Th2 balance differs according to the site of antigen exposure.

  9. Theoretical Considerations and a Mathematical Model for the Analysis of the Biomechanical Response of Human Keratinized Oral Mucosa

    PubMed Central

    Tsaira, Aikaterini; Karagiannidis, Panagiotis; Sidira, Margarita; Kassavetis, Spyros; Kugiumtzis, Dimitris; Logothetidis, Stergios; Naka, Olga; Pissiotis, Argirios; Michalakis, Konstantinos

    2016-01-01

    Removable complete and partial dentures are supported by the residual alveolar ridges consisting of mucosa, submucosa, periosteum, and bone. An understanding of the biomechanical behavior of the oral mucosa is essential in order to improve the denture-bearing foundations for complete and partially edentulous patients. The purpose of this paper was to examine the biomechanical behavior of the soft tissues supporting a removable denture and develop a model for that reason. Keratinized oral mucosa blocks with their underlying bone were harvested from the maxillary palatal area adjacent to the edentulous ridges of a cadaver. The compressive response of the oral mucosa was tested by using atomic force microscopy. The specimens were first scanned in order their topography to be obtained. The mechanical properties of the specimens were tested using a single crystal silicon pyramidal tip, which traversed toward the keratinized oral mucosa specimens. Loading-unloading cycles were registered and four mathematical models were tested using MATLAB to note which one approximates the force-displacement curve as close as possible: a. spherical, b. conical, c. third order polynomial, d. Murphy (fourth order polynomial, non-linear Hertzian based). The third order polynomial model showed the best accuracy in representing the force-displacement data of the tested specimens. A model was developed in order to analyze the biomechanical behavior of the human oral keratinized mucosa and obtain information about its mechanical properties. PMID:27621708

  10. Delayed contact sensitivity on the lips and oral mucosa due to propolis-case report.

    PubMed

    Brailo, V; Boras, Vanja Vucicevic; Alajbeg, I; Juras, Vidovic

    2006-07-01

    We report a rare case of a patient who was referred to the Department of Oral medicine in Zagreb, Croatia. The patient was 20 years old, otherwise healthy and not taking any medication. She presented with irregular erosions partially covered with pseudomembranes that involved both lips and retrocomissural mucosa. Discrete erosion was also noticed on her lower lingual gingiva in the area 42. She reported a propolis solution self-medication for treatment of recurrent aphthous ulcers. After ten days of propolis application, lip and oral lesions developed. Patch test to propolis was proven. We highlight the fact that some folk medicine medications, such as propolis, although being known for many decades to be helpful in various conditions, in some individuals might lead to unwanted side-effects due to its antigenic potential. Additionally, every colleague, during the differential diagnosis of the oral lesions must bear in mind unwanted reactions to folk medicine products.

  11. In vivo OCT study of neoplastic alterations of the oral cavity mucosa

    NASA Astrophysics Data System (ADS)

    Fomina, Julia V.; Gladkova, Natalia D.; Snopova, Ludmila B.; Shakhova, Natalia M.; Feldchtein, Felix I.; Myakov, Alexey V.

    2004-07-01

    The goal of our study was to conduct a statistical evaluation of the ability of optical coherence tomography (OCT) to detect neoplasia in vivo in oral cavity. The study enrolled 97 patients (35 volunteers with healthy mucosa of the oral cavity-group I, 41 patients with benign conditions-group II, 21 patients with dysplasia or carcinoma-group III). The diagnosis was established by a histopathology examination of biopsy material. Each biopsy site was imaged by OCT beforehand. Sensitivity of 83% and specificity of 98% were observed as a result of OCT image recognition of dysplastic/malignant versus benign/reactive conditions in the oral cavity. The interobserver agreement kappa was 0.76. Such sensitivity and specificity makes OCT a promising tool for non-invasive evaluation of tissue sites suspicious for high-grade dysplasia and cancer.

  12. A Comparative Proteomic Analysis of the Soluble Immune Factor Environment of Rectal and Oral Mucosa

    PubMed Central

    Romas, Laura M.; Hasselrot, Klara; Aboud, Lindsay G.; Birse, Kenzie D.; Ball, T. Blake; Broliden, Kristina; Burgener, Adam D.

    2014-01-01

    Objective Sexual transmission of HIV occurs across a mucosal surface, which contains many soluble immune factors important for HIV immunity. Although the composition of mucosal fluids in the vaginal and oral compartments has been studied extensively, the knowledge of the expression of these factors in the rectal mucosa has been understudied and is very limited. This has particular relevance given that the highest rates of HIV acquisition occur via the rectal tract. To further our understanding of rectal mucosa, this study uses a proteomics approach to characterize immune factor components of rectal fluid, using saliva as a comparison, and evaluates its antiviral activity against HIV. Methods Paired salivary fluid (n = 10) and rectal lavage fluid (n = 10) samples were collected from healthy, HIV seronegative individuals. Samples were analyzed by label-free tandem mass spectrometry to comprehensively identify and quantify mucosal immune protein abundance differences between saliva and rectal fluids. The HIV inhibitory capacity of these fluids was further assessed using a TZM-bl reporter cell line. Results Of the 315 proteins identified in rectal lavage fluid, 72 had known immune functions, many of which have described anti-HIV activity, including cathelicidin, serpins, cystatins and antileukoproteinase. The majority of immune factors were similarly expressed between fluids, with only 21 differentially abundant (p<0.05, multiple comparison corrected). Notably, rectal mucosa had a high abundance of mucosal immunoglobulins and antiproteases relative to saliva, Rectal lavage limited HIV infection by 40–50% in vitro (p<0.05), which is lower than the potent anti-HIV effect of oral mucosal fluid (70–80% inhibition, p<0.005). Conclusions This study reveals that rectal mucosa contains many innate immune factors important for host immunity to HIV and can limit viral replication in vitro. This indicates an important role for this fluid as the first line of defense

  13. Nuclear changes in oral mucosa of alcoholics and crack cocaine users.

    PubMed

    Webber, L P; Pellicioli, A C A; Magnusson, A S; Danilevicz, C K; Bueno, C C; Sant'Ana Filho, M; Rados, P V; Carrard, V C

    2016-02-01

    The effects of drugs of abuse on oral mucosa are only partly understood. The aims of the present study were to: (1) evaluate the frequency of nuclear changes in normal-appearing oral mucosa of alcoholics and crack cocaine users and (2) assess their association with cell proliferation rate. Oral smears were obtained from the border of the tongue and floor of the mouth of 26 crack cocaine users (24 males and 2 females), 29 alcoholics (17 males and 12 females), and 35 controls (17 males and 18 females). Histological slides were submitted to Feulgen staining to assess the frequency of micronuclei (MN), binucleated cells (BN), broken eggs (BE), and karyorrhexis (KR). A significant increase in the frequency of MN was observed in cells exfoliated from the tongue of crack cocaine users (p = 0.01), and alcoholics showed a higher frequency of KR in cells obtained from the floor of the mouth (p = 0.01). Our findings suggest that the use of crack cocaine induces clastogenic effects, whereas alcoholism is associated with higher degrees of keratinization in the floor of the mouth.

  14. Local anaesthesia through the action of cocaine, the oral mucosa and the Vienna group.

    PubMed

    López-Valverde, A; de Vicente, J; Martínez-Domínguez, L; de Diego, R Gómez

    2014-07-11

    Local anaesthesia through the action of cocaine was introduced in Europe by the Vienna group, which includeed Freud, Koller and Königstein. Before using the alkaloid in animal or human experimentation all these scientists tested it on their oral mucosa - so-called self-experimentation. Some of them with different pathologies (that is, in the case of Freud), eventually became addicted to the alkaloid. Here we attempt to describe the people forming the so-called 'Vienna group', their social milieu, their experiences and internal disputes within the setting of a revolutionary discovery of the times.

  15. Effects of oral intake of cetirizine HCl and desloratadine molecules on the middle ear mucosa: an experimental animal study.

    PubMed

    Songu, Murat; Ozkul, Yilmaz; Kirtay, Seyithan; Arslanoglu, Secil; Ozkut, Mahmut; Inan, Sevinc; Onal, Kazim

    2014-04-01

    We have planned to demonstrate histopathologic effects of mid- or long-term oral use of desloratadine and cetirizine HCl molecules on middle ear mucosa of rats. Thirty-six rats were randomized equally into six groups. Desloratadine groups received once daily doses of 1 mg/ml desloratadine for 30 (D30 Group) or 60 (D60 Group) days. The Cetirizine study groups were given once daily doses of 1 mg/ml cetirizine for 30 (S30 Group) or 60 (S60 Group) days. Control groups were given 2 cc physiologic saline using orogastric gavage method through a 12 G gavage catheter for 30 (K30 Group) or 60 (K60) days. At the end of 30 days, D30, S30 and K30 Groups were sacrificed. Tissue samples harvested from groups were evaluated between 1 and 4 Grades for histological characteristics of middle ear canal, eardrum, middle ear epithelium and connective tissue, edema, vascular congestion and inflammatory cells. In the control group no pathological finding was encountered in rats sacrificed on 30 and 60 days. No statistical difference was observed when groups were compared on external ear epithelial tissue, external ear sebaceous gland, middle ear inflammation, and middle ear capillary dilatation both on 30 and 60 days. Tympanic membrane collagen was more evident in D30 and D60 groups when compared with C30 and C60 groups. Comparison of histopathological grading results between 30 and 60 days revealed no significant changes. In conclusion, oral intake of cetirizine and desloratadine preparations has effects of tympanic membrane collagen, degrees of edema and vascular congestion being more prominent with desloratadine molecule.

  16. Identification of Helicobacter spp. in oral secretions vs. gastric mucosa of stray cats.

    PubMed

    Shojaee Tabrizi, A; Jamshidi, Sh; Oghalaei, A; Zahraei Salehi, T; Bayati Eshkaftaki, A; Mohammadi, M

    2010-01-06

    The definite mode of transmission of Helicobacter infection is largely unknown. This study was carried out primarily, to determine the existence of Helicobacter spp. in the oral secretions of stray cats as one of the possible routes of transmission and secondly, to evaluate the accordance between oral and gastric colonization of Helicobacter spp. in these cats. Forty-three adult stray cats were thus studied for the presence of Helicobacter species by quantitative rapid urease test (RUT), cytology and PCR. Helicobacter spp. were found in the oral secretions and gastric biopsies of 93% and 67.5% of the stray cats, respectively. There was not, however, any agreement observed between Helicobacter colonization at these two locations, at neither genus nor species level. These findings suggest that the oral cavity is routinely exposed to transient forms of bacteria and may temporarily harbor Helicobacter spp. Thus, oral cavity as a source of Helicobacter spp. may act as a reservoir for transmission and may not necessarily reflect the colonization status of the gastric mucosa.

  17. Localized Leishmaniasis of the oral mucosa. A report of three cases.

    PubMed

    García de Marcos, José Antonio; Dean Ferrer, Alicia; Alamillos Granados, Francisco; Ruiz Masera, Juan José; Cortés Rodríguez, Begoña; Vidal Jiménez, Alfredo; García Lainez, Ana; Lozano Rodríguez-Mancheno, Aquiles

    2007-08-01

    The term leishmaniasis comprises a group of diseases caused by different species of a protozoon called Leishmania. Leishmaniasis is found worldwide, and is considered to be endemic in 88 countries. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis and mucocutaneous leishmaniasis. Exclusive involvement of the mucosa is very rare. We present a series of three cases of mucosal leishmaniasis located in the oral cavity. The fact that all three cases were recorded in Spain (an area where L. infantum is endemic), suggests that the latter was the causal agent. The only manifestation of leishmaniasis disease in the described cases was the appearance of an oral lesion. Treatment was provided in the form of meglumine antimoniate in two patients, with a favorable response. One of the patients left the hospital after diagnosis, without receiving treatment, and the subsequent course is not known. A review is made of the literature on the subject.

  18. Effects of visible light irradiation on eugenol-treated oral mucosa.

    PubMed

    Fujisawa, Seiichiro; Muraoka, Eitoku; Nakazato, Yoshihiro; Okada, Norihisa

    2005-06-01

    The purpose of this study was to evaluate the histopathological effects of eugenol (EUG) and iso-eugenol (IsoEUG)--with or without visible light (VL) irradiation--on oral mucous membranes. Oral mucous membranes of mice were applied with three agents, EUG, IsoEUG, and aceton (as the control) in the absence or presence of VL irradiation. VL irradiation resulted in more tissue damage for EUG- or IsoEUG-treated mucosa compared to corresponding compounds without VL irradiation, and that damage under IsoEUG treatment was greater than that under EUG treatment. Necrosis, but not apoptosis, was preferentially expressed in EUG- or IsoEUG-treated mucous membranes in the presence of VL irradiation.

  19. Innate tissue fluorescence of the oral mucosa of controls and head-and-neck cancer patients

    NASA Astrophysics Data System (ADS)

    Savage, Howard E.; Kolli, Venkateswara; Ansley, John; Chandawarkar, Rajiv Y.; Alfano, Robert R.; Schantz, Stimson P.

    1995-04-01

    Base line spectral excitation and emission scans were defined for the oral mucosa in a population of 61 controls, 16 oral tongue cancer patients and 2 patients with tongue leukoplakia. A xenon-based fluorescence spectrophotometer (Mediscience Corp.) with a fiberoptic probe (Mediscience Corp.) was used to collect excitation and emission spectra. Two excitation scans ((lambda) Ex 200-360 nm, (lambda) Em 380 nm; (lambda) Ex 240-430 nm, (lambda) Em 450 nm) and two emission scans ((lambda) Ex 300 nm, (lambda) Em 320-580 nm; (lambda) Ex 340 nm, (lambda) Em 360-660 nm) were used to analyze the buccal mucosa (BM), hard palate (HP), floor of mouth (FOM) and dorsal tongue (DT) of 61 control individuals. In 41 controls the lateral tongue site (LT) was added. The same set of scans was performed on tumor lesions and contralateral normal tissues of 16 patients with lateral tongue tumors and on two individuals with leukoplakia of the tongue. Ratios of points on the individual scans were used to quantitate data. The excitation scan ((lambda) Ex 200-360 nm, (lambda) Em 380 nm) and the emission scan ((lambda) Ex 300 nm, (lambda) Em 320-580 nm) were able to statistically discriminate the HP and DT from the BM and FOM. The ratios of intensities of neoplastic mucosa and contralateral sites were significantly different with the excitation scans ((lambda) Ex 200-360 nm, (lambda) Em 380 nm, p < 0.001) and ((lambda) Ex 240-430 nm, (lambda) Em 450 nm, p < 0.01) and with the emission scan ((lambda) Ex 300 nm, (lambda) Em 320-580 nm, p < 0.001). Discrimination was significant with the emission scan ((lambda) Ex 340 nm, (lambda) Em 360- 660 nm, p < 0.07). Innate tissue fluorescence has potential as a monitor of cancer patients and populations at risk for head and neck cancer.

  20. Spectrally resolved fluorescence lifetime imaging to investigate cell metabolism in malignant and nonmalignant oral mucosa cells

    NASA Astrophysics Data System (ADS)

    Rück, Angelika; Hauser, Carmen; Mosch, Simone; Kalinina, Sviatlana

    2014-09-01

    Fluorescence-guided diagnosis of tumor tissue is in many cases insufficient, because false positive results interfere with the outcome. Improvement through observation of cell metabolism might offer the solution, but needs a detailed understanding of the origin of autofluorescence. With respect to this, spectrally resolved multiphoton fluorescence lifetime imaging was investigated to analyze cell metabolism in metabolic phenotypes of malignant and nonmalignant oral mucosa cells. The time-resolved fluorescence characteristics of NADH were measured in cells of different origins. The fluorescence lifetime of bound and free NADH was calculated from biexponential fitting of the fluorescence intensity decay within different spectral regions. The mean lifetime was increased from nonmalignant oral mucosa cells to different squamous carcinoma cells, where the most aggressive cells showed the longest lifetime. In correlation with reports in the literature, the total amount of NADH seemed to be less for the carcinoma cells and the ratio of free/bound NADH was decreased from nonmalignant to squamous carcinoma cells. Moreover for squamous carcinoma cells a high concentration of bound NADH was found in cytoplasmic organelles (mainly mitochondria). This all together indicates that oxidative phosphorylation and a high redox potential play an important role in the energy metabolism of these cells.

  1. Photofrin and 5-aminolevulinic acid permeation through oral mucosa in vitro

    NASA Astrophysics Data System (ADS)

    Flock, Stephen T.; Alleman, Anthony; Lehman, Paul; Blevins, Steve; Stone, Angie; Fink, Louis; Dinehart, Scott; Stern, Scott J.

    1994-07-01

    Photofrin and 5-aminolevulinic acid are photosensitizers that show promise in the photodynamic treatment of cancer, port-wine stains, atherosclerosis and viral lesions. Photofrin is a mixture of porphyrins which, upon the absorption of light, become temporarily cytotoxic. One side-effect associated with the use of Photofrin is long-term cutaneous photosensitivity. It is possible that topical application of this photosensitizing dye will ameliorate such a side-effect. Another way to avoid the cutaneous photosensitivity in photodynamic therapy is to use 5- aminolevulinic acid, which is a porphyrin precursor that causes an increase in the synthesis and concentration of the photosensitizer protoporphyrin IX. 5-aminolevulinic acid is usually applied topically, and so minimizes cutaneous photosensitivity while maximizing the local protoporphyrin concentration. There are a host of disorders in oral mucosa that are potentially treatable by photodynamic therapy. However, since stratum corneum presents an impermeable barrier to many pharmaceuticals, it is not clear that topical application of the photosensitizer will result in a clinically relevant tissue concentration. We have therefore studied the permeation behavior of Photofrin and 5-aminolevulinic acid by applying them to the surface of ex vivo oral mucosa tissue positioned by a Franz diffusion cell. In order to increase the permeability of the photosensitizer across the stratum corneum, we studied the effects of four different drug carriers: phosphate buffered saline, dimethylsulfoxide, ethanol and Azone with isopropyl alcohol.

  2. Comparison of three sampling instruments, Cytobrush, Curette and OralCDx, for liquid-based cytology of the oral mucosa.

    PubMed

    Reboiras-López, M D; Pérez-Sayáns, M; Somoza-Martín, J M; Antúnez-López, J R; Gándara-Vila, P; Gayoso-Diz, P; Gándara-Rey, J M; García-García, A

    2012-01-01

    Exfoliative cytology of the oral cavity is a simple and noninvasive technique that permits the study of epithelial cells. Liquid-based cytology is an auxiliary diagnostic tool for improving the specificity and sensitivity of conventional cytology. The objective of our study was to compare the quality of normal oral mucosa cytology samples obtained using three different instruments, Cytobrush®, dermatological curette and Oral CDx® for liquid-based cytology. One hundred four cytological samples of oral cavity were analyzed. Samples were obtained from healthy volunteer subjects using all three instruments. The clinical and demographic variables were age, sex and smoking habits. We analyzed cellularity, quality of the preparation and types of cells in the samples. All preparations showed appropriate preparation quality. In all smears analyzed, cells were distributed uniformly and showed no mucus, bleeding, inflammatory exudate or artifacts. We found no correlation between the average number of cells and the type of instrument. The samples generally consisted of two types of cells: superficial and intermediate. No differences were found among the cytological preparations of these three instruments. We did not observe basal cells in any of the samples analyzed.

  3. Evaluation of oral mucosa epithelium in type II diabetic patients by an exfoliative cytology method.

    PubMed

    Jajarm, Hassan Hosseinpour; Mohtasham, Nooshin; Moshaverinia, Maryam; Rangiani, Afsaneh

    2008-09-01

    Diabetes mellitus is a common metabolic disease that causes chronic hyperglycemia and disturbances in carbohydrate, lipid, and protein metabolism. Although diabetes can cause considerable cellular changes, this field has attracted little research. We therefore decided to evaluate the quantitative and qualitative changes in oral epithelial cells using an exfoliative cytology method. In 30 control individuals and 30 patients with type II diabetes, smears were obtained from two distinct oral sites: the buccal mucosa and tongue dorsum. The oral smears were stained using Papanicolaou solution. Quantitative and qualitative changes were evaluated in each slide. For this purpose, 50 clearly defined cells in each slide were microscopically evaluated, and photographs were subjected to computerized morphometric analysis. Cytoplasmic and nuclear areas in the diabetic group were significantly higher than in the control group. The cytoplasmic/nuclear ratio was lower in the control group. At both smear sites, the proportion of cells with nuclear changes was higher in the diabetic group. Diabetes mellitus can cause alterations in the oral epithelium that are detectable with this exfoliative cytology method. The method may be viable in evaluating this disease.

  4. Treating animal bites: susceptibility of Staphylococci from oral mucosa of cats.

    PubMed

    Muniz, I M; Penna, B; Lilenbaum, W

    2013-11-01

    Infected wounds determined by cats' bites represent high costs to public health, and their adequate treatment relies on the knowledge of the antimicrobial susceptibility of bacterial agents found in the oral microbiota. Members of the genus Staphylococcus sp. belong to the microbiota of the oral mucosa of cats and are frequently involved in secondary infections of these wounds. This study aimed to evaluate the antimicrobial susceptibility of Staphylococcus species isolated from oral mucosa of cats. Samples were collected from 200 clinically healthy cats and processed by standard bacteriological methods and tested for susceptibility to a panel of 16 antimicrobials. A total of 212 staphylococci isolates were obtained from 141 of the 200 cats (70.5%), and more than one colony was recognized in 53 cases. Coagulase-negative species were most frequently found (89.6%) distributed among Staphylococcus xylosus (50.9%), Staphylococcus felis (27.4%), Staphylococcus simulans (6.1%) and Staphylococcus sciuri (5.2%). Coagulase-positive species (10.4%) were distributed among Staphylococcus aureus (4.7%) and Staphylococcus intermedius group (SIG) (5.7%). Regarding to antimicrobial resistance, 178 isolates (83.9%) were resistant to at least one antimicrobial, and rifampicin showed the best results with 100% of sensitive strains. Conversely, high rates of resistance were observed for penicillin and tetracycline (56.1%). The 212 staphylococci isolates and 30 (14.1%) strains were resistant to methicillin (on the disc susceptibility test) and may be preliminarily considered as methicilin-resistant staphylococci. In conclusion, this study reports important rates of antimicrobial resistance among the species of Staphylococcus isolated from clinical specimens of cats, which must be considered for the treating of cats' bites in humans.

  5. Hypermethylation of the p16 gene in normal oral mucosa of smokers.

    PubMed

    von Zeidler, S Ventorin; Miracca, E C; Nagai, M A; Birman, E G

    2004-11-01

    The oral cavity is the sixth most common anatomical localization of head and neck carcinoma in men. Detection of oral carcinomas in the early asymptomatic stages improves cure rates and the quality of life. Tobacco smoking and alcohol drinking are the most important known risk factors for the development of head and neck tumors, suggesting that the exposure to these risk factors may increase the predisposition for genetic and epigenetic alterations, such as DNA methylation. The presence of methylated CpG islands in the promoter region of human genes can suppress their expression due to the presence of 5-methylcytosine that interferes with the binding of transcription factors or other DNA-binding proteins repressing transcription activity. Hypermethylation leading to the inactivation of some tumor suppressor genes, such as p16, has been pointed out as an initial event in head and neck cancer. Our aim was to evaluate an early diagnostic method of oral pre-cancerous lesions through the analysis of methylation of the p16 gene. DNA samples from normal oral mucosa and posterior tongue border from 258 smokers, without oral cancer, were investigated for the occurrence of p16 promoter hypermethylation. The methylation status of the p16 gene was analyzed using MS-PCR (methylation-sensitive restriction enzymes and PCR amplification), MSP (Methylation-specific PCR) or direct DNA sequence of bisulfite modified DNA. Hyper-methylation was detected in 9.7% (25/258) of the cases analyzed. These findings provide further evidence that epigenetic alteration, leading to the inactivation of the p16 tumor suppressor gene is an early event that might confer cell growth advantages contributing to the tumorigenic process. Thus, the detection of abnormal p16 methylation pattern may be a valuable tool for early oral cancer detection.

  6. Remodeling of the residual gastric mucosa after roux-en-y gastric bypass or vertical sleeve gastrectomy in diet-induced obese rats.

    PubMed

    Arapis, Konstantinos; Cavin, Jean Baptiste; Gillard, Laura; Cluzeaud, Françoise; Lettéron, Philippe; Ducroc, Robert; Le Beyec, Johanne; Hourseau, Muriel; Couvelard, Anne; Marmuse, Jean-Pierre; Le Gall, Maude; Bado, André

    2015-01-01

    Whereas the remodeling of intestinal mucosa after bariatric surgeries has been the matter of numerous studies to our knowledge, very few reported on the remodeling of the residual gastric mucosa. In this study, we analyzed remodeling of gastric mucosa after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in rats. Diet-induced obese rats were subjected to RYGB, VSG or sham surgical procedures. All animals were assessed for food intake, body-weight, fasting blood, metabolites and hormones profiling, as well as insulin and glucose tolerance tests before and up to 5 weeks post-surgery. Remodeling of gastric tissues was analyzed by routine histology and immunohistochemistry studies, and qRT-PCR analyses of ghrelin and gastrin mRNA levels. In obese rats with impaired glucose tolerance, VSG and RYGB caused substantial weight loss and rats greatly improved their oral glucose tolerance. The remaining gastric mucosa after VSG and gastric pouch (GP) after RYGB revealed a hyperplasia of the mucous neck cells that displayed a strong immunoreactivity for parietal cell H+/K+-ATPase. Ghrelin mRNA levels were reduced by 2-fold in remaining fundic mucosa after VSG and 10-fold in GP after RYGB. In the antrum, gastrin mRNA levels were reduced after VSG in line with the reduced number of gastrin positive cells. This study reports novel and important observations dealing with the remaining gastric mucosa after RYGB and VSG. The data demonstrate, for the first time, a hyperplasia of the mucous neck cells, a transit cell population of the stomach bearing differentiating capacities into zymogenic and peptic cells.

  7. Role of endogenous prostaglandins in protection of rat gastric mucosa by tripotassium dicitrate bismuthate.

    PubMed

    Malandrino, S; Bestetti, A; Fumagalli, G; Borsa, M; Viganó, T; Tonon, G

    1987-10-01

    Gross and microscopic examination of rat gastric mucosa demonstrated that intragastric administration to rats of tripotassium dicitrate bismuthate (TDB), a colloidal bismuth compound, protects against gastric lesions induced by 85% ethanol. Indomethacin, a prostaglandin synthetase inhibitor, significantly blocked the gastric mucosal protective effect of TDB. The release of gastric mucosal prostaglandins was greater in animals treated with TDB than in control animals, both time- and dose-dependently. These results seem to indicate involvement of prostaglandins in the action of TDB.

  8. PCR based detection of HPV 16 and 18 genotypes in normal oral mucosa of tobacco users and non-users.

    PubMed

    Pattanshetty, S; Kotrashetti, V S; Nayak, R; Bhat, K; Somannavar, P; Babji, D

    2014-08-01

    There is increasing evidence of a causal association between human papillomavirus (HPV) and oral squamous cell carcinoma (OSCC). Several studies have shown that HPV is associated with increased risk of oral cancer independent of exposure to tobacco and alcohol. The association is valid for HPVs 16 and 18, which generally are considered high risk types, because they have been detected in oral dysplastic lesions and cancers. We determined the baseline prevalence of HPVs 16 and 18 in normal oral mucosa of individuals with and without tobacco habit. PCR was used for DNA collected by oral smears to detect HPV 16/18 DNA in normal oral mucosa of 60 healthy individuals who were assigned to two groups of 30 subjects each. One group had a tobacco habit, the other did not. The tobacco user group comprised individuals who were tobacco chewers only. Sixty-five percent of individuals were positive for HPV 16/18 DNA, but HPV 16/18 positivity was less in individuals with tobacco habit than in those without tobacco habit. No significant association was found between the presence of HPVs and gender, age or duration of chewing habit, or between groups with and without a tobacco habit. We propose that HPVs16 and 18 commonly are present in normal oral mucosa and emphasize the importance of distinguishing clinical, subclinical and latent HPV infections when investigating HPVs and OSCC.

  9. The role of autofluorescence diagnostics in the diseases of oral mucosa

    NASA Astrophysics Data System (ADS)

    Kosciarz-Grzesiok, A.; Waskowska, J.; Kawczyk-Krupka, A.; Ledwon, A.; Misiak, A.; Latos, W.; Koszowski, R.; Sieron-Stoltny, K.; Sieron, A.

    2008-02-01

    Introduction. Life induced fluorescence (LIFE) diagnostics can be used as an imaging system of precancerous and neoplastic lesions of the oral mucosa. Neoplastic lesions are visible in pseudo colours, healthy tissue in green colour and abnormal tissue in red colour. All the observed colours present different intensity. Colour intensity is relevant to the grade of dysplasia, carcinoma progress and is called Numerological Value of Color Index (NCV). The aim of our study was to find correlation between autofluorescence diagnostics combined with NCV assessment and histopathological findings of taken specimen biopsies. Patients and methods. 10 patients participated in our study. Lesions affected a variety of intraoral sites. The most common location was: buccal, gingival and mandibular mucosa. Patients were examined using Life Induced Fluorescence diagnosis (400 - 750 nm wavelength) with Numerological Value of Color index (NCV) using Onco LIFE system. Afterwards the specimen biopsies from the lesions were taken and histopathological examination was performed. Results. Different NCV and dependence of NCV on the histopathological findings were observed. Conclusion. Diagnostic procedures with the application of white-light imaging with LIFE imaging is not only a significantly faster method and a better diagnostic tool of preneoplastic and neoplastic lesions, but there exist also correlations between measured NCV and histopathological diagnosis. The farther investigations are necessary in order to prove these preliminary findings.

  10. Raman fiberoptic probe for monitoring human tissue engineered oral mucosa constructs

    NASA Astrophysics Data System (ADS)

    Khmaladze, Alexander; Kuo, Shiuhyang; Okagbare, Paul; Marcelo, Cynthia L.; Feinberg, Stephen E.; Morris, Michael D.

    2013-02-01

    In oral and maxillofacial surgery, there is a need for tissue engineered constructs for dental implants, reconstructions due to trauma, oral cancer or congenital defects. A non-invasive quality monitoring of the fabrication of tissue engineered constructs during their production and implantation is a required component of any successful tissue engineering technique. We demonstrate the design and application of a Raman spectroscopic probe for rapid and noninvasive monitoring of Ex Vivo Produced Oral Mucosa Equivalent constructs (EVPOMEs). We conducted in vivo studies to identify Raman spectroscopic failure indicators for EVPOMEs (already developed in vitro), and found that Raman spectra of EVPOMEs exposed to thermal stress showed correlation of the band height ratio of CH2 deformation to phenylalanine ring breathing modes, providing a Raman metric to distinguish between viable and nonviable constructs. This is the first step towards the ultimate goal to design a stand-alone system, which will be usable in a clinical setting, as the data processing and analysis will be performed with minimal user intervention, based on already established and tested Raman spectroscopic indicators for EVPOMEs.

  11. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa

    PubMed Central

    Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M.

    2017-01-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses. PMID:28060843

  12. Co-administration of water containing magnesium ion prevents loxoprofen-induced lesions in gastric mucosa of adjuvant-induced arthritis rat.

    PubMed

    Nagai, Noriaki; Takeda, Atsushi; Itanami, Yuri; Ito, Yoshimasa

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) comprise one of the most frequently used classes of medicines in the world; however, NSAIDs have significant side effects, such as gastroenteropathy, and rheumatoid arthritis patients taking NSAIDs are more susceptible to NSAID-induced gastric lesions as compared to patients with other diseases. In Asian countries, loxoprofen has been used clinically for many years as a standard NSAID. We demonstrate the preventive effect of the co-administration of water containing magnesium ion (magnesium water, 1-200 µg/kg) on the ulcerogenic response to loxoprofen in adjuvant-induced arthritis (AA) rats. Oral administration of loxoprofen (100 mg/kg) caused hemorrhagic lesions in the gastric mucosa of AA rats 14 d after adjuvant injection, and, following loxoprofen administration, the lesion score of AA rats was significantly higher than that of normal rats. The expression of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide (NO) production in the gastric mucosa of AA rats were also increased by the administration of loxoprofen, and the increase in lesions and NO were prevented by the administration of aminoguanidine, an iNOS inhibitor. The co-administration of magnesium water decreased the ulcerogenic response to loxoprofen in AA rats. In addition, the co-administration of magnesium water attenuated the increase in iNOS mRNA expression and NO production in AA rats receiving loxoprofen. These results suggest that the oral co-administration of magnesium water to AA rats has a potent preventive effect on the ulcerogenic response to loxoprofen, probably by inhibiting the rise in iNOS and NO levels in the gastric mucosa.

  13. Concanavalin A and ricinus communis receptor sites in normal human oral mucosa.

    PubMed

    Dabelsteen, E; Fejerskov, O; Norén, O; Mackenzie, I C

    1978-01-01

    Fluorescein conjugates of concanavalin A (Con-A) and Ricinus communis fraction 120 (RCA120) were shown to bind to the cell surfaces of basal and spinous cell layers in oral buccal mucosa. Palatal epithelium showed distinct binding to basal and spinous cells; cell membranes in the granular layer occasionally bound Con-A and always RCA120. The ultrastructural localization of Con-A binding sites on exfoliated buccal cells was detected by the Con-A peroxidase staining method. The Con-A receptors were seen on the cell surface in association with the outer leaflet of the plasma membrane. The reaction products appeared as a homogeneous, electron-dense layer containing irregularly distributed globules.

  14. Blood flow and epithelial thickness in different regions of feline oral mucosa and skin.

    PubMed

    Johnson, G K; Squier, C A; Johnson, W T; Todd, G L

    1987-07-01

    The relationship between epithelial thickness and blood flow was examined in 6 mucosal and 3 skin regions of the cat. Blood flow to these tissues was determined using the radiolabelled microsphere method. From histologic sections the proportion of the tissue biopsy occupied by epithelium and the average epithelial thickness were calculated. The oral tissues had a significantly higher blood flow than the skin regions (p less than 0.05). In terms of epithelial thickness, the tissues could be divided into 4 groups (p less than 0.05). These were: a) palate; b) gingival regions and dorsum of the tongue; c) lip and buccal mucosa; d) all skin regions. When epithelial thickness was related to blood flow there was a significant positive correlation (p less than 0.005) indicating that a thicker epithelium is associated with a higher blood flow. This finding may reflect the greater metabolic demands of the thicker epithelia.

  15. Safety assessment of oral photodynamic therapy in rats.

    PubMed

    Fontana, Carla R; Lerman, Mark A; Patel, Niraj; Grecco, Clovis; Costa, Carlos A de Souza; Amiji, Mansoor M; Bagnato, Vanderlei S; Soukos, Nikolaos S

    2013-02-01

    Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a photosensitizer) and visible light to destroy target cells (e.g., malignant, premalignant, or bacterial cells). The aim of this study was to investigate the response of normal rat tongue mucosa to PDT following the topical application of hematoporphyrin derivative (Photogem®), Photodithazine®, methylene blue (MB), and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One hundred and thirty three rats were randomly divided in various groups: the PDT groups were treated with the photosensitizers for 10 min followed by exposure to red light. Those in control groups received neither photosensitizer nor light, and they were subjected to light exposure alone or to photosensitizer alone. Fluorescent signals were obtained from tongue tissue immediately after the topical application of photosensitizers and 24 h following PDT. Histological changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT treatment. Fluorescence was detected immediately after the application of the photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in all experimental groups at all evaluation time points. The results suggest that there is a therapeutic window where PDT with Photogem®, Photodithazine®, MB, and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria without damaging normal oral tissue.

  16. Indigestible material attenuated changes in apoptosis in the fasted rat jejunal mucosa.

    PubMed

    Kakimoto, Takashi; Fujise, Takehiro; Shiraishi, Ryosuke; Kuroki, Tsukasa; Park, Jae Myung; Ootani, Akifumi; Sakata, Yasuhisa; Tsunada, Seiji; Iwakiri, Ryuichi; Fujimoto, Kazuma

    2008-03-01

    We have previously demonstrated that fasting induced apoptosis and decreased cell proliferation in the rat intestinal mucosa. The aim was to investigate the effect of expanded polystyrene as indigestible material on apoptosis and cell proliferation in rat small intestinal mucosa during fasting. Male SD rats were divided into 3 groups. The first group was fed with chow and water ad libitum. The second group fasted for 72 hrs. The third group was fasted for 24 hrs and was fed expanded polystyrene. Intestinal apoptosis was evaluated by percent fragmented DNA assay, terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end-labeling (TUNEL) staining, and caspase-3 assay. Cell proliferation was analyzed by 5-bromo-2'-deoxyuridine (5-BrdU) uptake. Truncal vagotomy was performed to evaluate a role of the central nervous system. In the 72-hr fasted rat, mucosal height of the rat jejunum was decreased to 73% of that in rats fed ad libitum, and this decrease was partly restored to 90% in rats fed expanded polystyrene. The fragmented DNA was increased in fasted rats (28.0%) when compared with that in rats fed ad libitum (2.6%). The increase in fragmented DNA in fasted rats was recovered by feeding them expanded polystyrene (8.3%). TUNEL staining confirmed this result. The effect of polystyrene on apoptosis was decreased by truncal vagotomy. Expression of cleaved caspase-3 was increased in fasted rats, which was then decreased by feeding of expanded polystyrene. In contrast to apoptosis, feeding of expanded polystyrene had no reconstructive effect on 5-BrdU uptake in the intestinal epithelium, which was decreased by fasting to 60% of that in rats fed ad libitum. In conclusion, feeding of indigestible material partly restored the decrease in intestinal mucosal length in the fasted rats through the apoptotic pathway without any influence on BrdU uptake. Further exploration focused on the mechanism of this effect of indigestible material is required.

  17. The layered resolved microstructure and spectroscopy of mouse oral mucosa using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Zhuo, Shuangmu; Chen, Jianxin; Jiang, Xingshan; Xie, Shusen; Chen, Rong; Cao, Ning; Zou, Qilian; Xiong, Shuyuan

    2007-08-01

    The layered-resolved microstructure and spectroscopy of mouse oral mucosa are obtained using a combination of multiphoton imaging and spectral analysis with different excitation wavelengths. In the keratinizing layer, the keratinocytes microstructure can be characterized and the keratinizing thickness can be measured. The keratin fluorescence signal can be further characterized by emission maxima at 510 nm. In the epithelium, the cellular microstructure can be quantitatively visualized with depth and the epithelium thickness can be determined by multiphoton imaging excited at 730 nm. The study also shows that the epithelial spectra excited at 810 nm, showing a combination of NADH and FAD fluorescence, can be used for the estimation of the metabolic state in epithelium. Interestingly, a second-harmonic generation (SHG) signal from DNA was observed for the first time within the epithelial layer in backscattering geometry and provides the possibility of analyzing the chromatin structure. In the stroma, the combination of multiphoton imaging and spectral analysis excited at 850 nm in tandem can obtain quantitative information regarding the biomorphology and biochemistry of stroma. Specifically, the microstructure of collagen, minor salivary glands and elastic fibers, and the optical property of the stroma can be quantitatively displayed. Overall, these results suggest that the combination of multiphoton imaging and spectral analysis with different excitation wavelengths has the potential to provide important and comprehensive information for early diagnosis of oral cancer.

  18. Analysis of the influence of parenteral cancer chemotherapy on the health condition of oral mucosa

    PubMed Central

    Rahnama, Mansur; Madej-Czerwonka, Barbara; Jastrzębska-Jamrogiewicz, Izabela

    2015-01-01

    Aim of the study The present study was aimed at estimating the prevalence of oral complications in cancer patients receiving chemotherapy. Material and methods The study was conducted on a group of 58 patients treated with chemotherapy (study group). The control group consisted of 30 healthy patients. Dental status and oral mucosa were examined using the criteria of the National Cancer Institute Toxicity Criteria Scale. The levels of stimulated and unstimulated saliva flow were analysed. Results In the group of patients treated with chemotherapy, 59% of patients had inflammatory changes of the soft tissues of the mouth, such as erythema, erosions, or ulcers, which were discovered during dental examination. Such changes occurred in only 10% of patients in the control group. Six of the patients treated with chemotherapy reported pain with intensity was so severe that it caused swallowing difficulties. Patients in the study group frequently complained about the presence of dry mouth, taste disturbances, nausea, and vomiting. These symptoms occurred in 70% of patients undergoing oncological treatment. In both stimulated and unstimulated saliva secretion, the rates were significantly lower in patients from the research group, when compared to the control group. PMID:26199575

  19. Exfoliative cytology of the oral mucosa: comparison of two collection methods.

    PubMed

    Queiroz, Juliana Brusadin; Lima, Celina Faig; Burim, Rafael Augusto; Brandao, Adriana Aigotti Haberbeck; Cabral, Luiz Antonio Guimaraes; Almeida, Janete Dias

    2010-01-01

    This study compared the sampling efficacy of a cytobrush and metal spatula for exfoliative cytology of the oral mucosa. Thirty students with no detectable oral alterations upon clinical examination were submitted to exfoliative cytology of the lateral border of the tongue, using a metal spatula on the left side and a cytobrush on the right side. The smears were stained using the Papanicolaou technique and evaluated for cellularity, cell type, cell distribution, homogeneity, and cellular distortion, as well as the presence of mucus, inflammatory infiltrate, and hemorrhage. A statistical test (Z-test) with a 95% confidence interval (CI) showed a significant difference between the metal spatula and cytobrush in terms of cellularity (p = 0.02) and homogeneity (p = 0.01). No difference between the two methods was observed regarding cell type (p = 0.4, Z-test) or cell distribution for the 95% confidence interval (p = 0.2, Fisher's test). Cell distortion and the presence of mucus were observed in five cases that used the metal spatula and in two cases that used the cytobrush. No hemorrhage or inflammatory infiltrate was detected in any of the slides. Based on the results of this study, the cytobrush produced qualitatively better smears in terms of cellularity and homogeneity compared to the metal spatula.

  20. Interactions between ingested kaolinite and the intestinal mucosa in rat: proteomic and cellular evidences.

    PubMed

    Reichardt, François; Habold, Caroline; Chaumande, Bertrand; Ackermann, Alain; Ehret-Sabatier, Laurence; Le Maho, Yvon; Angel, Fabielle; Liewig, Nicole; Lignot, Jean-Hervé

    2009-02-01

    Although some of the effects of clay ingestion by humans and animals, such as gastrointestinal wellness and the increase in food efficiency are well known, the underlying mechanisms are not yet fully understood. Therefore, the interactions between the intestinal mucosa and kaolinite particles and their effects on mucosal morphology were observed using light microscopy (LM), transmission electron microscopy (TEM), conventional (CSEM) and environmental (ESEM) scanning electron microscopy combined with an EDX micro-analysis system. Kaolinite consumption, given with free access to rats, varied considerably from one animal to the other but was regular through time for each individual. Some kaolinite particles appeared chemically dissociated in the lumen and within the mucus barrier. Aluminium (Al) originating from ingested clay and present in the mucus layer could directly cross the intestinal mucosa. A significant increase in the thickness of the villi with large vacuoles at the base of the mucosal cells and a decrease in the length of enterocyte microvilli characterized complemented animals. The proteomic analyses of the intestinal mucosa of complemented rats also revealed several modifications in the expression level of cytoskeleton proteins. In summary, kaolinite particles ingested as food complement interact with the intestinal mucosa and modify nutrient absorption. However, these data, together with the potential neurotoxicity of Al, need further investigation.

  1. Characterization of epidermal growth factor receptors on plasma membranes isolated from rat gastric mucosa

    SciTech Connect

    Hori, R.; Nomura, H.; Iwakawa, S.; Okumura, K. )

    1990-06-01

    The binding of human epidermal growth factor (hEGF), beta-urogastrone, to plasma membranes isolated from rat gastric mucosa was studied to characterize gastric EGF receptors. The binding of ({sup 125}I)hEGF was temperature dependent, reversible, and saturable. A single class of binding sites for EGF with a dissociation constant of 0.42 nM and maximal binding capacity of 42 fmol/mg protein was suggested. There was little change in the binding of ({sup 125}I)hEGF upon addition of peptide hormones (secretin, insulin), antiulcer drugs (cimetidine), or an ulcer-inducing reagent (aspirin). Cross-linking of ({sup 125}I)hEGF to gastric plasma membranes with the use of disuccinimidyl suberate resulted in the labeling of a protein of 150 kDa. These results indicate the presence of EGF receptors on plasma membranes of rat gastric mucosa.

  2. Metabolism of heme and bilirubin in rat and human small intestinal mucosa.

    PubMed Central

    Hartmann, F; Bissell, D M

    1982-01-01

    Formation of heme, bilirubin, and bilirubin conjugates has been examined in mucosal cells isolated from the rat upper small intestine. Intact, viable cells were prepared by enzymatic dissociation using a combined vascular and luminal perfusion and incubated with an isotopically labeled precursor, delta-amino-[2,3-3H]levulinic acid. Labeled heme and bile pigment were formed with kinetics similar to those exhibited by hepatocytes. Moreover, the newly formed bilirubin was converted rapidly to both mono- and diglucuronide conjugates. In addition, cell-free extracts of small intestinal mucosa from rats or humans exhibited a bilirubin-UDP-glucuronyl transferase activity that was qualitatively similar to that present in liver. The data suggest that the small intestinal mucosa normally contributes to bilirubin metabolism. PMID:6806320

  3. [The x-ray microanalysis of the mucosa of the rat small intestine].

    PubMed

    Pogorelov, A G; Matys, Iu V

    1990-01-01

    A rat small intestine mucosa is shown to accumulate significant amount of potassium and chloride. There was found a correlation between the content of these chemical elements and glycoprotein compartmentalization in goblet cell secret, brush border of enterocytes and a mucus layer. In this connection a role of mucus glycoproteins in membrane digestion is discussed. For preparation of samples the cryotechniques of electron microscopy are used.

  4. Analysis of acute impact of oleoresin capsicum on rat nasal mucosa using scanning electron microscopy.

    PubMed

    Catli, Tolgahan; Acar, Mustafa; Olgun, Yüksel; Dağ, İlknur; Cengiz, Betül Peker; Cingi, Cemal

    2015-01-01

    Analysis of acute cellular changes seen in nasal mucosa of Wistar-Albino rats exposed to different doses of oleoresin capsicum for various time periods by means of scanning electron microscopy. Thirty-five Wistar-Albino rats were divided into five groups of seven rats each. 6-gram oleoresin capsicum per second was sprayed into cages of the groups except group 1. Spray times and duration of exposure to pepper gasses were different for each group. Thirty minutes after the exposure, the animals were killed and specimens from their nasal mucosas were harvested and examined under scanning electron microscope. Mucosal damage was scored from 0-4 points. Mean values of nasal mucosa damage scores of the groups were calculated and compared statistically. Average damage scores of the groups exposed to identical doses of oleoresin capsicum for various exposure times were compared and a statistically significant difference was seen between Groups 2 and 3 (p < 0.05), however the difference between Groups 4 and 5 was insignificant (p > 0.05). Average damage scores of the groups exposed to various doses for identical exposure times were compared, and statistically significant differences were observed between Groups 2 and 4 and also Groups 3 and 5 (p < 0.05). Outcomes of our study have demonstrated that pepper gas exerts destructive changes on rat nasal mucosa. The extent of these destructive changes increases with the prolonged exposure to higher doses. Besides, exposure time also stands out as an influential factor on the extent of the destructive changes.

  5. Evaluation of the morphological changes of gastric mucosa induced by a low concentration of acetic acid using a rat model.

    PubMed

    Nakao, Ken-ichiro; Ro, Ayako; Kibayashi, Kazuhiko

    2014-02-01

    Oral ingestion of concentrated acetic acid causes corrosive injury of the gastrointestinal tract. To assess the effects of a low concentration of acetic acid on gastric mucosa, we examined the gastric mucosal changes in rats at 1 and 3 days after the injection of 5% or 25% acetic acid into the gastric lumen. The area of the gastric ulcerative lesions in the 25% acetic acid group was significantly larger than that in the 5% acetic acid group. The lesion area was reduced significantly at 3 days after injection in the 5% acetic acid group, whereas no significant difference in lesion area was observed at 1 and 3 days in the 25% acetic acid group. Histologically, corrosive necrosis was limited to the mucosal layer in the 5% acetic acid group, whereas necrosis extended throughout the gastric wall in the 25% acetic acid group. At 3 days post-injection, the 25% acetic acid group showed widespread persistent inflammation, whereas the 5% acetic acid group showed widespread appearance of fibroblasts indicative of a healing process. These results indicate that a low concentration of acetic acid damages the gastric mucosa and that the degree of mucosal damage depends on the concentration of acetic acid.

  6. Diagnosis and indications for low-intensity laser therapy of the pathology of the oral cavity mucosa of patients with hematologic and gastroenteric diseases

    NASA Astrophysics Data System (ADS)

    Kunin, Anatoly A.; Minakov, E. V.; Sutscenko, A. V.; Vornovsky, V. A.; Dunaeva, S. V.; Stepanov, Nicolay N.; Shumilovitch, Bogdan R.

    1996-11-01

    In the recent years low intensity laser irradiation is made use of in stomatology with the view of treating numerous diseases of the oral cavity mucosa and parodontium. The oral cavity mucosa lesions caused by the internal organs diseases, especially those of blood and the gastroenteric tract, constitute a particular group. Such diseases are usually manifested by an inflammation, erosions, ulcers, hemorrhages. An abundant microflora of the oral cavity and diminished immunity of the patients contribute to the possibility of septicaemia development. Laser therapy of the oral cavity mucosa lesions according to strictly defined indications promotes rapid healing of ulcers, arresting the oral cavity mucosa inflammation, providing a reduction in bleeding and presents a safe prophylactic means of stomatogenic sepsis.

  7. Sodium-iodide symporter mediates iodide secretion in rat gastric mucosa in vitro.

    PubMed

    Josefsson, Malin; Evilevitch, Lena; Weström, Björn; Grunditz, Torsten; Ekblad, Eva

    2006-03-01

    In vivo studies on rats have demonstrated that considerable amounts of iodide are transported from the bloodstream into the gastric lumen. The mechanisms for and functional significance of this transport are poorly understood. Active (driven by Na(+)/K(+)-ATPase) iodide transport into thyroid follicular cells is mediated by the sodium-iodide symporter (NIS), which is also abundantly expressed in gastric mucosa. We aimed to further investigate the iodide transport in gastric mucosa and the possible role of NIS in this transport process. Iodide transport in rat gastric mucosa was studied in vitro in an Ussing chamber system using (125)I as a marker. The system allows measurements in both directions over a mucosal specimen. A considerable transport of iodide (from the serosal to the mucosal side) was established across the gastric mucosa, whereas in the opposite direction (mucosa to serosa), iodide transport was negligible. Sodium perchlorate (NaClO(4)), a competitive inhibitor of NIS, and ouabain, an inhibitor of the Na(+)/K(+)-ATPase, both attenuated gastric iodide transport from the serosal to the mucosal side. To investigate a possible neuroendocrine regulation of the iodide transport identified to occur from the serosal to the mucosal side of the stomach, thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP), histamine, or nitric oxide donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) was added. None of these substances influenced the iodide transport. We conclude that iodide is actively transported into the gastric lumen and that this transport is at least partly mediated by NIS. Additional investigations are needed to understand the regulation and significance of this transport.

  8. Biochemical indicators of implantation success of tissue-engineered oral mucosa.

    PubMed

    Kuo, S; Zhou, Y; Kim, H M; Kato, H; Kim, R Y; Bayar, G R; Marcelo, C L; Kennedy, R T; Feinberg, S E

    2015-01-01

    Real-time (RT) determination of the health of in vitro tissue-engineered constructs prior to grafting is essential for prediction of success of the implanted tissue-engineered graft. In addition, the US Food and Drug Administration requires specific release criteria in RT prior to the release of tissue-engineered devices for human use. In principle, assessing the viability and functionality of the cellular component can be achieved by quantifying the secretion of growth factors and chemokines of tissue-engineered constructs. Ex vivo-produced oral mucosa equivalents (EVPOMEs) were fabricated under thermally stressed conditions at 43 °C for 24 h to create a functionally compromised EVPOME. We used microchannel enzyme-linked immunosorbent assay to evaluate the functionality of the cellular component, oral keratinocytes, of stressed and unstressed EVPOMEs by measuring the release of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), human β-defensin 1 (hBD-1), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2) into the spent medium, which was collected on the same day prior to graft implantation into severe combined immunodeficiency mice. Implanted EVPOMEs' histology on the seventh postimplantation day was used to correlate outcomes of grafting to secreted amounts of IL-8, hBD-1, VEGF, TIMP-1, and TIMP-2 from corresponding EVPOMEs. Our findings showed that significantly higher levels of IL-8, hBD-1, and TIMP-2 were secreted from controls than from thermally stressed EVPOMEs. We also found a direct correlation between secreted VEGF and IL-8 and blood vessel counts of implanted EVPOMEs. We concluded that measuring the constitutive release of these factors can be used as noninvasive predictors of healthy tissue-engineered EVPOMEs in RT, prior to their implantation.

  9. Photodynamic detection in visualisation of cutaneous and oral mucosa premalignant and malignant lesions: two clinical cases

    NASA Astrophysics Data System (ADS)

    Jurczyszyn, Kamil; Ziólkowski, Piotr; Osiecka, Beata; Gerber, Hanna; Dziedzic, Magdalena

    2008-11-01

    Photodynamic diagnosis (PDD) is promising method of visualisation of premalignant and malignant lesions. PDD is consisted of two main agents: special chemical compound which is called photosensitizer and light. Photosensitizer has affinity to fast proliferating cells such as pre- or malignant. During light irradiation (with proper wavelength - corresponding to absorption peak of photosensitizer) photosensitizer gains energy and passes into excited singlet state S1. Returning to basic singlet state Sn, leads to fluorescence. Due to difference between concentration of photosensitizer in lesion and normal tissue it is possible to obtain high contrast image of lesion. Case #1: 53 years old woman with basal cell carcinoma (BCC) in nasal region; 20% delta-aminolevulinic acid as a precursor of photosensitizer on eucerin base was used. Case #2: 57 years old woman with multifocal oral leukoplakia on cheek mucosa and tongue; 2% chlorophyll gel as photosesitizer was used. All photographs were taken in white light without any filter and in blue and UV light with orange filter: in both cases the total area of the lesions appeared to be larger than it has been clinically observed. Thus, the PDD might be helpful in evaluation of margins of surgical excision of such lesions.

  10. Tissue-Engineered Constructs of Human Oral Mucosa Examined by Raman Spectroscopy

    PubMed Central

    Khmaladze, Alexander; Ganguly, Arindam; Kuo, Shiuhyang; Raghavan, Mekhala; Kainkaryam, Raghu; Cole, Jacqueline H.; Izumi, Kenji; Marcelo, Cynthia L.; Feinberg, Stephen E.

    2013-01-01

    A noninvasive quality monitoring of tissue-engineered constructs is a required component of any successful tissue-engineering technique. During a 2-week production period, ex vivo produced oral mucosa-equivalent constructs (EVPOMEs) may encounter adverse culturing conditions that might compromise their quality and render them ineffective. We demonstrate the application of near-infrared Raman spectroscopy to in vitro monitoring of EVPOMEs during their manufacturing process, with the ultimate goal of applying this technology in situ to monitor the grafted EVPOMEs. We identify Raman spectroscopic failure indicators for less-than optimal EVPOMEs that are stressed by higher temperature and exposure to higher than normal concentration of calcium ions. Raman spectra of EVPOMEs exposed to thermal and calcium stress showed correlation of the band height ratio of CH2 deformation to phenylalanine ring breathing modes, providing a Raman metric to distinguish between viable and nonviable constructs. We compared these results to histology and glucose consumption measurements, demonstrating that Raman spectroscopy is more sensitive and specific to changes in proteins' secondary structure not visible by H&E histology. We also exposed the EVPOMEs to rapamycin, a cell growth inhibitor and cell proliferation capacity preserver, and distinguished between EVPOMEs pretreated with 2 nM rapamycin and controls, using the ratio of the Amide III envelope to the phenylalanine band as an indicator. PMID:22992065

  11. IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils.

    PubMed

    Trautwein-Weidner, K; Gladiator, A; Nur, S; Diethelm, P; LeibundGut-Landmann, S

    2015-03-01

    Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and IL-17 is generally thought to act by regulating neutrophil mobilization and trafficking to the site of infection. Using a mouse model of oropharyngeal candidiasis (OPC), we found that strikingly the IL-17 pathway is not required for the neutrophil response to C. albicans. Mice deficient for the IL-17 receptor subunits IL-17 receptor A (IL-17RA) or IL-17RC or mice depleted of IL-17A and IL-17F exhibited a normal granulocyte colony-stimulating factor (G-CSF) and CXC-chemokine response and displayed no defect in neutrophil recruitment or function. Instead, the inability of these mice to clear the fungus was associated with a selective defect in the induction of antimicrobial peptides (AMPs) in the epithelium that resulted in persistent fungal colonization. Importantly, this antifungal mechanism of IL-17A and IL-17F did not extend to the closely related family member IL-17C. Together, these data uncouple IL-17-dependent effector mechanisms from the neutrophil response and reveal a compartmentalization of the antifungal defense in the oral mucosa providing a new understanding of IL-17-mediated mucosal immunity against C. albicans.

  12. IL-1 Coordinates the Neutrophil Response to C. albicans in the Oral Mucosa

    PubMed Central

    Altmeier, Simon; Toska, Albulena; Sparber, Florian; Teijeira, Alvaro; Halin, Cornelia; LeibundGut-Landmann, Salomé

    2016-01-01

    Mucosal infections with Candida albicans belong to the most frequent forms of fungal diseases. Host protection is conferred by cellular immunity; however, the induction of antifungal immunity is not well understood. Using a mouse model of oropharyngeal candidiasis (OPC) we show that interleukin-1 receptor (IL-1R) signaling is critical for fungal control at the onset of infection through its impact on neutrophils at two levels. We demonstrate that both the recruitment of circulating neutrophils to the site of infection and the mobilization of newly generated neutrophils from the bone marrow depended on IL-1R. Consistently, IL-1R-deficient mice displayed impaired chemokine production at the site of infection and defective secretion of granulocyte colony-stimulating factor (G-CSF) in the circulation in response to C. albicans. Strikingly, endothelial cells were identified as the primary cellular source of G-CSF during OPC, which responded to IL-1α that was released from keratinocytes in the infected tissue. The IL-1-dependent crosstalk between two different cellular subsets of the nonhematopoietic compartment was confirmed in vitro using a novel murine tongue-derived keratinocyte cell line and an established endothelial cell line. These data establish a new link between IL-1 and granulopoiesis in the context of fungal infection. Together, we identified two complementary mechanisms coordinating the neutrophil response in the oral mucosa, which is critical for preventing fungal growth and dissemination, and thus protects the host from disease. PMID:27632536

  13. Influence of microcystin-LR on the activity of membrane enzymes in rat intestinal mucosa.

    PubMed

    Moreno, I M; Mate, A; Repetto, G; Vázquez, C M; Cameán, A M

    2003-12-01

    The objective of the present study was to evaluate the effects of microcystin-LR (MCLR) on the activity of membrane enzymes from intestinal mucosa. In addition, serum chemistry and peroxidative status of both serum and intestinal homogenate were evaluated after treatment with MCLR. Wistar rats were treated with intraperitoneal injection of either 100 microg pure MCLR/Kg body weight or saline solution. A significant increase in liver weight and altered serum enzyme activities were found in MCLR-treated rats, indicating damage to the liver in these rats, as previously suggested. A higher specific activity of sucrase (1.5-fold) was observed after the administration of MCLR, whereas other intestinal apical membrane enzymes, such as lactase, maltase and alkaline phosphatase were not modified by the treatment. The specific activities of acid phosphatase and succinate dehydrogenase, markers for lysosomal and mitochondrial membranes, respectively, were also increased (32% and 60%, respectively) in treated rats. The analysis of lipid peroxidation showed that the peroxidative status was increased in both serum and intestinal mucosa from MCLR-treated rats, reflecting an excess production of oxygen free radicals induced by this cyanobacterial toxin. In conclusion, this study shows that acute exposure to MCLR affects the intestinal physiology by modifying the intestinal peroxidation status as well as the activity of membrane enzymes.

  14. The short-circuited everted sac of rat colon mucosa.

    PubMed

    Goerg, K J; Wanitschke, R; Soergel, K H; Wood, C M; Nell, G

    1981-01-01

    A short-circuited preparation of everted rat colon sacs is described. The serosal current electrode is a AgAgCl wire. A cylindrical agar bridge or AgAgCl electrode may be employed on the mucosal side. Effects of Ag+ ions liberated from the electrodes on ion transport could not be demonstrated. Fluid and sodium are absorbed ad bicarbonate secreted. Potassium and chloride movements are not significantly different form zero. The preparation remains stable for at least 2 h. Sodium absorption is diminished by 50% and bicarbonate secretion abolished in the absence of glucose. In principle, similar ion transport properties were found as in Ussing-chamber preparations. The advantage of the everted sac is the capability of measuring net transport of fluid and electrolytes simultaneously and directly because of the large surface/inner volume ratio of the sac.

  15. A study on the differences between oral squamous cell carcinomas and normal oral mucosas measured by Fourier transform infrared spectroscopy.

    PubMed

    Fukuyama, Y; Yoshida, S; Yanagisawa, S; Shimizu, M

    1999-01-01

    We investigated the differences of Fourier transform infrared (FTIR) spectra between oral squamous cell carcinoma (OSCC) and normal gingival epithelium (NGE) or normal subgingival tissue (NST). We used 15 specimens of OSCC which had not been treated before measurement and 10 of NGE or NST. We also used cultured oral squamous cell carcinoma (COSCC) and the tissue (MSCC) which massed for 3 months after the cultured oral squamous cell carcinoma was transplanted into the lower back of a rat. Those tissue spectra were compared with the purified human collagens and human keratin. One half of every tissue specimen was measured with FTIR and the other half was investigated histologically. The differences of FTIR spectra between OSCC and NGE were observed in the bands between 1431 and 1482 cm(-1) and between 1183 and 1274 cm(-1). The shoulder at 1368 cm(-1) tended to disappear in OSCC, and the peaks at 1246 and 1083 cm(-1) found in NGE tended to shift to those at 1242 and 1086 cm(-1) in OSCC, respectively. The infrared spectrum of NST was noticed to be strongly influenced by the presence of collagen. Significant differences were also observed in the second derivative FTIR spectra between OSCC and NGE. Our data suggested that this infrared technique is applicable to clinical diagnostics.

  16. Development and Evaluation of a Novel Mucoadhesive Film Containing Acmella oleracea Extract for Oral Mucosa Topical Anesthesia

    PubMed Central

    Santana de Freitas-Blanco, Verônica; Franz-Montan, Michelle; Groppo, Francisco Carlos; de Carvalho, João Ernesto; Figueira, Glyn Mara; Serpe, Luciano; Oliveira Sousa, Ilza Maria; Guilherme Damasio, Viviane Aparecida; Yamane, Lais Thiemi; de Paula, Eneida; Ferreira Rodrigues, Rodney Alexandre

    2016-01-01

    Purpose To develop an anesthetic mucoadhesive film containing Acmella oleracea (jambu) extract for topical use on oral mucosa. Methods Ethanolic extracts from aerial parts of jambu were prepared by maceration. Pigment removal was obtained by adsorption with activated carbon. Three mucoadhesive films were developed using a film casting method: 10 or 20% of crude jambu extract (10% JB and 20% JB), and 10% of crude jambu extract treated with activated carbon (10% JBC). The mucoadhesive films were characterized regarding their uniformity, thickness, pH, and spilanthol content, and their stability was evaluated during 120 days. Gas chromatography was used to quantify the amount of spilanthol. In vitro tests determined the permeation of spilanthol across pig esophageal epithelium mucosa in Franz diffusion cells. Topical anesthetic efficacy was assessed in vivo using a tail flick test in mice. Results The three mucoadhesive films showed physical stability and visual appearances suitable for use on oral mucosa. The permeation study revealed that the spilanthol from 10% JBC presented higher flux and permeability coefficient values, compared to 10% or 20% JB (p < 0.001). Moreover, 10% JBC showed better topical anesthetic efficacy than the other films (p < 0.01). Conclusion Mucoadhesive film containing crude extract of jambu treated with activated carbon is a potential alternative for oral, topical use, encouraging future clinical studies. PMID:27626796

  17. Cytological changes in the oral mucosa after use of a mouth rinse with alcohol: A prospective double blind control study

    PubMed Central

    Vera-Sempere, Francisco; Marzal, Cristina; Pellín-Carcelén, Ana; Martí-Bonmatí, Ezequiel; Bagan, Leticia

    2012-01-01

    Aim: The aim of this preliminary study was to detect cytological changes in the oral mucosa after using a mouth wash with alcohol. Material and Methods: A prospective double-blind, controlled study was performed, for 6 months. Group 1 consisted of 30 subjects who used a mouth rinse with 26.9% of alcohol [Listerine®] and Group 2 consisted of 30 subjects who used a mouth rinse with the same ingredients but with no alcohol. We obtained three cytological samples from the oral mucosa. The presence of cytological atypia, binucleation and karyorrhesis, and type of cells were studied. We also used a fluorescent in situ hybridization technique (FISH) in 15 samples in each group, for the micronucleus. Results: We found no clinical mucosal alteration after using the mouth wash at the end of the study in either group. We observed no cytological differences between the groups at the end of the study (p>0.05). Regarding the study of the micronucleus by FISH, we observed no significant difference between the groups (p>0.05). Conclusions: Our results showed no cytological alteration in patients using a mouth rinse with alcohol, but these findings should be considered preliminary results, to be confirmed in a greater sample of patients. Key words:Mouth wash, oral mucosa, cytological change, alcohol. PMID:23085712

  18. PM2.5-Induced Oxidative Stress and Mitochondrial Damage in the Nasal Mucosa of Rats

    PubMed Central

    Guo, Zhiqiang; Hong, Zhicong; Dong, Weiyang; Deng, Congrui; Zhao, Renwu; Xu, Jian; Zhuang, Guoshun; Zhang, Ruxin

    2017-01-01

    Exposure to PM2.5 (particulate matter ≤2.5 μm) increases the risk of nasal lesions, but the underlying mechanisms, especially the mechanisms leading to mitochondrial damage, are still unclear. Thus, we investigated the in vivo effects of PM2.5 exposure on the inflammatory response, oxidative stress, the enzyme activities of Na+K+-ATPase and Ca2+-ATPase, and the morphology and function of mitochondria in the nasal mucosa of rats. Exposure to PM2.5 occurred through inhalation of a PM2.5 solution aerosol. The results show that the PM2.5 exposure induced increased levels of malondialdehyde (MDA) and levels of proinflammatory mediators, including interleukin 6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α). These changes were accompanied by decreases in the activities of total superoxide dismutase (T-SOD), Na+K+-ATPase, and Ca2+-ATPase in rat nasal mucosa. PM2.5 significantly affected the expression of specific mitochondrial fission/fusion genes (OPA1, Mfn1, Fis1, and Drp1) in nasal mucosa. These changes were accompanied by abnormal alterations of mitochondrial structures, including mitochondrial swelling, cristae disorder, and even fission resulting from higher doses of PM2.5. Our data shows that oxidative damage, inflammatory response, and mitochondrial dysfunction may be the toxic mechanisms that cause nasal lesions after exposure to PM2.5. PMID:28146064

  19. Identification of gentian violet concentration that does not stain oral mucosa, possesses anti-candidal activity and is well tolerated.

    PubMed

    Jurevic, R J; Traboulsi, R S; Mukherjee, P K; Salata, R A; Ghannoum, M A

    2011-05-01

    Gentian violet (GV) is recommended for initial treatment of oral candidiasis in HIV-infected patients in resource-limited settings. Currently GV is not used because of its staining effects. In this study, we investigated the staining capacity of three different concentrations of GV to determine a concentration that does not cause staining. The selected concentration that did not cause staining was evaluated for its physical stability and antifungal activity. Fifteen healthy participants were randomized to rinse twice daily for 14 days with one of three GV concentrations: 0.1%, 0.0085%, or 0.00165%. Oral examination and intra-oral photographs were performed at baseline and at the end of therapy. Participants responded to a questionnaire to assess adverse events. Antifungal activity was evaluated using the Clinical and Laboratory Standard Institute methodology. GV at a concentration of 0.00165% did not stain the oral mucosa and was well tolerated. GV at a concentration of 0.00165% was stable and possessed antifungal activity when stored at certain temperatures for different time periods. Gentian violet solution at the concentration of 0.00165% does not stain the oral mucosa, is stable and possesses potent antifungal activity.

  20. Detection of Human Papilloma Virus (HPV) in oral mucosa of women with cervical lesions and their relation to oral sex practices

    PubMed Central

    2010-01-01

    Background Previous studies have either investigated the relationship of HPV with oral cancer or the prevalence of HPV on the oral cavity. The purpose of this investigation was to study the prevalence of HPV in oral cavity of women with oral sex practices and cervical lesions. Methods Forty six (46) non-smokers and non-alcoholic patients attended the "Clínica de Displasias" of "Ciudad Juarez" were sampled. This population had a CIN diagnosis sometime between the previous six months. On previous consent they filled out a questionnaire related to their oral sex practices. Afterwards one swab from cheeks and another from palate/gum were taken; PCR was used to determine generic HPV, HPV16 and HPV18. Results Seventy two percent (72%) of the patients stated to have oral sex practices regularly which all of them were positive to HPV either in oral mucus, palate/gum or both. The total of the given results showed that 35% had HPV16; among those distributed in 26% with regular oral sex practices and 9% stated as never practiced oral sex. An association was found between oral HPV16 positivity and progression to cervical CIN advanced lesions. On the other hand HPV18 was not detected. The frequency of HPV16 was higher in buccal mucosa (23%) versus palate/gum (16%). Conclusions This study suggests that buccal HPV16 infection is associated with CIN progression. PMID:21129222

  1. Regulation of serotonin release from enterochromaffin cells of rat cecum mucosa

    SciTech Connect

    Simon, C.; Ternaux, J.P. )

    1990-05-01

    The release of endogenous serotonin or previously taken up tritiated serotonin from isolated strips of rat cecum mucosa containing enterochromaffin cells was studied in vitro. Release of tritiated serotonin was increased by potassium depolarization and was decreased by tetrodotoxin, veratridine and the absence of calcium. Endogenous serotonin was released at a lower rate than tritiated serotonin; endogenous serotonin release was stimulated by potassium depolarization but was unaffected by tetrodotoxin, veratridine or the absence of calcium. Carbachol, norepinephrine, clonidine and isoproterenol decreased release of tritiated serotonin but had less or reverse effect on release of endogenous serotonin. The results suggest two different serotoninergic pools within the enterochromaffin cell population.

  2. Binding of TH-iloprost to rat gastric mucosa: a pitfall in performing radioligand binding assays

    SciTech Connect

    Beinborn, M.; Kromer, W.; Staar, U.; Sewing, K.F.

    1985-09-01

    Binding of TH-iloprost was studied in a 20,000 x g sediment of the rat gastric mucosa. When pH in both test tubes for total and non-specific binding was kept identical, no displaceable binding of iloprost could be detected. When no care was taken to keep the pH identical in corresponding test tubes of the binding assay, changes in pH simulated specific and displaceable binding of iloprost. Therefore it is concluded that - in contrast to earlier reports - it is not possible to demonstrate specific iloprost binding using the given method.

  3. Human papillomavirus-32-associated focal epithelial hyperplasia accompanying HPV-16-positive papilloma-like lesions in oral mucosa.

    PubMed

    Liu, Na; Wang, Jiayi; Lei, Lei; Li, Yanzhong; Zhou, Min; Dan, Hongxia; Zeng, Xin; Chen, Qianming

    2013-05-01

    Human papillomavirus infection can cause a variety of benign or malignant oral lesions, and the various genotypes can cause distinct types of lesions. To our best knowledge, there has been no report of 2 different human papillomavirus-related oral lesions in different oral sites in the same patient before. This paper reported a patient with 2 different oral lesions which were clinically and histologically in accord with focal epithelial hyperplasia and oral papilloma, respectively. Using DNA extracted from these 2 different lesions, tissue blocks were tested for presence of human papillomavirus followed by specific polymerase chain reaction testing for 6, 11, 13, 16, 18, and 32 subtypes in order to confirm the clinical diagnosis. Finally, human papillomavirus-32-positive focal epithelial hyperplasia accompanying human papillomavirus-16-positive oral papilloma-like lesions were detected in different sites of the oral mucosa. Nucleotide sequence sequencing further confirmed the results. So in our clinical work, if the simultaneous occurrences of different human papillomavirus associated lesions are suspected, the multiple biopsies from different lesions and detection of human papillomavirus genotype are needed to confirm the diagnosis.

  4. Neuropeptide Y enhances olfactory mucosa responses to odorant in hungry rats.

    PubMed

    Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

    2012-01-01

    Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes.

  5. Neuropeptide Y Enhances Olfactory Mucosa Responses to Odorant in Hungry Rats

    PubMed Central

    Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

    2012-01-01

    Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes. PMID:23024812

  6. Oxygen consumption and chloride secretion in rat distal colon isolated mucosa.

    PubMed

    Saraví, Fernando D; Saldeña, Teobaldo A; Carrera, Cristian A; Ibañez, Jorge E; Cincunegui, Liliana M; Carra, Graciela E

    2003-09-01

    The aerobic metabolic cost of chloride secretion was studied in rat distal colon isolated mucosa under several conditions by simultaneous measurement of short-circuit current and oxygen consumption under conditions that preserve vectorial ion transport. A low-chloride solution and the presence of bumetanide plus diphenylamine-2-carboxylate reduced short-circuit current by 75% and oxygen consumption by 25%. Ouabain decreased short-circuit current by 93% and oxygen consumption by 32%. Serotonin increased both variables by 59% and 33%, respectively. Bumetanide and diphenylamine-2-carboxylate reduced but did not abolish the effect of serotonin on short-circuit current and oxygen consumption. Changes in short-circuit current and oxygen consumption were linearly correlated under all conditions tested. It is concluded that, in the unstimulated rat distal colon epithelium, chloride secretion accounts for about 75% of ouabain-sensitive short-circuit current and oxygen consumption. Stimulated chloride secretion may demand over 40% of total oxygen consumption.

  7. Changes of glycoconjugate expression in nasal respiratory mucosa of rats exposed to welding fumes.

    PubMed

    Jeong, Gil Nam; Jo, Un Bock; Yu, Il Je

    2007-09-01

    To investigate the effects of welding fumes on the glycoconjugates in nasal respiratory mucosa, male Sprague-Dawley rats were exposed to manual metal arc stainless steel (MMA-SS) welding fumes at a concentration of 56-76 mg/m(3) total suspended particulate for 2 h/day in an inhalation chamber for 90 days. During the exposure period, the experimental animals were sacrificed after 2 h and 15, 30, 60, and 90 days of exposure; then sections were examined using lectin histochemistry. Some remarkable changes, such as destroyed cilia, desquamation and mucification of epithelial cells, and destruction of nasal septal glands, were seen in the welding fume-exposed groups. Specific changes in the lectin binding patterns were also observed in the welding fume-exposed rats. The Ricinus communis agglutinin-I (RCA-I) staining of the cilia and columnar cells increased slightly when compared with the unexposed rats. The RCA-I and Ulex europaeus agglutinin-I (UEA-I) staining of the goblet cells also increased as the exposure continued. The mucigenous epithelial cells reacted with Bandeiraea simplicifolia lectin-I (BSL-I), RCA-I, and succinylated wheat germ agglutinin A (sWGA) after 15 days of exposure, which was not visible in the control group. The dorsal septal glands exhibited an affinity with peanut agglutinin (PNA), BSL-I, and RCA-I, which was also not visible in the control group. The affinity for Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), PNA, sWGA, BSL-I, and UEA-I in the ventral septal glands of the welding fume-exposed groups tended to increase, whereas the concanavalin A (Con A) reactivity in the dorsal septal glands decreased slightly. In conclusion, it was assumed that the changes in the glycoconjugate residues in the nasal respiratory mucosa of the welding fume-exposed rats represented important components of defense mechanisms against the toxicants in the welding fumes.

  8. Performance of full-pupil line-scanning reflectance confocal microscopy in human skin and oral mucosa in vivo

    PubMed Central

    Larson, Bjorg; Abeytunge, Sanjeewa; Rajadhyaksha, Milind

    2011-01-01

    Point-scanning reflectance confocal microscopes continue to be successfully translated for detection of skin cancer. Line-scanning, with the use of a single scanner and a linear-array detector, offers a potentially smaller, simpler and lower cost alternative approach, to accelerate widespread dissemination into the clinic. However, translation will require an understanding of imaging performance deep within scattering and aberrating human tissues. We report the results of an investigation of the performance of a full-pupil line-scanning reflectance confocal microscope in human skin and oral mucosa, in terms of resolution, optical sectioning, contrast, signal-to-noise ratio, imaging and the effect of speckle noise. PMID:21750780

  9. Bacillus species are present in chewing tobacco sold in the United States and evoke plasma exudation from the oral mucosa.

    PubMed

    Rubinstein, Israel; Pedersen, Gerald W

    2002-09-01

    Five Bacillus species, predominantly Bacillus megaterium and Bacillus pumilus, were isolated from two popular brands of commercially available chewing tobacco [(5.0 +/- 1) x 10(6) CFU/ml of supernatant; results for four experiments]. Moreover, the supernatant of the Bacillus culture evoked plasma exudation from postcapillary venules in the intact hamster cheek pouch, exudation that was mediated by the kallikrein/kinin metabolic pathway. Taken together, these data indicate that Bacillus species contaminate chewing tobacco commercially available in the United States and elaborate a potent exogenous virulence factor(s) that injures the oral mucosa.

  10. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  11. Periodontal disease level-butyric acid amounts locally administered in the rat gingival mucosa induce ER stress in the systemic blood.

    PubMed

    Cueno, Marni E; Saito, Yuko; Ochiai, Kuniyasu

    2016-05-01

    Periodontal diseases have long been postulated to contribute to systemic diseases and, likewise, it has been proposed that periodontal disease treatment may ameliorate certain systemic diseases. Short-chain fatty acids (SCFA) are major secondary metabolites produced by oral anaerobic bacteria and, among the SCFAs, butyric acid (BA) in high amounts contribute to periodontal disease development. Periodontal disease level-butyric acid (PDL-BA) is found among patients suffering from periodontal disease and has previously shown to induce oxidative stress, whereas, oxidative stress is correlated to endoplasmic reticulum (ER) stress. This would imply that PDL-BA may likewise stimulate ER stress, however, this was never elucidated. A better understanding of the correlation between PDL-BA and systemic ER stress stimulation could shed light on the possible systemic effects of PDL-BA-related periodontal diseases. Here, PDL-BA was injected into the gingival mucosa and the systemic blood obtained from the rat jugular was collected at 0, 15, 60, and 180 min post-injection. Collected blood samples were purified and only the blood cytosol was used throughout this study. Subsequently, we measured blood cytosolic GADD153, Ca(2+), representative apoptotic and inflammatory caspases, and NF-κB amounts. We found that PDL-BA presence increased blood cytosolic GADD153 and Ca(2+) amounts. Moreover, we observed that blood cytosolic caspases and NF-κB were activated only at 60 and 180 min post-injection in the rat gingival mucosa. This suggests that PDL-BA administered through the gingival mucosa may influence the systemic blood via ER stress stimulation and, moreover, prolonged PDL-BA retention in the gingival mucosa may play a significant role in ER stress-related caspase and NF-κB activation. In a periodontal disease scenario, we propose that PDL-BA-related ER stress stimulation leading to the simultaneous activation of apoptosis and inflammation may contribute to periodontal disease

  12. [Reconstruction of oral mucosa with a micro-vascularized fascia-cutaneous flap from the forearm].

    PubMed

    Burgueño García, Miguel; Cebrián Carretero, José Luis; Muñoz Caro, Jesús Manuel; Arias Gallo, Javier

    2002-01-01

    Epidermoid carcinoma of jugal mucosa is an aggressive tumor. Its treatment is based on broad excision and reconstruction in order to avoid fibrosis and restriction of mouth opening. Neck dissection and radiotherapy are indicated in selected cases. We display our experience with microvascularized flaps with the aim of preventing the flaws. We reconsider 8 patients (representing 10 flaps) handle in our Department. Besides we discuss other therapeutic alternatives after the growth's removal. The conclusion reached is that the mucovascularized forearm flaps give a great quantity of thin tissue and therefore so results to be the best option for the reconstruction of the jugal mucosa.

  13. Peroxidation in intestinal mucosa of normal and iron-overloaded rats differing in selenium status

    SciTech Connect

    Mahoney, A.W.; Vega, S. )

    1991-03-15

    Material in the digesta may lead to lipid peroxidation of the intestinal mucosa. To study the effect of Se deficiency ({minus}Se) and Fe overload (++Fe) on mucosal free radical damage, 60 220g rats in four groups were fed torula yeast diet for 20d. Fe-overload was caused in two groups by three IM injections of Fe dextran given on days 4, 9, and 14. Fe-control rats (+Fe) were sham-injected with n-saline. Se-control rats (+Se) were given Na{sub 2}SeO{sub 3}-supplemented drinking water. Se deficiency reduced liver and mucosal glutathione peroxidase activity, but Fe overload did not. Serum, liver and mucosal Fe was higher in the Fe-overloaded rats. Fe and Se treatments did not affect hemoglobin level, but Fe-overload reduced weight gain. Fe overload increased liver and mucosal thiobarbituric acid reactive substances (TBARS), but Se status did not affect them. On days 5-9, CBrCL{sub 3}, an environmental pollutant and lipid peroxidation initiator which must be activated by cytochrome P-450, was gavaged in 10 rats from each group; the higher dose increased mucosal TBARS in Fe-overloaded rats but not Se-deficient ones. But, the lower CBrCL{sub 3} dose did not affect mucosal TBARS. Liver TBARS was not affected by CBrCL{sub 3}; however, the highest liver and mucosal TBARS levels occurred in the {minus}Se++Fe rats given the higher CBrCL{sub 3} dose. Liver cytochrome P-450 activity was not affected by Fe{minus} nor Se status.

  14. Transcriptomic responses in the oral cavity of F344 rats and B6C3F1 mice following exposure to Cr(VI): Implications for risk assessment

    PubMed Central

    Rager, Julia E.; Suh, Mina; Ring, Caroline L.; Proctor, Deborah M.; Haws, Laurie C.; Fry, Rebecca C.; Harris, Mark A.

    2016-01-01

    Exposure to hexavalent chromium [Cr(VI)] in drinking water was previously reported to increase oral tumor incidence in F344 rats. To investigate the mode of action for these tumors, transcriptomic profiles in oral mucosa samples of F344 rats and B6C3F1 mice were analyzed following exposure to 0.1–180 ppm Cr(VI) for 7 or 90 days. In rats, genome‐wide microarray analyses identified no significantly differentially expressed genes (DEGs) at either time point. In mice, 14 and 1 DEGs were respectively identified after 7 and 90 days of exposure. Therefore, relaxed statistical criteria were employed to identify potential DEGs (pDEGs), followed by high‐throughput benchmark dose modeling to identify responsive pDEGs for pathway enrichment analysis. This identified 288 and 168 pDEGs in the rat oral mucosa, of which only 20 and 7 showed evidence of dose‐response. No significant pathway enrichment was obtained with either pDEG or dose‐responsive pDEG lists. Similar results were obtained in mice. These analyses indicate a negligible transcriptional response in the oral mucosa of both species. Comparison of the total number of gene changes in the oral mucosa of rats and mice with responses in the duodenum of animals from the same study demonstrated remarkable dose‐response concordance across tissues and species as a function of tissue chromium concentration. The low chromium levels in the oral mucosa and negligible transcript response are consistent with an absence of tissue lesions. These findings are used to compare the merits of linear and nonlinear approaches for deriving toxicity criteria based on the oral tumors in rats. Environ. Mol. Mutagen. 57:706–716, 2016. © 2016 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc. PMID:27859739

  15. Increased vascular permeability in rat nasal mucosa induced by substance P and stimulation of capsaicin-sensitive trigeminal neurons.

    PubMed

    Lundblad, L; Saria, A; Lundberg, J M; Anggård, A

    1983-01-01

    Electrical stimulation of the maxillary branches of the trigeminal nerve induced an increase in vascular permeability to macromolecules and an interstitial edema in the nasal mucosa of the rat, as indicated by extravasation of Evans blue. In animals that had been treated neonatally with capsaicin, the effect of trigeminal nerve stimulation was abolished. Local application of capsaicin or substance P (SP) also induced a significant Evans blue extravasation in the nasal mucosa. In capsaicin-pretreated animals the effect of SP was still present, while the permeability increase induced by capsaicin was abolished. In conclusion, chemogenic irritation of the nasal mucosa by capsaicin induces edema probably via a local axon reflex inducing release of SP. Capsaicin-sensitive SP-containing afferents in the nasal mucosa may also be involved in the pathogenesis of nasal congestion seen in various types of rhinitis.

  16. Measurement of tumor-associated mutations in the nasal mucosa of rats exposed to varying doses of formaldehyde.

    PubMed

    Meng, Fanxue; Bermudez, Edilberto; McKinzie, Page B; Andersen, Melvin E; Clewell, Harvey J; Parsons, Barbara L

    2010-01-01

    This study examined the potential induction of tumor-associated mutations in formaldehyde-exposed rat nasal mucosa using a sensitive method, allele-specific competitive blocker-PCR (ACB-PCR). Levels of p53 codon 271 CGT to CAT and K-Ras codon 12 GGT to GAT mutations were quantified in nasal mucosa of rats exposed to formaldehyde. In addition, nasal mucosa cell proliferation was monitored because regenerative cell proliferation is considered a key event in formaldehyde-induced carcinogenesis. Male F344 rats (6-7 weeks old, 5 rats/group) were exposed to 0, 0.7, 2, 6, 10, and 15 ppm formaldehyde for 13 weeks (6 h/day, 5 days/week). ACB-PCR was used to determine levels of p53 and K-Ras mutations. Although two of five untreated rats had measureable spontaneous p53 mutant fractions (MFs), most nasal mucosa samples had p53 MFs below 10(-5). All K-Ras MF measurements were below 10(-5). No dose-related increases in p53 or K-Ras MF were observed, even though significant increases in bromodeoxyuridine incorporation demonstrated induced cell proliferation in the 10 and 15 ppm formaldehyde-treatment groups. Therefore, induction of tumor-associated p53 mutation likely occurs after several other key events in formaldehyde-induced carcinogenesis.

  17. Usage of low-intensity laser radiation for the treatment of the inflammatory processes of the oral cavity mucosa after applying removable plate dentures

    NASA Astrophysics Data System (ADS)

    Kalivradzhiyan, Edvard; Lesnykh, Nikolay; Kunin, Vadim; Mutafyan, Mikhail

    1995-04-01

    Effective methods of reveling overload zones of the oral mucosa under the bases of plane dentures, the effect of low intensity laser radiation ont he increase of its resistance are discussed. At present removable plate dentures of different modifications to a certain degree restore aesthetic proportions of the face, phonetics and malfunction of the teeth and jaws. Besides, removable bridge are known not to secure even distribution of mastication pressure along the whole dentures bed which results in the development of inflammatory and dystrophic processes, and, finally in the accelerated atrophy of the oral mucosa and bony tissue of the alveolar process of upper and alveolar parts of the mandible. Many papers are devoted to the anti-inflammatory effect of laser therapy. Improvement of metabolic processes and revascularization of the dentures bed mucosa, normalization of the oral microflora structure, anesthetizing effect is noted too. At the same time there are no papers about studying the therapeutic effect of low intensity laser radiation intraumatic dentures stomatitis, inflammation of the oral mucosa in the literature available for us. To increase the functional effectiveness of removable plate dentures, profilaxy of inflammation and dystrophic phenomena and to decrease adaptation period we have developed methods of early detection of overload zone of oral mucosa at the initial stages of acute inflammation with the help of macrohistochemical reaction. Visible with the naked eye for the timely and precise correction of the dentures.

  18. Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats

    NASA Technical Reports Server (NTRS)

    Yoshida, S.; Leskiw, M. J.; Schluter, M. D.; Bush, K. T.; Nagele, R. G.; Lanza-Jacoby, S.; Stein, T. P.

    1992-01-01

    The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

  19. Myenteric neurons and intestinal mucosa of diabetic rats after ascorbic acid supplementation

    PubMed Central

    de Freitas, Priscila; Natali, Maria Raquel Marçal; Pereira, Renata Virginia Fernandes; Neto, Marcilio Hubner Miranda; Zanoni, Jacqueline Nelisis

    2008-01-01

    AIM: To investigate the effect of ascorbic acid (AA) dietary supplementation on myenteric neurons and epithelial cell proliferation of the jejunum of adult rats with chronic diabetes mellitus. METHODS: Thirty rats at 90 d of age were divided into three groups: Non-diabetic, diabetic and diabetic treated with AA (DA) (1 g/L). After 120 d of treatment with AA the animals were killed. The myenteric neurons were stained for myosin-V and analyzed quantitatively in an area of 11.2 mm2/animal. We further measured the cellular area of 500 neurons per group. We also determined the metaphasic index (MI) of the jejunum mucosa layer of about 2500 cells in the intestinal crypts, as well as the dimensions of 30 villi and 30 crypts/animal. The data area was analyzed using the Olympus BX40 microscope. RESULTS: There was an increase of 14% in the neuronal density (792.6 ± 46.52 vs 680.6 ± 30.27) and 4.4% in the cellular area (303.4 ± 5.19 vs 291.1 ± 6.0) respectively of the diabetic group treated with AA when compared to control diabetic animals. There were no significant differences in MI parameters, villi height or crypt depths among the groups. CONCLUSION: Supplementation with AA in the diabetic animal promoted moderate neuroprotection. There was no observation of alteration of the cellular proliferation of the jejunum mucosa layer of rats with chronic diabetes mellitus with or without supplementation with AA. PMID:19030205

  20. Povidone-iodine-induced cell death in cultured human epithelial HeLa cells and rat oral mucosal tissue.

    PubMed

    Sato, So; Miyake, Masao; Hazama, Akihiro; Omori, Koichi

    2014-07-01

    Although povidone-iodine (PVP-I) has been used as a gargle since 1956, its effectiveness and material safety have been remained controversial. The aim of this study was to investigate the toxicity of PVP-I to epithelial cells in a concentration range significantly lower than that used clinically. Study design was in vitro laboratory investigations and in vivo histological and immunologic analysis. We examined the effects of PVP-I at concentrations of 1 × 10(-2) to 1 × 10(3) μM and 1 × 10(-4) to 1 × 10 μM on HeLa cells as a model of epithelial cells and rat oral mucosa, respectively, after 1 or 2 days of exposure. Annexin V/FLUOS was used to distinguish live, apoptotic and necrotic cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was also used to observe whether apoptotic epithelial cells exist in rat oral mucosa after 1 day of exposure of PVP-I. HeLa cells developed concentration-dependent cytotoxicity, and epithelium of rat oral mucosa was thinned in a concentration-dependent manner. HeLa cell apoptosis increased after 1 × 10(0) μM of PVP-I exposure for 2 days. In the TUNEL method, many apoptotic epithelial cells were observed in the rat oral mucosa after 1 day of exposure to diluted 1 × 10(-2) μM of PVP-I, but minimal apoptotic epithelial cells were observed using 1 × 10(-3) μM of PVP-I. Our findings suggest that exposure to PVP-I, of which concentrations are even lower than those used clinically, causes toxicity in epithelial cells. This knowledge would help us better understand the risk of the use of PVP-I against mucosa.

  1. Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa.

    PubMed

    Furne, J; Springfield, J; Koenig, T; DeMaster, E; Levitt, M D

    2001-07-15

    Colonic bacteria release large quantities of the highly toxic thiols hydrogen sulfide (H(2)S) and methanethiol (CH(3)SH). These gases rapidly permeate the colonic mucosa, and tissue damage would be expected if the mucosa could not detoxify these compounds rapidly. We previously showed that rat cecal mucosa metabolizes these thiols via conversion to thiosulfate. The purpose of the present study in rats was to determine if this conversion of thiols to thiosulfate is (a) a generalized function of many tissues, or (b) a specialized function of the colonic mucosa. The tissues studied were mucosa from the cecum, right colon, mid-colon, ileum, and stomach; liver; muscle; erythrocytes; and plasma. The metabolic rate was determined by incubating homogenates of the various tissues with H(2)(35)S and CH(3)(35)SH and measuring the rate of incorporation of (35)S into thiosulfate and sulfate. The detoxification activity of H(2)S (expressed as nmol/mg per min) that resulted in thiosulfate production was at least eight times greater for cecal and right colonic mucosa than for the non-colonic tissues. Thiosulfate production from CH(3)SH was at least five times more rapid for cecal and right colonic mucosa than for the non-colonic tissues. We conclude that colonic mucosa possesses a specialized detoxification system that allows this tissue to rapidly metabolize H(2)S and CH(3)SH to thiosulfate. Presumably, this highly developed system protects the colon from what otherwise might be injurious concentrations of H(2)S and CH(3)SH. Defects in this detoxification pathway possibly could play a role in the pathogenesis of various forms of colitis.

  2. [A comparative study on the responses of blood vessels of oral mucosa to thermal stimulation in dentulous and edentulous subjects].

    PubMed

    Naitoh, T; Torii, K; Kobayashi, Y

    1989-08-01

    The purpose of this experiment was to clarify the characteristic changes of vasculature in edentulous alveolar mucosa and the effect of wearing a complete denture during sleep. Thermal stimulations were applied to the oral mucosa of five normal subjects and five completely edentulous patients and the responses of blood vessels were observed using both Impedance Plethysmography (IMP) and Reflection Photoelectric Plethysmography (RPP). Quantitative comparisons were made between edentulous patients and dentulous normal subjects, and between patients wearing complete dentures during sleep and those who do not. The following results were obtained. 1) The responses of blood vessels were divided into four groups. Type 1 showed dilatation in IMP and RPP. Type 2 showed dilatation but had late initial rising in IMP. Type 3 showed initial contraction in either or both IMP and RPP, and followed by dilatation few seconds later. Type 4 showed no changes in RPP but dilatation in IMP. 2) There was definite difference between edentulous and dentulous subjects in the frequency of exhibition of each type. Especially for the edentulous patients type 4 was observed in all stimulation temperature. 3) For the dentulous subjects there were more cases showing responses of RPP in digital apex than those do not. This was most conspicuous at the 50 degrees C stimulation. However for the edentulous patients there were about equal number of each cases. 4) The responses of blood vessels for both dentulous and edentulous subjects became greater and blood volume increased both with time at each temperature and as the stimulation temperature were raised. However the increase in the response was greater for the edentulous patients when the stimulation temperature was raised from 0 degrees C to 50 degrees C. 5) The responses of blood vessels became greater after two weeks when complete dentures were worn during sleep at night. And when dentures were not worn during sleep the responses decreased to a

  3. Receptors for the lectins wheat germ. Ricinus communis I and soybean in ameloblastomas and normal oral mucosa.

    PubMed

    Vedtofte, P; Dabelsteen, E

    1981-11-01

    The histological distribution of receptors for the lectins Wheat germ (WGA). Ricinus communis I (RCA I) and Soybean (SBA) was examined in ameloblastomas and normal oral mucosa from 12 patients. The study utilized fluorescein-conjugated WGA, RCA I and SBA. Cell-membrane bound receptors for these 3 lectins were demonstrated in the spinous cell layer of the normal oral mucosa. WGA and RCA I receptors were also located in the basal cell layer, whereas SBA receptors were not detectable there. Cell-membrane bound WGA receptors were shown in the epithelial cells of the ameloblastomas. Titrations showed significant differences in staining reactivity related to the morphology of the peripheral epithelial cells of the ameloblastomas. The distribution of RCA I and SBA receptors in the peripheral cells was also related to the morphology of these cells and was independent of the histological types of the tumours. It is suggested that the distribution of these receptors is related to cellular activities such as cell differentiation and cell migration in the tumour and therefore possibly reflects the biological behavior of the tumours.

  4. Effectiveness of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa.

    PubMed

    Kurita, Hiroshi; Kamata, Takahiro; Li, Xiangjun; Nakanishi, Yoshitaka; Shimane, Tetsu; Koike, Takeshi

    2012-03-01

    The purpose of this retrospective study was to assess the effect of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa. The historical control group had dysplastic or malignant mucosal lesions resected solely on the evidence of direct inspection and palpation. In the vital staining group tissue was resected only after vital staining with iodine solution. Seven of 25 patients in the conventional group developed recurrent dysplastic or cancerous oral mucosa around the primary site, while no patient among 23 reported recurrence in the vital staining group (p<0.01). Kaplan-Meier assessment showed that the 5-year primary control rate was 100% in the vital staining group and 75% in the conventional group. Although this retrospective study has some limitations, the results suggest that vital staining with iodine may be useful in reducing the incidence of recurrence of dysplastic or cancerous epithelium at a primary site. Further well-controlled study is essential.

  5. Parenteral nutrition supplemented with short-chain fatty acids: effect on the small-bowel mucosa in normal rats.

    PubMed

    Koruda, M J; Rolandelli, R H; Bliss, D Z; Hastings, J; Rombeau, J L; Settle, R G

    1990-04-01

    When enteral nutrition is excluded from animals maintained solely with total parenteral nutrition (TPN), atrophy of the intestinal mucosa is observed. Short-chain fatty acids (SCFAs) are produced in the colon by the fermentation of dietary carbohydrates and fiber polysaccharides and have been shown to stimulate mucosal-cell mitotic activity in the intestine. This study compared the effects of an intravenous and an intracecal infusion of SCFAs on the small-bowel mucosa. Rats received standard TPN, TPN with SCFAs (sodium acetate, propionate, and butyrate), TPN with an intracecal infusion of SCFAs, or rat food. After 7 d jejunal and ileal mucosal weights, DNA, RNA, and protein were determined. Standard TPN produced significant atrophy of the jejunal and ileal mucosa. Both the intracecal and intravenous infusion of SCFAs significantly reduced the mucosal atrophy associated with TPN. The intravenous and intracolonic infusion of SCFAs were equally effective in inhibiting small-bowel mucosal atrophy.

  6. Squamous cell carcinoma of the oral mucosa after release of submucous fibrosis and bilateral small radial forearm flap reconstruction.

    PubMed

    Celik, Naci; Wei, Fu-chan; Chang, Yang-ming; Yang, Wen-guei; Chen, Da-jeng; Tsai, Chi-ying

    2002-07-01

    carcinoma of the intraoral mucosa. High risk of cancer occurrence strongly indicates the importance of an earlier and more aggressive surgical approach toward submucous fibrosis, and long-term follow-up on a regular basis. The purpose of an early and aggressive approach to submucous fibrosis is to provide a good quality of life to the patient by improving oral hygiene and oral intake quality and at the same time to obtain a sufficient mouth opening, which is mandatory for the inspection of the excision site and the remaining oral mucosa during follow-up.

  7. Expression of neuropeptide W in rat stomach mucosa: regulation by nutritional status, glucocorticoids and thyroid hormones.

    PubMed

    Caminos, Jorge E; Bravo, Susana B; García-Rendueles, María E R; Ruth González, C; Garcés, Maria F; Cepeda, Libia A; Lage, Ricardo; Suárez, Miguel A; López, Miguel; Diéguez, Carlos

    2008-02-07

    Neuropeptide W (NPW) is a recently identified neuropeptide that binds to G-protein-coupled receptor 7 (GPR7) and 8 (GPR8). In rodent brain, NPW mRNA is confined to specific nuclei in hypothalamus, midbrain and brainstem. Expression of NPW mRNA has also been confirmed in peripheral organs such as stomach. Several reports suggested that brain NPW is implicated in the regulation of energy and hormonal homeostasis, namely the adrenal and thyroid axes; however the precise physiological role and regulation of peripheral NPW remains unclear. In this study, we examined the effects of nutritional status on the regulation of NPW in stomach mucosa. Our results show that in this tissue, NPW mRNA and protein expression is negatively regulated by fasting and food restriction, in all the models we studied: males, females and pregnant females. Next, we examined the effect of glucocorticoids and thyroid hormones on NPW mRNA expression in the stomach mucosa. Our data showed that NPW expression is decreased in this tissue after glucocorticoid treatment or hyperthyroidism. Conversely, hypothyroidism induces a marked increase in the expression of NPW in rat stomach. Overall, these data indicate that stomach NPW is regulated by nutritional and hormonal status.

  8. Vulnerability of Gastric Mucosa in Diabetic Rats, Its Pathogenesis and Amelioration by Cuminum cyminum.

    PubMed

    Vador, N; Jagtap, Aarti G; Damle, Archana

    2012-09-01

    Various studies have indicated that peptic ulcers occurring during the course of diabetic state are more severe and often associated with complications such as gastrointestinal bleeding. This study is the first attempt to understand the pathogenesis of gastric ulcers occurring during the diabetic state considering alternate biochemical pathways using suitable markers and its amelioration by Cuminum cyminum. In this study, diabetic rats showed a progressive increase in the stomach advanced glycated end products formation, gastric mucosal tumour necrosis factor-α and Thiobarbituric acid reactive substances levels as compared to normal control (nondiabetic) rats. There was decrease in gastric mucosal content, antioxidant enzymes and cellular ATPase enzyme levels of diabetic gastric mucosa when compared to the normal control group. mRNA expression of epidermal growth factor was found to be significantly higher as compared to normal control animals. Further methanol extract of Cuminum cyminum treatment to diabetic animals caused a reduction in blood glucose, and ulcer score when compared to diabetic control rats. It significantly increased gastric mucus content, antioxidant status and cellular ATPase enzyme levels as compared to diabetic control animals. Methanol extract of Cuminum cyminum inhibited advanced glycated end products formation in vitro as well as in vivo.

  9. [Transport of mPEG-PLGA nanoparticles across the rat nasal mucosa].

    PubMed

    Wang, Jun-Teng; Lin, Dong-Hai; Qin, Li-Fang; Wen, Zhen; Guo, Gui-Ping

    2013-05-01

    To investigate the effects of particle size, mPEG molecular weight, coating density and zeta potential of monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles on their transportation across the rat nasal mucosa, mPEG-PLGA-NPs with different mPEG molecular weights (M(r) 1 000, 2 000) and coating density (0, 5%, 10%, 15%) and chitosan coated PLGA-NP, which loaded coumarin-6 as fluorescent marker, were prepared with the nanoprecipitation method and emulsion-solvent evaporation method, and determine their particle size, zeta potential, the efficiency of fluorescent labeling, in vitro leakage rate and the stability with the lysozyme were determined. The effects of physical and chemical properties on the transmucosal transport of the fluorescent nanoparticles were investigated by confocal laser scanning microscopy (CLSM). The result showed that the size of nanoparticles prepared with nanoprecipitation method varied between 120 and 200 nm; the size of nanoparticles prepared with emulsion-solvent evaporation method varied between 420 and 450 nm. Nanoparticles dispersed uniformly; the zeta potential of PLGA-NPs was negative; mPEG-PLGA-NPs was close to neutral; chitosan coated PLGA-NPs was positive; and the efficiency of fluorescent labeling were higher than 80%. In vitro leak was less than 5% within 4 h and nanoparticles were basically stable with lysozyme. The CLSM results show that the transportation efficiency of mPEG-PLGA-NPs with a high PEG coating density and high mPEG molecular weight was significantly higher than that of uncoated PLGA nanoparticles and also that of chitosan coated PLGA-NPs (P < 0.05). The hydrophilcity, zeta potential and particle size of nanoparticles play important roles on the efficiency of mPEG-PLGA nanoparticles to transport across the rat nasal mucosa.

  10. Effects of aging in the expression of NOD-like receptors and Inflammasome-related genes in oral mucosa

    PubMed Central

    Ebersole, Jeffrey L.; Kirakodu, Sreenatha; Novak, M. John; Exposto, Cristina R.; Stromberg, Arnold J.; Shen, Shu; Orraca, Luis; Gonzalez-Martinez, Janis; Gonzalez, Octavio A.

    2015-01-01

    SUMMARY The molecular changes underlying the higher risk of chronic inflammatory disorders during aging remain incompletely understood. Molecular variations in the innate immune response related to recognition and interaction with microbes at mucosal surfaces could be involved in aging-related inflammation. We developed an ontology analysis of 20 NOD-like receptors (NLRs) and 7 inflammasome-related genes (IRGs) in healthy and inflamed/periodontitis oral mucosal tissues from young, adolescent, adult and aged nonhuman primates (Macaca mulatta) using the GeneChip® Rhesus Macaque Genome array. Validation of some of the significant changes was done by qRT-PCR. The expression of NLRB/NAIP, NLRP12, and AIM2 increased with aging in healthy mucosa whereas NLRC2/NOD2 expression decreased. Although higher expression levels of some NLRs were generally observed with periodontitis in adult mucosal tissues (e.g., NLRB/NAIP, NLRP5, and NLRX1), various receptors (e.g., NLRC2/NOD2, and NLRP2) and the inflammasome adaptor protein ASC, exhibited a significant reduction in expression in aged periodontitis tissues. Accordingly, the expression of NLR-activated innate immune genes, such as HBD3 and IFNB1, was impaired in aged but not adult periodontitis tissues. Both adult and aged tissues showed significant increase in IL-1β expression. These findings suggest that the expression of a subset of NLRs appears to change with aging in healthy oral mucosa, and that aging-related oral mucosal inflammation could involve an impaired regulation of the inflammatory and antimicrobial response associated with down-regulation of specific NLRs and IRGs. PMID:26197995

  11. Voluntary Oral Administration of Losartan in Rats

    PubMed Central

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-01-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents. PMID:26424254

  12. Voluntary Oral Administration of Losartan in Rats.

    PubMed

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-09-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents.

  13. Hematology and serum biochemistry of Indian spectacled cobra (Naja naja) and Indian rat snake (Ptyas mucosa)

    PubMed Central

    Muliya, Sanath Krishna; Bhat, Mudraje Narayana

    2016-01-01

    Aim: To study the hematology and serum biochemistry parameters of Indian spectacled cobra (Naja naja) and Indian rat snake (Ptyas mucosa) and to evaluate the differences in the same between captive and wild populations. Materials and Methods: Animals were categorized into four groups, viz., wild Indian spectacled cobra (n=10), wild Indian rat snakes (n=10), captive Indian spectacled cobra (n=10), and captive Indian rat snake (n=10). The snakes were restrained with restraint tubes, and 2 ml of blood was collected from either heart or ventral coccygeal vein. Hematological examinations were performed manually and serum biochemistry assays were performed on semi-automated clinical chemistry analyzer. Results: The values of total erythrocyte count, packed cell volume, and hemoglobin were slightly low in captive spectacled cobras and captive rat snakes compared to wild ones, whereas total leukocyte count was found to be slightly high in wild spectacled cobras compared to captive ones. All the recorded values of biochemical and electrolyte analytes were found to be well within expected range for snakes except for total protein and chloride levels in both the species which was slightly above the expected range. Conclusion: The hematology and serum biochemistry intervals of the two most common Indian snakes are presented here. The data will be useful in routine health evaluations and aiding in better medical management of the species studied. Since this study is the first to report complete hematologic and blood biochemical ranges for the study species, observations made here can also be used as referral intervals for future use. PMID:27651683

  14. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.

    PubMed

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-03-30

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

  15. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

    PubMed Central

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-01-01

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis. PMID:27025263

  16. Single nucleotide polymorphisms of mucosa-associated lymphoid tissue 1 in oral carcinoma cells and gingival fibroblasts.

    PubMed

    Oyama, Go; Midorikawa, Toshiaki; Matsumoto, Yasutaka; Takeyama, Mayu; Yamada, Kenji; Nozawa, Takaomi; Morikawa, Masako; Imai, Kazushi

    2013-07-01

    Oral carcinoma patients with inactivation of mucosa-associated lymphoid tissue 1 (MALT1) expression worsen their prognoses. Although the genetic mutation could be responsible for the inactivation, no information is available at present. In the present study, genomic DNA of oral carcinoma cells (HOC313, TSU, HSC2, HSC3, KOSC2, KOSC3, SCCKN, OSC19, Ca9.22, and Ho1u1 cells) and normal gingival fibroblasts (GF12 cells) derived from a Japanese population were amplified by polymerase chain reaction using primer sets spanning MALT1 exons, and nucleotide substitutions were analyzed by the single strand conformation polymorphism analysis. The substitutions were commonly observed in all cells, which express MALT1 at various levels. The substitutions at exons 1 and 9 were located at the 5' untranslated region and replaced (336)Asp to Asn, respectively, and others were positioned at the introns. Among the intronic substitutions, four were matched with the single nucleotide polymorphisms (SNPs) registered at the database. Since all cells were derived from a Japanese population, all substitutions detected are the SNPs. Absence of the carcinoma cell-specific mutation suggests that the inactivation of MALT1 expression but not the mutation promotes oral carcinoma progression.

  17. Miconazole-loaded nanostructured lipid carriers (NLC) for local delivery to the oral mucosa: improving antifungal activity.

    PubMed

    Mendes, A I; Silva, A C; Catita, J A M; Cerqueira, F; Gabriel, C; Lopes, C M

    2013-11-01

    Miconazole is a widely used antifungal agent with poor aqueous solubility, which requires the development of drug delivery systems able to improve its therapeutic activity. For this purpose, a miconazole-loaded nanostructured lipid carriers (NLC) dispersion was prepared and characterized. Further, the dispersion was used to prepare a NLC-based hydrogel formulation proposed as an alternative system to improve the local delivery of miconazole to the oral mucosa. NLC dispersion showed particles in the nanometer range (≈ 200 nm) with low polidispersity index (<0.3), good physical stability and high encapsulation efficiency (>87%). A controlled miconazole release was observed from NLC and NLC-based hydrogel formulations, in contrast to a commercial oral gel formulation, which demonstrated a faster release. Additionally, it was observed that the encapsulation of miconazole in the NLC improved its antifungal activity against Candida albicans. Therefore, it was demonstrated that the encapsulation of miconazole in NLC allows for obtaining the same therapeutic effect of a commercial oral gel formulation, using a 17-fold lower dose of miconazole.

  18. Orally administered phenylbutazone causes oxidative stress in the equine gastric mucosa.

    PubMed

    Martínez Aranzales, J R; Cândido de Andrade, B S; Silveira Alves, G E

    2015-06-01

    Phenylbutazone (PBZ) is widely used in equine medicine, and its side effects on the gastrointestinal tract are well known. The inhibition of prostaglandins and the oxidative stress induced by nonsteroidal anti-inflammatory drugs (NSAIDs) are described as mechanisms of gastric mucosal injury in humans. In horses, only the secondary effect of changes in cyclooxygenases is related to gastric mucosal injury. The objective of this study was to evaluate the effect of PBZ on certain antioxidative/oxidative parameters of the gastric mucosa. The concentrations of antioxidants and oxidants (superoxide dismutase, SOD; catalase, CAT; nitric oxide, NO; total glutathione, GSH; myeloperoxidase, MPO; and malondialdehyde, MDA), PGE2 levels, and the ulcerative lesions score were assessed. The results demonstrated decreased levels of antioxidant variables, increased levels of oxidant variables, and alterations in the prostaglandin E2 (PGE2 ), myeloperoxidase (MPO), and glutathione (GSH) levels. In conclusion, PBZ induces oxidative stress in the gastric glandular mucosa of horses by changing the antioxidant-oxidant balance of this surface, which might be regarded as another mechanism of injury in the horse stomach.

  19. A histochemical comparison of methyl green-pyronin, and hematoxylin and eosin for detecting apoptotic cells in oral squamous cell carcinoma, oral leukoplakia, oral submucous fibrosis and normal oral mucosa.

    PubMed

    Sumedha, S; Kotrashetti, V S; Somannavar, P; Nayak, R; Babji, D

    2015-05-01

    Analysis of apoptotic cells in oral pathological states could be useful for determining the rates of tissue turnover, which would help determine prognosis. The use of histochemical stains such as hematoxylin and eosin (H & E) and methyl green-pyronin (MGP) can provide a simple and cost-effective method for detecting apoptotic cells. We compared the efficacy of MGP and H & E for detecting apoptotic cells in oral squamous cell carcinoma (OSCC), oral leukoplakia (OL), oral submucous fibrosis (OSMF) and normal oral mucosa (NOM). Ten cases each of OSCC, OSMF, OL and NOM were retrieved from the archives and two serial sections were stained, one with H & E and the other with MGP. Apoptotic cells were identified at 100 x magnification and the apoptotic index was calculated. Apoptotic cells were distinguished more readily in MGP stained sections than in those stained with H & E. Also, the apoptotic cell count was greater in OSCC compared to OL, OSMF and NOM. We concluded that MGP staining can be used as a routine, cost-effective method for detecting apoptotic cells.

  20. Site and mechanisms of action of kinins in rat ileal mucosa

    SciTech Connect

    Warhurst, G.; Lees, M.; Higgs, N.B.; Turnberg, L.A.

    1987-03-01

    Kinin-induced secretion in the intestine is accompanied by marked increases in mucosal adenosine 3',5'-cyclic monophosphate (cAMP) and prostanoids that undoubtedly contribute to the overall secretory responses. The authors have investigated the effects of kallidin on the phospholipase-prostanoid-cAMP pathway in whole ileal mucosa and in epithelial cells isolated from the same tissue in the rat. Kallidin (1 ..mu..M) stimulated a marked rise in PG (prostaglandin) E/sub 2/ release from the serosal surface of stripped ileal mucosa within 1-2 min, which correlated closely with the rise in mucosal short-circuit current. Mucosal cAMP levels were also increased two to threefold by kallidin. However, kinins were unable to elicit effects under the same conditions in suspensions of viable epithelial cells. PGE/sub 2/ release was unaffected by kallidin or bradykinin at concentrations up to 100 ..mu..M, whereas cAMP levels could be stimulated by forskolin and PGE/sub 2/ but not by kinin. Studies of intestinal phospholipase A/sub 2/ (PLA/sub 2/) activity also suggest a nonepithelial site for kinin action. In the intestine, PLA/sub 2/ activity was found to be concentrated within the subepithelium with significantly lower levels in the epithelium itself. In addition, kallidin was unable to influence phospholipid labeling (an indirect measure of PLA/sub 2/ activity) in cells incubated with (/sup 14/C) arachidonic acid. These studies suggest that kinins initiate increases in intestinal prostaglandin and cAMP production within the subepithelium and not by a direct action on epithelial cells.

  1. Effects of an orabase formulation with ethanolic extract of Malva sylvestris L. in oral wound healing in rats.

    PubMed

    Kovalik, Ana Cristina; Bisetto, Paula; Pochapski, Márcia Thaís; Campagnoli, Eduardo Baulm; Pilatti, Gibson Luiz; Santos, Fábio André

    2014-05-01

    Malva sylvestris L. is widely used in medicine for treatment of inflammatory processes. The plant has anti-inflammatory properties due to substances such as mucilage, flavonoids, and tannins. A mouthwash with leaves from the plant can be used for the treatment of wounds in the oral mucosa. The aim of this study was to assess the wound healing effect of Malva sylvestris L. on a palate mucosa wound in rats. After intraperitoneal anesthesia, a 4-mm-diameter excisional wound was made in the center of the palatal mucosa of 136 rats, using a punch-out biopsy tool. Eight animals were used as baseline wound. The remaining rats were divided into four groups: CO, control; OB, orabase vehicle; CX, 2% chlorhexidine; and MA, 20% Malva in orabase. At 24 h postoperatively, the animals were immobilized without anesthetic to apply 25 mg of each substance twice a day, totaling 50 mg daily. The wound areas were measured photographically and the reepithelialization rates were determined histologically (%) after 0, 3, 7, 15, and 21 days. The data were analyzed by ANOVA and Tukey post hoc test. Similar healing pattern was observed among the groups (P>.05; ANOVA). According to the methodology, Malva sylvestris L. extract had no effect on wound healing in the palatal mucosa of rats.

  2. Er,CR:YSGG lasers induce fewer dysplastic-like epithelial artefacts than CO2 lasers: an in vivo experimental study on oral mucosa.

    PubMed

    González-Mosquera, A; Seoane, J; García-Caballero, L; López-Jornet, P; García-Caballero, T; Varela-Centelles, P

    2012-09-01

    Our aim was to assess wounds made by lasers (CO(2) and Er,Cr:YSGG) for their epithelial architectural changes and width of damage. We allocated 60 Sprague-Dawley(®) rats into groups: glossectomy by CO(2) laser at 3 different wattages (n=10 in each); glossectomy by Er,Cr:YSGG laser at two different emissions (n=10 in each), and a control group (n=10). Histological examination assessed both prevalence and site of thermal artefacts for each group. Both lasers (CO(2) and Er,Cr:YSGG) caused the same type of cytological artefacts. The 3W Er,Cr:YSGG laser produced the fewest cytological artefacts/specimen, and was significantly different from the other experimental groups: 3W CO(2) laser (95% CI=0.8 to 1.0); the 6W CO(2) laser (95% CI=0.1 to 2.0) and the 10W CO(2) laser (95% CI=1.1 to 3.0). CO(2) lasers (3-10W) generate epithelial damage that can simulate dysplastic changes with cytological atypia that affects mainly the basal and suprabasal layers. Irradiation with Er,CR:YSGG laser (2-4W) produces significantly fewer cellular artefacts and less epithelial damage, which may be potentially useful for biopsy of oral mucosa.

  3. Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs.

    PubMed

    Tschachojan, Viktoria; Schroer, Henrike; Averbeck, Nicole; Mueller-Klieser, Wolfgang

    2014-11-01

    Oral mucositis is a severe complication of radiotherapy. Hence, it may constitute a serious medical safety risk for astronauts during extended space flights, such as missions to Mars, during which they are exposed to heavy-ion irradiation. For risk assessment of developing radiation-induced mucositis, a three-dimensional (3D) organotypic oral mucosa model was irradiated with 12C heavy ions or X‑rays. The present study focused mainly on early radiation‑induced effects, such as the activation of nuclear factor κB (NFκB) and the expression or release of pro-inflammatory marker molecules. The 3D oral mucosa models with or without peripheral blood mononuclear cells (PBMCs) were irradiated with X‑rays or 12C heavy ions followed by snap freezing. Subsequently, cryosections were derived from the specimens, which were immunostained for analysis of compactness, DNA double strand breaks (DSB) and activation of NFκB. Radiation‑induced release of interleukin 6 (IL6) and interleukin 8 (IL8) was quantified by ELISA. Quantification of the DNA damage in irradiated mucosa models revealed distinctly more DSB after heavy-ion irradiation compared to X‑rays at definite time points, suggesting a higher gene toxicity of heavy ions. NFκB activation was observed after treatment with X‑rays or 12C particles. ELISA analyses showed significantly higher IL6 and IL8 levels after irradiation with X‑rays and 12C particles compared to non-irradiated controls, whereas co‑cultures including PBMCs released 2 to 3-fold higher interleukin concentrations compared to mucosa models without PBMCs. In this study, we demonstrated that several pro-inflammatory markers are induced by X‑rays and heavy-ion irradiation within an oral mucosa model. This suggests that oral mucositis indeed poses a risk for astronauts on extended space flights.

  4. Valuation of exfoliative cytology as prediction factor in oral mucosa lesions.

    PubMed

    Brunotto, Mabel; Zárate, Ana María; Cismondi, Adriana; Fernández, María del Carmen; Noher de Halac, Rita Inés

    2005-07-01

    The aim of this study was immunolabeling oncoproteins Ck14, p53, p21 and Bcl-2 in order to evaluate their expression in premalignant and malignant stomatological lesions in oral epithelial, and to compare this expression with exfoliative cytology alterations in the same patients. It was studied biopsies and cytologies of 13 subjects with oral lichen planus, with or without Human Papilloma Virus (HPV), leukoplakia and squamous cell carcinoma clinically diagnosed and confirmed by anatomopathological studies. The oral lichen planus lesion presented binuclei orange cells; and in leukoplakia lesions only orange stained was observed; meanwhile koilocytes, inflammatory cells, enlarge nuclear volume and pathogenic microorganisms were observed in the HPV infections and squamous cells carcinoma (SCC). The Ck14, p53, p21 and Bcl-2 proteins were found modified in the leukoplakia, oral lichen planus and cancer. Cytological alterations and positive immunolabeling or over-expression of Ck14 cytokeratine in the upper epithelial stratus should be indicator of malignant transformations as doing subsequence exams.

  5. Immunohistochemical expression of basement membrane proteins of verrucous carcinoma of the oral mucosa.

    PubMed

    Arduino, Paolo G; Carrozzo, Marco; Pagano, Marco; Broccoletti, Roberto; Scully, Crispian; Gandolfo, Sergio

    2010-06-01

    Squamous cell carcinoma (SCC) of the oral cavity is an extremely invasive tumour of stratified squamous epithelium that spreads throughout degradation of the basement membrane (BM) and extra-cellular matrix. Oral verrucous carcinoma (VC) is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. It also has a different clinical behaviour from classical oral SCC. We investigated the immunohistochemical expression of laminin, laminin-5, collagen IV and fibronectin in VC, severe epithelial dysplasia (SED) and SCC in order to analyse if the pattern of these molecules expression contributes to the differences in the biological behaviour of these diseases. The staining pattern of laminin was less intensive in SCC compared with SED and VC, and collagen IV expression was increased in VC compared with SED. Discontinuities of laminin, collagen IV and fibronectin were more evident in SED than in VC. This study indicates that VC has a biological behaviour different from SED or SCC, observable by immunohistochemistry in the BM zone.

  6. Non-specific labelling of mast cells in feline oral mucosa--a potential problem in immunohistochemical studies.

    PubMed

    Harley, R; Gruffydd-Jones, T J; Day, M J

    2002-01-01

    Non-specific labelling of mast cells was found to occur in formalin-fixed sections of feline oral mucosa during immunohistochemical procedures. The phenomenon occurred when normal goat, rabbit or mouse serum was applied as a negative control in place of primary antibodies. In addition, with murine isotype-specific negative control reagents, non-specific labelling of mast cells was intense when IgG2b was applied as the primary reagent, but absent or mild when IgGl or IgG2a isotypes were utilized. The non-specific labelling could be eliminated or diminished by reducing the pH of the washing and dilution buffers from 7.4 to 6.0, or by preincubating sections with heparin. The non-specific binding could also be abolished by preincubating sections with heparinase-I. The results suggest that the non-specific binding was mediated by heparin present within feline oral mucosal mast cells. These findings illustrate the importance of the inclusion of adequate control sections in immunohistochemical studies.

  7. [Histochemical detection of glycoproteins and glycosaminoglycans in the respiratory mucosa of albino rats during estrous cycle, pregnancy and puerperium].

    PubMed

    Pontes, P A; Simões, M J; Merzel, J

    1989-11-01

    In this work we attempted to detect, with histochemical methods, the possible modifications in the mucus of the respiratory mucosa of albino female rats during estral cycle, pregnancy and puerperium. Based on its results, it was possible to conclude that: a--There were no modifications in the nature of the epithelial and supraepithelial mucus during the studied periods: b--The Alcian Blue staining from lamina propria is absent during pregnancy and present during puerperium.

  8. Effect of the hexapeptide dalargin on ornithine decarboxylase activity in the duodenal mucosa of rats with experimental duodenal ulcer

    SciTech Connect

    Yarygin, K.N.; Shitin, A.G.; Polonskii, V.M.; Vinogradov, V.A.

    1987-08-01

    The authors study the effect of dalargin on ornithine decarboxylase in homogenates of the duodenal ulcer from rats with experimental duodenal ulcer induced by cysteamine. Activity of the enzyme was expressed in pmoles /sup 14/CO/sub 2//mg protein/h. Protein was determined by Lowry's method. The findings indicate that stimulation of ornithine decarboxylase and the antiulcerative effect of dalargin may be due to direct interaction of the peptide with cells of the intestinal mucosa and with enterocytes.

  9. Factors influencing pyrroline 5-carboxylate synthesis from glutamate by rat intestinal mucosa mitochondria

    SciTech Connect

    Henslee, J.G.; Wakabayashi, Y.; Small, C.; Jones, M.E.

    1983-10-15

    Factors influencing pyrroline 5-carboxylate (P5C) synthesis from glutamate by a subcellular fraction enriched in mitochondria of rat small intestinal mucosa have been studied. P5C synthesis decreased rapidly if this subcellular fraction was preincubated at 20 degrees C in the absence of substrates; this effect suggests that the enzyme(s) catalyzing P5C synthesis from glutamate (P5C synthase) is unstable in the absence of substrates. In the presence of substrates P5C synthesis increased linearly for the first 30 min of incubation, suggesting that the substrates promote enzyme stability. Pyridoxal 5'-phosphate is an effective inhibitor of P5C synthase whereas pyridoxamine 5'-phosphate and pyridoxal are not inhibitory. Potassium phosphate, KCl, and KBr each inhibited P5C synthase but potassium-Hepes (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) did not. Potassium phosphate was the most potent inhibitor followed by KBr, and then KCl. These results suggest P5C synthase is sensitive to anion inhibition. Both L-ornithine and D-ornithine inhibited P5C synthase; L-proline did not inhibit. Several analogs of ornithine and proline were also tested and none was found to inhibit P5C synthase; the inhibition by ornithine is, therefore, rather specific and it may prove to contribute to the regulation of metabolism of these amino acids.

  10. Effect of genetically modified corn on the jejunal mucosa of adult male albino rat.

    PubMed

    Ibrahim, Marwa A A; Okasha, Ebtsam F

    2016-11-01

    Genetically modified (GM) plants expressing insecticidal traits offer a new strategy for crop protection. GM-corn contains Bacillus thuringiensis (Bt) genes producing delta endotoxins in the whole plant. Diet can influence the characteristics of the gastrointestinal tract altering its function and structure. The aim of this study was to evaluate the effect of GM-corn on the histological structure of jejunal mucosa of adult male albino rat using different histological, immunohistochemical and morphometrical methods. Twenty adult male albino rats were divided into two equal groups; control and GM-corn fed group administered with 30% GM-corn for 90days. Specimens from the jejunum were processed for light and electron microscopy. Immunohistochemical study was carried out using antibody against proliferating cell nuclear antigen (PCNA). Different morphometrical parameters were assessed. Specimens from GM-corn fed group showed different forms of structural changes. Focal destruction and loss of the villi leaving denuded mucosal surface alternating with stratified areas were observed, while some crypts appeared totally disrupted. Congested blood capillaries and focal infiltration with mononuclear cells were detected. Significant upregulation of PCNA expression, increase in number of goblet cells and a significant increase in both villous height and crypt depth were detected. Marked ultrastructural changes of some enterocytes with focal loss of the microvillous border were observed. Some enterocytes had vacuolated cytoplasm, swollen mitochondria with disrupted cristae and dilated rough endoplasmic reticulum (rER). Some cells had dark irregular nuclei with abnormally clumped chromatin. It could be concluded that consumption of GM-corn profoundly alters the jejunal histological structure.

  11. Tetrodotoxin-sensitive and -insensitive relaxations in the rat oesophageal tunica muscularis mucosae.

    PubMed Central

    Akbarali, H I; Bieger, D; Triggle, C R

    1986-01-01

    1. Relaxation responses were produced by vagal and field stimulation, respectively, of the whole oesophagus preparation from the rat and of the isolated tunica muscularis mucosae (t.m.m.) preparation from the rat. These relaxation responses persisted in the presence of antagonists of histamine, serotonin, noradrenaline and acetylcholine. 2. Unlike vagally evoked relaxation, that evoked by low-frequency field stimulation, i.e. field-stimulated relaxation (f.s.r.) was generally resistant to tetrodotoxin (TTX). 3. Both types of relaxations exhibited remarkable temperature sensitivity and were abolished by lowering the bath temperature from 37 to 28 degrees C. 4. TTX-resistant relaxations were also produced by scorpion (Leiurus quinquestriatus) venom, the calcium ionophore, A23187 (calimycin) and by increasing the extracellular potassium by 2 mM. The failure of these agents to inhibit f.s.r. is inconsistent with a releasing and/or depleting action on any endogenous mediator. 5. Relaxations produced by vasoactive intestinal peptide (VIP) could be blocked by alpha-chymotrypsin which, however, failed to abolish f.s.r., suggesting that VIP is not the mediator of f.s.r. 6. F.s.r. was completely blocked by the calcium channel antagonists, verapamil (10(-6) M), nifedipine (10(-7) M), and by magnesium (20 mM). 7. Our results indicate that TTX-insensitive relaxations in the isolated t.m.m. are dependent upon extracellular calcium, are due to activation of potential-operated calcium channels and are not mediated by VIP. PMID:3114474

  12. Surgical Outcomes of Porcine Acellular Dermis Graft in Anophthalmic Socket: Comparison with Oral Mucosa Graft

    PubMed Central

    Teo, Livia; Woo, Young Jun; Kim, Dong Kyu; Kim, Chang Yeom

    2017-01-01

    Purpose We describe our experience with the Permacol graft in anophthalmic socket reconstruction, and compare it to the autologous buccal mucosal graft, emphasizing the postoperative vascularization and contraction of each graft. Methods This was a retrospective comparative study. We measured the time necessary for the graft surface to be completely vascularized, as well as the fornix depth of the conjunctival sac in anophthalmic patients. Results Ten patients underwent Permacol graft reconstruction, with 44 undergoing buccal mucosal graft reconstruction. Seven eyelids (70%) in the Permacol group had a good outcome, with improvement in lower eyelid position and prosthesis retention. Nine out of 10 eyelids (90%) in this group showed complete vascularization of the graft at 2.6 ± 1.9 months postoperatively, while the grafted buccal mucosa was fully vascularized at 1.1 ± 0.3 months postoperatively (p < 0.01). Postoperative fornix depth in the Permacol group was 9.1 ± 2.2 mm, compared to 14.9 ± 4.5 mm in the buccal mucosal graft group (p < 0.01). Mean increases in fornix depth were 33.1% and 67.9% of the mean vertical length of the implanted graft. Conclusions The Permacol graft can be useful as spacer graft material in anophthalmic socket patients. It takes longer to vascularize, and undergoes greater graft shrinkage with time, compared to the buccal mucosal graft. PMID:28243018

  13. Oral mucosa as a source of Mycobacterium leprae infection and transmission, and implications of bacterial DNA detection and the immunological status.

    PubMed

    Martinez, T S; Figueira, M M N R; Costa, A V; Gonçalves, M A; Goulart, L R; Goulart, I M B

    2011-11-01

    Leprosy is an important health problem in Brazil despite extensive use of multidrug therapy. The nasal mucosa is the preferential site of entry and exit of Mycobacterium leprae, and although lesions have been found in the oral mucosa, its potential involvement in the transmission of leprosy bacilli has never been investigated. We investigated the presence of the M. leprae DNA in buccal swabs of leprosy patients (334) and household contacts (1288) through polymerase chain reaction (PCR), and correlated this with clinical and laboratorial evaluations. The overall positivity for patients and contacts was 18.26% and 6.83%, respectively. Subclinical infection among contacts was considered when PCR and anti-PGL-1 ELISA presented positive results. This study provides evidence that the oral mucosa may be a secondary site of M. leprae transmission and infection, and contacts with bacillary DNA may be actively involved in transmission. We have also shown that bacilli DNA is more frequently found in the oral mucosa of PB patients. Our findings have great epidemiological relevance and indicate an additional strategy for leprosy control programmes and dental clinics.

  14. Effects of curcumin and capsaicin irradiated with visible light on murine oral mucosa.

    PubMed

    Okada, Norihisa; Muraoka, Eitoku; Fujisawa, Seiichiro; Machino, Mamoru

    2012-01-01

    The purpose of this study was to evaluate the histopathological effects of curcumin and capsaicin, with or without visible light (VL) irradiation for 5 min, on the oral mucous membrane in mice. Capsaicin-treated, but not curcumin-treated, buccal epithelium exhibited slight tissue damage; VL irradiation caused excessive tissue damage, particularly when combined with the former treatment. The TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method demonstrated that both capsaicin and curcumin induced apoptosis, with the apoptotic effect of capsaicin appearing at an early stage of application. VL irradiation increased the number of apoptotic cells, particularly those upon in the capsaicin-treated area. Capsaicin and curcumin acted as photosensitizers exposure to VL, in the presence of oxygen. Curcumin and capsaicin with VL irradiation could thus be used for photodynamic therapy in the clinical setting, especially in precancerous oral diseases.

  15. Automated segmentation of oral mucosa from wide-field OCT images (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Goldan, Ryan N.; Lee, Anthony M. D.; Cahill, Lucas; Liu, Kelly; MacAulay, Calum; Poh, Catherine F.; Lane, Pierre

    2016-03-01

    Optical Coherence Tomography (OCT) can discriminate morphological tissue features important for oral cancer detection such as the presence or absence of basement membrane and epithelial thickness. We previously reported an OCT system employing a rotary-pullback catheter capable of in vivo, rapid, wide-field (up to 90 x 2.5mm2) imaging in the oral cavity. Due to the size and complexity of these OCT data sets, rapid automated image processing software that immediately displays important tissue features is required to facilitate prompt bed-side clinical decisions. We present an automated segmentation algorithm capable of detecting the epithelial surface and basement membrane in 3D OCT images of the oral cavity. The algorithm was trained using volumetric OCT data acquired in vivo from a variety of tissue types and histology-confirmed pathologies spanning normal through cancer (8 sites, 21 patients). The algorithm was validated using a second dataset of similar size and tissue diversity. We demonstrate application of the algorithm to an entire OCT volume to map epithelial thickness, and detection of the basement membrane, over the tissue surface. These maps may be clinically useful for delineating pre-surgical tumor margins, or for biopsy site guidance.

  16. Oral manifestations in Urbach--Wiethe disease (lipoglycoproteinosis; lipoid proteinosis; hyalinosis cutis et mucosae).

    PubMed

    Hofer, P A; Bergenholtz, A

    1975-01-01

    The oral manifestations in 27 patients with Urbach--Wiethe disease (UWD) discovered in Northern Sweden are described. The oral regions most frequently affected are the lips, the back of the tongue, the frenulum of the tongue, the palate and the back wall of the pharynx. The general impression is that older patients usually have more marked manifestations than younger, indicating that the oral lesions may become more severe with increasing age. Histopathologically, the disorder is essentially a microangiopathy in which the walls of small blood vessels are thick and PAS-positive, indicating the presence of glycoproteins. In clinically affected regions there are usually PAS-positive extravascular deposits. In material used of lipid histochemical studies, sudanophil droplets were found in the vessel walls. By staining with osmium tetroxide the osmium is--contrary to previous assumptions--in some way bound to the droplets, but for unknown reasons is not reduced to a coloured product. The binding of osmium was demonstrated by the OTAN (osmium textroxide alpha-naphthylamine) method. The exact significance of this finding awaits further studies. The implications of dental anomalies occurring in UWD are discussed.

  17. Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

    NASA Astrophysics Data System (ADS)

    Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

    2011-12-01

    Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

  18. [The informative value of determination of the cytological status of nasal and oral mucosae in the assessment of the quality of water].

    PubMed

    Beliaeva, N N; Rakhmanin, Iu A; Gorelova, Zh Iu; Aleksandrova, V P; Aleksandrovskiĭ, S B; Shamarin, A A; Sevost'ianova, E M

    2005-01-01

    The nasal and oral mucosal cytological status was studied in children of a control kindergarten who used boiled Moscow tap water and in those of two experimental kindergartens who had drunk bottled "Troitsa" water supplemented by a fortified "Zolotoy Shar" drink for 6 months. Impression smears were taken from their nasal and oral mucosae twice: before and 6 months after water use. The data presented indicate that the use of the water of improved quality in its trace and vitamin contents may be used in preventive and rehabilitative medicine as it leads to improvement of the nasal and oral cytological status, by normalizing and/or positively affecting the latter.

  19. Interferon-γ-loaded collagen scaffolds reduce myofibroblast numbers in rat palatal mucosa.

    PubMed

    Jansen, Richard G; van Kuppevelt, Toin H; Daamen, Willeke F; Kuijpers-Jagtman, Anne M; Von den Hoff, Johannes W

    2011-02-01

    Wound contraction and scar formation after cleft palate repair lead to growth impairment of the maxilla and midface. Myofibroblasts play a key role in these processes. The application of an interferon-γ (IFN-γ)-loaded collagen scaffold after surgery might reduce the differentiation of myofibroblasts. In this study, the tissue response to IFN-γ-loaded collagen scaffolds was evaluated after implantation in the palate of rats. Scaffolds, with or without IFN-γ, were implanted submucoperiosteally in the palate of two groups of 25 five-week-old male Wistar rats. Groups of five rats were sacrificed at 1, 2, 4, 8, and 16 weeks post-implantation and processed for histological analyses. On haematoxylin and eosin-stained sections, the cell density and number of giant cells within the scaffolds were determined. Blood vessels, inflammatory cells, and myofibroblasts were detected by immunohistochemistry. The data for cell density, blood vessels, and giant cells were compared with a two-way analysis of variance. The scores for myofibroblasts and inflammation were compared by a rank sum test. A mild and rapidly subsiding inflammatory and foreign body response was found in both groups. Angiogenesis had already begun after 1 week, showed a peak after 4 weeks, and declined thereafter. IFN-γ induced a faster influx of host cells and a major reduction in myofibroblast numbers. The scaffolds might be suitable for future applications in oral surgery.

  20. Preservation of epithelial progenitor cells from collagenase-digested oral mucosa during ex vivo cultivation

    PubMed Central

    Hsueh, Yi-Jen; Huang, Shiang-Fu; Lai, Jui-Yang; Ma, Shih-Chieh; Chen, Hung-Chi; Wu, Sung-En; Wang, Tze-Kai; Sun, Chi-Chin; Ma, Kevin Sheng-Kai; Chen, Jan-Kan; Lai, Chyong-Huey; Ma, David Hui-Kang

    2016-01-01

    To avoid xenogeneic infection, we report a novel protocol for producing animal-derived component-free oral mucosal epithelial cells (OMECs) sheet for transplantation, in which collagenase was used to replace dispase II/trypsin-EDTA for digesting oral mucosal tissue, and human platelet-derived PLTMax to replace fetal bovine serum. The resulting epithelial aggregates were expanded on de-epithelialized amniotic membranes without 3T3 feeder cells, and serum-free EpiLife was used to reduce contamination by submucosal mesenchymal cells. The OMEC sheets thus generated showed similar positive keratin 3/76-positive and keratin 8-negative staining patterns compared with those generated by the original protocol. Colony formation efficiency assay, BrdU label retention assay, and p63 and p75NTR immunostaining results indicated that higher proliferative potentials and more progenitor cells were preserved by the modified protocol. TaqMan array analysis revealed that the transcription of integrin-linked kinase (ILK) was up-regulated along with an increase in β-catenin signaling and its downstream cell cycle modulators, cyclin D1 and p27KIP1. Furthermore, ILK silencing led to the inhibition of nuclear β-catenin accumulation, suppressed p63 expression, and reduced the expression of cyclin D1 and p27KIP1; these observations suggest that ILK/β-catenin pathway may be involved in cell proliferation regulation during the ex vivo expansion of OMECs for transplantation purposes. PMID:27824126

  1. Oral epithelial atypical changes in apparently healthy oral mucosa exposed to smoking, alcohol, peppers and hot meals, using the AgNOR and Papanicolaou staining techniques.

    PubMed

    Ahmed, Hussain Gadelkarim; Ebnoof, Syda Omer M Ali; Hussein, Mohmmed Omer M; Gbreel, Afra Yousif A

    2010-07-01

    To evaluate cytological atypical changes in apparently healthy oral mucosa exposed to smoking, alcohol, hot meals, and peppers using the AgNOR and Papanicolaou methods. A total of 180 individuals were evaluated, of which 60 were smokers, 34 were alcohol users, 52 were habitual peppers and hot meal (exposed) consumers, 24 were non-exposed, and 10 were patients with Oral Squamous Cell Carcinoma (OSCC), as an internal control. Cytological materials were obtained by brushing of buccal mucosa, on the border of the tongue and on the floor of the mouth, and participants underwent the Papanicolaou test for cytological changes and AgNOR staining for evaluation of the mean number of AgNOR dots per nucleus. SPSS program was used to perform the Pearson chi-square test. The 95% confidence level, Odds Ratio (OR), and the 95% Confidence Intervals (CI) were used. The features of cytological atypia were verified among 10 individuals, including 5 smokers, 2 alcohol users, 2 hot meals and peppers consumers, and one non-exposed. For atypia among tobacco smokers, the adjusted Odds Ratio (OR) and the 95% CI were found to be 2 (0.246-16.24). Increased keratinization was detected among 27 (45%) of the smokers (P < 0.0001), 17 (32.7%) of the pepper and hot meals consumers (P < 0.005), 4 (11.8%) of the alcohol consumers, and among 2 (3.7%) of the non-exposed group. Statistical analyses revealed a greater mean number of AgNORs per nucleus in smokers (3.68) followed by (2.82) alcohol consumers, compared to the habitual peppers and hot meal consumers (2.28) and the non-exposed group (2.00). What's more, 80% of the smears with cytological atypia were identified with 6 +/- 2 AgNOR mean count. The increase of the variables suggests that the evaluation of epithelial atypical changes in individuals exposed to smoking and alcohol carcinogens may be a useful screening tool. While hot meals and peppers did not seem to be a risk for oral mucosal proliferation, they increased the potency of

  2. Analysis of plasma metabolic biomarkers in the development of 4-nitroquinoline-1-oxide-induced oral carcinogenesis in rats

    PubMed Central

    KONG, XIANGLI; YANG, XIAOQIN; ZHOU, JINGLIN; CHEN, SIXIU; LI, XIAOYU; JIAN, FAN; DENG, PENGCHI; LI, WEI

    2015-01-01

    The aim of the present study was to identify time-dependent changes in the expression of metabolic biomarkers during the various stages of oral carcinogenesis to provide an insight into the sequential mechanism of oral cancer development. An 1H nuclear magnetic resonance (NMR)-based metabolomics approach was used to analyze the blood plasma samples of Sprague-Dawley rats exhibiting various oral lesions induced by the administration of 4-nitroquinoline-1-oxide (4NQO) in drinking water. The 1H NMR spectra were processed by principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) to determine the metabolic differences between the three developmental stages of oral mucosa cancer (health, oral leukoplakia [OLK] and oral squamous cell carcinoma [OSCC]). The variable importance in projection (VIP) score derived from the PLS-DA model was used to screen for important metabolites, whose significance was further verified through analysis of variance (ANOVA). Data from the present study indicated that 4NQO-induced rat oral carcinogenesis produced oral pre-neoplastic and neoplastic lesions and provided an effective model for analyzing sequential changes in the 1H NMR spectra of rat blood plasma. The 1H NMR-based metabolomics approach clearly differentiates between healthy, OLK and OSSC rats in the PCA and PLS-DA models. Furthermore, lactic acid, choline, glucose, proline, valine, isoleucine, aspartic acid and 2-hydroxybutyric acid demonstrated VIP>1 in the PLS-D model and P<0.05 with ANOVA. It was also identified that increases in lactic acid, choline and glucose, and decreases in proline, valine, isoleucine, aspartic acid and 2-hydroxybutyric acid may be relative to the characteristic mechanisms of oral carcinogenesis. Therefore, these plasma metabolites may serve as metabolic biomarkers in oral carcinogenesis and assist in the early diagnosis and preventive treatment of oral cancer. PMID:25435976

  3. Metastasis of renal clear-cell carcinoma to the oral mucosa, an atypical location.

    PubMed

    Maestre-Rodríguez, Oscar; González-García, Raúl; Mateo-Arias, Jesús; Moreno-García, Carlos; Serrano-Gil, Herminia; Villanueva-Alcojol, Laura; Campos-de-Orellana, Ana Ma; Monje-Gil, Florencio

    2009-11-01

    The majority of cases of metastatic tumors involve the mandible and some the maxilla but they are considerably less common in intraoral soft tissues. In addition, the primary tumor is known in the majority of cases; although in one-third of such cases, metastasis is the first clinical manifestation. The most common primary tumors metastasizing to the mouth are lung carcinoma in men and breast carcinoma in women. An oral metastasis implies a serious prognosis, as in the majority of patients there is multiple organ involvement at the time of diagnosis. We present the case of a 52-year old patient with renal pathology who came to the emergency room due to a rapidly increasing gingival tumor. With the provisional clinical diagnosis of a pyogenic granuloma,the tumor was excised. Subsequent anatomopathological analysis revealed a tumor metastasis compatible with clear-cell carcinoma, and its renal origin was confirmed by means of immunohistochemical techniques.

  4. p53 mutation is rare in oral mucosa brushings from patients previously treated for a head and neck squamous cell carcinoma.

    PubMed

    Acha-Sagredo, Amelia; Ruesga, Maria T; Rodriguez, Carlos; Aguirregaviria, Jose I; de Pancorbo, Marian M; Califano, Joseph A; Aguirre, Jose M

    2009-08-01

    Mutations of the tumour suppressor gene p53 are common in human cancer, and seem to be an early event in head and neck squamous cell carcinomas. The aim of our study was to determine the status of the tumour suppressor gene p53 in the oral mucosa of patients previously treated for a head and neck squamous cell carcinoma, at risk of developing an oral squamous cell carcinoma, but without oral clinical lesions. Oral brushings from 87 patients were sequenced with matched genomic DNA. No mutations were found in exons 5, 7 and 8, whereas in exon 6 silent mutations (n=6) and a polymorphism (n=7) were found. Mutation of the tumour suppressor gene p53 does not seem to be a frequent event in patients at risk but without oral lesions.

  5. Novel papillomavirus isolated from the oral mucosa of a polar bear does not cluster with other papillomaviruses of carnivores.

    PubMed

    Stevens, Hans; Rector, Annabel; Bertelsen, Mads F; Leifsson, Pall S; Van Ranst, Marc

    2008-05-25

    Papillomatosis has been documented in several carnivores, and papillomavirus (PV) types have been characterized from lesions in a number of carnivore species: the canine oral PV (COPV), the Felis domesticus PV type 1 (FdPV-1) isolated from a Persian cat, the Procyon lotor PV type 1 (PlPV-1) isolated from a raccoon, the canine PV type 2 (CPV-2) from a dog's foot pad lesion and the canine PV type 3 (CPV-3) associated with a canine epidermodysplasia verruciformis - like disease. A tissue sample was taken from a papillomatous lesion on the oral mucosa of a polar bear (Ursus maritimus). Extracted DNA was used as a template for multiply primed rolling-circle amplification (RCA), and restriction enzyme analysis of the RCA product indicated the presence of papillomaviral DNA. The genome of this PV was cloned and the complete genomic sequence was determined. The Ursus maritimus PV type 1 (UmPV-1) genome counts 7582 basepairs and is smaller than that of other papillomaviruses from carnivore species. UmPV-1 contains the typical noncoding region NCR1, but unlike the carnivore PVs of the Lambda genus, UmPV-1 does not possess a second noncoding region NCR2. Phylogenetic analysis based on a nucleotide sequence alignment of the L1 ORF of UmPV-1 and 51 other PV types indicates that UmPV-1 does not cluster with any of the other carnivore PVs, but branches off near the root of the common branch of the genus Alphapapillomavirus.

  6. Comparison of divided and full pupil configurations for line-scanning confocal microscopy in human skin and oral mucosa

    NASA Astrophysics Data System (ADS)

    Larson, Bjorg; Abeytunge, Sanjeewa; Glazowski, Chris; Rajadhyaksha, Milind

    2012-02-01

    Confocal point-scanning microscopy has been showing promise in the detection, diagnosing and mapping of skin lesions in clinical settings. The noninvasive technique allows provides optical sectioning and cellular resolution for in vivo diagnosis of melanoma and basal cell carcinoma and pre-operative and intra-operative mapping of margins. The imaging has also enabled more accurate "guided" biopsies while minimizing the otherwise large number of "blind" biopsies. Despite these translational advances, however, point-scanning technology remains relatively complex and expensive. Line-scanning technology may offer an alternative approach to accelerate translation to the clinic. Line-scanning, using fewer optical components, inexpensive linear-array detectors and custom electronics, may enable smaller, simpler and lower-cost confocal microscopes. A line is formed using a cylindrical lens and scanned through the back focal plane of the objective with a galvanometric scanner. A linear CCD is used for detection. Two pupil configurations were compared for performance in imaging human tissue. In the full-pupil configuration, illumination and detection is made through the full objective pupil. In the divided pupil approach, half the pupil is illuminated and the other half is used for detection. The divided pupil configuration loses spatial and axial resolution due to a diminished NA, but the sectioning capability and rejection of background is improved. Imaging in skin and oral mucosa illustrate the performance of the two configurations.

  7. Preliminary study of genotoxicity evaluation of orthodontic miniscrews on mucosa oral cells by the alkaline comet assay.

    PubMed

    Martín-Cameán, Ana; Puerto, María; Jos, Ángeles; Azqueta, Amaya; Iglesias-Linares, Alejandro; Solano, Enrique; Cameán, Ana M

    2015-01-01

    Miniscrew implants are widely used nowadays in orthodontic treatments due to their good results in clinical practice. However, data regarding the biocompatibility of commercially available orthodontic miniscrews and temporary devices are very scarce, and their role as genotoxicity inducers has been not previously evaluated with the alkaline comet assay. The aim of this study was to investigate the DNA damage in buccal cells of patients subjected to orthodontic treatments. The alkaline comet assay has been applied in oral mucosa cells from patients treated with conventional orthodontic treatment in comparison to patients treated additionally with miniscrews, non-treated volunteers (control) and smoking volunteers (positive control). The application of orthodontic appliances and miniscrews induced significant and similar (2-fold) increases of %DNA in tail in comparison to control group. Females experienced a significant increase in %DNA in all the treatments in comparison to the control group, whereas males showed significant damage only with the combined orthodontic and miniscrew treatment. In conclusion, conventional orthodontic appliances induced genotoxicity, and the incorporation of miniscrews assayed did not imply any additional increase of DNA damage.

  8. SU-D-16A-02: A Novel Methodology for Accurate, Semi-Automated Delineation of Oral Mucosa for Radiation Therapy Dose-Response Studies

    SciTech Connect

    Dean, J; Welsh, L; Gulliford, S; Harrington, K; Nutting, C

    2014-06-01

    Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in

  9. Pharmacokinetics of oral ketorolac in the rat.

    PubMed

    Granados-Soto, V; Flores-Murrieta, F J

    1995-10-01

    The pharmacokinetics of ketorolac, a potent analgesic agent used for relief of moderate to severe pain, has been studied in rats who received oral doses of 1, 3.2 or 5.6 mg/kg of ketorolac tromethamine. Blood samples were obtained at selected times during 24 h after medication, and ketorolac concentrations were determined by high performance liquid chromatography. After administration of ketorolac, blood concentrations increased rapidly reaching a dose-dependent maximal concentration in about 20 min. Then, concentrations decayed with a half-life of about 6 h. A linear increase in Cmax and AUC as a function of the dose was observed, and not statistically significant difference was observed in AUC/dose or Cmax/dose between doses, indicating that pharmacokinetics of ketorolac is linear in the range of doses studied.

  10. Gastrin upregulates the prosurvival factor secretory clusterin in adenocarcinoma cells and in oxyntic mucosa of hypergastrinemic rats.

    PubMed

    Fjeldbo, Christina Sæten; Bakke, Ingunn; Erlandsen, Sten Even; Holmseth, Jannicke; Lægreid, Astrid; Sandvik, Arne K; Thommesen, Liv; Bruland, Torunn

    2012-01-01

    We show that the gastric hormone gastrin induces the expression of the prosurvival secretory clusterin (sCLU) in rat adenocarcinoma cells. Clusterin mRNA was still upregulated in the presence of the protein synthesis inhibitor cycloheximide, although at a lower level. This indicates that gastrin induces clusterin transcription independently of de novo protein synthesis but requires de novo protein synthesis of signal transduction pathway components to achieve maximal expression level. Luciferase reporter assay indicates that the AP-1 transcription factor complex is involved in gastrin-mediated activation of the clusterin promoter. Gastrin-induced clusterin expression and subsequent secretion is dependent on sustained treatment, because removal of gastrin after 1-2 h abolished the response. Neutralization of secreted clusterin by a specific antibody abolished the antiapoptotic effect of gastrin on serum starvation-induced apoptosis, suggesting that extracellular clusterin is involved in gastrin-mediated inhibition of apoptosis. The clusterin response to gastrin was validated in vivo in hypergastrinemic rats, showing increased clusterin expression in the oxyntic mucosa, as well as higher levels of clusterin in plasma. In normal rat oxyntic mucosa, clusterin protein was strongly expressed in chromogranin A-immunoreactive neuroendocrine cells, of which the main cell type was the histidine decarboxylase-immunoreactive enterochromaffin-like (ECL) cell. The association of clusterin with neuroendocrine differentiation was further confirmed in human gastric ECL carcinoids. Interestingly, in hypergastrinemic rats, clusterin-immunoreactive cells formed distinct groups of diverse cells at the base of many glands. Our results suggest that clusterin may contribute to gastrin's growth-promoting effect on the oxyntic mucosa.

  11. Protective effect of Weikang decoction and partial ingredients on model rat with gastric mucosa ulcer

    PubMed Central

    Fan, Tuo-Ying; Feng, Qing-Qing; Jia, Chun-Rong; Fan, Qun; Li, Chun-An; Bai, Xue-Lian

    2005-01-01

    AIM: To investigate the protective mechanisms of Weikang (WK) decoction on gastric mucosae. METHODS: Ninety rats were randomly divided into nine groups of 10 each, namely group, model group, group with large WK dosage, group with medium WK dosage, group with small WK dosage, group with herbs of jianpiyiqi (strengthening the spleen and replenishing qi), group with herbs of yangxuehuoxue (invigorating the circulation of and nourishing the blood), group with herbs of qingrejiedu (clearing away the heat-evils and toxic materials), group with colloidal bismuth pectin (CBP) capsules. According to the method adopted by Yang Xuesong, except normal control group, chronic gastric ulcer was induced with 100% acetic acid. On the sixth day after moldmaking, WK decoction was administered, respectively at doses of 20, 10 and 5 g/kg to rats of the WK groups, or the groups with herbs of jianpiyiqi, yangxuehuoxue and qingrejiedu, 10 mL/kg was separately administered to each group every day. For the group with CBP capsules, medicine was dissolved with water and doses 15 times of human therapeutic dose were administered (10 mL/kg solution containing 0.35% CBP). Rats of other groups were fed with physiological saline (10 mL/kg every day). Administration lasted for 16 d. Rats were killed on d 22 after mold making to observe changes of gastric mucosa. The mucus thickness of gastric mucosa surface was measured. Levels of epidermal growth factor (EGF) in gastric juice, nitric oxide (NO) in gastric tissue, endothelin (ET) in plasma, superoxide dismutase (SOD) in plasma, malondialdehyde (MDA) in plasma and prostaglandin I2 (PGI2) were examined. RESULTS: Compared with control group, ulceration was found in gastric mucosa of model group rats. The mucus thickness of gastric mucosa surface, the levels of EGF, NO, 6-K-PGF1α and SOD decreased significantly in the model group (EGF: 0.818±0.18 vs 2.168±0.375, NO: 0.213±0.049 vs 0.601±0.081, 6-K-PGF1α: 59.7±6.3 vs 96.6±8.30, SOD: 128.6±15

  12. Interaction of Lactobacillus fermentum BGHI14 with Rat Colonic Mucosa: Implications for Colitis Induction

    PubMed Central

    Lukic, Jovanka; Strahinic, Ivana; Milenkovic, Marina; Golic, Natasa; Kojic, Milan; Topisirovic, Ljubisa

    2013-01-01

    The present study was carried out to test the colonic mucosal response of rats to oral supplementation with Lactobacillus fermentum BGHI14 and to correlate the tissue reaction to trinitrobenzenesulfonate (TNBS)-induced colitis with mucosal barrier alterations caused by bacterial ingestion. An immune cell-mediated reaction of healthy colonic tissue was noticed after bacterial feeding. After prolonged bacterial treatment, the observed reaction had retreated to normality, but the mRNA levels of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) remained elevated. These data point to the chronic low-grade inflammation that could be caused by long-term probiotic consumption. Although no detrimental effects of bacterial pretreatment were noticed in colitic rats, at least in the acute state of disease, the results obtained in our study point to the necessity of reassessment of existing data on the safety of probiotic preparations. Additionally, probiotic effects in experimental colitis models might depend on time coordination of disease induction with treatment duration. PMID:23851097

  13. Effect of cadmium on Fe/sup +3/-transferrin formation in the rat intestinal mucosa

    SciTech Connect

    Sugawara, N.; Chen, B.Q.; Sugawara, C.; Miyake, H.

    1988-07-01

    The effect of cadmium (Cd) on iron (Fe) metabolism has been an important subject for Cd toxicity, since anemia is usually observed in Itai-Itai patients who are exposed for long periods to Cd from the surrounding environment. It was previously accepted that Cd-induced anemia was not dependent on the route of administration. Thereafter, however, it was shown that oral Cd administration was essential for the development of anemia. Studies suggest that one of the possible sensitive sites of competition between Cd and Fe is in the gastrointestinal tract. Cd competes with Fe at one or more steps in the transport system and these metals undergo the same step(s) during their absorption. An hypothesis implies that these two metals possess a common carrier. Two Fe-binding proteins, ferritin and transferrin are well documented in the case of Fe deficiency but not in Cd exposed animals. Recently, the authors reported that the status of mucosal Fe-binding proteins in rats fed with Cd was similar to that in the Fe deficient rats. The present work was performed in an attempt to clarify the effect of in vivo and in vitro Cd on mucosal transferrin formation, which is one of two main Fe-binding proteins.

  14. Trophic action of epidermal growth factor on the pancreas and gastroduodenal mucosa in rats.

    PubMed Central

    Dembiński, A; Gregory, H; Konturek, S J; Polański, M

    1982-01-01

    1. Epidermal growth factor (EGF) infused subcutaneously in a dose of 10 micrograms/kg . h but not 1 microgram/kg . h inhibited spontaneous gastric acid and pepsin secretion, whereas when given intragastrically in a dose of 10 micrograms/kg . h it failed to affect this secretion. 2. EGF injected intraperitoneally at 8 h intervals for 24 h significantly stimulated DNA synthesis in the gastroduodenal mucosa and the pancreas, whereas when administered intragastrically it stimulated DNA synthesis only in the gastroduodenal mucosa but not in the pancreas. 3. Chronic parenteral administration of EGF significantly increased the DNA and RNA contents of the gastroduodenal mucosa and the pancreas. 4. This study demonstrates that parenteral EGF is a potent inhibitor of gastric secretion and trophic agent for the gastroduodenal mucosa and pancreas, and that the gastric inhibitory and trophic effects of EGF are the results of two separate mechanisms. PMID:6180163

  15. Dual-wavelength excitation to reduce background fluorescence for fluorescence spectroscopic quantitation of erythrocyte zinc protoporphyrin-IX and protoporphyrin-IX from whole blood and oral mucosa

    NASA Astrophysics Data System (ADS)

    Hennig, Georg; Vogeser, Michael; Holdt, Lesca M.; Homann, Christian; Großmann, Michael; Stepp, Herbert; Gruber, Christian; Erdogan, Ilknur; Hasmüller, Stephan; Hasbargen, Uwe; Brittenham, Gary M.

    2014-02-01

    Erythrocyte zinc protoporphyrin-IX (ZnPP) and protoporphyrin-IX (PPIX) accumulate in a variety of disorders that restrict or disrupt the biosynthesis of heme, including iron deficiency and various porphyrias. We describe a reagent-free spectroscopic method based on dual-wavelength excitation that can measure simultaneously both ZnPP and PPIX fluorescence from unwashed whole blood while virtually eliminating background fluorescence. We further aim to quantify ZnPP and PPIX non-invasively from the intact oral mucosa using dual-wavelength excitation to reduce the strong tissue background fluorescence while retaining the faint porphyrin fluorescence signal originating from erythrocytes. Fluorescence spectroscopic measurements were made on 35 diluted EDTA blood samples using a custom front-face fluorometer. The difference spectrum between fluorescence at 425 nm and 407 nm excitation effectively eliminated background autofluorescence while retaining the characteristic porphyrin peaks. These peaks were evaluated quantitatively and the results compared to a reference HPLC-kit method. A modified instrument using a single 1000 μm fiber for light delivery and detection was used to record fluorescence spectra from oral mucosa. For blood measurements, the ZnPP and PPIX fluorescence intensities from the difference spectra correlated well with the reference method (ZnPP: Spearman's rho rs = 0.943, p < 0.0001; PPIX: rs = 0.959, p < 0.0001). In difference spectra from oral mucosa, background fluorescence was reduced significantly, while porphyrin signals remained observable. The dual-wavelength excitation method evaluates quantitatively the ZnPP/heme and PPIX/heme ratios from unwashed whole blood, simplifying clinical laboratory measurements. The difference technique reduces the background fluorescence from measurements on oral mucosa, allowing for future non-invasive quantitation of erythrocyte ZnPP and PPIX.

  16. Upregulated Expression of Transient Receptor Potential Cation Channel Subfamily V Receptors in Mucosae of Patients with Oral Squamous Cell Carcinoma and Patients with a History of Alcohol Consumption or Smoking

    PubMed Central

    Sakakibara, Akiko; Sakakibara, Shunsuke; Kusumoto, Junya; Takeda, Daisuke; Hasegawa, Takumi; Akashi, Masaya; Minamikawa, Tsutomu; Hashikawa, Kazunobu; Terashi, Hiroto; Komori, Takahide

    2017-01-01

    Objectives Transient receptor potential cation channel (subfamily V, members 1–4) (TRPV1–4) are expressed in skin and neurons and activated by external stimuli in normal mucosae of all oral cavity sites. The oral cavity is exposed to various stimuli, including temperature, mechanical stimuli, chemical substances, and changes in pH, and, notably, the risk factors for oncogenic transformation in oral squamous epithelium are the same as the external stimuli received by TRPV1–4 receptors. Hence, we examined the relationship between oral squamous cell carcinoma (SCC) and TRPV1–4 expression. Materials and Methods Oral SCC patients (n = 37) who underwent surgical resection were included in this study. We investigated the expression of TRPV1–4 by immunohistochemical staining and quantification of TRPV1–4 mRNA in human oral mucosa. In addition, we compared the TRPV1–4 levels in mucosa from patients with SCC to those in normal oral mucosa. Results The receptors were expressed in oral mucosa at all sites (tongue, buccal mucosa, gingiva, and oral floor) and the expression was stronger in epithelia from patients with SCC than in normal epithelia. Furthermore, alcohol consumption and tobacco use were strongly associated with the occurrence of oral cancer and were found to have a remarkable influence on TRPV1–4 receptor expression in normal oral mucosa. In particular, patients with a history of alcohol consumption demonstrated significantly higher expression levels. Conclusion Various external stimuli may influence the behavior of cancer cells. Overexpression of TRPV1-4 is likely to be a factor in enhanced sensitivity to external stimuli. These findings could contribute to the establishment of novel strategies for cancer therapy or prevention. PMID:28081185

  17. Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats.

    PubMed

    Pelser, Andries; Müller, Douw G; du Plessis, Jeanetta; du Preez, Jan L; Goosen, Colleen

    2002-09-01

    The intranasal route of administration provides a potential useful way of administering a range of systemic drugs. In order to assess the feasibility of this approach for the treatment of nausea and vomiting, doxylamine succinate was studied in rats for the pharmacokinetics (AUC, C(max), t(max)) following intranasal, oral and intravenous administrations. Subjects (six male Sprague-Dawley rats per time interval for each route of administration) received 2-mg doses of doxylamine succinate orally and I-mg doses intranasally and intravenously, respectively. The various formulations were formulated in isotonic saline (0.9% w/v) at 25 +/- 1 degrees C. Doxylamine succinate concentrations in plasma were determined with a high-performance liquid chromatographic assay and a liquid-liquid extraction procedure. Intranasal and oral bioavailabilities were determined from AUC values relative to those after intravenous dosing. Intranasal bioavailability was greater than that of oral doxylamine succinate (70.8 vs 24.7%). The intranasal and oral routes of administration differed significantly from the intravenous route of administration. Peak plasma concentration (C(max)) was 887.6 ng/ml (S.D. 74.4), 281.4 ng/ml (S.D. 24.6) and 1296.4 ng/ml (S.D. 388.9) for the intranasal, oral and intravenous routes, respectively. The time to achieve C(max) for the intranasal route (t(max)=0.5 h) was faster than for the oral route (t(max)=1.5 h), but no statistically significant differences between the C(max) values were found using 95% confidence intervals. The results of this study show that doxylamine succinate is rapidly and effectively absorbed from the nasal mucosa.

  18. Histology of the Oral Mucosa in Patients With BRONJ at III Stage: A Microscopic Study Proves the Unsuitability of Local Mucosal Flaps

    PubMed Central

    Lorenzo, Sara Di; Trapassi, Alberto; Corradino, Bartolo; Cordova, Adriana

    2013-01-01

    Background Bisphosphonate Osteonecrosis of the Jaw (BRONJ) is a newly recognized condition reported in patients treated with aminobisphosphonates (BF). BRONJ is defined as the presence of exposed necrotic alveolar bone that does not resolve over a period of 8 weeks in a patient taking bisphosphonates who has not had radiotherapy to the jaw. Treatment protocols have been outlined, but trials and outcomes of treatment and long-term follow-up data are not yet available. In 2004 an expert panel outlined recommendations for the management of bisphosphonate-associated osteonecrosis of the jaws. Through the histological study of the oral mucosa over the bone necrosis and around the osteonecrosis area in 8 patients affected by BRONJ at III stage, the authors highlight the inappropriateness of the local mucosal flaps to cover the losses of substance of the jaw, BF-related. Methods Mucosa tissue was taken from 8 patients, affected by BRONJ, III stage. The samples taken from the mucosa around and over the osteonecrosis area were fixed with formalin and an ematossilina-eosin dichromatic coloring was carried out. Results The samples of mucosa showed pathognomonic signs of cell suffering that prove that in these patients using local mucosa flaps is inappropriate. Conclusions The authors suggest that only a well vascularized flap as free flap must be used to cover the osteonecrosis area in patients with BRONJ stage III. Because of the structural instability of the mucosa in patients suffering of osteonecrosis Bf related the local flaps are prone to ulceration and to relapse. PMID:23390472

  19. Immunohistochemical Expression of CD105 and TGF-β1 in Oral Squamous Cell Carcinoma and Adjacent Apparently Normal Oral Mucosa and its Correlation With Clinicopathologic Features.

    PubMed

    Nair, Sindhu; Nayak, Ramakant; Bhat, Kishore; Kotrashetti, Vijayalakshmi S; Babji, Deepa

    2016-01-01

    Angiogenesis in oral squamous cell carcinomas (OSCC) is essential for its growth, invasion, and metastasis. This entails a shift in the balance between proangiogenic and antiangiogenic factors. CD105 and TGF-β1 are 2 such proangiogenic factors wherein CD105 exerts its angiogenic effect by binding to and modulating the TGF-β1 pathway. A total of 50 resected specimens of OSCC were considered. One tissue specimen was taken from tumor proper and another specimen from adjacent apparently normal mucosa (AANM). Both tissues were immunohistochemically stained using CD105 and TGF-β1 antibodies. The expression of each antibody was individually assessed and then compared. Pearson χ test was used for statistical comparison of expression. CD105 was significantly expressed in OSCC as compared with AANM and also correlated with increasing TNM stage. The mean microvessel density was higher in OSCC. TGF-β1 was significantly expressed in epithelium of OSCC as compared with AANM. On comparing expression of TGF-β1 and CD105, 79.54% of endothelial cells expressed positivity for both molecules. Both CD105 and TGF-β1 were increased in OSCC, although based on our results CD105 alone can be used as a prognostic marker. On the basis of immunohistochemical expression of CD105 and TGF-β1 in endothelial cells, our results demonstrate that CD105 acts as one of the receptors of TGF-β1 on endothelial cells and induces the angiogenic pathway in OSCC.

  20. Controlled noxious chemical stimulation: responses of rat trigeminal brainstem neurones to CO2 pulses applied to the nasal mucosa.

    PubMed

    Anton, F; Peppel, P; Euchner, I; Handwerker, H O

    1991-02-25

    The nasal mucosa of halothane-anesthetized rats was stimulated with defined CO2 pulses. Recordings were performed from single trigeminal brainstem neurons to characterize their responses to this controlled chemical irritation. All cells examined with this stimulus displayed graded discharges to increasing concentrations of CO2. Enhanced responses were obtained in a group of neurons when the duration of the interstimulus interval was increased. The application of chemical irritants, notably mustard oil or acetic acid induced vigorous ongoing discharges in all cells tested. The CO2 stimulation method described here thus provides an ideal model for the quantitative physiological and pharmacological examination of chemically induced nociception.

  1. Efficiency of systemic versus intralesional bone marrow-derived stem cells in regeneration of oral mucosa after induction of formocresol induced ulcers in dogs

    PubMed Central

    Aly, Lobna A.; El-Menoufy, Hala; Sadeq, Hesham S.; Ragae, Alyaa; Sabry, Dina

    2014-01-01

    Background: Bone marrow mesenchymal stem cells (BMSCs) are the key to regenerative wound healing. MSCs have spatial memory and respond to local environment. The goal of this study was to evaluate the use of systemic and intralesional transplantation of BMSCs for regeneration of oral mucosa in an in vivo dog model. Materials and Methods: Transplantation of undifferentiated green fluorescent protein (GFP)-labeled autologous BMSCs systemically, submucosally or vehicle (saline) was injected around the chemically induced oral ulcer in each group of 18 adult dogs. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) and collagen genes was detected in biopsies from all ulcers. One way ANOVA was used to compare between means of the three groups. Results were considered significant at P < 0.05. Results: Flow cytometric analysis of the MSCs at the passage 3 showed that these cells were negative for CD45 (2.39%). They expressed high levels of CD29 (98.34%). Frozen fluorescence microscopy of sections of the cell-treated oral tissue of all groups indicated that the GFP-transduced implanted cells were integrated within the transplanted tissues. The treatment resulted in dramatic wound edge activation and resurfacing of oral mucosa wound. Conclusion: Our results revealed that BMSCs may be labeled with (GFP), in order to know the distribution of these cells after administration, and suggest that intralesional administration is an appropriate procedure to achieve acceptable regeneration of the previously injured oral mucosa more than systemic route. PMID:24932192

  2. Whole-body localization of 14C-tocopheryl acetate in the rat following oral administration.

    PubMed

    Fand, I; McNally, W P

    1981-03-01

    The whole-body localization of dl-alpha-[3, 4-14C2]-tocopheryl acetate was examined in the rat for intervals ranging between 12-96 hr following administration of a single oral dose. Quantitative evaluation of the macroautoradiograms revealed a rapid removal of 14C-vitamin E equivalents from the blood and gut and their accumulation in body tissues. When the densitometric data were expressed as dpm/mm2, the values for radioactivity uptake by the adrenal cortex were systematically the highest of all tissues examined for all time periods. At 12-96 hr after dosing, high activity was noted in spleen, bone marrow, liver, lymph nodes and fat; moderate activity was observed in myocardium, lung, gastric mucosa, pituitary, blood, hair follicles, Harder's gland and nasal mucosa; low values were found in brain, skeletal muscle and spinal cord. The nearly complete exclusion of radiovitamin E from the brain and its localization to the choroid plexus implied the operation of a blood-brain barrier. Labeled vitamin E uptake in brain, salivary glands and skeletal muscle was essentially linear and increased with time over 12-96 hr. For both early and late sacrifice periods, a differential pattern of 14C-radioactivity uptake was observed with the pituitary, where the pars nervosa exhibited 2.8 times greater activity than the pars distalis. The significance of the findings is discussed in relation to the suggested role of vitamin E in pituitary-adrenal functions, hemopoiesis and oral physiology.

  3. Effect of Semax on homeostasis of gastric mucosa in albino rats.

    PubMed

    Zhuikova, S E; Smirnova, E A; Bakaeva, Z V; Samonina, G E; Ashmarin, I P

    2000-09-01

    The ACTH(4-7)analogue Semax administered intraperitoneally in a dose of 50 microg/kg 1 h before exposure to ulcerogenic factors (ethanol, water immersion immobilization stress) protected gastric mucosa from damage. Postoperative treatment with Semax for 5 days after application of glacial acetic acid on the mucosa prevented acetic acid-induced ulcers and promoted their healing. The antiulcer effects of Semax in the studied dose were comparable with those of tripeptide Pro-Gly-Pro in a dose of 1 mg/kg.

  4. Comparative evaluation of genotoxicity by micronucleus assay in the buccal mucosa over comet assay in peripheral blood in oral precancer and cancer patients.

    PubMed

    Katarkar, Atul; Mukherjee, Sanjit; Khan, Masood H; Ray, Jay G; Chaudhuri, Keya

    2014-09-01

    Early detection and quantification of DNA damage in oral premalignancy or malignancy may help in management of the disease and improve survival rates. The comet assay has been successfully utilised to detect DNA damage in oral premalignant or malignancy. However, due to the invasive nature of collecting blood, it may be painful for many unwilling patients. This study compares the micronucleus (MN) assay in oral buccal mucosa cells with the comet assay in peripheral blood cells in a subset of oral habit-induced precancer and cancer patients. For this, MN assay of exfoliated epithelial cells was compared with comet assay of peripheral blood leucocytes among 260 participants, including those with oral lichen planus (OLP; n = 52), leukoplakia (LPK; n = 51), oral submucous fibrosis (OSF; n = 51), oral squamous cell carcinoma (OSCC; n = 54) and normal volunteers (n = 52). Among the precancer groups, LPK patients showed significantly higher levels of DNA damage as reflected by both comet tail length (P < 0.0001) and micronuclei (MNi) frequency (P = 0.0009). The DNA damage pattern in precancer and cancer patients was OLP < OSF < LPK < OSCC, and with respective oral habits, it was multiple habits > cigarette + khaini > cigarette smokers > areca + khaini > areca. There was no significant difference in the comet length and MNi frequency between males and females who had oral chewing habits. An overall significant correlation was observed between MNi frequency and comet tail length with r = 0.844 and P < 0.0001. Thus, the extent of DNA damage evaluation by the comet assay in peripheral blood cells is perfectly reflected by the MN assay on oral exfoliated epithelial cells, and MNi frequency can be used with the same effectiveness and greater efficiency in early detection of oral premalignant conditions.

  5. The role and application of exfoliative cytology in the diagnosis of oral mucosa pathology - contemporary knowledge with review of the literature.

    PubMed

    Kazanowska, Krzysztofa; Hałoń, Agnieszka; Radwan-Oczko, Małgorzata

    2014-01-01

    On the basis of the current available literature, the authors have presented a short description of cytological examination and its application in the oral mucosa disease diagnostic process. Furthermore, the advantages and disadvantages of this method are described. The available diagnostic tools used for oral smears were reviewed as well as more and more often available methods which aim at making the diagnosis process more accurate and more favorable for patients. Oral cytology analysis may, in the near future, be a very useful examination for patients in terms of diagnostics and monitoring, not only during the treatment but also afterwards. The authors would like to demonstrate what a beneficial tool this cytological examination could be as a fast and cheap cancer prophylactic test. This opinion is based on the fact that this cytological method has significantly improved the detection of uterine cervical cancer during a gynecological examination since the introduction of the Papanicolau technique in the 40s.

  6. Efficacy of krypton laser photodynamic therapy for oral mucosa dysplasia in 9,10-dimethyl-1,2-benzanthracene-treated hamsters.

    PubMed

    Shen, Lingyue; Xu, Qing; Li, Pingping; Zhou, Guoyu

    2013-11-01

    The present study aimed to evaluate the efficacy of krypton laser photodynamic therapy (PDT) with PsD-007 for the treatment of oral mucosa dysplasia in 9,10-dimethyl-1,2-benzanthracene (DMBA)-treated hamsters. A DMBA-induced hamster cheek pouch model of precancerous lesions was created and the resultant 25 hamsters were divided into five groups. The right side was treated with PDT and the left side was used as the positive control. Following systemic anesthesia, an incision was made in the groin area to expose the femoral vein. PsD-007 was administered intravenously through the femoral vein. Various doses of photosensitizer were used to treat groups A-E. Subsequent to closing the incision, the right side of the buccal mucosa was irradiated with light using the krypton laser at a wavelength of 413 nm, a power density of 150 mW/cm(2) and an irradiation time of 20 min. At six weeks post-surgery, the response was analyzed using histological examinations of the buccal pouch mucosa. A total of 24 hamsters completed the six-week observation period, as one hamster from group C died in the second week following the PDT. Of all 24 irradiated sides, 15 formed normal mucosal tissues and nine demonstrated mild dysplasia. Of the total control sides, six developed moderate dysplasia, five developed severe dysplasia and 13 progressed to carcinoma in situ or squamous cell carcinoma (SCC). The results revealed a significant difference between the two sides (P<0.01) and the various doses of the PsD-007 groups. When the PsD-007 dose was >10 mg/kg, there was no statistical difference (P>0.05). PsD-007-mediated krypton laser PDT is effective for the treatment of oral mucosa dysplasia in hamsters.

  7. Physiologically based pharmacokinetic model for rats and mice orally exposed to chromium.

    PubMed

    Kirman, C R; Hays, S M; Aylward, L L; Suh, M; Harris, M A; Thompson, C M; Haws, L C; Proctor, D M

    2012-10-25

    A multi-compartment physiologically based pharmacokinetic (PBPK) model was developed to describe the behavior of Cr(III) and Cr(VI) in rats and mice following long-term oral exposure. Model compartments were included for GI lumen, oral mucosa, forestomach/stomach, small intestinal mucosa (duodenum, jejunum, ileum), blood, liver, kidney, bone, and a combined compartment for remaining tissues. Data from ex vivo Cr(VI) reduction studies were used to characterize reduction of Cr(VI) in fed rodent stomach fluid as a second-order, pH-dependent process. For model development, tissue time-course data for total chromium were collected from rats and mice exposed to Cr(VI) in drinking water for 90 days at six concentrations ranging from 0.1 to 180 mg Cr(VI)/L. These data were used to supplement the tissue time-course data collected in other studies with oral administration of Cr(III) and Cr(VI), including that from recent NTP chronic bioassays. Clear species differences were identified for chromium delivery to the target tissue (small intestines), with higher concentrations achieved in mice than in rats, consistent with small intestinal tumor formation, which was observed upon chronic exposures in mice but not in rats. Erythrocyte:plasma chromium ratios suggest that Cr(VI) entered portal circulation at drinking water concentrations equal to and greater than 60 mg/L in rodents. Species differences are described for distribution of chromium to the liver and kidney, with liver:kidney ratios higher in mice than in rats. Overall, the PBPK model provides a good description of chromium toxicokinetics, with model predictions for tissue chromium within a factor of 3 for greater than 80% of measurements evaluated. The tissue data and PBPK model predictions indicate a concentration gradient in the small intestines (duodenum > jejunum > ileum), which will be useful for assessing the tumor response gradient observed in mouse small intestines in terms of target tissue dose. The rodent PBPK

  8. Transmission of human papillomavirus DNA from patient to surgical masks, gloves and oral mucosa of medical personnel during treatment of laryngeal papillomas and genital warts.

    PubMed

    Ilmarinen, Taru; Auvinen, Eeva; Hiltunen-Back, Eija; Ranki, Annamari; Aaltonen, Leena-Maija; Pitkäranta, Anne

    2012-11-01

    The risk of occupational human papillomavirus (HPV) transmission from patient to medical personnel during laser vaporization procedures remains controversial. The purpose of this study was to determine the risk of HPV transmission from the patient to the protective surgical masks, gloves and oral mucosa of medical personnel during the treatment of laryngeal papillomas and genital warts. The study involved five male patients scheduled for the surgical treatment of laryngeal papillomas, and five male patients undergoing carbon dioxide (CO(2)) laser treatment for urethral warts. Oral mucosa specimens were obtained from the study patients and the employees pre- and postoperatively. Samples were collected from the HPV-infected patient tissue, and from the surgical masks and gloves used by the employees. A total of 120 samples were analyzed for the presence of HPV DNA by PCR, using the degenerated MY09/11/HMB01 primers. After the papilloma procedures, the surgeons' gloves tested HPV positive in one of the five cases and those of the surgical nurse in three of the five cases. After the treatment of genital warts, HPV DNA corresponding to the patient tissue specimens was present in all the samples obtained from the surgical gloves of the operators. All oral mucosa samples obtained from 18 different employees tested HPV negative, as did the surgical mask specimens. According to our study, HPV may contaminate protective equipment, most of all surgical gloves, but transmission of HPV DNA to medical personnel is unlikely to occur provided that protective surgical gloves and masks are applied and disposed of properly.

  9. Verrucous carcinoma of the oral mucosa: An epidemiological and follow-up study of patients treated with surgery in 5 last years

    PubMed Central

    Dean-Ferrer, Alicia; Alamillos-Granados, Francisco J.; Heredero-Jung, Susana; García-García, Blas; Ruiz-Masera, Juan J.; Arévalo-Arévalo, Rafael; Zafra-Camacho, Francisco; Valenzuela-Salas, Borja

    2014-01-01

    Introduction: Oral Verrucous Carcinoma (OVC) is described apart of the Squamous Cell Carcinoma (SCC) due to its specific properties. The objective of our study is to show our series of cases of OVC and to compare with the SCC in terms of clinical manifestations, epidemiology, histopathology, treatment and follow-up. Material and Methods: This is a retrospective study of all the OVC treated in our department between January-2007 and December-2011. The analyzed variables were sex, age, localization in the oral cavity, histopathology, number of biopsies needed to diagnose OVC, TNM classification, treatment and recurrences during follow-up. Results: Our sample was composed by n=14 patients, 57% female, with a mean age of 69.14 years. The most common localization was buccal mucosa (n=5). Seven patients were diagnosed of OVC with the first biopsy. TNM classification was: pT1: 7 patients, pT2: 3 patients, pT3: 3 patients, pT4: 1 patient. No cervical metastases were observed either in cervical neck dissection or during the follow-up of the patients. The treatment was surgery with clinical resection margins up to 1 cm in all cases, followed by radiotherapy in selected cases. Only n=1 patient (7.69%) presented a recurrence after 34 months of follow-up. The overall survival rate was 92.85%. Conclusions: In our population, OVC represents the 6.16% of all oral cavity and oropharynx cancer, and is more frequent in female patients above 70 years old. It uses to rise over a previous lesion, and usually affects the buccal mucosa. In patients with high suspicious lesions, more than one biopsy may be needed to diagnose OVC. No patient showed cervical dissemination. In our experience, treatment based on local resection, without cervical neck dissection, could be a good option for these patients. Key words:Verrucous carcinoma, squamous cell carcinoma, oral cancer, oral cavity, epidemiology, follow-up. PMID:24880446

  10. Effects on gastric mucosa induced by dental bleaching – an experimental study with 6% hydrogen peroxide in rats

    PubMed Central

    PAULA, Anabela Baptista; DIAS, Maria Isabel; FERREIRA, Manuel Marques; CARRILHO, Teresa; MARTO, Carlos Miguel; CASALTA, João; CABRITA, António Silvério; CARRILHO, Eunice

    2015-01-01

    The value of aesthetic dentistry has precipitated several developments in the investigation of dental materials related to this field. The free marketing of these products is a problem and it is subject to various interpretations regarding its legality. There are several techniques for tooth whitening, the most used one being the external bleaching. It is the later version of such technique that poses the greatest danger of ingesting the product. The present study analysed the systemic effect of these products when they are swallowed. Objective This experimental study aimed to observe the effects of a tooth whitening product, whose active agent is 6% hydrogen peroxide, on the gastric mucosa of healthy and non-tumour gastric pathology animals. Material and Methods Fifty Wistar-Han rats were used and then distributed into 5 groups, one for control and four test groups in which the bleaching product was administered in animals with and without non-tumour gastric pathology (induced by the administration of 1 sample of 50% ethanol and 5% of drinking water during 6 days) at different times of study by gavage. There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in IV and VA groups. Changes in spleen weight relative to body weight revealed no statistically significant changes. An analysis of the frequency was performed on the results of macroscopic observation of the gastric mucosa. Results The gastric mucosa revealed lesions in all manipulated groups, being more frequent in groups III and IV. It appears that there is a synergism when using hydrogen peroxide and 50% ethanol in the same group. Conclusion Therefore, it seems that there are some signs of toxicity 3 to 4 days after administration of 6% hydrogen peroxide. The prescription of these therapies must be controlled by the clinician and the risks must be minimized. PMID:26537721

  11. Influence of acrylamide on the gastric mucosa of adult albino rats and the possible protective role of rosemary.

    PubMed

    El-Mehi, Abeer E; El-Sherif, Neveen M

    2015-06-01

    Acrylamide is a common chemical found in heated starchy foods especially potato products. We investigated, for the first time, the effect of acrylamide, alone or with rosemary, on the structure of gastric mucosa of adult male albino rats. Stomach sections were examined using light and scanning electron microscopy. Quantitative immmunohistochemical assessments of the expression of caspase-3, inducible NO synthase (iNOS) and epidermal growth factor receptor (EPGR) were performed. Our results showed that acrylamide produced mucosal erosions and depletion of the protective surface mucus together with widespread inflammatory infiltration. In addition, there was significantly increased expression of caspase-3 and iNOS and weak expression of EPGR. Rosemary exerted a protective effect against acrylamide-induced gastric toxicity via reducing oxidative stress, apoptosis and inflammation as well as accelerating the healing process. The results of this work add to the known toxic effects of acrylamide and provide a new insight into the possible use of rosemary to ameliorate these effects.

  12. [Solcoseryl--dental adherent paste in the treatment of acute radiation-induced inflammation of oral mucosa, gingivae and tongue].

    PubMed

    Kryst, L; Kowalik, S; Bartkowski, S; Henning, G

    1990-07-01

    On the basis of a study carried out in three teaching departments of maxillofacial surgery the effect was analysed of Solcoseryl dental adherent paste and Linomag in the treatment of acute radiation-induced stomatitis. Both drugs were effective but Solcoseryl was superior to the other drug since it accelerated healing by about 50% and formed a protecting dressing on the inflamed mucosa.

  13. A light and electron microscopic study of the changes in the duodenal mucosa induced by sustained pentagastrin stimulation of gastic acid secretion in young rats.

    PubMed Central

    Patrick, W. J.; Denham, D.; Hawkins, W.; Forrest, A. P.

    1975-01-01

    The histological and electron microscopic changes in the duodenal mucosa have been studied over an 8-week experimental period in rats whose gastric acid secretion was stimulated by pentagastrin in a medium of beeswax and mineral oil, and in controls that received injections of beeswax and mineral oil only. The changes leading of final disintegration of the epithelium are described in detail. The main aim of the experiment--to induce mucous change in the duodenal mucosa--was not realized. Images Figs. 1-2 Figs. 3-4 Figs. 5-6 Figs. 7-8 Fig. 9 PMID:1222117

  14. [THE INFLUENCE OF NANODISPERSE CERIUM DIOXIDE ON ONTOGENETIC CHANGES OF ANTIOXIDANT SYSTEM IN THE MUCOSA OF THE STOMACH AND COLON IN RATS].

    PubMed

    Iefimenko, O Yu; Savchenko, I O; Falalyeyeva, T M; Beregova, T V; Zholobak, N M; Shcherbakov, O B; Malyukin, Yu V; Spivak, M Ya

    2015-01-01

    It was established that with age the content of lipid peroxidation products increased in the mucosa of the stomach: Diene conjugates by 30%, products which react to thiobarbituric acid by 285% and Schif bases by 181%. Nanodisperse cerium dioxide (NCD) reduced the content of lipid peroxidation in the gastric mucosa in old rats: Diene conjugates by 43 %, products which react to thiobarbituric acid by 51% and Schif bases by 44% relative to the control group of rats given age. Similarly, it was established that the content of Diene conjugates increased by 40%, products which react to thiobarbituric acid by 114% and Schif bases by 132% in the mucosa of the colon of old rats. NDC significant reduced the content of products which react to thiobarbituric acid by 69% and Schyf basics by 132%. In the stomach superoxide dismutase (by 43%) and catalase activity (by 24%) decreases with age, while in the colon superoxide dismutase activity increases (by 43%). In the colon NCD significant decreased superoxide dismutase (by 34%) and catalase activity (by 21%) relative to controls. Thus, the NDC restores lipid peroxidation in the gastric mucosa and colon, in which develops oxidative stress with age.

  15. Real-time quantification of proteins secreted by artificial connective tissue made from uni- or multidirectional collagen I scaffolds and oral mucosa fibroblasts.

    PubMed

    Bustos, Rosa Helena; Suesca, Edward; Millán, Diana; González, José Manuel; Fontanilla, Marta R

    2014-03-04

    Previously, we found that oral autologous artificial connective tissue (AACT) had a different protein secretion profile to that of clot-embedded AACT. Other oral mucosa substitutes, having different cell types and scaffolds, had dissimilar secretion profiles of proteins (including that for AACT) that influence healing outcome; thus, to ascertain the profiles of factors secreted by artificial tissue and whether they are influenced by their microstructure might help in understanding their bioactivity. An important component of tissue microstructure is the fiber orientation of the scaffold used for manufacturing it. This work developed a surface plasmon resonance (SPR) methodology to quantify factors secreted by oral artificial connective tissue (ACT) in culture medium, and a method to manufacture unidirectional laminar collagen I scaffolds. The SPR methodology was used for assessing differences in the protein secretion profile of ACT made with collagen scaffolds having different fiber orientation (unidirectional vs multidirectional). Oral fibroblasts seeded onto unidirectional scaffolds increased the secretion of six factors involved in modulating healing compared to those seeded onto multidirectional scaffolds. Histological analysis of uni- and multidirectional ACT showed that cells differ in their alignment and morphology. This SPR-methodology led to nanoscale detection of paracrine factors and might be useful to study biomarkers of three-dimensional cell growth, cell differentiation, and wound-healing progression.

  16. Strain differences in toxicity of oral cadmium intake in rats.

    PubMed

    Ninkov, Marina; Popov Aleksandrov, Aleksandra; Mirkov, Ivana; Demenesku, Jelena; Mileusnic, Dina; Jovanovic Stojanov, Sofija; Golic, Natasa; Tolinacki, Maja; Zolotarevski, Lidija; Kataranovski, Dragan; Brceski, Ilija; Kataranovski, Milena

    2016-10-01

    Influence of genetic background on toxicity of oral cadmium (Cd) administration (30 days, in drinking water; 5 ppm and 50 ppm of cadmium) was examined in Albino Oxford (AO) and Dark Agouti (DA) rats. Similar cadmium deposition was noted in gut and draining mesenteric lymph nodes (MLN) of both strains but intensity and/or the pattern of responses to cadmium in these tissues differ. Less intense intestinal damage and leukocyte infiltration was observed in gut of cadmium-exposed AO rats. While gut-associated lymph node cells of DA rats responded to cadmium with an increase of cell proliferation, oxidative activity, IFN-γ, IL-17 production and expression, no changes of these activities of MLN cells of cadmium-treated AO rats were observed. Spleen, which accumulated cadmium comparable to MLN, responded to metal by drop in cell viability and by reduced responsiveness of proliferation and cytokine production to stimulation in DA rats solely, which suggest tissue dependence of cadmium effects. More pronounced cadmium effects on MLN and spleen cells of DA rats (which accumulated similar cadmium doses as AO rats), showed greater susceptibility of this strain to cadmium. The results presented, for the first time, depict the influence of genetic background to effects of oral cadmium administration.

  17. Effect of somatostatin on the growth of gastrointestinal mucosa and pancreas in rats. Role of endogenous gastrin.

    PubMed Central

    Dembiński, A; Warzecha, Z; Konturek, S J; Schally, A V

    1987-01-01

    This study was undertaken to determine the influence of somatostatin on the growth of gastric, duodenal, and pancreatic tissue in rats placed on liquid diet. In the first part of the study animals were fed an elemental liquid diet for 10 days and then killed, and the growth of the oxyntic gland area of the stomach, 2 cm segments of duodenum and pancreatic tissue was determined. Feeding an elemental diet caused a decrease in organ weight, nucleic acid contents and serum gastrin level. Subsequent addition of pentagastrin prevented this reduction in organ weight and RNA and DNA contents while somatostatin failed to affect the decrease in growth parameters or serum gastrin level in tests with or without addition of pentagastrin. In a second part of the study, sham operated and antrectomised rats were used. Antrectomy caused a significant decrease in serum gastrin concentration and resulted in a significant reduction in the weight and RNA and DNA contents of the tissue tested. As in liquid diet, subsequent administration of pentagastrin prevented the reduction in the growth parameters both in tests with and without somatostatin. These results suggest that somatostatin inhibits the growth of the gastroduodenal mucosa by a mechanism involving, at least in part, the suppression of gastrin release. PMID:2446962

  18. Enzymatic conversion of all-trans-. beta. -carotene to retinal by a cytosolic enzyme from rabbit and rat intestinal mucosa

    SciTech Connect

    Lakshman, M.R.; Mychkovsky, I.; Attlesey, M. )

    1989-12-01

    Enzymatic conversion of all-trans-{beta}-carotene to retinal by a partially purified enzyme from rabbit and rat intestinal mucosa was demonstrated. The enzymatic product was characterized based on the following evidence: (i) the product gave rise to its O-ethyloxime by treatment with O-ethylhydroxylamine with an absorption maximum at 363 nm in ethanol characteristics of authentic retinal O-ethyloxime. High-pressure liquid chromatography (HPLC) of this derivative yielded a sharp peak with a retention time of 7.99 min corresponding to the authentic compound; (ii) the mass spectrum of the O-ethyloxime of the enzymatic product was identical to that of authentic retinal O-ethyloxime; (iii) the specific activity of the enzymatically formed ({sup 14}C)retinal O-ethyloxime remained constant even after repeated crystallization; (iv) the enzymatic product exhibited an absorption maximum at 370 nm in light petroleum characteristic of authentic retinal. This retinol was enzymatically esterified to retinyl palmitate by rat pancreatic esterase with a retention time of 10 min on HPLC corresponding to authentic retinyl palmitate. Thus, the enzymatic product of {beta}-carotene cleavage by the partially purified intestinal enzyme was unequivocally confirmed to be retinal.

  19. Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin

    PubMed Central

    Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J

    2016-01-01

    The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247

  20. Individual differences in oral nicotine intake in rats.

    PubMed

    Nesil, Tanseli; Kanit, Lutfiye; Collins, Allan C; Pogun, Sakire

    2011-01-01

    To study individual differences in nicotine preference and intake, male and female rats were given free access to a choice of oral nicotine (10 or 20 mg/L) or water for 24 h/day for periods of at least six weeks, starting at adolescence or adulthood. A total of 341 rats, were used in four different experiments; weight, nicotine intake and total liquid consumption were recorded weekly. Results show that rats can discriminate nicotine from water, can regulate their intake, and that there are readily detected individual differences in nicotine preference. Ward analyses indicated that the animals could be divided into minimum, median and maximum preferring subgroups in all experiments. The effect of saccharine on nicotine intake was also evaluated; although the addition of saccharine increased total intake, rats drank unsweetened nicotine solutions and those with higher preferences for nicotine, preferred nicotine over water with or without saccharine added. Nicotine reduced weight gain and the effect was more pronounced in females than males. The average nicotine consumption of adolescent rats was higher than adults and nicotine exposure during adolescence reduced nicotine intake in adult rats. About half of the rats which had access to nicotine as adolescents and also as adults had a persistent pattern of consumption; the behavior was very stable in the female minimum preferring groups and a much higher ratio of rats sustained their adolescent behavior as adults. The change in preference was more pronounced when there was an interval between adolescent and adult exposure; female rats showed a more stable behavior than males suggesting a greater role for environmental influences on males. In conclusion, marked individual differences were observed in oral nicotine intake as measured in a continuous access 2-bottle choice test. Age and sex of the subjects and previous exposure to nicotine are significant factors which affect preference in rats.

  1. A robust method for assessing chemically induced mutagenic effects in the oral cavity of transgenic Big Blue® rats.

    PubMed

    Young, Robert R; Thompson, Chad M; Dinesdurage, Harshini R; Elbekai, Reem H; Suh, Mina; Rohr, Annette C; Proctor, Deborah M

    2015-08-01

    The Big Blue® (BB) in vivo mutation assay uses transgenic rodents to measure treatment-induced mutations in virtually any tissue. The BB assay can be conducted in rats or mice and is ideal for investigating tissue-specific mutagenic mode of action of tumor induction. Some tissues such as oral mucosa have not been thoroughly studied. Due to the small quantity and cartilaginous nature of oral cavity tissues, development of special prosection and DNA isolation methods was required to permit robust analysis of mutations in these tissues. Improved surgical methods permitted collection of adequate and reproducible quantities of tissue (∼45 mg gingiva/buccal and ∼30 mg gingiva/palate). Optimized DNA isolation methods included use of liquid nitrogen pulverization, homogenization, nuclei pelleting, digestion, and phenol/chloroform extraction, to yield sufficient quantities of DNA from these tissues. In preliminary optimization work, mutant frequency (MF) in tongue and gingiva was increased in rats exposed to the promutagen, benzo[a]pyrene, and the direct mutagen, N-ethyl-N-nitrosourea. The oral cavity carcinogen, 4-nitroquinoline-1-oxide (4-NQO; 10 ppm in drinking water; 28 days), was qualified as a positive control for mutagenesis in oral tissues since it caused significant increases in cII MFs in gingiva/palate (50.2-fold) and gingiva/buccal tissues (21.3-fold), but not in liver or bone marrow (0.9- and 1.4-fold, respectively). These results are consistent with the observation that 4-NQO primarily induces tumors in oral cavity. Results also demonstrate the utility of the BB rat mutation assay and optimized methods for investigation of oral cavity mutagenicity, and by extension, analysis of other small and cartilaginous tissues.

  2. Effect of dietary boron on 5-fluorouracil induced oral mucositis in rats

    PubMed Central

    Aras, Mutan Hamdi; Sezer, Ufuk; Erkilic, Suna; Demir, Tuncer; Dagli, Seyda Nur

    2013-01-01

    Objective: The aim of this study was to evaluate the effect of boron on 5-fluorouracil (5-FU)–induced oral mucositis in rats. Materials and Methods: Sixty-four male Wistar albino rats were injected with 5-FU on days 1 and 3. The right cheek pouch mucosa was scratched with the tip of an 18-G needle, dragged twice in a linear movement, on days 3 and 5. The animals were randomly divided into two groups of 32: boron group (BG) and control group (CG). Rats in the CG did not receive any treatment, whereas the others were fed boron (3 mg·kg-1·day-1) by gavage. The animals were sacrificed on day 3 (n = 8), 6 (n = 8), 9 (n = 8), and 12 (n = 8), and the cheek pouch was removed for histopathological analysis. Results: On day 3, both groups showed necrosis and active inflammation, but the inflammation was mild in CG and moderate in BG. On day 6, both BG and CG showed necrosis; in the CG, there was moderate inflammation, and in the BG, there was severe inflammation and granulation tissue around the necrotic area. On day 9, re-epithelization began in both groups, and there were no differences between groups. Re-epithelization was complete in both groups on day 12. Conclusion: We found no beneficial effect of boron in healing oral mucositis. Additional research is warranted to elucidate the pathogenic inflammatory mechanisms involved in mucositis and the prophylactic and therapeutic roles of antioxidants. PMID:24926211

  3. THE ENDOCRINE CELLS IN THE EPITHELIUM OF THE GASTROINTESTINAL MUCOSA OF THE RAT

    PubMed Central

    Forssmann, W. G.; Orci, L.; Pictet, R.; Renold, A. E.; Rouiller, C.

    1969-01-01

    The authors of this study examine the question of whether the so-called enterochromaffin or argentaffin cells of the gastrointestinal tract should be considered as a single cell type. The systematic application of purely morphologic methods has led to the conclusion that the epithelium of the gastrointestinal mucosa comprises endocrine cells of several types. This conclusion is primarily based on the uneven and characteristic distribution of the various cell types along the intestinal tract, an observation precluding the interpretation that the different types correspond to diverse functional stages of the same cell. A specific endocrine function may be attributed to each of the given cell types recognized so far on account of their appearance and their localization in characteristic areas of the gastrointestinal tract. It is acknowledged, however, that a purely morphological study leaves room for doubt. The first cell type is probably responsible for the formation of 5-hydroxytryptamine. Cells of type II are morphologically comparable to the pancreatic A cells and may, therefore, be called intestinal A cells. Cell type III comprises intestinal D cells since their appearance corresponds to that of pancreatic D cells. Cell type IV might well be responsible for catecholamine production, whereas gastrin is in all probability produced in endocrine cell type V. As yet, the thorough morphological study of the gastrointestinal epithelium does not provide information as to additional distinct cellular sites of production of the several other hormones isolated from different parts of the gut. PMID:5765761

  4. Chromosome damage and cytotoxicity in oral mucosa cells after 2 months of exposure to anabolic steroids (decadurabolin and winstrol) in weight lifting.

    PubMed

    Martins, Renato A; Gomes, Guilherme A S; Aguiar, Odair; Medalha, Carla C; Ribeiro, Daniel A

    2010-12-01

    The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated buccal mucosa cells from anabolic steroid users after 2 months of exposure. Two experimental groups consisting of 15 adult males who practise weight lifting and are anabolic steroid users or 15 adult males who practise weight lifting, but are non-anabolic steroid users, were recruited. In addition, 20 sedentary males, who do not practise any physical activity regularly, were matched by age with experimental groups. No significant statistical differences (p>0.05) were noticed in individuals who practise physical activity only. On the other hand, an increase of micronucleated cells (MNCs) in anabolic steroid (decadurabulin and Winstrol) users was observed. Regarding cytotoxic parameters, the same observation has occurred, that is, significant statistical differences (p<0.05) were noticed in the group exposed to anabolic steroids when compared with other controls, as depicted by high frequencies of pyknosis, karyolysis and karyorrhexis. Taken together, our results suggest that genomic instability and cytotoxicity are induced by anabolic steroid administration in oral mucosa cells as assessed by the micronucleus test.

  5. Oral administration of hyaluronan reduces bone turnover in ovariectomized rats.

    PubMed

    Ma, Jenny; Granton, Patrick V; Holdsworth, David W; Turley, Eva A

    2013-01-16

    The effect of oral hyaluronan (HA) on bone loss in ovariectomized (OVX) 3-month-old rats was measured using serum markers of bone turnover and bone mineral density. OVX rats were administered 1 mg/kg HA (OVX + HA) or phosphate-buffered saline (PBS) (OVX + PBS) by oral gavage (5 days/week for 54 days). Additional controls included sham ovariectomy with PBS gavage (Sham + PBS) and no treatment. Oral administration of HA resulted in approximately 50% (p < 0.05) increases in serum HA. Gel filtration analyses showed this was high molecular weight HA (300-500 kDa). Osteopenia was mild due to the young age of the animals. Thus, ovariectomy resulted in a 30% increase in serum collagen N-terminal telopeptides (p < 0.001), a 20% increase in serum nitrate/nitrite levels (p = 0.05), and a 5-6% decrease in femur bone mineral density/content (p < 0.05). HA gavage blunted the development of osteopenia in this model as determined by preventing the 30% increase in serum collagen N-terminal telopeptide levels (p < 0.001) and by reducing bone mineral content loss from 6 to 4%. These results show that oral supplements of HA (gavage solution, 0.12% solution) significantly reduce bone turnover associated with mild osteopenia in rats.

  6. Nickel-Related Intestinal Mucositis in IBS-Like Patients: Laser Doppler Perfusion Imaging and Oral Mucosa Patch Test in Use.

    PubMed

    Borghini, Raffaele; Puzzono, Marta; Rosato, Edoardo; Di Tola, Marco; Marino, Mariacatia; Greco, Francesca; Picarelli, Antonio

    2016-09-01

    Nickel (Ni) is often the trigger of irritable bowel syndrome (IBS)-like gastrointestinal disorders: its ingestion may cause allergic contact mucositis, identifiable by means of oral mucosa patch test (omPT). OmPT effectiveness has been proven, but it is still an operator-dependent method. Laser Doppler perfusion imaging (LDPI) was tested to support omPT in Ni allergic contact mucositis diagnosis. Group A: 22 patients with intestinal/systemic symptoms related to the ingestion of Ni-containing foods. Group B: 12 asymptomatic volunteers. Ni-related symptoms and their severity were tested by a questionnaire. All patients underwent Ni omPT with clinical evaluation at baseline (T0), after 30 min (T1), after 2 h (T2), and after 24-48 h (T3). LDPI was performed to evaluate the mean mucosal perfusion at T0, T1, and T2. Statistical analysis was performed by ANOVA test and Bonferroni multiple-comparison test. All 22 Ni-sensitive patients (group A) presented oral mucosa hyperemia and/or edema at T2. Eight out of the same 22 patients presented a local delayed vesicular reaction at T3 (group A1), unlike the remaining 14 out of 22 patients (group A2). All 12 patients belonging to control group B did not show any alteration. The mean mucosal perfusion calculated with LDPI showed an increase in both subgroups A1 and A2. In group B, no significant perfusion variations were observed. LDPI may support omPT for diagnostic purposes in Ni allergic contact mucositis. This also applies to symptomatic Ni-sensitive patients without aphthous stomatitis after 24-48 h from omPT and that could risk to miss the diagnosis.

  7. Effects of titanium dioxide nanoparticles on small intestinal mucosa in rats.

    PubMed

    Onishchenko, G E; Erokhina, M V; Abramchuk, S S; Shaitan, K V; Raspopov, R V; Smirnova, V V; Vasilevskaya, L S; Gmoshinski, I V; Kirpichnikov, M P; Tutelyan, V A

    2012-12-01

    Penetration of titanium dioxide nanoparticles into enterocytes after their administration into isolated loop of rat small intestine was shown in vivo by transmission electron microscopy. Using electron diffraction, titanium dioxide nanoparticles were identified in the apical regions of the cells under plasma membranes and in deeper parts of the cytoplasm as solitary objects or small aggregations. Water dispersions of nanoparticles (3-h exposure to high concentrations) caused no appreciable morphological changes in enterocyte ultrastructure. A 28-day subacute intragastric administration of water dispersion of nanoparticles to rats led to titanium accumulation in the liver, their level was significantly higher than in the control group, which was shown by mass spectrometry with inductive-bound plasma. These data indicated the possibility of penetration of titanium dioxide nanoparticles through the gastrointestinal barrier under near-physiological conditions.

  8. Hydrogen sulfide upregulated mRNA expressions of sodium bicarbonate cotransporter1, trefoil factor1 and trefoil factor2 in gastric mucosa in rats

    PubMed Central

    Cheraghi, Parisa; Mard, Seyyed Ali; Nagi, Tahereh

    2016-01-01

    Hydrogen sulfide (H2S) has been shown to protect the gastric mucosa through several protective mechanisms but till now its effect on mRNA expression of sodium bicarbonate cotransporter 1 (NBC1), trefoil factor1 (TFF1) and trefoil factor2 (TFF2) was not investigated. This study was aimed to evaluate the effect of H2S on mRNA expression of NBC1, TFF1 and TFF2 in rat gastric mucosa in response to gastric distention. Thirty two rats were randomly assigned into four equal groups. They were control (C), distention (D), propargylglycine (PAG)-, and NaHS-treated groups. To evaluate the effect of exogenous and endogenous H2S on gene expression of NBC1, TFF1 and TFF2, two groups of rats were received H2S donor, intra-peritoneal NaHS (80 µg Kg-1), and PAG (50 mg kg-1), accompanied to stimulate the gastric acid secretion, respectively. Under general anesthesia and laparotomy, a catheter was inserted into the stomach through duodenum for instillation of isotonic saline for gastric distention. Ninety min after beginning the experiment, animals were sacrificed and the gastric mucosa was collected to determine total acid content of gastric effluents and to quantify the mRNA expression of studied genes by quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that A) gastric distention increased the level of mRNA expressions of NBC1, TFF1 and TFF2; B) these levels in NaHS-treated rats were significantly higher than those in Distention group; and C) PAG decreased the expression levels of NBC1 and TFF1. The Findings showed H2S upregulated gene expression of NBC1, TFF1 and TFF2 in gastric mucosa. PMID:28144424

  9. Characteristics of β-galactosidase in the mucosa of the small intestine of infant rats. Physicochemical properties

    PubMed Central

    Kraml, Jiří; Koldovský, Otakar; Heringová, Aleša; Jirsová, Věra; Kácl, Karel; Ledvina, Miloš; Pelichová, Hana

    1969-01-01

    1. The characteristics of acid and neutral β-galactosidases isolated chromatographically from homogenates of the mucosa of the jejunum and ileum of suckling rats were studied. 2. The minimal molecular weight of the acid β-galactosidase, as estimated by gel filtration on Sephadex G-200, was in the range 83000–105000, whereas for the neutral β-galactosidase the estimated molecular weight was in the range 360000–510000. 3. The acid and neutral β-galactosidases were inhibited competitively by galactono-(1→4)-lactone, with respective Ki values of 0·15mm and 1·1mm. Only the acid β-galactosidase was inhibited competitively by sodium galactonate (Ki 0·17mm). 4. Heat inactivation of both β-galactosidases occurred according to first-order kinetics. The neutral enzyme was more labile, but bovine serum albumin protected acid enzyme only. 5. Urea treatment inactivated both β-galactosidases, the neutral β-galactosidase being more sensitive than the acid β-galactosidase. 6. No differences were found between preparations from the jejunum and ileum. PMID:5820646

  10. Transforming growth factor alpha protection against drug-induced injury to the rat gastric mucosa in vivo.

    PubMed Central

    Romano, M; Polk, W H; Awad, J A; Arteaga, C L; Nanney, L B; Wargovich, M J; Kraus, E R; Boland, C R; Coffey, R J

    1992-01-01

    This study was designed to determine whether transforming growth factor alpha (TGF alpha) protects rat gastric mucosa against ethanol- and aspirin-induced injury. Systemic administration of TGF alpha dose-dependently decreased 100% ethanol-induced gastric mucosal injury; a dose of 50 micrograms/kg delivered intraperitoneally 15 min before ethanol decreased macroscopic mucosal injury by > 90%. At the microscopic level, TGF alpha prevented deep gastric necrotic lesions and reduced disruption of surface epithelium. Pretreatment with orogastric TGF alpha (200 micrograms/kg) only partially (40%) decreased macroscopic ethanol damage. Intraperitoneal administration of TGF alpha at a dose of 10 micrograms/kg, which does not significantly inhibit gastric acid secretion, decreased aspirin-induced macroscopic damage by > 80%. TGF alpha protection does not seem to be mediated by prostaglandin, glutathione, or ornithine decarboxylase-related events, as evidenced by lack of influence of the inhibition of their production. Pretreatment with the sulfhydryl blocking agent N-ethylmaleimide partially abolished (40%) the protective effect of TGF alpha. In addition, systemic administration of TGF alpha resulted in a two-fold increase in tyrosine phosphorylation of phospholipase C-gamma 1 and in a time- and dose-dependent increase in levels of immunoreactive insoluble gastric mucin; these events occurred in a time frame consistent with their participation in the protective effect of TGF alpha. Images PMID:1281834

  11. Effects of polymer-based, silver nanoparticle-coated silicone splints on the nasal mucosa of rats.

    PubMed

    Şevik Eliçora, Sultan; Erdem, Duygu; Dinç, Aykut Erdem; Altunordu Kalaycı, Özlem; Hazer, Baki; Yurdakan, Gamze; Külah, Canan

    2017-03-01

    Infection is a serious complication after nasal packing that otolaryngologists seek to avoid. The aim of this study is to investigate the use of silver (Ag) nanoparticle, which serves as antimicrobial agents, with nasal tampons. The study design is an experimental animal model and the setting is tertiary referral center. Twenty-four rats were randomized into the following four groups: (1) control group (n = 6); (2) silicone nasal splint (SNS) group (n  =  6); (3) polypropylene-grafted polyethylene glycol (PP-g-PEG) amphiphilic graft copolymer-coated SNS group (n  =  6); and (4) Ag nanoparticle-embedded PP-g-PEG (Ag-PP-g-PEG) amphiphilic graft copolymer-coated SNS group (n  =  6). These tampons were applied to rats for 48 h, after which they were removed in a sterile manner, and the rats were sacrificed. The nasal septa of the rats were excised, and assessments of tissue changes in the nasal mucosa were compared among the groups. The removed tampons were microbiologically examined, and quantitative analyses were made. When the groups were compared microbiologically, there were no significant differences in bacterial colonization rates of coagulase-negative Staphylococcus spp. among the three groups (p = 0.519), but there was a statistically significant difference among bacterial colonization rates of Heamophilus parainfluenzae and Corynebacterium spp. (p = 0.018, p = 0.004). We found that H. parainfluenzae grew less robustly in the Ag-PP-g-PEG than the PP-g-PEG group (p = 0.017). However, we found no significant difference between the Ag-PP-g-PEG and SNS groups, or between the SNS and PP-g-PEG groups. The growth of Corynebacterium spp. did not differ significantly between the Ag-PP-g-PEG and SNS groups (p = 1.000). When Group 4 was compared with Group 2, the former showed less inflammation. Compared with other tampons, Ag-PP-g-PEG amphiphilic graft copolymer-coated silicone nasal tampons caused less microbiological colonization and

  12. Exploring beyond the oral mucosa in patients affected with autoimmune blistering diseases: the importance of endoscopic procedures.

    PubMed

    España, A; Fernandez, S

    2016-09-14

    Autoimmune blistering diseases (AIBD) comprise several entities characterized by the presence of autoantibodies targeted against structural proteins either in desmosomes or in the dermoepidermal junction of polystratified squamous epithelium. Patients develop blisters, erosions in cutaneous surfaces or mucosas. Diagnosis is based on the characteristic mucocutaneous lesions, the typical findings on histological studies and direct immunofluorescence assays, and the presence of specific autoantibodies against the epidermal antigens. It may not be possible for dermatologists to appropriately explore the nose and throat (NT). Thus, a clinical exploration by endoscopic procedures of NT may be a useful tool during the conventional dermatological exam. The aims of this review are to draw attention to the most frequent NT manifestations in AIBD patients, and underline the utility of endoscopic procedures to achieve a more successful and rationale management of patients. Additionally, we will provide brief information related to the anatomical structures and type of epithelium in NT areas which may explain the extent and type of NT involvement in AIBD. Endoscopic exploration in AIBD patients is important for several reasons. Firstly, it will allow the real NT mucosal involvement in each patient to be determined, thus making a differential diagnosis during the endoscopic exam possible, based on the localization of mucosal lesions. Secondary mucosal morbidity can also be ruled out. Secondly, the clinical response to treatment may be established, especially in NT mucosa, as these are anatomical areas subjected to important local traumas, and physiological functions such as breathing, swallowing, speech production and phonation may be damaged. Therefore, a multidisciplinary management in AIBD is mandatory by both dermatologists and otorhinolaryngologists, adding the clinical exploration by endoscopic procedures of NT to the conventional dermatological exam in all AIBD patients

  13. Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa.

    PubMed

    Hasegawa, Mayumi; Cheng, Jun; Maruyama, Satoshi; Yamazaki, Manabu; Abé, Tatsuya; Babkair, Hamzah; Saito, Chikara; Saku, Takashi

    2016-05-01

    The intercellular deposit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells.

  14. Effect of Cigarette Smoke on Wound Healing of the Septal Mucosa of the Rat

    PubMed Central

    Trombitas, Veronica; Nagy, Alina; Berce, Cristian; Tabaran, Flaviu; Albu, Silviu

    2016-01-01

    Objectives/Hypothesis. Proper wound healing following endoscopic sinus surgery (ESS) is influenced by several factors, like cigarette smoke (CS) exposure. This study aims to assess the influence of cigarette smoke on the healing of induced septal mucosal lesion in rats. Methods. Unilateral nasal wounds were created by means of the interdental brush in seventy-four-week-old male rats. Animals were randomly divided into two groups: control group and CS exposure group, each comprising 35 animals, divided into five groups (n = 7). Animals were sacrificed in groups of seven on day 2 and then on days 5, 14, and 28 and finally on day 42 following wound induction. Results. Histological analysis of mucosal specimens shows important changes at the CS exposure group. Starting with the infiltrates of neutrophils, eosinophils, macrophages, and lymphocytes, the histological changes were continued with the Goblet cell proliferation, ciliated cells loss, fibrosis, and epithelial and subepithelial hypertrophy. Conclusion. In this experimental model of nasal wound healing we demonstrated the deleterious effects of chronic CS exposure. The adverse effects of CS exposure are firstly a postponement of the healing process and secondly the persistence of inflammation which becomes chronic. PMID:27042668

  15. Early ultrastructural changes in rat duodenal mucosa associated with cysteamine-induced ulcer

    SciTech Connect

    Pfeiffer, C.J.; Pfeiffer, D.C.; Szabo, S.

    1987-02-01

    The early morphologic sequelae induced by the duodenal ulcerogen, cysteamine, have been studied in rats by transmission electron microscopy. Cysteamine was administered per os at 70 mg/100 g body wt to groups of female rats sacrificed at 30 min, 1, 2, 4, 8, 12, 20, and 24 hr after chemical treatment, and duodenal tissue sampled from the antimesenteric side of the proximal duodenum, where ulcers develop, was studied. Emphasis was placed on early times as our previous scanning electron microscopic data had demonstrated enhanced in situ cellular necrosis and surface cavitation at 2-4 hr after cysteamine treatment. Results indicated intracellular changes as early as 30 min after treatment and prior to damage of the columnar cell microvilli or epithelial tight junctions. A staging of observed cellular degenerative changes suggested early apical endoplasmic reticular swelling and loss of cytoplasmic ground substance, followed later by moderate internal disruption of mitochondria. Through these stages the cell surface microvilli remained morphologically normal. Subsequently, microvilli degenerated and mitochondrial fine structure became severely disrupted and cell contents were expelled. Deeper villous changes such as separation of columnar cells from the lamina propria and alterations of selected elements within the lamina propria were observed. These data suggest that intracellular cytotoxic reactions at the villous tips occur early and may precede the influence of intraluminal damaging factors induced by cysteamine.

  16. Acute and Subacute Oral Toxicity of Periodate in Rats

    DTIC Science & Technology

    2014-11-17

    sodium periodate via oral gavage resulted in a cascade of effects that were secondary to kidney toxicity. Decreased mass of ovaries and epididymides and...testicular degeneration were observed in sodium periodate groups with signs of kidney toxicity. These groups also exhibited decreased T3 and T4 in the...presence of decreased TSH, a pattern associated with uremia. Sodium periodate exposed rats exhibited both activation of the innate immune system and

  17. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

    PubMed Central

    Onal, Ozkan; Yetisir, Fahri; Sarer, A. Ebru Salman; Zeybek, N. Dilara; Onal, C. Oztug; Yurekli, Banu; Celik, H. Tugrul; Sirma, Ayse; Kılıc, Mehmet

    2015-01-01

    Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented

  18. Kinetics of changes in the crypts of the jejunal mucosa of dimethylhydrazine-treated rats.

    PubMed Central

    Sunter, J. P.; Appleton, D. R.; Wright, N. A.; Watson, A. J.

    1978-01-01

    When symmetrical 1,2 dimethylhydrazine was administered to rats by weekly s.c. injection, 37% of the animals had developed small intestinal carcinomas after 21-27 weeks. These lesions were largely localized to duodenum and upper jejunum. At the same time there was a diffuse crypt hyperplasia in the jejunum which affected all the treated animals, not just those with neoplasms. This marked hyperplasia was preceded by a modest sustained crypt elongation which was seen soon after DMH injections began. In these hyperplastic jejunal crypts the absolute size of the proliferative compartment was increased, but the growth fraction calculated from labelling studies appeared to fall, probably by reduction in relative size of the proliferating population within the proliferative compartment. No convincing alteration in actual cell-cycle time was observed in the abnormal crypts. There was a slight (25%) increase in cell-production rate in the abnormal crypts. Images Fig. 1 PMID:656298

  19. Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats

    PubMed Central

    Noh, Keumhan; Nepal, Mahesh Raj; Jeong, Ki Sun; Kim, Sun-A; Um, Yeon Ji; Seo, Chae Shin; Kang, Mi Jeong; Park, Pil-Hoon; Kang, Wonku; Jeong, Hye Gwang; Jeong, Tae Cheon

    2015-01-01

    Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats. PMID:25767690

  20. Protection of the Oral Mucosa by Salivary Histatin-5 against Candida albicans in an Ex Vivo Murine Model of Oral Infection

    PubMed Central

    Peters, Brian M.; Zhu, Jingsong; Fidel, Paul L.; Scheper, Mark A.; Hackett, William; Shaye, Sara El; Jabra-Rizk, Mary Ann

    2010-01-01

    The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction C. albicans can become a pathogen causing recurrent infections. Yet, the role of host oral innate immunity in the development of candidiasis is not fully elucidated. Specifically, the host salivary antimicrobial peptide histatin-5 (Hst-5) has been proposed to play a protective role in the oral cavity against C. albicans. However, investigations demonstrating its efficacy oral tissue have been lacking. To that end in this study, an ex vivo murine model of infection was developed. Viable C. albicans counts and histopathological analyses demonstrated a significant protective effect for Hst-5 on mouse oral tissue against C. albicans. More importantly, host saliva exerted a comparable anti-candidal effect. However, this effect was neutralized upon treatment of saliva with proteases and C. albicans, previously shown to degrade Hst-5, indicating that Hst-5 is likely the salivary component responsible for the observed protection. Combined, the findings from this study demonstrate for the first time the efficacy of salivary Hst-5 in protecting host tissue against C. albicans infection, thereby affirming the therapeutic potential of this natural host peptide. PMID:20491938

  1. Differential Induction of CYP1A1 and CYP1B1 by Benzo[a]pyrene in Oral Squamous Cell Carcinoma Cell Lines and by Tobacco Smoking in Oral Mucosa

    PubMed Central

    Chi, Angela C.; Appleton, Kathryn; Henriod, Joel B.; Krayer, Joe W.; Marlow, Nicole M.; Bandyopadhyay, Dipankar; Sigmon, Ryan C.; Kurtz, David T.

    2009-01-01

    Polyaromatic hydrocarbons, including benzo[a]pyrene (BP), are major tobacco carcinogens. Their carcinogenic effects require metabolic activation by cytochrome p450 (CYP) enzymes. Relative CYP isoform expression is related to tissue-specific tobacco-related squamous cell carcinoma (SCC) susceptibility. There have been conflicting reports regarding relative CYP1A1 and CYP1B1 oral expression, and information regarding CYP1B1 expression in oral tissues is limited. OBJECTIVE To quantify BP- and tobacco-induced CYP1A1 and CYP1B1 expression in oral SCC cells and oral mucosa. STUDY DESIGN Real-time qPCR was performed to measure 1) BP-induced CYP1A1 and CYP1B1 mRNA expression in seven oral/other head and neck SCC cell lines 2) CYP1A1 and CYP1B1 mRNA expression in gingiva from 22 smokers and 24 nonsmokers. RESULTS SCC lines exhibited either similar induction of both isoforms or preferential CYP1A1 induction (CYP1A1-to-CYP1B1 ratios 0.8-4.3). In contrast, gingival tissues from smokers exhibited preferential CYP1B1 induction. Marked interindividual variation in CYP1A1 and CYP1B1 expression was observed among smokers. CONCLUSIONS In vitro conditions may not account for factors that modulate expression in vivo. Interindividual variation in inducible CYP1A1 and CYP1B1 expression may account in part for variation in tobacco-related oral SCC risk. PMID:19576839

  2. Genotoxic Evaluation of Mexican Welders Occupationally Exposed to Welding-Fumes Using the Micronucleus Test on Exfoliated Oral Mucosa Cells: A Cross-Sectional, Case-Control Study

    PubMed Central

    Jara-Ettinger, Ana Cecilia; López-Tavera, Juan Carlos; Zavala-Cerna, María Guadalupe; Torres-Bugarín, Olivia

    2015-01-01

    Background An estimated 800,000 people worldwide are occupationally exposed to welding-fumes. Previous studies show that the exposure to such fumes is associated with damage to genetic material and increased cancer risk. In this study, we evaluate the genotoxic effect of welding-fumes using the Micronucleus Test on oral mucosa cells of Mexican welders. Material and Methods We conducted a cross-sectional, matched case-control study of n = 66 (33 exposed welders, and 33 healthy controls). Buccal mucosa smears were collected and stained with acridine orange, observed under 100x optical amplification with a fluorescence lamp, and a single-blinded observer counted the number of micronuclei and other nuclear abnormalities per 2,000 observed cells. We compared the frequencies of micronuclei and other nuclear abnormalities, and fitted generalised linear models to investigate the interactions between nuclear abnormalities and the exposure to welding-fumes, while controlling for smoking and age. Results Binucleated cells and condensed-chromatin cells showed statistically significant differences between cases and controls. The frequency of micronuclei and the rest of nuclear abnormalities (lobed-nuclei, pyknosis, karyolysis, and karyorrhexis) did not differ significantly between the groups. After adjusting for smoking, the regression results showed that the occurrence of binucleated cells could be predicted by the exposure to welding-fumes plus the presence of tobacco consumption; for the condensed-chromatin cells, our model showed that the exposure to welding-fumes is the only reliable predictor. Conclusions Our findings suggest that Mexican welders who are occupationally exposed to welding-fumes have increased counts of binucleated and condensed-chromatin cells. Nevertheless, the frequencies of micronuclei and the rest of nuclear abnormalities did not differ between cases and controls. Further studies should shed more light on this subject. PMID:26244938

  3. Peripheral blood lymphocyte typing as a useful tool to objectify the oral mucosa patch test in the diagnosis of allergic contact mucositis to nickel.

    PubMed

    Di Tola, Marco; Amodeo, Rachele; Marino, Mariacatia; Tabacco, Fabio; Casale, Rossella; Bove, Maurizio; Rossi, Alfredo; Cardelli, Patrizia; Picarelli, Antonio

    2014-06-01

    Nickel (Ni) exposure through the intestinal mucosa may cause a hypersensitivity reaction recently defined as allergic contact mucositis (ACM). This condition is identifiable by the oral mucosa patch test (omPT), a qualitative and subjective examination that requires clinical expertise. Our aim was to evaluate if a peripheral blood lymphocyte typing performed before and after the omPT for Ni may be able to objectify this examination for diagnostic purposes. Thirty patients with symptoms referable to the ingestion of Ni-rich foods were subjected to omPT for Ni. Before and after the omPT, each patient underwent blood sampling for the typing of total lymphocytes and their subsets (T, T helper or Th, T cytotoxic or Tc, B, natural killer or NK). Statistical analysis was performed by Student t test and receiver operating characteristic (ROC) curve analysis. According to the omPT outcomes, 18 patients were defined as Ni-sensitive and the remaining 12 as controls. In Ni-sensitive patients, the number of total, T, Th, Tc, and B lymphocytes/μL whole blood increased after the omPT (p<0.0001 for the first three, p=0.0004 and p=0.0001 for the last two lymphocyte types). No omPT-dependent lymphocyte increase was observed in controls. The post/pre omPT cell ratio, especially if calculated for Th lymphocytes, appears to be an effective index for diagnostic purposes (sensitivity=100%, specificity=83.3%, Youden index=0.833, area under curve (AUC)=0.926, p<0.0001). In conclusion, the peripheral blood lymphocyte typing with calculation of post/pre omPT cell ratio has the potential to support the omPT in diagnosing ACM, with the advantage of providing quantitative and objective data.

  4. Areca nut-induced buccal mucosa fibroblast contraction and its signaling: a potential role in oral submucous fibrosis--a precancer condition.

    PubMed

    Chang, Mei-Chi; Lin, Li-Deh; Wu, Hui-Lin; Ho, Yuan-Soon; Hsien, Hsiang-Chi; Wang, Tong-Mei; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

    2013-05-01

    Betel quid (BQ) chewing is an oral habit that increases the risk of oral cancer and oral submucous fibrosis (OSF), a precancerous condition showing epithelial atrophy and tissue fibrosis. Persistent fibroblast contraction may induce the fibrotic contracture of tissue. In this study, we found that areca nut extract (ANE) (200-1200 µg/ml) stimulated buccal mucosa fibroblast (OMF)-populated collagen gel contraction. Arecoline but not arecaidine-two areca alkaloids, slightly induced the OMF contraction. Exogenous addition of carboxylesterase (2U/ml) prevented the arecoline- but not ANE-induced OMF contraction. OMF expressed inositol triphosphate (IP3) receptors. ANE-induced OMF (800 µg/ml) contraction was inhibited by U73122 [phospholipase C (PLC) inhibitor] and 2-aminoethoxydiphenyl borate (IP3 receptor antagonist), respectively. Ethylene glycol tetraacetic acid and verapamil, two calcium mobilization modulators, also suppressed the ANE-induced OMF contraction. ANE induced calcium/calmodulin kinase II and myosin light chain (MLC) phosphorylation in OMF. Moreover, W7 (a Ca(2+)/calmodulin inhibitor), HA1077 (Rho kinase inhibitor), ML-7 (MLC kinase inhibitor) and cytochalasin B (actin filament polymerization inhibitor) inhibited the ANE-induced OMF contraction. Although ANE elevated reactive oxygen species (ROS) level in OMF, catalase, superoxide dismutase and N-acetyl-L-cysteine showed no obvious effect on ANE-elicited OMF contraction. These results indicate that BQ chewing may affect the wound healing and fibrotic processes in OSF via inducing OMF contraction by ANE and areca alkaloids. AN components-induced OMF contraction was related to PLC/IP3/Ca(2+)/calmodulin and Rho signaling pathway as well as actin filament polymerization, but not solely due to ROS production.

  5. Noninvasive assessment of the risk of tobacco abuse in oral mucosa using fluorescence spectroscopy: a clinical approach

    NASA Astrophysics Data System (ADS)

    Nazeer, Shaiju S.; Asish, Rajashekharan; Venugopal, Chandrashekharan; Anita, Balan; Gupta, Arun Kumar; Jayasree, Ramapurath S.

    2014-05-01

    Tobacco abuse and alcoholism cause cancer, emphysema, and heart disease, which contribute to high death rates, globally. Society pays a significant cost for these habits whose first demonstration in many cases is in the oral cavity. Oral cavity disorders are highly curable if a screening procedure is available to diagnose them in the earliest stages. The aim of the study is to identify the severity of tobacco abuse, in oral cavity, as reflected by the emission from endogenous fluorophores and the chromophore hemoglobin. A group who had no tobacco habits and another with a history of tobacco abuse were included in this study. To compare the results with a pathological condition, a group of leukoplakia patients were also included. Emission from porphyrin and the spectral filtering modulation effect of hemoglobin were collected from different sites. Multivariate analysis strengthened the spectral features with a sensitivity of 60% to 100% and a specificity of 76% to 100% for the discrimination. Total hemoglobin and porphyrin levels of habitués and leukoplakia groups were comparable, indicating the alarming situation about the risk of tobacco abuse. Results prove that fluorescence spectroscopy along with multivariate analysis is an effective noninvasive tool for the early diagnosis of pathological changes due to tobacco abuse.

  6. Oral subchronic exposure to silver nanoparticles in rats.

    PubMed

    Garcia, Tania; Lafuente, Daisy; Blanco, Jordi; Sánchez, Domènec J; Sirvent, Juan J; Domingo, José L; Gómez, Mercedes

    2016-06-01

    Because of their extremely small size, silver nanoparticles (AgNPs) show unique physical and chemical properties, with specific biological effects, which make them particularly attractive for being used in a number of consumer applications. However, these properties also influence the potential toxicity of AgNPs. In this study, we assessed the potential toxic effects of an in vivo oral sub-chronic exposure to polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) in adult male rats. We also assessed if oral PVP-AgNPs exposure could alter the levels of various metals (Fe, Mg, Zn and Cu) in tissues. Rats were orally given 0, 50, 100 and 200 mg/kg/day of PVP-AgNPs. Silver (Ag) accumulation in tissues, Ag excretion, biochemical and hematological parameters, metal levels, as well as histopathological changes and subcellular distribution following PVP-AgNPs exposure, were also investigated. After 90 days of treatment, AgNPs were found within hepatic and ileum cells. The major tissue concentration of Ag was found in ileum of treated animals. However, all tissues of PVP-AgNPs-exposed animals showed increased levels of Ag in comparison with those of rats in the control group. No harmful effects in liver and kidney, as well as in biochemical markers were noted at any treatment dose. In addition, no hematological or histopathological changes were found in treated animals. However, significant differences in Cu and Zn levels were found in thymus and brain of PVP-AgNPs-treated rats.

  7. Nanocrystalline cerium dioxide efficacy for prophylaxis of erosive and ulcerative lesions in the gastric mucosa of rats induced by stress.

    PubMed

    Golyshkin, Dmytro; Kobyliak, Nazarii; Virchenko, Oleksandr; Falalyeyeva, Tetyana; Beregova, Tetyana; Ostapchenko, Lyudmyla; Caprnda, Martin; Skladany, Lubomir; Opatrilova, Radka; Rodrigo, Luis; Kruzliak, Peter; Shcherbokov, Alexandr; Spivak, Mykola

    2016-12-01

    In our previous works, the important therapeutic properties of nanocrystalline cerium dioxide such as strong antioxidant ability, prebiotical and antibiotic activity were shown. Such properties were obtained due to stabilization of nanoparticles with precise size 3-7nm. Such modification of nanocrystalline cerium dioxide has contributed to its remarkable efficacy and low toxicity. We have carried out the investigation of toxicity of the nanodrug and revealed that in the condition of the acute toxicity test, LD 50 was 2000mg/kg when it was administered per os. This indicator is approximately 1000 times greater than effective dose of the compound that proved the possibility of its usage for humans. Considering the strong antioxidant properties of this substance, we have performed the investigation of the influence of nanocrystalline cerium dioxide on the erosive-ulcerative lesions in gastric mucosa of rats induced by Selye's restraint stress. It was established that the studied compound significantly reduced the lesions area by 58.3% (p<0.05) induced by Selye's restraint stress. The attenuation of inflammation and decrease of lipid peroxidation in the conditions of gastric lesions and prophylactic administration of nanocrystalline cerium dioxide were shown. That was confirmed by the decrease of pro-inflammatory cytokines content (interleukin (IL) 1β, 12B p40) and raise of anti-inflammatory cytokines content (IL-10 and transforming growth factor β). Measurement of lipid peroxidation products has proved the antioxidant properties of nanocrystalline cerium dioxide as it decreased the content of conjugated dienes and thiobarbituric acid active products in the conditions of gastric ulceration induced by stress.

  8. Protective Effect of Huoxiang Zhengqi Oral Liquid on Intestinal Mucosal Mechanical Barrier of Rats with Postinfectious Irritable Bowel Syndrome Induced by Acetic Acid

    PubMed Central

    Liu, Yao; Liu, Wei; Peng, Qiu-Xian; Peng, Jiang-Li; Yu, Lin-Zhong; Hu, Jian-Lan

    2014-01-01

    In this study, a rat model with acetic acid-induced PI-IBS was used to study the role of HXZQ oral liquid in repairing the colonic epithelial barrier and reducing intestinal permeability. Pathomorphism of colonic tissue, epithelial ultrastructure, DAO activity in serum, and the protein expression of ZO-1 and occludin were examined to investigate protective effect mechanisms of HXZQ on intestinal mucosa barrier and then present experimental support for its use for prevention and cure of PI-IBS. PMID:25254052

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

    PubMed Central

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

    2017-01-01

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

  10. Regulation of GLUT5 gene expression in rat intestinal mucosa: regional distribution, circadian rhythm, perinatal development and effect of diabetes.

    PubMed Central

    Castelló, A; Gumá, A; Sevilla, L; Furriols, M; Testar, X; Palacín, M; Zorzano, A

    1995-01-01

    1. GLUT5 gene expression was studied in small intestine under a variety of conditions characterized by altered intestinal absorption of monosaccharides. 2. RNA-blotting studies showed that GLUT5 mRNA was abundantly expressed in rat and rabbit intestine and kidney, but it was not detected in heart or brown adipose tissue. GLUT5 mRNA levels were higher in the upper segments of the small intestine (duodenum and proximal jejunum) than in the lower segments (distal jejunum and ileum). 3. The intestinal expression of GLUT5 mRNA in rat proximal jejunum showed circadian rhythm. A 12-fold increase in GLUT5 mRNA levels was detected at the end of the light cycle and at the beginning of the dark cycle when compared with the early light period. In keeping with this, GLUT5 protein content in brush-border membranes was also increased at the beginning of the dark cycle compared with that in the light period. 4. In streptozotocin-induced diabetes an 80% increase in GLUT5 mRNA levels in mucosa from the proximal jejunum was detected under conditions in which enhanced intestinal absorption of monosaccharides has been reported. 5. The intestinal expression of GLUT5 mRNA showed regulation during perinatal development. Levels of GLUT5 mRNA were low during fetal life, increased progressively during the postnatal period and reached levels comparable with the adult state after weaning. Weaning on to a high-fat diet partially prevented the induction of GLUT5 gene expression. 6. Our results indicate that GLUT5 gene expression is tightly regulated in small intestine. Regulation involves maximal expression in the upper part of the small intestine, circadian rhythm, developmental regulation dependent on the fat and carbohydrate content in the diet at weaning and enhanced expression in streptozotocin-induced diabetes. Furthermore, changes observed in intestinal GLUT5 expression correlate with reported alterations in intestinal absorption of fructose. This suggests a regulatory role for GLUT5 in

  11. Disposition of 2-mercaptobenzimidazole in rats dosed orally or intravenously

    SciTech Connect

    El Dareer, S.M.; Kalin, J.R.; Tillery, K.F.; Hill, D.L.

    1984-01-01

    The disposition of (/sup 14/C)-labeled 2-mercaptobenzimidazole (MBI) in male Fischer-344 rats dosed orally (49 or 0.5 mg/kg) or intravenously (0.5 mg/kg) was determined. Absorption of the oral dose was evident, since, in 72 h, most of the radioactivity administered by either route appeared in the urine. Smaller amounts appeared in the feces. In 4 h, 12% of the radioactivity from an intravenous dose of 0.5 mg/kg was excreted in the bile of rats with biliary cannulas. For rats dosed intravenously, the half-life for disappearance of unchanged MBI from plasma was 125 min. In contrast, the terminal half-life for loss of radioactivity from blood was 83 h. The concentration of total radioactivity was higher in liver and kidney tissue than in blood. One of the major urinary metabolites was identified as benzimidazole, and a minor component was tentatively identified as unchanged MBI. Neither of these could be detected in bile. 8 references, 6 figures, 1 table.

  12. [Candida carriage in the oral mucosa of a student population: adhesiveness of the strains and predisposing factors].

    PubMed

    Negroni, M; González, M I; Levin, B; Cuesta, A; Iovanniti, C

    2002-01-01

    The aim of this study was to establish oral carriage of Candida and possible factors associated to their virulence in young adults and their relation with local and general situations considered as predisposing factors. Samples were obtained from dorsum tongue in 70 students attending the Faculty of Dentistry (University of Buenos Aires) average age: 23, all in healthy oral conditions. Of these, 21.42% were Candida positive. These samples were seeded in CHROMagar. Candida identification was completed in milk agar and Fungichrom 1. The following species were identified: 11 Candida albicans (C.a), 2 Candida parapsilosis (C.p) and 1 Candida glabrata (C.g). In one case, 2 species (C.a and C.g) were isolated in the same sample. Virulence was determined as adherence capacity by biofilm or in vitro plaque formation and hydrophobicity. Different host factors were analyzed statistically to establish their importance as predisposing factors to allow Candida colonization. Adherence of C.a. was found to be similar in all C.a. strains, whereas significant differences were found between C.a. and C.p. and between C.a. and C.g. Only the antiseptic mouthrinse and the diet were significant among the considered factors.

  13. Role of gastrin in the development of gastric mucosa, ECL cells and A-like cells in newborn and young rats.

    PubMed

    Björkqvist, Maria; Dornonville de la Cour, Charlotta; Zhao, Chun-Mei; Gagnemo-Persson, Rebecca; Håkanson, Rolf; Norlén, Per

    2002-10-15

    Histamine-producing ECL cells and ghrelin-producing A-like cells are endocrine/paracrine cell populations in the acid-producing part of the rat stomach. While the A-like cells operate independently of gastrin, the ECL cells respond to gastrin with mobilization of histamine and chromogranin A (CGA)-derived peptides, such as pancreastatin. Gastrin is often assumed to be the driving force behind the postnatal development of the gastric mucosa in general and the ECL cells in particular. We tested this assumption by examining the oxyntic mucosa (with ECL cells and A-like cells) in developing rats under the influence of YF476, a cholecystokinin-2 (CCK(2)) receptor antagonist. The drug was administered by weekly subcutaneous injections starting at birth. The body weight gain was not affected. Weaning occurred at days 15-22 in both YF476-treated and age-matched control rats. Circulating gastrin was low at birth and reached adult levels 2 weeks after birth. During and after weaning (but not before), YF476 greatly raised the serum gastrin concentration (because of abolished acid feedback inhibition of gastrin release). The weight of the stomach was unaffected by YF476 during the first 2-3 weeks after birth. From 4 to 5 weeks of age, the weight and thickness of the gastric mucosa were lower in YF476-treated rats than in controls. Pancreastatin-immunoreactive cells (i.e. all endocrine cells in the stomach) and ghrelin-immunoreactive cells (A-like cells) were few at birth and increased gradually in number until 6-8 weeks of age (control rats). At first, YF476 did not affect the development of the pancreastatin-immunoreactive cells, but a few weeks after weaning, the cells were fewer in the YF476 rats. The ECL-cell parameters (oxyntic mucosal histamine and pancreastatin concentrations, the histidine decarboxylase (HDC) activity, the HDC mRNA levels and serum pancreastatin concentration) increased slowly until weaning in both YF476-treated and control rats. From then on, there

  14. Oxidatively Damaged DNA in Rats Exposed by Oral Gavage to C60 Fullerenes and Single-Walled Carbon Nanotubes

    PubMed Central

    Folkmann, Janne K.; Risom, Lotte; Jacobsen, Nicklas R.; Wallin, Håkan; Loft, Steffen; Møller, Peter

    2009-01-01

    Background C60 fullerenes and single-walled carbon nanotubes (SWCNT) are projected to be used in medicine and consumer products with potential human exposure. The hazardous effects of these particles are expected to involve oxidative stress with generation of oxidatively damaged DNA that might be the initiating event in the development of cancer. Objective In this study we investigated the effect of a single oral administration of C60 fullerenes and SWCNT. Methods We measured the level of oxidative damage to DNA as the premutagenic 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in the colon mucosa, liver, and lung of rats after intragastric administration of pristine C60 fullerenes or SWCNT (0.064 or 0.64 mg/kg body weight) suspended in saline solution or corn oil. We investigated the regulation of DNA repair systems toward 8-oxodG in liver and lung tissue. Results Both doses of SWCNT increased the levels of 8-oxodG in liver and lung. Administration of C60 fullerenes increased the hepatic level of 8-oxodG, whereas only the high dose generated 8-oxodG in the lung. We detected no effects on 8-oxodG in colon mucosa. Suspension of particles in saline solution or corn oil yielded a similar extent of genotoxicity, whereas corn oil per se generated more genotoxicity than the particles. Although there was increased mRNA expression of 8-oxoguanine DNA glycosylase in the liver of C60 fullerene-treated rats, we found no significant increase in repair activity. Conclusions Oral exposure to low doses of C60 fullerenes and SWCNT is associated with elevated levels of 8-oxodG in the liver and lung, which is likely to be caused by a direct genotoxic ability rather than an inhibition of the DNA repair system. PMID:19479010

  15. Mouse papillomavirus MmuPV1 infects oral mucosa and preferentially targets the base of the tongue

    PubMed Central

    Cladel, Nancy M.; Budgeon, Lynn R; Balogh, Karla K.; Cooper, Timothy K.; Hu, Jiafen; Christensen, Neil D.

    2015-01-01

    In 2010, a new mouse papillomavirus, MmuPV1, was discovered in a colony of NMRI- Foxn1nu /Foxn1nu athymic mice in India. This finding was significant because it was the first papillomavirus to be found in a laboratory mouse. In this paper we report successful infections of both dorsal and ventral surfaces of the rostral tongues of outbred athymic nude mice. We also report the observation that the base of the tongue, the area of the tongue often targeted by cancer-associated high-risk papillomavirus infections in humans, is especially susceptible to infection. A suitable animal model for the study of oral papillomavirus infections, co-infections, and cancers has long been sought. The work presented here suggests that such a model is now at hand. PMID:26609937

  16. Urinary metabolites of daidzin orally administered in rats.

    PubMed

    Yasuda, T; Ohsawa, K

    1998-09-01

    In a study on the metabolism of flavonoids, the isoflavone glycoside daidzin was orally administered to rats. Urine samples were collected and treated with beta-glucuronidase and arylsulfatase. Aglycone daidzein (M3) and other three metabolites, 3',4',7-trihydroxyisoflavone (M1), 4',7-dihydroxyisoflavanone (M2) and 4',7-dihydroxyisoflavan (M4) were isolated from the urine following treatment with enzymes. The structures of M1, M2 and M4 were determined on the basis of chemical and spectral data.

  17. 13-Week oral toxicity study with isomaltulose (Palatinose) in rats.

    PubMed

    Jonker, D; Lina, B A R; Kozianowski, G

    2002-10-01

    The potential subchronic oral toxicity of isomaltulose (Palatinose) was examined by administering this substance in the diet to groups of 20 male and 20 female Wistar rats at levels of 0, 2.5, 5 and 10% for 13 consecutive weeks. Daily clinical observations, body weight, food conversion efficiency, food and water consumption were not affected at any stage of the study. Ophthalmoscopy, haematology, clinical chemistry, urinalysis, organ weights, gross and histopathological examination, neurobehavioural observations, motor activity assessment and the results of an immunotoxicity screen did not reveal any abnormalities related to the ingestion of the test substance. In conclusion, the administration of isomaltulose at dietary levels up to 10% for 13 consecutive weeks was well tolerated without any signs of toxicity. The overall intake at this level corresponded to 7.0 and 8.1 g/kg body weight/day in male and female rats, respectively.

  18. Raman spectroscopic analysis of human tissue engineered oral mucosa constructs (EVPOME) perturbed by physical and biochemical methods

    NASA Astrophysics Data System (ADS)

    Khmaladze, Alexander; Ganguly, Arindam; Raghavan, Mekhala; Kuo, Shiuhyang; Cole, Jacqueline H.; Marcelo, Cynthia L.; Feinberg, Stephen E.; Izumi, Kenji; Morris, Michael D.

    2012-01-01

    We show the application of near-infrared Raman Spectroscopy to in-vitro monitoring of the viability of tissue constructs (EVPOMEs). During their two week production period EVPOME may encounter thermal, chemical or biochemical stresses that could cause development to cease, rendering the affected constructs useless. We discuss the development of a Raman spectroscopic technique to study EVPOMEs noninvasively, with the ultimate goal of applying it in-vivo. We identify Raman spectroscopic failure indicators for EVPOMEs, which are stressed by temperature, and discuss the implications of varying calcium concentration and pre-treatment of the human keratinocytes with Rapamycin. In particular, Raman spectra show correlation of the peak height ratios of CH2 deformation to phenylalanine ring breathing, providing a Raman metric to distinguish between viable and nonviable constructs. We also show the results of singular value decomposition analysis, demonstrating the applicability of Raman spectroscopic technique to both distinguish between stressed and non-stressed EVPOME constructs, as well as between EVPOMEs and bare AlloDerm® substrates, on which the oral keratinocytes have been cultured. We also discuss complications arising from non-uniform thickness of the AlloDerm® substrate and the cultured constructs, as well as sampling protocols used to detect local stress and other problems that may be encountered in the constructs.

  19. The Effect of Propolis in Healing Injured Nasal Mucosa: An Experimental Study

    PubMed Central

    El-Anwar, Mohammad Waheed; Abdelmonem, Said; Abdelsameea, Ahmed A.; AlShawadfy, Mohamed; El-Kashishy, Kamal

    2016-01-01

    Introduction  Mechanical trauma to the nasal mucosa increases the risk of synechia formation, especially after chronic rhinosinusitis and nasal surgeries. Objective  This study was carried to assess the effect of propolis administration in healing injured nasal mucosa in rats. Methods  We randomly divided eighteen rats into three equal experimental groups: (1) non-treated group; (2) gum tragacanth (suspending agent for propolis) treated group; and (3) propolis treated group. The non-treated group received no treatment for 15 days. The second group received gum tragacanth administration (5 ml/kg, orally) once daily for 15 days. The third group received propolis suspension orally at a dose of 100 mg/kg once daily for 15 days. At the beginning of this study, we induced unilateral mechanical nasal trauma on the right nasal mucosa of all rats in the three groups using a brushing technique. A pathologist stained tissue samples using hematoxylin and examined eosin by using a light microscope. Results  The severity of inflammation was milder with the absence of ulcerations in the propolis treated group compared with the non-treated and gum tragacanth groups. Goblet cell and ciliated cell loss was substantially lower in patients treated with propolis compared with groups without treatment and those treated with gum tragacanth. Conclusion  Propolis decreased inflammation and enhanced healing of wounds of the nasal mucosa in rats. PMID:27413403

  20. Effect of Acute Stress on Immune Cell Counts and the Expression of Tight Junction Proteins in the Duodenal Mucosa of Rats

    PubMed Central

    Lee, Hong Sub; Kim, Dong-Kyu; Kim, Young Bae

    2013-01-01

    Background/Aims Duodenal immune alterations have been reported in a subset of patients with functional dyspepsia (FD). The aim of this study was to investigate the effect of acute stress on immune cell counts and the expression of tight junction proteins in the duodenal mucosa. Methods Twenty-one male rats were divided into the following three experimental groups: 1) the nonstressed, control group, 2) the 2-hour-stressed group, and 3) the 4-hour-stressed group. Eosinophils, mast cells and CD4+ and CD8+ T lymphocytes in the duodenal mucosa were counted. The protein and mRNA expressions of occludin and zonula occludens-1 (ZO-1) were examined. Results Eosinophils, mast cells and CD8+ T lymphocyte counts did not differ between the stressed and control groups. The number of CD4+ T lymphocytes and the protein and mRNA expressions of occludin and ZO-1 were significantly lower in the 4-hour-stressed group compared with the control group. The plasma adrenocorticotrophic hormone and cortisol levels of the 4-hour-stressed group were significantly higher than those of the control group. Conclusions Acute stress reduces the number of CD4+ T lymphocytes and the expression of tight junction proteins in the duodenal mucosa, which might be associated with the duodenal immune alterations found in a subset of FD patients. PMID:23560155

  1. Antimicrobial Decapeptide KSL-W Attenuates Candida albicans Virulence by Modulating Its Effects on Toll-Like Receptor, Human Beta-Defensin, and Cytokine Expression by Engineered human Oral Mucosa

    DTIC Science & Technology

    2011-02-02

    University, Quebec, QC, Canada b Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, Fort Sam Houston, TX, USA...innate immunity of epithelial cells in prevent - ing Candida infection of the oral mucosa. Primary epithelial cells obtained from various sources...play a role in preventing microbial infections [8,19,45]. Generally, these antimicrobial peptides exhibit selective toxicity for microorganisms and

  2. Effects of Different Concentrations of Fluoride in Oral Mucosal Cells in Albino Rats

    PubMed Central

    Prakash, P.Ajay; Rao, T.Madhusudhan

    2015-01-01

    Introduction Fluoride has been described to be physiologically essential for the normal development and growth of human beings. However, it is well known that excessive fluoride causes skeletal, nonskeletal and dental complications. Therefore, outlining the cytogenetic effects induced by fluorosis is necessary. Objectives To evaluate the cytomorphology of exfoliated oral mucosal cells among various concentrations of fluoride. Study design: Study group comprised of 12 Albino Wistar rats, categorized into A,B and C groups (fed with 25 ppm,50 ppm and 100 ppm concentration of NaF), each group consisting of 4 rats, with 4 controls (fed with 1ppm concentration of NaF in distilled water). Each group was fed for a period of 42 days. Materials and Methods Cytological smears were taken from the buccal mucosa of each group after 42 days of fluoride administration. The samples were stained with the papanicolaou method and assessed for Cytomorphometrical changes in maximum diameter of nucleus, minimum diameter of nucleus, perimeter of the nucleus, maximum diameter of the cell, minimum diameter of the cell and perimeter of the cell by image analysis software and the results were statistically analysed using SPSS software. Results Mean values of maximum diameter, minimum diameter and perimeter of the nucleus increased in fluoride induced study groups when compared to controls and the results showed that p-value was statistically significant (p-value: 0.000, 0.001). Mean value of maximum diameter, minimum diameter and perimeter of the cell decreased in fluoride induced subjects when compared with controls which were statistically not significant (p-value: 0.791, 0.600 & 0.719). A continuous increase in the nuclear size and decrease in the cell size was identified in fluoride induced groups as compared to controls. Conclusion The observations of our present study revealed that cellular changes occur with severity of fluorosis. These cellular morphological changes may possibly

  3. Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

    PubMed Central

    Chen, Chun-Han; Chang, Cheng-Chih; Shih, Tsung-Hsien; Aljuffali, Ibrahim A; Yeh, Ta-Sen; Fang, Jia-You

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery. PMID:25848259

  4. High- and ultrahigh-field magnetic resonance imaging of naïve, injured and scarred vocal fold mucosae in rats

    PubMed Central

    Kishimoto, Ayami Ohno; Kishimoto, Yo; Young, David L.; Zhang, Jinjin

    2016-01-01

    ABSTRACT Subepithelial changes to the vocal fold mucosa, such as fibrosis, are difficult to identify using visual assessment of the tissue surface. Moreover, without suspicion of neoplasm, mucosal biopsy is not a viable clinical option, as it carries its own risk of iatrogenic injury and scar formation. Given these challenges, we assessed the ability of high- (4.7 T) and ultrahigh-field (9.4 T) magnetic resonance imaging to resolve key vocal fold subepithelial tissue structures in the rat, an important and widely used preclinical model in vocal fold biology. We conducted serial in vivo and ex vivo imaging, evaluated an array of acquisition sequences and contrast agents, and successfully resolved key anatomic features of naïve, acutely injured, and chronically scarred vocal fold mucosae on the ex vivo scans. Naïve lamina propria was hyperintense on T1-weighted imaging with gadobenate dimeglumine contrast enhancement, whereas chronic scar was characterized by reduced lamina propria T1 signal intensity and mucosal volume. Acutely injured mucosa was hypointense on T2-weighted imaging; lesion volume steadily increased, peaked at 5 days post-injury, and then decreased – consistent with the physiology of acute, followed by subacute, hemorrhage and associated changes in the magnetic state of hemoglobin and its degradation products. Intravenous administration of superparamagnetic iron oxide conferred no T2 contrast enhancement during the acute injury period. These findings confirm that magnetic resonance imaging can resolve anatomic substructures within naïve vocal fold mucosa, qualitative and quantitative features of acute injury, and the presence of chronic scar. PMID:27638667

  5. Extracts of ECL-cell granules/vesicles and of isolated ECL cells from rat oxyntic mucosa evoke a Ca2+ second messenger response in osteoblastic cells.

    PubMed

    Larsson, B; Gritli-Linde, A; Norlén, P; Lindström, E; Håkanson, R; Linde, A

    2001-03-02

    Surgical removal of the acid-producing part of the stomach (oxyntic mucosa) reduces bone mass through mechanisms not yet fully understood. The existence of an osteotropic hormone produced by the so-called ECL cells has been suggested. These cells, which are numerous in the oxyntic mucosa, operate under the control of circulating gastrin. Both gastrin and an extract of the oxyntic mucosa decrease blood calcium and stimulate Ca2+ uptake into bone. Conceivably, gastrin lowers blood calcium indirectly by releasing a hypothetical hormone from the ECL cells. The present study investigated, by means of fura-2 fluorometry, the effect of extracts of preparations enriched in ECL cell granules/vesicles from rat oxyntic mucosa on mobilization of intracellular Ca2+ in three osteoblast-like cell lines, UMR-106.01, MC3T3-E1 and Saos-2, and of extracts of isolated ECL cells in UMR-106.01 cells. The extracts were found to induce a dose-related rapid increase in intracellular Ca2+ concentrations in the osteoblast-like cells. The response was not due to histamine or pancreastatin, known ECL cell constituents, and could be abolished by pre-digesting the extracts with exo-aminopeptidase. The results show that the increase in [Ca2+](i) reflects a mobilization of Ca2+ from the endoplasmic reticulum. The observation of an increase in [Ca2+](i) also in murine embryonic fibroblasts show that the response is not limited to osteoblastic cells. The finding that the extracts evoked a typical Ca2+ -mediated second messenger response in osteoblastic cells provides evidence for the existence of a novel osteotropic peptide hormone (gastrocalcin), produced in the ECL cells, and supports the view that gastrectomy-induced osteopathy may reflect a lack of this hormone.

  6. Acute Oral and Intraperitoneal Toxicity Study of WR242511 and WR269410 in Rats

    DTIC Science & Technology

    1993-07-14

    survivors were also necropsied. The acute oral LD50 of WR242511 tartrate in male rats, administered in 1% Methylcellulose/O.4% Tween 80 by gavage, was...administered orally. The acute oral LDS0 of WR269410 in male rats, administered in 1% Methylcellulose/O.4% Tween 80 by gavage, was approximately four-fold...formulations in 0.1% Methylcellulose/O.4% Tween 80 at high enough concentrations to produce lethality, WR269410 was administered intraperitoneally as a

  7. Overexpression of cyclooxygenase-2 in rat oral cancers and prevention of oral carcinogenesis in rats by selective and nonselective COX inhibitors.

    PubMed

    McCormick, David L; Phillips, Jonathan M; Horn, Thomas L; Johnson, William D; Steele, Vernon E; Lubet, Ronald A

    2010-01-01

    Oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide (NQO) show substantial overexpression of cyclooxygenase-2 (COX-2) when compared with adjacent phenotypically normal oral tissues. By contrast, neither 5-lipoxygenase (LOX) nor 12-LOX is overexpressed in rat oral cancers. Two chemoprevention studies were done to test the resulting hypothesis that COX-2 is a useful target for oral cancer chemoprevention in the rat. In both studies, male F344 rats received drinking water exposure to NQO (20 ppm) for 10 weeks, followed by administration of chemopreventive agents from week 10 until study termination at week 26. In the first study, groups of rats were fed basal diet (control), or basal diet supplemented with the selective COX-2 inhibitor celecoxib (500 or 1,500 mg/kg diet), the nonselective COX inhibitor piroxicam (50 or 150 mg/kg diet), or the 5-LOX inhibitor zileuton (2,000 mg/kg diet). In the second study, rats were fed basal diet (control) or basal diet supplemented with nitric oxide-naproxen (180 or 90 mg/kg diet), a nonselective COX inhibitor that shows reduced gastrointestinal toxicity. When compared with dietary controls, celecoxib decreased oral cancer incidence, cancer invasion score, and cancer-related mortality. Piroxicam decreased cancer-related mortality and cancer invasion score, whereas nitric oxide-naproxen decreased oral cancer incidence and cancer invasion score. By contrast, zileuton showed no chemopreventive activity by any parameter assessed. These data show that both selective and nonselective inhibitors of COX-2 can prevent NQO-induced oral carcinogenesis in rats. The chemopreventive activity of COX inhibitors may be linked to overexpression of their enzymatic target in incipient oral neoplasms.

  8. Oral Fertility and Early Embryonic Development Study of WR242511 Tartrate in Rats

    DTIC Science & Technology

    1995-12-21

    ORAL FERTILITY AND EARLY EMBRYONIC DEVELOPMENT STUDY OF WR242511 TARTRATE IN RATS PRECOHABITATION AND COHABITATION PHASES [ DMH SUMMARY OF WEIGHT...Classification) Oral Fertility and Early Embryonic Development Study of WR242511 Tartrate in Rats 12. PERSONAL AUTHOR(S) Levine, Barry S...This study evaluated the toxic potential of WR242511 Tartrate on reproductive capability in CD® male and female rats . WR242511 Tartrate is being

  9. Vermilion Reconstruction with Genital Mucosa

    PubMed Central

    Weyandt, Gerhard H.; Woeckel, Achim; Kübler, Alexander C.

    2016-01-01

    Summary: Functional and aesthetical reconstruction, especially of the upper lip after ablative tumor surgery, can be very challenging. The skin of the lip might be sufficiently reconstructed by transpositional flaps from the nasolabial or facial area. Large defects of the lip mucosa, including the vestibule, are even more challenging due to the fact that flaps from the inner lining of the oral cavity often lead to functional impairments. We present a case of multiple vermilion and skin resections of the upper lip. At the last step, we had to resect even the whole vermilion mucosa, including parts of the oral mucosa of the vestibule, leaving a bare orbicularis oris muscle. To reconstruct the mucosal layer, we used a mucosal graft from the labia minora and placed it on the compromised lip and the former transpositional flaps for the reconstructed skin of the upper lip with very good functional and aesthetic results. PMID:27579226

  10. Vermilion Reconstruction with Genital Mucosa.

    PubMed

    Müller-Richter, Urs D A; Weyandt, Gerhard H; Woeckel, Achim; Kübler, Alexander C

    2016-05-01

    Functional and aesthetical reconstruction, especially of the upper lip after ablative tumor surgery, can be very challenging. The skin of the lip might be sufficiently reconstructed by transpositional flaps from the nasolabial or facial area. Large defects of the lip mucosa, including the vestibule, are even more challenging due to the fact that flaps from the inner lining of the oral cavity often lead to functional impairments. We present a case of multiple vermilion and skin resections of the upper lip. At the last step, we had to resect even the whole vermilion mucosa, including parts of the oral mucosa of the vestibule, leaving a bare orbicularis oris muscle. To reconstruct the mucosal layer, we used a mucosal graft from the labia minora and placed it on the compromised lip and the former transpositional flaps for the reconstructed skin of the upper lip with very good functional and aesthetic results.

  11. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    PubMed

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation.

  12. Oral salmon calcitonin improves fasting and postprandial glycemic control in lean healthy rats.

    PubMed

    Feigh, M; Nielsen, R H; Hansen, C; Henriksen, K; Christiansen, C; Karsdal, M A

    2012-02-01

    A novel oral form of salmon calcitonin (sCT) was recently demonstrated to improve both fasting and postprandial glycemic control and induce weight loss in diet-induced obese and insulin-resistant rats. To further explore the glucoregulatory efficacy of oral sCT, irrespective of obesity and metabolic dysfunction, the present study investigated the effect of chronic oral sCT treatment on fasting and postprandial glycemic control in male lean healthy rats. 20 male rats were divided equally into a control group receiving oral vehicle or an oral sCT (2 mg/kg) group. All rats were treated twice daily for 5 weeks. Body weight and food intake were monitored during the study period and fasting blood glucose, plasma insulin and insulin sensitivity were determined and an oral glucose tolerance test (OGTT) performed at study end. Compared with the vehicle group, rats receiving oral sCT had improved fasting glucose homeostasis and insulin resistance, as measured by homeostatic model assessment of insulin resistance index (HOMA-IR), with no change in body weight or fasting plasma insulin. In addition, the rats receiving oral sCT had markedly reduced glycemia and insulinemia during OGTT. This is the first report showing that chronic oral sCT treatment exerts a glucoregulatory action in lean healthy rats, irrespective of influencing body weight. Importantly, oral sCT seems to exert a dual treatment effect by improving fasting and postprandial glycemic control and insulin sensitivity. This and previous studies suggest oral sCT is a promising agent for the treatment of obesity-related insulin resistance and type 2 diabetes.

  13. Development of the juxta-oral organ in rat embryo.

    PubMed

    Velasco, J R Mérida; De La Cuadra Blanco, C; Velasco, J A Mérida

    2012-05-01

    The aim of this work is to clarify the development and morphology of the juxta-oral organ (JOO) in rat embryos from Day (E)14 to 19. Furthermore, in the region of the JOO, an analysis was made of the expression of the monoclonal antibody HNK-1, which recognizes cranial neural-crest cells. In this study, we report that JOO develops from an epithelial condensation at the end of the transverse groove of the primitive mouth at E14. During E15, it invaginates and is disconnected from the oral epithelium. At E16, the JOO forms an solid epithelial cord with three parts (anterior, middle, and posterior) and is related to the masseter, temporal, medial pterygoid, and tensor veli palatini muscles. During E17-19, no significant changes were detected in their position. Both the mesenchyme caudal to the anlage of the JOO at E14, as well as the mesenchyme that surrounds the bud of the JOO at E15, expressed positivity for HNK-1. Our results suggest that the mesenchyme surrounding the JOO at E15 could emit some inductive signal for the JOO to reach its position at E16. This work shows for the first time that the cranial neural-crest-derived mesenchyme participates in the development of the JOO.

  14. Adaptation to physical training in rats orally supplemented with glycerol.

    PubMed

    Andrade, Eric Francelino; Lobato, Raquel Vieira; de Araújo, Ticiana Vasques; Orlando, Débora Ribeiro; Vicente da Costa, Diego; de Oliveira Silva, Víviam; Rogatto, Gustavo Puggina; Zangeronimo, Márcio Gilberto; Rosa, Priscila Vieira; Pereira, Luciano José

    2015-01-01

    We evaluated training adaptation and physical performance parameters in rats orally supplemented with glycerol, glucose, or saline, and submitted to moderate aerobic exercise. Thirty male rats were trained for 6 weeks and administered the supplements during the last 4 weeks of the experiment. Animals were distributed in a completely randomized factorial 2 × 3 design (with or without exercise and 3 substrates). Data were subjected to analysis of variance (ANOVA) and means were compared using the Student-Newmann-Keuls test at 5%. Among the trained animals, none of the substances caused differences in the percentages of protein, fat, or water content in the carcass. Compared with the sedentary animals, the trained animals supplemented with saline and glucose showed a higher protein percentage in the carcass. The relative mass of the heart and adrenal glands was higher in the trained animals. Glycerol improved the protein content in non-trained animals and increased the relative adrenal mass in both groups. Glycerol reduced the variation in levels of lactate and aspartate aminotransferase (AST) during the last exercise session. There was no difference between groups regarding the relative mass of the thymus and gastrocnemius or with the diameter of muscle fibers or the neutrophil-lymphocyte ratio. Supplementation with glycerol was efficient at attenuating variation in AST and lactate levels during exercise.

  15. Effect of Zoledronate on Oral Wound Healing in Rats

    PubMed Central

    Yamashita, Junro; Koi, Kiyono; Yang, Dong-Ye; McCauley, Laurie K.

    2010-01-01

    Purpose Osteonecrosis of the jaw (ONJ) is a growing concern in patients who receive bisphosphonates which target osteoclasts. Since osteoclasts play multifunctional roles in the bone marrow, their suppression likely affects bone homeostasis and alters wound healing of the jaw. The objective was to delineate the impact of osteoclast suppression in the bone marrow and wound healing of the jaw. Experimental Design Zoledronate was administered to senile rats for 14 weeks. A portion of the gingiva was removed to denude the palatal bone. Gene expression in the bone marrow was assessed and histologic sections analyzed to determine the wound healing status. Results Angiogenesis-related genes, CD31 and VEGF-A, were not altered by zoledronate. VEGF-C, which plays a role in lymphangiogenesis, was suppressed. There was a decrease in gene expression of Tcirg1 and MMP-13. Bone denudation caused extensive osteocyte death indicative of bone necrosis. In zoledronate-treated rats, the necrotic bone was retained in the wound while, in controls, osteoclastic resorption of the necrotic bone was prominent. Even though large necrotic bone areas existed in zoledronate-treated rats, overlaying soft tissue healed clinically. Immunohistochemical staining showed rich vascularity in the overlaying soft tissue. Conclusions Zoledronate therapy impacts bone marrow by suppressing genes associated with lymphoangiogenesis and tissue remodeling, such as VEGF-C and MMP-13. Zoledronate was associated with impaired osseous wound healing but had no effect on angiogenic markers in the bone marrow or soft tissue wound healing. Zoledronate selectively blunts healing in bone but does not effect soft tissue healing in the oral cavity. PMID:21149614

  16. The fate of dienochlor administered orally and dermally to rats.

    PubMed

    Quistad, G B; Mulholland, K M; Skinner, W S

    1986-09-15

    Within four days of receiving a single oral dose (1 mg/kg) of [U-ring-14C]dienochlor [bis(pentachloro-2,4-cyclopentadien-1-yl)] female rats excreted 2 and 88% of the applied 14C in urine and feces, respectively. Metabolites could not be identified and the preponderance of the fecal radioactivity consisted of unextractable 14C-labeled residues. Within 1 day virtually all of the dienochlor had been degraded by rats, with only traces of parent dienochlor in excreta and tissues. After four days only 2% of the applied dose remained in tissues (mainly kidney, liver, and gastrointestinal tract). Pharmacokinetic studies with blood plasma and bile showed dienochlor (and/or its metabolites) to be poorly absorbed. Rats were exposed dermally for 24 hr to [14C]dienochlor formulated as Pentac WP miticide both as an aqueous suspension and as an undiluted wettable powder. Half of the dose adhered to the skin and the other half was found in gauze patches used to protect the treated skin. After a 24-hr exposure over 60% of the radiolabel that adhered to skin was removed by washing with an aqueous soap solution and 86% of this rinsing solution was unmetabolized dienochlor. The dienochlor and its metabolites were transported inefficiently from the application site; only 1% of the applied dose was detected in urine plus feces and less than or equal to 0.2% in tissues. With application rates that simulate field exposure by humans, the actual residue of dienochlor and metabolites in skin (i.e., not removable by washing) is about thirteen times higher following exposure to dienochlor as undiluted wettable powder than as an aqueous suspension.

  17. Osteolipoma of the buccal mucosa.

    PubMed

    de Castro, Alvimar-Lima; de Castro, Eni-Vaz-Franco-Lima; Felipini, Renata-Callestini; Ribeiro, Ana-Carolina-Prado; Soubhia, Ana-Maria-Pires

    2010-03-01

    Lipomas are benign mesenchymal neoplasms of soft tissue that can be found in any part of the human body. Conversely, their presence in the oral mucosa is rather uncommon, with approximately 4% of the cases occurring in the oral cavity. In such cases, they are likely to have originated from mature adipose tissue and to be among several described histological variants of lipomas, which are identified according to the predominant type of tissue. There is a rare lipoma, known as an osteolipoma or an ossifying lipoma; however, little has been written this type of lipoma characterized by a classical lipoma with areas of osseous metaplasia. Considering the few cases of oral osteolipomas previously described in the English-related literature and the consequent risk of misdiagnosis and overtreatment, this paper describes an extreme case of an osteolipoma affecting the buccal mucosa of an adult patient. This paper focuses particularly on the pathogenesis of this lesion and the discussion of a correct diagnosis.

  18. Topical treatment of the buccal mucosa and wounded skin in rats with a triamcinolone acetonide-loaded hydrogel prepared using an electron beam.

    PubMed

    Choi, Soon Gil; Baek, Eun Jung; Davaa, Enkhzaya; Nho, Young-Chang; Lim, Youn-Mook; Park, Jong-Seok; Gwon, Hui-Jeong; Huh, Kang Moo; Park, Jeong-Sook

    2013-04-15

    In this study, a triamcinolone acetonide-loaded hydrogel was prepared by electron beam irradiation and evaluated for use as a buccal mucoadhesive drug delivery system. A poloxamer was modified to have vinyl end groups for preparation of the hydrogel via an irradiation cross-linking reaction. Carbopol was introduced to improve the mucoadhesive properties of the hydrogel. The in vitro release of triamcinolone acetonide from the hydrogel was examined at 37 °C. To investigate the topical therapeutic effect of triamcinolone acetonide on wounded rat skin and buccal mucosa, the appearance and histological changes were evaluated for 15 days after treatment with saline, triamcinolone acetonide solution, triamcinolone acetonide hydrogel, and blank hydrogel, respectively. Triamcinolone acetonide was released constantly from the gel formulation at 37 °C and reach 100% at about 48 h. After 15 days, in the skin of the group treated with the triamcinolone acetonide-loaded hydrogel, the wound was almost completely free of crust and a number of skin appendages, including hair follicles, had formed at the margins of the tissue. Moreover, the inflammatory response in the buccal mucosa was milder than that in the other groups, and the wound surface was completely covered with regenerating, hyperkeratotic, thickened epithelial cells. Our results indicate that the triamcinolone-acetonide hydrogel showed sustained drug release behavior, while causing no significant histopathological changes in buccal and skin tissues. Therefore, this hydrogel system may be a powerful means of drug delivery for buccal administration with controlled release and no tissue irritation.

  19. [Effect of gaseous hypoxic mixture GHM-10 on the intestinal death of Wistar rats and Na+,K+-ATPase activity of the plasma membrane of the small intestine mucosa after irradiation].

    PubMed

    Strelkov, R B; Dvoretskiĭ, A I; Kucherenko, N G

    1986-01-01

    It was shown that gas hypoxic mixture containing O2 (10%) and N2 (90%) significantly decreases "intestinal" death of Wistar rats on the 5th day following irradiation and normalizes Na+,K+-ATPase activity of the small intestine mucosa plasma membranes.

  20. Distribution of creatinine following intravenous and oral administration to rats.

    PubMed

    Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

    1981-05-01

    To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

  1. Effects of ε-viniferin, a dehydrodimer of resveratrol, on transepithelial active ion transport and ion permeability in the rat small and large intestinal mucosa.

    PubMed

    Karaki, Shin-Ichiro; Ishikawa, Junji; Tomizawa, Yuka; Kuwahara, Atsukazu

    2016-05-01

    ε-Viniferin is a dehydrodimer of resveratrol, a polyphenol synthesized in many plants, including grapevine. The present study investigated the effects of ε-viniferin and resveratrol on epithelial secretory and barrier functions in isolated rat small and large intestinal mucosa. Mucosa-submucosa tissue preparations of various segments of the rat large and small intestines were mounted on Ussing chambers, and short-circuit current (Isc) and tissue conductance (Gt) were continuously measured. The mucosal addition of ε-viniferin (>10(-5) mol/L) and resveratrol (>10(-4) mol/L) to the cecal mucosa, which was the most sensitive region, induced an increase in Isc and a rapid phase decrease (P-1) followed by rapid (P-2) and broad (P-3) peak increases in Gt in concentration-dependent manners. Mucosal ε-viniferin (10(-4) mol/L), but not resveratrol (10(-4) mol/L), increased the permeability of FITC-conjugated dextran (4 kDa). The mucosal ε-viniferin-evoked changes in Isc (Cl(-) secretion), but not in Gt, were attenuated by a selective cyclooxygenase (COX)-1 inhibitor and a selective EP4 prostaglandin receptor. The mucosal ε-viniferin-evoked increase in Isc was partially attenuated, and P-2, but not P-1 or P-3, change in Gt was abolished by a transient receptor potential cation channel, subfamily A, member 1 (TRPA1) inhibitor. Moreover, the mucosal ε-viniferin concentration-dependently attenuated the mucosal propionate (1 mmol/L)-evoked increases in Isc and Gt Immunohistochemical studies revealed COX-1-immunoreactive epithelial cells in the cecal crypt. The present study showed that mucosal ε-viniferin modulated transepithelial ion transport and permeability, possibly by activating sensory epithelial cells expressing COX-1 and TRPA1. Moreover, mucosal ε-viniferin decreased mucosal sensitivity to other luminal molecules such as short-chain fatty acids. In conclusion, these results suggest that ε-viniferin modifies intestinal mucosal transport and barrier

  2. Simultaneous exposure of excess fluoride and calcium deficiency alters VDR, CaR, and calbindin D 9 k mRNA levels in rat duodenal mucosa.

    PubMed

    Tiwari, S; Gupta, S K; Kumar, K; Trivedi, R; Godbole, M M

    2004-10-01

    Fluoride ingestion reduces intestinal calcium absorption; its molecular basis has not been studied. We studied the mRNA expression of calcium-sensing receptor (CaR), vitamin D receptor (VDR) and calbindin D 9 k (D 9 k) by northern blot analysis in the duodenal mucosa of rats. Weanling pups fed with chow diet containing adequate calcium (0.5% w/w) and drinking water (NaF < 1 ppm) served as controls (Group I) and were studied at 9 and 15 weeks. The pups, born to rats fed with a calcium-deficient diet (0.03%) and excess fluoride water (NaF 50 ppm), were continued on the same diet and water (Group II) until 9 weeks of age. Subsequently, Group II rats were divided into 4 subgroups; 3 subgroups with fluoride free water [II-A adequate calcium, II-B excess calcium (Ca 2%) and II-D calcium deficient], whereas II-C received fluorinated water and adequate calcium diet until 15 weeks. At 9 weeks, as compared to group-I, group-II had decreased VDR (P < 0.001) and D 9 k mRNA (P < 0.001), whereas CaR mRNA levels increased (P < 0.05). At 15 weeks, as compared to group-I, VDR mRNA further reduced in group II-D (P < 0.001) and II-C (P < 0.001), whereas it increased in group II-A. Removal of fluoride ingestion and calcium replenishment increased D 9 k mRNA expression, maximally in adequate calcium group (P < 0.001), while it was further reduced in group II-C (P < 0.001). CaR expression decreased significantly in all the groups. We conclude that excess fluoride reduces the mRNA levels of VDR and D 9 k in the duodenal mucosa of rats, thereby possibly reducing calcium absorption. Calcium supplementation with simultaneous fluoride removal improves their expression.

  3. Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats

    SciTech Connect

    Lee, Sang-wook; Jung, Kwon Il; Kim, Yeun Wha B.S.; Jung, Heun Don; Kim, Hyun Sook; Hong, Joon Pio . E-mail: joonphong@amc.seoul.kr

    2007-03-15

    Purpose: We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model. Methods and Materials: Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 {+-} 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 {mu}g/mL (Group 3), or 100 {mu}g/mL (Group 4) rhEGF three times per day. Results: Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 {mu}g/mL or 100 {mu}g/mL rhEGF. Conclusion: These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats.

  4. Effect of Transplantation of Bone Marrow Derived Mesenchymal Stem Cells and Platelets Rich Plasma on Experimental Model of Radiation Induced Oral Mucosal Injury in Albino Rats

    PubMed Central

    El Kholy, Samar; El Rouby, Dalia; Rashed, Laila; Shouman, Tarek

    2017-01-01

    Normal tissue damage following radiotherapy is still a major problem in cancer treatment. Therefore, the current work aimed at exploring the possible role of systemically injected bone marrow derived mesenchymal stem cells (BM-MSCs) and/or locally injected platelet rich plasma (PRP) in ameliorating the side effects of ionizing radiation on the rat's tongue. Twelve rats served as control group (N) and 48 rats received a single radiation dose of 13 Gy to the head and neck region; then, they were equally divided into 4 experimental groups: irradiated only (C), irradiated + MSCs (S), irradiated + (PRP) (P), and combined group (PS). Animal scarification occurred in 3 and 7 days after radiation. Then, tongues were dissected and examined histologically and for expression of bcl-2 by RT-PCR. Histological examination of the treated groups (S), (P), and (PS) revealed an obvious improvement in the histological structure of the tongue, compared to group (C), in addition to upregulated expression of bcl-2, indicating decreased apoptotic activity. Conclusion. BM-MSCs and PRP have shown positive effect in minimizing the epithelial atrophy of normal oral mucosa after regional radiotherapy, which was emphasized by decreasing apoptotic activity in these tissues. Nevertheless, combined use of BM-MSCs and PRP did not reveal the assumed synergetic effect in oral tissue protection. PMID:28337218

  5. Effects of ECL cell extracts and granule/vesicle-enriched fractions from rat oxyntic mucosa on cAMP and IP(3) in rat osteoblast-like cells.

    PubMed

    Larsson, Birgitta; Norlén, Per; Lindström, Erik; Zhao, Dawei; Håkanson, Rolf; Linde, Anders

    2002-06-15

    The existence of an osteotropic hormone (referred to as gastrocalcin) in the ECL cells of the gastric mucosa has been suggested. Both gastrin and an extract of the oxyntic mucosa lower blood Ca(2+) and stimulate Ca(2+) uptake into bone. The ECL cells are known to operate under gastrin control and, conceivably, gastrin lowers blood Ca(2+) indirectly by releasing the hypothetical ECL cell hormone. We have shown earlier that extracts of isolated ECL cells or of the granule/vesicle fraction of the oxyntic mucosa evoke a typical Ca(2+)-mediated second messenger response in osteoblastic cells. In the present study, we characterize this response further. An increase in intracellular inositol 1,4,5-trisphosphate (IP(3)) concentration was observed after treatment of UMR-106.01 osteoblast-like cells with extracts of ECL cells or granule/vesicle-enriched fractions from oxyntic mucosa. Intracellular cyclic adenosine monophosphate (cAMP) concentrations were not affected. Inhibition of phospholipase C (PLC) by U-73122 abolished the increase in [Ca(2+)](i). Preincubation of UMR-106.01 cells with pertussis toxin, which blocks many G-proteins, did not prevent the increases in IP(3) and [Ca(2+)](i). It was also found that the novel peptide hormone ghrelin, produced in the A-like cells of the oxyntic mucosa, did not evoke any Ca(2+) signal in osteoblastic cells. The results indicate that the extracts mediate their effects through a pertussis toxin-insensitive mechanism, and that binding to a receptor leads to activation of PLC and production of IP(3) resulting in increased [Ca(2+)](i). The putative osteotropic hormone is distinct from ghrelin.

  6. Histological changes in the nasal mucosa in rats after long-term exposure to formaldehyde and wood dust.

    PubMed

    Holmström, M; Wilhelmsson, B; Hellquist, H

    1989-01-01

    Wood dust is a well known nasal carcinogen in man, as formaldehyde is in rats. In certain occupational environments, combined exposure to wood dust and formaldehyde is common. Little is known about the effects of this combination. A pilot study was performed on four groups of Sprague-Dawley rats: one exposed to wood dust (25 mg/m3), another to formaldehyde (12.4 ppm) and a third to both wood dust and formaldehyde; the fourth group served a control group. After 104 weeks of exposure the nose and lungs were examined histologically. One well differentiated squamous cell carcinoma was found in the formaldehyde group. Squamous cell metaplasia was found significantly more often among the formaldehyde-exposed rats. Squamous cell metaplasia with dysplasia was most frequently observed, however, in the group exposed to both formaldehyde and wood dust. There were also significantly more rats with pulmonary emphysema in the groups exposed to wood dust than in the other groups.

  7. Characterization of the rat oral microbiome and the effects of dietary nitrate.

    PubMed

    Hyde, Embriette R; Luk, Berkley; Cron, Stanley; Kusic, Lenka; McCue, Tyler; Bauch, Tonya; Kaplan, Heidi; Tribble, Gena; Petrosino, Joseph F; Bryan, Nathan S

    2014-12-01

    The nitrate-nitrite-NO pathway to nitric oxide (NO) production is a symbiotic pathway in mammals that is dependent on nitrate reducing oral commensal bacteria. Studies suggest that by contributing NO to the mammalian host, the oral microbiome helps maintain cardiovascular health. To begin to understand how changes in oral microbiota affect physiological functions such as blood pressure, we have characterized the Wistar rat nitrate reducing oral microbiome. Using 16S rRNA gene sequencing and analysis we compare the native Wistar rat tongue microbiome to that of healthy humans and to that of rats with sodium nitrate and chlorhexidine mouthwash treatments. We demonstrate that the rat tongue microbiome is less diverse than the human tongue microbiome, but that the physiological activity is comparable, as sodium nitrate supplementation significantly lowered diastolic blood pressure in Wistar rats and also lowers blood pressure (diastolic and systolic) in humans. We also show for the first time that sodium nitrate supplementation alters the abundance of specific bacterial species on the tongue. Our results suggest that the changes in oral nitrate reducing bacteria may affect nitric oxide availability and physiological functions such as blood pressure. Understanding individual changes in human oral microbiome may offer novel dietary approaches to restore NO availability and blood pressure.

  8. Study of orexins signal transduction pathways in rat olfactory mucosa and in olfactory sensory neurons-derived cell line Odora: multiple orexin signalling pathways.

    PubMed

    Gorojankina, Tatiana; Grébert, Denise; Salesse, Roland; Tanfin, Zahra; Caillol, Monique

    2007-06-07

    Orexins A and B (OxA and OxB) are multifunctional neuropeptides implicated in the regulation of energy metabolism, wakefulness but also in a broad range of motivated behaviours. They signal through two G-protein-coupled receptors: orexin receptor 1 and 2 (Ox1R and Ox2R). The orexins and their receptors are present at all levels of the rat olfactory system: epithelium, bulb, piriform cortex but their signalling mechanisms remain unknown. We have studied orexins signal transduction pathways in the rat olfactory mucosa (OM) and in the Odora cell line derived from olfactory sensory neurons and heterologously expressing Ox1R or Ox2R. We have demonstrated by western blot and RT-PCR that multiple components of adenylyl cyclase (AC) and phospholipase C (PLC) signalling pathways were identical in OM and Odora cells. OxA and OxB induced a weak increase in IP3 in OM; they induced a significant rise in cAMP and IP3 in Odora transfected cells, suggesting the activation of AC and PLC pathways. Both OxA and OxB induced intracellular calcium elevation and transient activation of MAP kinases (ERK42/44) in Odora/Ox1R and Odora/Ox2R cells. These results suggest the existence of multiple orexins signalling pathways in Odora cells and probably in OM, corresponding to different possible roles of these peptides.

  9. Oral Nucleotides Only Minimally Improve 5-Fluorouracil-Induced Mucositis in Rats.

    PubMed

    Mashtoub, Suzanne; Feo, Benjamin; Whittaker, Alexandra L; Lymn, Kerry A; Martinez-Puig, Daniel; Howarth, Gordon S

    2015-01-01

    Chemotherapy-induced mucositis is characterized by inflammation and ulceration of the intestinal mucosa, compromising intestinal function. Exogenous nucleotides have been reported to repair the mucosa. The nucleotide preparation, Nucleoforce F0328 (Nucleoforce), was investigated for its potential to ameliorate intestinal mucositis in rats. Female Dark Agouti rats (n = 8/group) were gavaged once daily with Nucleoforce (175 mg/kg) or water from Days 0 to 8 and injected (i.p.) with 5-fluorouracil (5-FU; 150 mg/kg) or saline on Day 5. Histological parameters (disease severity, crypt depth, and villus height measurements) and myeloperoxidase activity were quantified. P < 0.05 was considered significant. Jejunal and ileal histological disease severity scores were significantly increased by 5-FU, compared to normal controls (P < 0.05). Nucleoforce treatment in 5-FU-injected rats significantly reduced jejunal and ileal disease severity compared to 5-FU controls (P < 0.05). In 5-FU-injected rats, jejunal and ileal villus heights and crypt depths were significantly decreased compared to 5-FU controls, with no additional Nucleoforce effect (P > 0.05). Intestinal myeloperoxidase activity was significantly elevated by 5-FU (8.8-fold), compared to normal controls (P < 0.05), which was not normalized by Nucleoforce treatment (P > 0.05). Nucleoforce only partially improved parameters associated with experimentally-induced mucositis. Future studies could investigate increased concentrations, more frequent administration, or protective microencapsulation delivery methods, to increase bioavailability.

  10. Mainstream cigarette smoke exposure alters cytochrome P4502G1 expression in F344 rat olfactory mucosa

    SciTech Connect

    Hotchkiss, J.A.; Nikula, K.J.; Lewis, J.L.; Finch, G.L.; Belinsky, S.A.; Dahl, A.R.

    1994-11-01

    Inhalation of mainstream cigarette smoke (MCS) by rats results in multifocal rhinitis, mucous hypersecretion, nasal epithelial hyperplasia and metaplasia, and focal olfactory mucosal atrophy. In humans, cigarette smoking causes long-term, dose-related alterations in olfactory function in both current and former smokers. An olfactory-specific cytochrome P450 has been identified in rabbits and rats. The presence of olfactory-specific P450s, as well as relatively high levels of other biotransformation enzymes, such as NADPH-cytochrome P450 reductase and UDP-glucuronosyl transferase, in the olfactory neuroepithelium suggest that these enzyme systems may play a role in olfaction. This hypothesis is strengthened by the observation that, in rats, the temporal gene activation of P4502G1 coincides with the postnatal increase in the sensitivity of olfactory response to odorants. The purpose of this investigation was to examine the effect of MCS exposure on P4502G1 protein expression.

  11. Different cardiovascular protective effects of quercetin administered orally or intraperitoneally in spontaneously hypertensive rats.

    PubMed

    Galindo, P; González-Manzano, S; Zarzuelo, M J; Gómez-Guzmán, M; Quintela, A M; González-Paramás, A; Santos-Buelga, C; Pérez-Vizcaíno, F; Duarte, J; Jiménez, R

    2012-06-01

    We tested whether the administration procedure of quercetin affects its metabolite profile and antihypertensive activity. Spontaneously hypertensive rats (SHR) were randomly assigned to four experimental treatments: (1) 1 mL of 1% methylcellulose by oral gavage and 2% DMSO i.p. (control group); (2) 10 mg kg⁻¹ quercetin by oral gavage once daily and 2% DMSO i.p.; (3) 10 mg kg⁻¹ quercetin by oral gavage divided in two daily doses (5 + 5 at 12 h intervals) and 2% DMSO i.p.; (4) 1 mL of 1% methylcellulose by oral gavage and 10 mg kg⁻¹ quercetin i.p. injection. Rats were treated daily for 5 weeks. Single dose and two daily doses, in a long-term oral treatment were equally efficient, both restoring the impaired aortic endothelium-dependent vasodilatation and reducing mesenteric contractile response to phenylephrine, systolic blood pressure, heart rate, and heart and kidney hypertrophy. Attenuation of vascular NADPH oxidase-driven O₂⁻ production was also found in orally treated rats. Intraperitoneal administration reduced, to lesser extent than oral administration, the increased systolic blood pressure, being without effect to the endothelial dysfunction and vascular oxidative stress. In contrast, greater levels of metabolites were quantified following intraperitoneal compared to oral administration at any time point, except for higher plasma methylated quercetin aglycone in oral as compared to intraperitoneal administration at 2 but not at 8 h. In conclusion, oral quercetin was superior to intraperitoneal administration for the protection from cardiovascular complications in SHR. No differences were found between the oral administration as a single daily dose or divided into two daily doses.

  12. Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery.

    PubMed

    Kumar, Niyanta N; Gautam, Mohan; Lochhead, Jeffrey J; Wolak, Daniel J; Ithapu, Vamsi; Singh, Vikas; Thorne, Robert G

    2016-08-25

    Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13-17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain.

  13. Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery

    PubMed Central

    Kumar, Niyanta N.; Gautam, Mohan; Lochhead, Jeffrey J.; Wolak, Daniel J.; Ithapu, Vamsi; Singh, Vikas; Thorne, Robert G.

    2016-01-01

    Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13–17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain. PMID:27558973

  14. Oral inoculation of live or dead third-stage larvae of Anisakis simplex in rats suggests that only live larvae induce production of antibody specific to A. simplex.

    PubMed

    Abe, Niichiro; Teramoto, Isao

    2014-03-01

    Live Anisakis simplex third-stage larvae (L3) penetrate gastrointestinal mucosa after they are ingested in raw or undercooked seafood, thereafter causing gastrointestinal manifestations and allergic manifestations such as urticaria and anaphylaxis. These allergic reactions are mediated by specific IgE to L3 allergens, especially excretory-secretory (ES) allergens. Recent evidences suggest that only live larvae can cause allergic reactions, although cases attributable to ingestion of cooked, frozen seafood have been reported. Therefore the risk of Anisakis-associated hypersensitivity by ingestion of properly cooked and frozen fish remains controversial. No prior report describes the kinetics of antibody production in experimental animals after oral inoculation with dead L3. This study used ELISA to assess antibody production in rats inoculated orally with dead L3. Positive absorbance value in IgG, IgM, and IgE specific to ES antigen from L3 were found in rats inoculated with live L3 but not with dead L3 (frozen, heated, cut, or homogenized). At one week post re-inoculation with live or frozen L3 to the initially sensitized rats, the absorbance value of the specific IgM and IgE to ES antigen elevated quickly and highly in rats that had been re-inoculated with live L3, but they decreased slightly or did not change in rats inoculated with frozen L3. These results suggest that only ingestion of live L3 can produce the specific antibody and induce initial and secondary sensitizations to L3.

  15. Spatial Localization and Binding of the Probiotic Lactobacillus farciminis to the Rat Intestinal Mucosa: Influence of Chronic Stress

    PubMed Central

    Raymond, Arthur; Mercade-Loubière, Myriam; Salvador-Cartier, Christel; Ringot, Bélinda; Léonard, Renaud; Fourquaux, Isabelle; Ait-Belgnaoui, Afifa; Loubière, Pascal; Théodorou, Vassilia; Mercier-Bonin, Muriel

    2015-01-01

    The present study aimed at detecting the exogenously applied probiotic Lactobacillus farciminis in rats, after exposure to IBS-like chronic stress, based on 4-day Water Avoidance Stress (WAS). The presence of L. farciminis in both ileal and colonic mucosal tissues was demonstrated by FISH and qPCR, with ileum as the preferential niche, as for the SFB population. A different spatial distribution of the probiotic was observed: in the ileum, bacteria were organized in micro-colonies more or less close to the epithelium whereas, in the colon, they were mainly visualized far away from the epithelium. When rats were submitted to WAS, the L. farciminis population substantially decreased in both intestinal regions, due to a stress-induced increase in colonic motility and defecation, rather than a modification of bacterial binding to the intestinal mucin Muc2. PMID:26367538

  16. Oral administration of stavudine induces hyperalgesia without affecting activity in rats.

    PubMed

    Weber, Juliane; Mitchell, Duncan; Kamerman, Peter R

    2007-12-05

    We have investigated whether long-term oral administration of the nucleoside reverse transcriptase inhibitor (NRTI) stavudine affects nociception in Sprague-Dawley rats, and whether any changes of nociception are accompanied by deterioration in activity and appetite. Stavudine (50 mg kg(-1)) was administered to rats orally once daily for six weeks in gelatine cubes. Mechanical hyperalgesia of the tail was assessed using a bar algometer, and thermal hyperalgesia by tail immersion in 49 degrees C water. Withdrawal latencies were compared to those of rats receiving placebo gelatine cubes. Withdrawal latencies to the noxious thermal challenge were not affected by stavudine, but those to the mechanical challenge were significantly decreased in rats receiving stavudine, compared to rats receiving placebo, from week three to week six of drug administration (P<0.05, ANCOVA with Newman Keuls post-hoc comparisons). The overall condition of the rats was assessed by recording daily voluntary wheel running distance and maximum running speed, food intake and body mass. Daily stavudine administration did not adversely affect voluntary running activity, appetite or growth. We have shown that long-term daily oral administration of the NRTI stavudine results in mechanical hyperalgesia in rats within three weeks without affecting appetite, growth and physical activity.

  17. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    PubMed

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines.

  18. Recent mouse and rat methods for the study of experimental oral candidiasis

    PubMed Central

    Costa, Anna CBP; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio OC

    2013-01-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis. PMID:23715031

  19. Recent mouse and rat methods for the study of experimental oral candidiasis.

    PubMed

    Costa, Anna C B P; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio O C

    2013-07-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis.

  20. Effect of oral glutamine administration on bacterial tanslocation, endotoxemia, liver and ileal morphology, and apoptosis in rats with obstructive jaundice.

    PubMed

    Margaritis, Vassilios G; Filos, Kriton S; Michalaki, Marina A; Scopa, Chrisoula D; Spiliopoulou, Iris; Nikolopoulou, Vassiliki N; Vagianos, Constantine E

    2005-10-01

    Postoperative complications in patients with obstructive jaundice remain increased when associated with endotoxemia and the inflammatory response due to gut barrier failure. Administration of glutamine has been proposed to maintain the integrity of the gut mucosa and thus reduce bacterial translocation (BT), but the effects of this pretreatment on apoptosis and histologic morphology of various organs affected by BT in obstructive jaundice have not been studied. We therefore studied the effects of oral glutamine supplementation on endotoxemia, BT, liver and terminal ileal morphology, and apoptosis in an experimental model of obstructive jaundice. A total of 60 male Wistar rats were randomly divided into four groups of 15 each: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL + glutamine (4.5 g/kg/day in drinking water). Ileal samples for histology, DNA and protein content, liver biopsies, mesenteric lymph nodes (MLNs) for culture, and portal and systemic blood samples for endotoxin measurements were obtained 10 days later. Compared to the controls, a significant increase in contaminated MLN and liver samples and increased endotoxemia were noted in group III (p < 0.01) but were significantly reduced in group IV (p < 0.05). Group IV also had a significantly higher number of mitoses per crypt (M/c) (p < 0.05), less apoptotic body counts (ABCs) (p < 0.05), and a higher DNA content than did group III (p < 0.05). Liver biopsies from group III displayed typical changes of large duct obstruction that significantly improved after glutamine treatment, with decreased ductular proliferation. We concluded that supplementation of oral glutamine in the presence of obstructive jaundice ameliorates BT, endotoxemia, and apoptosis and improves the ileal and liver histology.

  1. Prolonged use of the food dye tartrazine (FD&C yellow no 5) and its effects on the gastric mucosa of Wistar rats.

    PubMed

    Moutinho, I L D; Bertges, L C; Assis, R V C

    2007-02-01

    Tartrazine is one of the most widely used artificial foods, drugs and cosmetic dyes. It is a nitrous derivative and is known to cause allergic reactions such as asthma and urticaria, as well as having been the focus of studies on mutagenesis and carcinogenesis due to its transformation into aromatic amine sulfanilic acid after being metabolized by the gastrointestinal microflora. 45 male Wistar rats were assigned to a control group (A) or a treatment one (B). The treatment group received 7.5 mg x kg(-1) x day(-1) of tartrazine daily in drinking water offered ad libitum for ten months from weaning to the age of twelve months. There was a significant increase in the number of lymphocytes and eosinophils of the gastric antrum mucosa. No carcinogenetic changes in any gastric area were observed during the study. As tartrazine belongs to the azo class, it is still a possible food carcinogen. Other studies with different doses and schedules, observing their effects associated to other carcinogens should be carried out if their safe use is to be recommended.

  2. Transcriptome and proteome profiling of colon mucosa from quercetin fed F344 rats point to tumor preventive mechanisms, increased mitochondrial fatty acid degradation and decreased glycolysis.

    PubMed

    Dihal, Ashwin A; van der Woude, Hester; Hendriksen, Peter J M; Charif, Halima; Dekker, Lennard J; Ijsselstijn, Linda; de Boer, Vincent C J; Alink, Gerrit M; Burgers, Peter C; Rietjens, Ivonne M C M; Woutersen, Ruud A; Stierum, Rob H

    2008-01-01

    Quercetin has been shown to act as an anticarcinogen in experimental colorectal cancer (CRC). The aim of the present study was to characterize transcriptome and proteome changes occurring in the distal colon mucosa of rats supplemented with 10 g quercetin/kg diet for 11 wk. Transcriptome data analyzed with Gene Set Enrichment Analysis showed that quercetin significantly downregulated the potentially oncogenic mitogen-activated protein kinase (Mapk) pathway. In addition, quercetin enhanced expression of tumor suppressor genes, including Pten, Tp53, and Msh2, and of cell cycle inhibitors, including Mutyh. Furthermore, dietary quercetin enhanced genes involved in phase I and II metabolism, including Fmo5, Ephx1, Ephx2, and Gpx2. Quercetin increased PPARalpha target genes, and concomitantly enhanced expression of genes involved in mitochondrial fatty acid (FA) degradation. Proteomics performed in the same samples revealed 33 affected proteins, of which four glycolysis enzymes and three heat shock proteins were decreased. A proteome-transcriptome comparison showed a low correlation, but both pointed out toward altered energy metabolism. In conclusion, transcriptomics combined with proteomics showed that dietary quercetin evoked changes contrary to those found in colorectal carcinogenesis. These tumor-protective mechanisms were associated with a shift in energy production pathways, pointing at decreased cytoplasmic glycolysis and toward increased mitochondrial FA degradation.

  3. Disruption of the ECM33 gene in Candida albicans prevents biofilm formation, engineered human oral mucosa tissue damage and gingival cell necrosis/apoptosis.

    PubMed

    Rouabhia, Mahmoud; Semlali, Abdelhabib; Chandra, Jyotsna; Mukherjee, Pranab; Chmielewski, Witold; Ghannoum, Mahmoud A

    2012-01-01

    In this study we demonstrated that ΔCaecm33 double mutant showed reduced biofilm formation and causes less damage to gingival mucosa tissues. This was confirmed by the reduced level of necrotic cells and Bax/Bcl2 gene expression as apoptotic markers. In contrast, parental and Caecm33 mutant strains decreased basement membrane protein production (laminin 5 and type IV collagen). We thus propose that ECM33 gene/protein represents a novel target for the prevention and treatment of infections caused by Candida.

  4. Disruption of the ECM33 Gene in Candida albicans Prevents Biofilm Formation, Engineered Human Oral Mucosa Tissue Damage and Gingival Cell Necrosis/Apoptosis

    PubMed Central

    Rouabhia, Mahmoud; Semlali, Abdelhabib; Chandra, Jyotsna; Mukherjee, Pranab; Chmielewski, Witold; Ghannoum, Mahmoud A.

    2012-01-01

    In this study we demonstrated that ΔCaecm33 double mutant showed reduced biofilm formation and causes less damage to gingival mucosa tissues. This was confirmed by the reduced level of necrotic cells and Bax/Bcl2 gene expression as apoptotic markers. In contrast, parental and Caecm33 mutant strains decreased basement membrane protein production (laminin 5 and type IV collagen). We thus propose that ECM33 gene/protein represents a novel target for the prevention and treatment of infections caused by Candida. PMID:22665950

  5. Effect of vitamin A deficiency on permeability of the small intestinal mucosa for macromolecules in adult rats

    SciTech Connect

    Gmoshinskii, I.V.; Khvylya, S.I.; Kon', I.Ya.

    1987-07-01

    The authors study the effect of experimental vitamin A deficiency on absorption of macromolecules of hen's ovalbumin in the intestine. An electron-microscopic study of permeability of small intestine enterocytes for particles of colloidal lanthanum hydroxide La(OH)/sub 3/ was carried out at the same time. The concentration of unsplit hen's ovalbumin in the blood of the rats used in the experiment was determined by competitive radioimmunoassay. Samples of serum were incubated with indicator doses of /sup 125/I-OA. Radioactivity of the precipitates was measured.

  6. In vivo determination of aluminum, cobalt, chromium, copper, nickel, titanium and vanadium in oral mucosa cells from orthodontic patients with mini-implants by Inductively coupled plasma-mass spectrometry (ICP-MS).

    PubMed

    Martín-Cameán, Ana; Jos, Angeles; Puerto, Maria; Calleja, Ana; Iglesias-Linares, Alejandro; Solano, Enrique; Cameán, Ana M

    2015-10-01

    Miniscrews are used as orthodontic anchorage devices in the dentistry clinical practice but the in vivo metallic release from these structures has been not previously investigated. The aim of this study was to determine the content of Al, Co, Cr, Cu, Ni, Ti and V in oral mucosa cells of control subjects, patients under orthodontic treatment and with both, orthodontic treatment and miniscrew, in order to know the contribution of these mini-implants to the total metallic content. ICP-MS measurements revealed the following ascending order: Cr

  7. Kinetic characteristics and toxic effects of benzalkonium chloride following intravascular and oral administration in rats.

    PubMed

    Xue, Yuying; Hieda, Yoko; Kimura, Kojiro; Takayama, Koji; Fujihara, Junko; Tsujino, Yoshio

    2004-11-05

    Kinetic characteristics and toxic effects of benzalkonium chloride (BZK) following injection via jugular vein (JV), femoral artery (FA) and oral administration (PO) were experimentally investigated using rats. The BZK concentrations in blood and tissues (lung, liver and kidney) were determined by high-performance liquid chromatography with solid phase extraction. Toxic doses of 15 and 250 mg/kg of BZK were used for intravascular (JV and FA) and PO administration, respectively. The fatal effects appeared soon after the dose in JV-rats, while delayed in FA- or PO-rats. The blood BZK concentrations and the elimination half-lives were similar between JV- and FA-rats, while the distribution of BZK in tissues was slightly different. In PO administration, the rats that aspirated BZK into their lungs had some symptoms, while the rats that did not aspirate BZK appeared to be normal. The BZK concentrations in blood and tissues were significantly higher in the aspirated PO-rats. The toxic degree of BZK was correlated with the BZK concentration in orally dosed rats. Lung and kidney had higher BZK concentrations compared to blood or liver, and they could be the target organs of BZK.Keyword: Benzalkonium chloride

  8. Acute Oral Toxicity of Nitroguanidine in Male and Female Rats

    DTIC Science & Technology

    1988-03-01

    Baker HJ, Lindsey JR, Weisbroth SH, eds. Mycoplasmal and rickettsial diseases. In: The laboratory rat . Volume I. Biology and...were used for Limit Test animals. Pretest conditioning: Cuarantine/acclimation 10-24 Aug 84. Justification: The laboratory rat has proven to be

  9. Metabolism of oral ALA combined small dose HPD in the small rat glioma

    NASA Astrophysics Data System (ADS)

    Wang, Yu; Zhu, Jing; Zhang, Hui-Guo; Yan, Ming; Lu, Liping

    2005-07-01

    Objective: Research on the metabolism of oral ALA combined small dose HPD in the small rat glioma to find the optimal oral dose and diagnostic time for the ALA-photodynamic diagnosis and therapy of brain glioma. Methods: Measure the fluorescence spectra of tumor in the treatment groups and control group and of brain tissue of no-tumor group with different doses of ALA taken orally combined injectd small dose HPD and different time before and after take ALA when irradiated by laser. We analyzed the spectrum of fluorescence of every groups with optical multichannel analyzer (OMA) and compared it each other. Result: The maximum ratio (Itumor/Inomal ) of fluorescence was obtained at 60mg/kg of ALA taken orally and 6-8h after ALA taken. Conclusion: The optimal oral dose is 60mg/kg of ALA and the optimal measure time is 6-8 hours after ALA taken.

  10. Immunohistochemical analysis of type III collagen expression in the lingual mucosa of rats during organogenesis of the tongue.

    PubMed

    Iwasaki, Shin-Ichi; Asami, Tomoichiro; Wanichanon, Chaitip; Yoshizawa, Hideki; Aoyagi, Hidekazu

    2008-07-01

    We examined the distribution of immunofluorescence due to immunostaining of type III collagen, differential interference contrast (DIC) images and images obtained in the transmission mode after toluidine blue staining by laser-scanning microscopy of semi-ultrathin sections of epoxy resin-embedded samples, during morphogenesis of the filiform papillae, keratinization of the lingual epithelium, and myogenesis of the rat tongue. Immunoreactivity specific for type III collagen was distributed widely in the mesenchymal connective tissue in fetuses on day 15 after conception (E15), at which time the lingual epithelium was composed of one or two layers of cuboidal cells and the lingual muscle was barely recognizable. Immunoreactivity specific for type III collagen was clearly detected on the lamina propria in fetuses on E17 and E19, and it was relatively distinct just beneath the lingual epithelium. Immunoreactivity specific for type III collagen was sparsely distributed on the connective tissue around the developing lingual muscle. In fetuses on E19, the epithelium became clearly stratified and squamous. At postnatal stages from newborn (P0) to postnatal day 14 (P14), keratinization of the lingual epithelium advanced gradually with the development of filiform papillae. On P0, myogenesis of the tongue was almost completed. The intensity of the fluorescence immunoreactivity specific for type III collagen at postnatal stages was almost same as that on E19. The immunoreactivity around the fully mature muscle was relatively distinct between P0 and P14. Thus, type III collagen appeared in conjunction with the morphogenesis of filiform papillae and the keratinization of the lingual epithelium as well as in the connective tissue that surrounded the lingual muscle during myogenesis of the rat tongue.

  11. Bolus oral or continuous intestinal amino acids reduce hypothermia during anesthesia in rats.

    PubMed

    Imoto, Akinobu; Yokoyama, Takeshi; Suwa, Kunio; Yamasaki, Fumiyasu; Yatabe, Tomoaki; Yokoyama, Reiko; Yamashita, Koichi; Selldén, Eva

    2010-01-01

    We hypothesized that, with oral or intestinal administration of amino acids (AA), we may reduce hypothermia during general anesthesia as effectively as with intravenous AA. We, therefore, examined the effect of bolus oral and continuous intestinal AA in preventing hypothermia in rats. Male Wistar rats were anesthetized with sevoflurane for induction and with propofol for maintenance. In the first experiment, 30 min before anesthesia, rats received one bolus 42 mL/kg of AA solution (100 g/L) or saline orally. Then for the next 3 h during anesthesia, they received 14 mL/kg/h of AA and/or saline intravenously. They were in 4 groups: I-A/A, both AA; I-A/S, oral AA and intravenous saline; I-S/A, oral saline and intravenous AA; I-S/S, both saline. In the second experiment, rats received 14 mL/kg/h duodenal AA and/or saline for 2 h. They were in 3 groups: II-A/S, duodenal AA and intravenous saline; II-S/A, duodenal saline and intravenous AA; II-S/S, both saline. Core body temperature was measured rectally. After the second experiment, serum electrolytes were examined. In both experiments, rectal temperature decreased in all groups during anesthesia. However, the decrease in rectal temperature was significantly less in groups receiving AA than in groups receiving only saline. In the second experiment, although there was no significant difference in the decrease in body temperature between II-A/S and II-S/A, Na(+) concentration was significantly lower in II-S/A. In conclusion, AA, administered orally or intestinally, tended to keep the body temperature stable during anesthesia without disturbing electrolyte balance. These results suggest that oral or enteral AA may be useful for prevention of hypothermia in patients.

  12. Experimental candidosis and recovery of Candida albicans from the oral cavity of ovariectomized rats.

    PubMed

    Junqueira, Juliana Campos; Colombo, Carlos Eduardo Dias; Martins, Joyce da Silva; Koga Ito, Cristiane Yumi; Carvalho, Yasmin Rodarte; Jorge, Antonio Olavo Cardoso

    2005-01-01

    The aim of this study was to analyze the development of candidosis and the recovery of C. albicans from the oral cavity of ovariectomized and sham-ovariectomized rats. One hundred and twenty-four rats originally negative for Candida spp. in the oral cavity were divided into two groups: ovariectomized and sham-ovariectomized. Fifty-eight ovariectomized and the same quantity of sham-ovariectomized rats were inoculated with C. albicans for the study of candidosis development and recovery of yeast. Four animals from each group were not inoculated with yeast suspension and were submitted to tongue dorsum morphologic analysis by optical and scanning electron microscopy. The development of candidosis in the tongue dorsum was observed by optical and scanning electron microscopy in the periods of 6 hr, 24 hr, 7 days and 15 days after the last inoculation. Recovery of C. albicans was performed by oral samples plating on Sabouraud agar after 1, 2, 5 and 7 days and progressively at each 15-day interval until negative cultures for yeasts were obtained. The results were analyzed by Mann-Whitney and Student's t tests. The tongue dorsum of sham-ovariectomized and ovariectomized rats, not infected by Candida, presented normal aspect. Among the infected rats, the ovariectomized group showed less occurrence of candidosis lesions and lower recovery of C. albicans from the oral cavity in relation to the sham-ovariectomized group. It could be concluded that candidosis was less frequent from the oral cavities of ovariectomized rats in relation to sham-ovariectomized.

  13. Quantitative assessment of oral mucosa and labial minor salivary glands in patients with Sjögren’s syndrome using swept source OCT

    PubMed Central

    Grulkowski, Ireneusz; Nowak, Jan K.; Karnowski, Karol; Zebryk, Paweł; Puszczewicz, Mariusz; Walkowiak, Jaroslaw; Wojtkowski, Maciej

    2013-01-01

    Three-dimensional imaging of the mucosa of the lower lip and labial minor salivary glands is demonstrated in vivo using swept source optical coherence tomography (OCT) system at 1310 nm with modified interface. Volumetric data sets of the inner surface of the lower lip covering ~230 mm2 field are obtained from patients with Sjögren’s syndrome and a control group. OCT enables high-resolution visualization of mucosal architecture using cross-sectional images as well as en-face projection images. Comprehensive morphometry of the labial minor salivary glands is performed, and statistical significance is assessed. Statistically significant differences in morphometric parameters are found when subgroups of patients with Sjögren’s syndrome are analyzed. PMID:24466492

  14. Mucosal pemphigus vulgaris anti-Dsg3 IgG is pathogenic to the oral mucosa of humanized Dsg3 mice.

    PubMed

    Culton, Donna A; McCray, Suzanne K; Park, Moonhee; Roberts, James C; Li, Ning; Zedek, Daniel C; Anhalt, Grant J; Cowley, Dale O; Liu, Zhi; Diaz, Luis A

    2015-06-01

    There are two major clinical subsets of pemphigus vulgaris (PV)-mucosal PV (mPV) and mucocutaneous PV (mcPV). The mPV subset exhibits anti-human desmoglein (Dsg) 3 autoantibodies that fail to recognize murine Dsg3 (mDsg3); thus, passive transfer experiments of mPV IgG into wild-type (WT) mice have been unsuccessful at inducing disease. We therefore generated a fully humanized Dsg3 (hDSG3) murine model utilizing a hDsg3 transgenic animal crossed to the mDsg3 knockout line. Expression of hDsg3 in the mucosa rescues the mDsg3 knockout phenotype. Well-characterized mPV sera bind mucosal epithelia from the hDsg3 mice, but not mucosal tissues from WT mice, as detected by indirect immunofluorescence (IF). The majority of mPV sera preferentially recognize hDsg3 compared with mDsg3 by immunoprecipitation as well. Passive transfer of mPV IgG into adult hDsg3 mice, but not WT mice, induces suprabasilar acantholysis in mucosal tissues, thus confirming the pathogenicity of mPV anti-hDsg3 IgG in vivo. Human anti-hDsg3 antibodies are detected in perilesional mucosa as well as in sera of recipient mice by IF. These findings suggest that the Dsg3 epitopes targeted by pathogenic mPV IgG are human specific. This hDsg3 mouse model will be invaluable in studying the clinical transition from mPV to mcPV.

  15. Mucosal pemphigus vulgaris anti-Dsg3 IgG are pathogenic to the oral mucosa of humanized Dsg3 mice

    PubMed Central

    Culton, Donna A.; McCray, Suzanne K.; Park, Moonhee; Roberts, James C.; Li, Ning; Zedek, Daniel C.; Anhalt, Grant J.; Cowley, Dale; Liu, Zhi; Diaz, Luis A.

    2015-01-01

    There are two major clinical subsets of pemphigus vulgaris (PV), mucosal PV (mPV) and mucocutaneous PV (mcPV). The mPV subset exhibits anti-human desmoglein (Dsg) 3 autoantibodies that fail to recognize murine Dsg3; thus, passive transfer experiments of mPV IgG into WT mice have been unsuccessful at inducing disease. We therefore generated a fully humanized Dsg3 (hDSG3) murine model utilizing a human Dsg3 transgenic animal crossed to the murine Dsg3 knockout line. Expression of hDsg3 in the mucosa rescues the murine Dsg3 knockout phenotype. Well characterized mPV sera bind mucosal epithelia from the hDsg3 mice, but not mucosal tissues from WT mice by as detected by indirect immunofluorescence. The majority of mPV sera preferentially recognize hDsg3 compared to mDsg3 by immunoprecipitation as well. Passive transfer of mPV IgG into adult hDsg3 mice, but not WT mice, induces suprabasilar acantholysis in mucosal tissues, thus confirming pathogenicity of mPV anti-hDsg3 IgG in vivo. Human anti-hDsg3 antibodies are detected in perilesional mucosa as well as in sera of recipient mice by immunofluorescence. These findings suggest that the Dsg3 epitopes targeted by pathogenic mPV IgG are human specific. This hDsg3 mouse model will be invaluable in studying the clinical transition from mPV to mcPV. PMID:25695683

  16. Oral administration of piperine for the control of aflatoxin intoxication in rats

    PubMed Central

    Gagini, Thalita B.; Silva, Robson E.; Castro, Isabela S.; Soares, Breno A.; Lima, Marco E.F.; Brito, Marilene F.; Mazur, Carlos; Direito, Glória M.; Danelli, Maria das Graças M.

    2010-01-01

    Aflatoxins are mycotoxins that have important toxic effects on human and animal health, even if consumed at low doses. The oral administration of piperine (1.12 mg/kg) during 23 days in rats seemingly interfered with the toxicity of aflatoxins, decreasing hepatic injuries and the leukocyte depletion in experimentally intoxicated animals. PMID:24031502

  17. Pharmacokinetics and dosimetry of the anti-androgen vinclozolin after oral administration inthe rat

    EPA Science Inventory

    Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and...

  18. Effect of a thiolated polymer on oral paclitaxel absorption and tumor growth in rats.

    PubMed

    Föger, Florian; Malaivijitnond, Suchinda; Wannaprasert, Thanakul; Huck, Christian; Bernkop-Schnürch, Andreas; Werle, Martin

    2008-02-01

    The anticancer agent paclitaxel is currently commercially available only as an infusion due to its low oral bioavailability. An oral formulation would be highly beneficial for patients. Besides the low solubility, the main reason for the limited oral bioavailability of paclitaxel is that it is a substrate of the efflux pump P-glycoprotein (P-gp). Recently, it has been demonstrated that P-gp can be inhibited by thiolated polymers. In this study, an oral paclitaxel formulation based on thiolated polycarbophil was evaluated in vivo in wild-type rats and in mammary cancer-induced rats. The paclitaxel plasma level after a single administration of paclitaxel was observed for 12 h in healthy rats. Moreover, cancer-induced rats were treated weekly for 5 weeks with the novel formulation. It was demonstrated that (1) co-administration of thiolated polycarbophil significantly improved paclitaxel plasma levels, (2) a more constant pharmacokinetic profile could be achieved and (3) the tumor growth was reduced. These effects can most likely be attributed to P-gp inhibition. According to the achieved results, thiolated polymers are believed to be interesting tools for the delivery of P-gp substrates such as paclitaxel.

  19. Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat

    PubMed Central

    2015-01-01

    A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted in compounds with subnanomolar levels of potency. The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat. PMID:26819673

  20. Oral Pyridostigmine Administration in Rats: Effects on Thermoregulation, Clinical Chemistry, and Performance in the Heat

    DTIC Science & Technology

    1984-01-01

    PERIOD COVERED " N Oral pyridostigmine administration in rats: .T 0 PTPR C E -,effects a thermoregulation, clinical chemistry , and performance in the heat...thermoregulation, clinical chemistry , and performance in the heat R. Francesconi, R. Hubbard, C. Matthew, N. Leva, J. Youxng, and V. Pense US Amny

  1. Safety of red ginseng oil for single oral administration in Sprague–Dawley rats

    PubMed Central

    Bak, Min-Ji; Kim, Kyu-Bong; Jun, Mira; Jeong, Woo-Sik

    2013-01-01

    The single oral administration of red ginseng oil (5000 mg/kg) to Sprague–Dawley rats induced no changes in behavioral patterns, clinical signs, and body weight, and hepatotoxicity parameters such as aspartate aminotransferase and alanine aminotransferase for 14 d. Therefore, these results suggest that the red ginseng oil is safe and nontoxic acutely. PMID:24558315

  2. Comparative metabolism studies of hexabromocyclododecane (HBCD) diastereomers in male rats following a single oral dose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively 42% of dose for alpha-HBCD,...

  3. Oral modafinil facilitates intracranial self-stimulation in rats: comparison with methylphenidate.

    PubMed

    Lazenka, Matthew F; Negus, S Stevens

    2017-01-25

    Modafinil is a low-potency inhibitor of dopamine transporters (DAT) approved clinically to promote wakefulness. In most procedures used for abuse-liability assessment, modafinil produces effects similar to those of abused DAT inhibitors such as cocaine and methylphenidate, although modafinil often shows lower effectiveness. However, modafinil has failed to maintain drug self-administration or produce conditioned place preferences in rats. The low potency and poor solubility of modafinil complicate its delivery by parenteral routes of administration commonly used in rats, and this may contribute toward negative results. This study evaluated the effects of orally administered modafinil in rats using an assay of intracranial self-stimulation (ICSS) that has been used to examine the effects of other DAT inhibitors. Adult male Sprague-Dawley rats equipped with electrodes in the medial forebrain bundle responded for pulses of brain stimulation that varied across a range of frequencies (158-56 Hz) during daily behavioral sessions. Modafinil (20-600 mg/kg, orally) and methylphenidate (1.0-10 mg/kg, intraperitoneally; 3.2-32 mg/kg, orally) produced dose-dependent and time-dependent facilitation of ICSS, an effect produced by abused DAT inhibitors and other classes of abused drugs. These results are in agreement with other evidence for stimulant-like abuse liability of modafinil and show the sensitivity of ICSS to orally administered drug.

  4. Suppression of the Hypothalamic-Pituitary-Adrenal Axis after Oral Hydrocortisone Succinate Ingestion in Rats

    PubMed Central

    Mims, Robert B.

    1978-01-01

    Groups of Holtzman female rats were fed 10 mg/day of hydrocortisone succinate orally to study the responsiveness of the hypothalamic-pituitary-adrenal axis to acute stress. Pituitary ACTH content, plasma ACTH, adrenal venous corticosterone, and adrenal weights were studied simultaneously in experimental and control rats before, during, and up to two weeks after oral hydrocortisone administration. There was a significant decrease in pituitary ACTH content (p=<0.001), suppression of plasma ACTH and corticosterone in response to acute stress (p=<0.001), and adrenal atrophy during and following oral hydrocortisone administration. After discontinuing the hydrocortisone it required three to five days for the rats to respond adequately to acute stress. However, it was seven to ten days post-hydrocortisone before plasma ACTH and corticosterone responses to acute stress had returned to basal values, but decreased pituitary ACTH content and partial adrenal atrophy continued throughout the ten-day post-hydrocortisone study interval. Recovering from the suppressive effects of oral hydrocortisone was more rapid than following parenteral hydrocortisone. However, oral hydrocortisone causes identical but less sustained suppression of the hypothalamic-pituitary-adrenal axis as observed in animals treated with parenteral glucocorticoid preparations. PMID:212574

  5. [Oral fluid bacteriocidal activity in complex diagnostics of oral disbiosis].

    PubMed

    Rabinovich, O F; Abramova, E S

    2012-01-01

    The possibility of examination of oral fluid bacteriocidal activity in complex diagnostics of oral mucosa disbiosis was evaluated. Thirty-seven patients were included in complex clinical and laboratory studies. The patients were divided in two groups: main group (30 patients exhibiting various grades of oral mucosa disbiosis) and control group (7 patients with no signs of oral disbiosis). The oral fluid bacteriocidal activity was examined by means of laser flow cytometry. Study results proved oral fluid bacteriocidal activity increase to correlate with the grade of oral mucosa disbiosis thus confirming the usefulness of the method in complex diagnostics of oral disbiosis.

  6. Actions of Angeli's salt, a nitroxyl (HNO) donor, on ion transport across mucosa-submucosa preparations from rat distal colon.

    PubMed

    Pouokam, Ervice; Bell, Anna; Diener, Martin

    2013-09-05

    The aim of this study was to investigate whether nitroxyl (HNO), a redox variant of the radical gasotransmitter nitric oxide (NO) with therapeutically promising properties, affects colonic ion transport. Changes in short-circuit current (Isc) induced by the HNO donor Angeli's salt were recorded in Ussing chambers. Cytosolic Ca(2+) concentration was measured with fura-2. The nitroxyl donor induced a concentration-dependent increase in Isc across rat distal colon which was due to a stimulation of chloride secretion. The secretion induced by Angeli's salt (5×10(-4)mol/l) was not altered by the NO scavenger 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (carboxy-PTIO), but was abolished by the HNO scavenger l-cysteine. The response was not dependent on the activity of soluble guanylate cyclase or enteric neurons, but was inhibited by indomethacin. Experiments with apically permeabilized epithelia revealed the activation of basolateral K(+) channels and a stimulation of the current carried by the basolateral Na(+)-K(+)-pump by Angeli's salt. The secretion induced by Angeli's salt was reduced in the absence of extracellular Ca(2+). A prominent increase in the cytosolic Ca(2+) concentration was evoked by Angeli's salt predominantly in subepithelial cells within the submucosa, which had the same dependence on extracellular Ca(2+) as the Angeli's salt-induced Cl(-) secretion. Consequently, Angeli's salt induces a soluble guanylate cyclase-independent, Ca(2+)-dependent Cl(-) secretion via activation of the Na(+)-K(+)-ATPase and of basolateral K(+) channels. Cyclooxygenase metabolites produced within the submucosa seem to be involved in this response.

  7. Oral dose of citrus peel extracts promotes wound repair in diabetic rats.

    PubMed

    Ahmad, M; Ansari, M N; Alam, A; Khan, T H

    2013-10-15

    Diabetic patients wound healing is slower than the healthy individuals. Three citrus peel extracts; Lemon (Citrus limon), Grapes fruits (Citrus paradise) and Orange (Citrus sinensis) promote wound healing in experimental animals. This study investigated the effect of oral treatment with citrus peel extracts on wound repair of the skin of diabetic rats. The extracts were estimated for vitamin C and total carotenoid contents prior to animal study. Diabetes mellitus was induced in rats by intraperitoneal injection of a single dose of streptozotocin (STZ, 75 mg kg(-1) b.wt.). One week after diabetes induction, full thickness excision wounds were made in hyperglycemic rats and were divided groups, each containing 6 rats. The different test group animals were treated with different citrus peel extract orally at the dose of 400 mg kg(-1) body weight daily for 12 days. The blood glucose, body weight and rate of wound closure of each rat were measured every 3rd day during the experimental period. At the end of experiment, granular tissues of wounds were removed and estimated for hydroxylproline and total protein content. The results showed significant reduction in blood glucose and time to wound closure. Tissue growth and collagen synthesis were significantly higher as determined by total protein and hydroxyl proline content. From our experimental data, we propose that oral administration of citrus peel extracts has a therapeutic potential in the treatment of chronic wounds in diabetes.

  8. Pharmacokinetics of omeprazole after intravenous and oral administration to rats with liver cirrhosis induced by dimethylnitrosamine.

    PubMed

    Lee, Dae Y; Lee, Inchul; Lee, Myung G

    2007-02-07

    The aim of this study is to report the pharmacokinetics of omeprazole after intravenous (20 mg/kg) and oral (40 mg/kg) administration to rats with liver cirrhosis induced by dimethylnitrosamine (cirrhotic rats) with respect to CYP isozyme changes. The expressions of CYP1A2 and 3A1 decreased in cirrhotic rats and omeprazole is reported to be mainly metabolized via CYP1A1/2, 2D1, and 3A1/2 in male Sprague-Dawley rats. Hence, the pharmacokinetics of omeprazole could be changed in cirrhotic rats. After intravenous administration to cirrhotic rats, the AUC (1180 microg min/ml versus 474 microg min/ml) and CL(NR) (17.4 ml/min/kg versus 42.3 ml/min/kg) of omeprazole were significantly greater and slower, respectively, than the controls. This could be due to decrease in the expressions of CYP1A2 and 3A1 in cirrhotic rats. The significantly slower CL(NR) could be supported by significantly slower in vitro CL(int) for the disappearance of omeprazole from hepatic microsomal study (0.102 ml/min/mg protein versus 0.144 ml/min/mg protein) and slower hepatic blood flow rate in cirrhotic rats. After oral administration to cirrhotic rats, the AUC difference was considerably greater (451% versus 149%) than that after intravenous administration, possibly due to decrease in intestinal first-pass effect of omeprazole in addition to decrease in hepatic metabolism of omeprazole in cirrhotic rats.

  9. Absorption, metabolism and excretion of cobimetinib, an oral MEK inhibitor, in rats and dogs.

    PubMed

    Takahashi, Ryan H; Ma, Shuguang; Yue, Qin; Kim-Kang, Heasook; Yi, Yijun; Ly, Justin; Boggs, Jason W; Fettes, Alec; McClory, Andrew; Deng, Yuzhong; Hop, Cornelis E C A; Khojasteh, S Cyrus; Choo, Edna F

    2017-01-01

    1. The absorption, metabolism and excretion of cobimetinib, an allosteric inhibitor of MEK1/2, was characterized in mass balance studies following single oral administration of radiolabeled ((14)C) cobimetinib to Sprague-Dawley rats (30 mg/kg) and Beagle dogs (5 mg/kg). 2. The oral dose of cobimetinib was well absorbed (81% and 71% in rats and dogs, respectively). The maximal plasma concentrations for cobimetinib and total radioactivity were reached at 2-3 h post-dose. Drug-derived radioactivity was fully recovered (∼90% of the administered dose) with the majority eliminated in feces via biliary excretion (78% of the dose for rats and 65% for dogs). The recoveries were nearly complete after the first 48 h following dosing. 3. The metabolic profiles indicated extensive metabolism of cobimetinib prior to its elimination. For rats, the predominant metabolic pathway was hydroxylation at the aromatic core. Lower exposures for cobimetinib and total radioactivity were observed in male rats compared with female rats, which was consistent to in vitro higher clearance of cobimetinib for male rats. For dogs, sequential oxidative reactions occurred at the aliphatic portion of the molecule. Though rat metabolism was well-predicted in vitro with liver microsomes, dog metabolism was not. 4. Rats and dogs were exposed to the two major human circulating Phase II metabolites, which provided relevant metabolite safety assessment. In general, the extensive sequential oxidative metabolism in dogs, and not the aromatic hydroxylation in rats, was more indicative of the metabolism of cobimetinib in humans.

  10. Quercetin does not alter the oral bioavailability of Atorvastatin in rats.

    PubMed

    Koritala, Rekha; Challa, Siva Reddy; Ragam, Satheesh Kumar; Geddam, Lal Babu; Venkatesh Reddy Challa, Venkatesh Reddy; Devi, Renuka; Sattenapalli, Srinu; Babu, Narendra

    2015-09-01

    The study was undertaken to evaluate the effect of Quercetin on the pharmacokinetics of Atorvastatin Calcium. In-vivo Pharmacokinetic studies were performed on rats in a single dose study and multiple dose study. Rats were treated with Quercetin (10 mg/kg) and Atorvastatin Calcium (20 mg/kg) orally and blood samples were collected at (0) pretreatment and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24 hours post treatment. Plasma concentrations of Atorvastatin were estimated by HPLC method. Quercetin treatment did not significantly alter the pharmacokinetic parameters of atorvastatin like AUC(0-24), AUC(0-α) , T(max), C(max) and T(½) in both single dose and multiple dose studies of Atorvastatin Calcium. Quercetin does not alter the oral bioavailability of Atorvastatin Calcium in rats.

  11. Oral administration of corn zein hydrolysate stimulates GLP-1 and GIP secretion and improves glucose tolerance in male normal rats and Goto-Kakizaki rats.

    PubMed

    Higuchi, Noriyuki; Hira, Tohru; Yamada, Nao; Hara, Hiroshi

    2013-09-01

    We have previously demonstrated that ileal administration of the dietary protein hydrolysate prepared from corn zein (ZeinH) stimulated glucagon-like peptide-1 (GLP-1) secretion and attenuated hyperglycemia in rats. In this study, to examine whether oral administration of ZeinH improves glucose tolerance by stimulating GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion, glucose tolerance tests were performed in normal Sprague-Dawley male rats and diabetic Goto-Kakizaki (GK) male rats. The test solution was gavaged before ip glucose injection in normal rats or gavaged together with glucose in GK rats. Blood samples were collected from the tail vein or by using the jugular catheter to measure glucose, insulin, GLP-1, and GIP levels. In the ip glucose tolerance test, oral administration of ZeinH (2 g/kg) significantly suppressed the glycemic response accompanied by an immediate increase in plasma GLP-1 and GIP levels in normal rats. In contrast, oral administration of another dietary peptide, meat hydrolysate, did not elicit a similar effect. The glucose-lowering effect of ZeinH was attenuated by a GLP-1 receptor antagonist or by a GIP receptor antagonist. Furthermore, oral ZeinH induced GLP-1 secretion and reduced glycemic response in GK rats under the oral glucose tolerance test. These results indicate that the oral administration of the dietary peptide ZeinH improves glucose tolerance in normal and diabetic rats by its incretin-releasing activity, namely, the incretinotropic effect.

  12. Periluminal Distribution of HIV-Binding Target Cells and Gp340 in the Oral, Cervical and Sigmoid/Rectal Mucosae: A Mapping Study.

    PubMed

    Patyka, Mariia; Malamud, Daniel; Weissman, Drew; Abrams, William R; Kurago, Zoya

    2015-01-01

    Studies have shown that the transmission of HIV is most likely to occur via rectal or vaginal routes, and rarely through oral exposure. However, the mechanisms of virus entry at mucosal surfaces remain incompletely understood. Prophylactic strategies against HIV infection may be attainable once gaps in current knowledge are filled. To address these gaps, we evaluated essentially normal epithelial surfaces and mapped the periluminal distribution of CD4+ HIV target cells, including T cells and antigen-presenting cells, and an HIV-binding molecule gp340 that can be expressed by epithelial cells in secreted and cell-associated forms. Immunohistochemistry for CD4, CD16, CD3, CD1a and gp340 in human oral, rectal/sigmoid and cervical mucosal samples from HIV-negative subjects demonstrated that periluminal HIV target cells were more prevalent at rectal/sigmoid and endocervical surfaces lined by simple columnar epithelium, than at oral and ectocervical surfaces covered by multilayered stratified squamous epithelium (p<0.001). gp340 expression patterns at these sites were also distinct and strong in oral minor salivary gland acini and ducts, including ductal saliva, in individual rectum/sigmoid and endocervix periluminar columnar cells, and in ectocervix squamous cells. Only weak expression was noted in the oral non-ductal squamous epithelium. We conclude that periluminal HIV target cells, together with periluminal epithelial cell-associated gp340 appear to be most accessible for HIV transmission at rectal/sigmoid and endocervical surfaces. Our data help define vulnerable structural features of mucosal sites exposed to HIV.

  13. A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis

    PubMed Central

    Elvington, M; Blichmann, P; Qiao, F; Scheiber, M; Wadsworth, C; Luzinov, I; Lucero, J; Vertegel, A; Tomlinson, S

    2014-01-01

    While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of proteins. We describe a novel pellet formulation consisting of cross-linked dextran coated with an acrylic co-polymer that protects the complement inhibitor CR2-Crry from destruction in the gastrointestinal tract. CR2-Crry containing pellets administered by gavage, were characterized using a therapeutic protocol in a mouse model of dextran sulphate sodium (DSS)-induced colitis. Oral treatment of established colitis over a 5-day period significantly reduced mucosal inflammation and injury, with similar therapeutic benefit whether or not the proton pump inhibitor, omeprazole, was co-administered. Reduction in injury was associated with the targeting of CR2-Crry to the mucosal surface and reduced local complement activation. Treatment had no effect on systemic complement activity. This novel method for oral delivery of a targeted protein complement inhibitor will reduce systemic effects, thereby decreasing the risk of opportunistic infection, as well as lowering the required dose and treatment cost and improving patient compliance. Furthermore, the novel delivery system described here may provide similar benefits for administration of other protein-based drugs, such as anti-tumour necrosis factor-α antibodies. PMID:24730624

  14. Role of TLR4/NF-κB in Damage to Intestinal Mucosa Barrier Function and Bacterial Translocation in Rats Exposed to Hypoxia

    PubMed Central

    Luo, Han; Guo, Ping; Zhou, Qiquan

    2012-01-01

    The role of Toll-like receptor 4 (TLR4)/nuclear factor-kappa-B (NF-κB) in intestinal mucosal barrier damage and bacterial translocation under hypoxic exposure is unclear. Here, we investigated their role using an acute hypobaric hypoxia model. Adult Sprague-Dawley rats were divided into control (C), hypoxia (H), hypoxia+NF-κB inhibitor pyrrolidinedithiocarbamic acid (PDTC) (100 mg. kg) (HP), hypoxia+0.5 mg/kg lipopolysaccharide (HPL), and hypoxia+PDTC+LPS (HPL) group. Except control group, other four groups were placed in a hypobaric chamber set at 7000 m. Samples were collected at 72 h after pressure reduction. Damage in ultrastructure of the intestinal tract was examined by transmission electron microscopy and bacterial translocation was detected by cultivation. Kinetic turbidimetric assay was used to measure the serum LPS. ELISA was performed to detect TNF-α and IL-6 serum concentrations. Fluorescent quantitative RT-PCR was used to measure TLR4 mRNA levels was measured using quantitative RT-PCR and protein of NF-κB p65 was measured by western blotting. Different degrees of intestinal mucosa damage were observed in groups H and HL. The damage was significantly alleviated after blockage of the TLR4/NF-κB signaling pathway. PDTC- treatment also reversed hyoxia- and LPS-induced bacterial translocation rate and increased serum levels of LPS, TNF-α, and IL-6. TLR4 mRNA levels and NF-κB p65 expression were consistent with the serum factor results. This study suggested that TLR4 and NF-κB expression increased in rat intestinal tissues after acute hypoxia exposure. PDTC-treatment reversed TLR4 and NF-κB upregulation and alleviated damage to the intestinal tract and bacterial translocation. Thus, the TLR4/NF-κB signaling pathway may be critical to the mechanism underlying hypoxia-induced damage to intestinal barrier function and bacterial translocation. PMID:23082119

  15. CARDIOVASCULAR AND THERMOREGULATORY RESPONSE TO ORAL TOLUENE IN THE RAT.

    EPA Science Inventory

    Toluene and other volatile organic compounds have often been shown to affect behavior in animals when given by inhalation, and less effective when given orally. Previous work showed that toluene increased heart rate (HR) and motor activity (MA), and reduced core temperature (Tc) ...

  16. Subchronic Oral Toxicity of Sodium Tungstate in Sprague-Dawley Rats.

    PubMed

    McCain, Wilfred C; Crouse, Lee C B; Bazar, Mathew A; Roszell, Laurie E; Leach, Glenn J; Middleton, John R; Reddy, Gunda

    2015-01-01

    The subchronic toxicity of sodium tungstate dihydrate aqueous solution in male and female Sprague-Dawley rats was evaluated by daily oral gavage of 0, 10, 75, 125, or 200 mg/kg/d for 90 days. Measured parameters included food consumption, body weight measurements, hematology, clinical chemistry, and histopathological changes. There was a significant decrease in food consumption and body weight gain in males at 200 mg/kg/d from days 77 to 90; however, there was no effect in food consumption and body weights in females. There were no changes in the hematological and clinical parameters studied. Histopathological changes were seen in kidney of male and female and epididymis of male rats. Histopathological changes were observed in the kidneys of male and female rats dosed at 125 or 200 mg/k/d consisting of mild to severe cortical tubule basophilia in 2 high-dose groups. Histological changes in epididymides included intraluminal hypospermia with cell debris in the 200 mg/kg/d dosed male rats. Histopathological changes were observed in the glandular stomach including inflammation and metaplasia in the high-dose groups (125 or 200 mg/kg/d) of both sexes of rats. Based on histopathology effects seen in the kidneys, the lowest observable adverse effect level was 125 mg/kg/d and the no observable adverse effect level was 75 mg/kg/d in both sexes of rats for oral subchronic toxicity.

  17. Detection and Specific Enumeration of Multi-Strain Probiotics in the Lumen Contents and Mucus Layers of the Rat Intestine After Oral Administration.

    PubMed

    Lee, Hee Ji; Orlovich, David A; Tagg, John R; Fawcett, J Paul

    2009-12-01

    Although the detection of viable probiotic bacteria following their ingestion and passage through the gastrointestinal tract (GIT) has been well documented, their mucosal attachment in vivo is more difficult to assess. In this study, we investigated the survival and mucosal attachment of multi-strain probiotics transiting the rat GIT. Rats were administered a commercial mixture of the intestinal probiotics Lactobacillus acidophilus LA742, Lactobacillus rhamnosus L2H and Bifidobacterium lactis HN019 and the oral probiotic Streptococcus salivarius K12 every 12 h for 3 days. Intestinal contents, mucus and faeces were tested 6 h, 3 days and 7 days after the last dose by strain-specific enumeration on selective media and by denaturing gradient gel electrophoresis. At 6 h, viable cells and DNA corresponding to all four probiotics were detected in the faeces and in both the lumen contents and mucus layers of the ileum and colon. Viable probiotic cells of B. lactis and L. rhamnosus were detected for 7 days and L. acidophilus for 3 days after the last dose. B. lactis and L. rhamnosus persisted in the ileal mucus and colon contents, whereas the retention of L. acidophilus appeared to be relatively higher in colonic mucus. No viable cells of S. salivarius K12 were detected in any of the samples at either day 3 or 7. The study demonstrates that probiotic strains of intestinal origin but not of oral origin exhibit temporary colonisation of the rat GIT and that these strains may have differing relative affinities for colonic and ileal mucosa.

  18. Oral L-glutamine administration attenuated cutaneous wound healing in Wistar rats.

    PubMed

    Goswami, Saurabh; Kandhare, Amit; Zanwar, Anand A; Hegde, Mahabaleshwar V; Bodhankar, Subhash L; Shinde, Sudhir; Deshmukh, Shahaji; Kharat, Ravindran

    2016-02-01

    The objective of this study was to evaluate the wound healing potential of L-glutamine in laboratory rats using excision and incision wound models. Excision wounds of size 500 mm(2) and depth 2 mm were made on the dorsal portion of male Wistar rats (230-250 g) and were used for the study of oral L-glutamine (1 g/kg) treatment on the rate of contraction of wound and epithelisation. Histological evaluation of wound tissue was also performed. Six-centimetre-long two linear-paravertebral incisions in male Wistar rats (230-250 g) were used to study the effect of L-glutamine (1 g/kg, p.o.) treatment on tensile strength, total protein and hydroxyproline content in the incision model. Oral administration of L-glutamine (1 g/kg) significantly decreased wound area, epithelisation period and wound index, whereas the rate of wound contraction significantly increased (P < 0·001) when compared with vehicle control rats in the excision wound model. Tensile strength, hydroxyproline content and protein level were significantly increased (P < 0·001) in L-glutamine (1 g/kg, p.o.)-treated rats when compared with vehicle control rats in the incision wound model. Histological evaluation of wound tissue from L-glutamine (1 g/kg, p.o.)-treated rats showed complete epithelialisation with new blood vessel formation and high fibrous tissues in the excision wound model. In conclusion, oral administration of l-glutamine (1 g/kg) promotes wound healing by acting on various stages of wound healing such as collagen synthesis, wound contraction and epithelialisation.

  19. Narrow band (light) imaging of oral mucosa in routine dental patients. Part I: Assessment of value in detection of mucosal changes.

    PubMed

    Truelove, Edmond L; Dean, David; Maltby, Samuel; Griffith, Matthew; Huggins, Kimberly; Griffith, Mickealla; Taylor, Stuart

    2011-01-01

    The purpose of this investigation was to determine the value of adding narrow band (light) imaging (NBI) to the standard oral soft tissue examination process used to detect mucosal change. A total of 620 dental patients who came to the clinic for regular dental evaluation or for treatment of acute dental problems were given a standard oral soft tissue examination by dental students under faculty supervision. The results of the white light examination were recorded after the tissues were examined with NBI, at which point areas with a loss of fluorescence (LOF) were recorded. The nature of the tissue change was classified clinically as normal variation, inflammatory, traumatic, dysplastic, or other, and patients were categorized depending on their clinical findings: normal, need follow-up visit, or immediate biopsy. Risk factors related to oral dysplasia also were recorded. The addition of NBI added between one and two minutes to the examination process. Of the 620 examinations, an area with an LOF suggestive of pathology was detected in 69 subjects (11.1%). After a second immediate evaluation, 28 of the 69 subjects were scheduled for follow-up or biopsy. None of the lesions discovered in these 28 subjects had been detected using standard (white light) examination. Adding NBI to the routine clinical examination resulted in detection of changes not seen with white light examination in 11.1% of patients; of these, a small but important number were found to have otherwise undetected persistent changes representing inflammatory lesions or potentially dangerous oral dysplasia. Adding NBI as an adjunctive diagnostic procedure improved the quality and outcome of the examination process.

  20. Pharmacokinetic evaluation of the interaction between oral kaempferol and ethanol in rats.

    PubMed

    Zhou, Zhaoxiang; Wang, Meng; Guo, Zengjun; Zhang, Xiaoying

    2016-12-01

    This study was aimed at investigating the effect of ethanol on oral bioavailability of kaempferol in rats, namely, at disclosing their possible interaction. Kaempferol (100 or 250 mg kg-1 bm) was administered to the rats by oral gavage with or without ethanol (600 mg kg-1 bm) co-administration. Intravenous administration (10 and 25 mg kg-1 bm) of kaempferol was used to determine the bioavailability. The concentration of kaempferol in plasma was estimated by ultra high performance liquid chromatography. During coadministration, a significant increase of the area under the plasma concentration-time curve as well as the peak concentration were observed, along with a dramatic decrease in total body clearance. Consequently, the bioavailability of kaempferol in oral control groups was 3.1 % (100 mg kg-1 bm) and 2.1 % (250 mg kg-1 bm). The first was increased by 4.3 % and the other by 2.8 % during ethanol co-administration. Increased permeability of cell membrane and ethanolkaempferol interactions on CYP450 enzymes may enhance the oral bioavailability of kaempferol in rats.

  1. Gut Microbiota in a Rat Oral Sensitization Model: Effect of a Cocoa-Enriched Diet

    PubMed Central

    Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J.; Franch, Àngels

    2017-01-01

    Increasing evidence is emerging suggesting a relation between dietary compounds, microbiota, and the susceptibility to allergic diseases, particularly food allergy. Cocoa, a source of antioxidant polyphenols, has shown effects on gut microbiota and the ability to promote tolerance in an oral sensitization model. Taking these facts into consideration, the aim of the present study was to establish the influence of an oral sensitization model, both alone and together with a cocoa-enriched diet, on gut microbiota. Lewis rats were orally sensitized and fed with either a standard or 10% cocoa diet. Faecal microbiota was analysed through metagenomics study. Intestinal IgA concentration was also determined. Oral sensitization produced few changes in intestinal microbiota, but in those rats fed a cocoa diet significant modifications appeared. Decreased bacteria from the Firmicutes and Proteobacteria phyla and a higher percentage of bacteria belonging to the Tenericutes and Cyanobacteria phyla were observed. In conclusion, a cocoa diet is able to modify the microbiota bacterial pattern in orally sensitized animals. As cocoa inhibits the synthesis of specific antibodies and also intestinal IgA, those changes in microbiota pattern, particularly those of the Proteobacteria phylum, might be partially responsible for the tolerogenic effect of cocoa. PMID:28239436

  2. Sex differences in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone in the Sprague-Dawley rat.

    PubMed

    Chan, Samuel; Edwards, Stephen R; Wyse, Bruce D; Smith, Maree T

    2008-03-01

    1. The pharmacokinetics and oxidative metabolism of oxycodone were investigated following intravenous and oral administration in male and female Sprague-Dawley (SD) rats. 2. High-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS-MS) was used to quantify plasma concentrations of oxycodone and its oxidative metabolites noroxycodone and oxymorphone following administration of single bolus intravenous (5 mg/kg) and oral (10 mg/kg) doses of oxycodone. 3. The mean (+/-SEM) clearance of intravenous oxycodone was significantly higher in male than female SD rats (4.9 +/- 0.3 vs 3.1 +/- 0.3 L/h per kg, respectively; P < 0.01). Mean areas under the plasma concentration versus time curves (AUC) for oxycodone were significantly higher in female than male SD rats following intravenous (approximately 1.6-fold; P < 0.01) and oral (approximately sevenfold; P < 0.005) administration. 4. The oral bioavailability of oxycodone was low (at 1.2 and 5.0%, respectively) in male and female SD rats, a finding consistent with high first-pass metabolism. Noroxycodone : oxycodone AUC ratios were significantly higher in male than female SD rats after intravenous (approximately 2.4-fold; P < 0.005) and oral (approximately 12-fold; P < 0.005) administration. 5. Circulating oxymorphone concentrations remained very low following both routes of administration. Noroxycodone : oxymorphone AUC ratios were greater in male than female SD rats after intravenous (approximately 13- and fivefold, respectively) and oral (approximately 90- and sixfold, respectively) administration. 6. Sex differences were apparent in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone. Systemic exposure to oxycodone was greater in female compared with male SD rats, whereas systemic exposure to metabolically derived noroxycodone was higher in male than female SD rats. 7. Oral administration of oxycodone to the SD rat is a poor model of the human for

  3. [13-week subchronic oral toxicity study of ammonium sulfate in rats].

    PubMed

    Takagi, H; Onodera, H; Yun, L; Yasuhara, K; Koujitani, T; Mitsumori, K; Hirose, M

    1999-01-01

    A 13-week subchronic oral toxicity study of ammonium sulfate was performed in both sexes of F344 rats by feeding them a CRF-1 powder diet containing concentrations of 0%, 0.38%, 0.75%, 1.5%, and 3.0% of the substance. Rats were randomly divided into 5 groups each consisting of 10 males and 10 females. Male animals in the 3% group exhibited diarrhea during the administration period. No changes indicating obvious ammonium sulfate toxicity were observed in the body weights, organ weights, hematological, serum biochemical, or histopathological examinations. Based on these results, the NOEL (no-observed-effect level) of ammonium sulfate for F344 rats was judged to be 1.5% in males (886 mg/kg/day) and 3% in females (1975 mg/kg/day), and the MTD (maximally tolerated dose) for 2-year carcinogenicity studies in F344 rats was concluded to be 3.0% or more in the diet.

  4. Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

    PubMed

    Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-02-01

    Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

  5. Supplementation with L-glutamine prevents tumor growth and cancer-induced cachexia as well as restores cell proliferation of intestinal mucosa of Walker-256 tumor-bearing rats.

    PubMed

    Martins, Heber Amilcar; Sehaber, Camila Caviquioli; Hermes-Uliana, Catchia; Mariani, Fernando Augusto; Guarnier, Flavia Alessandra; Vicentini, Geraldo Emílio; Bossolani, Gleison Daion Piovezana; Jussani, Laraine Almeida; Lima, Mariana Machado; Bazotte, Roberto Barbosa; Zanoni, Jacqueline Nelisis

    2016-12-01

    This study aimed to evaluate the intestinal mucosa of the duodenum and jejunum of Walker-256 tumor-bearing rats supplemented with L-glutamine. Thirty-two male 50-day-old Wistar rats (Rattus norvegicus) were randomly divided into four groups: control (C), control supplemented with 2 % L-glutamine (GC), Walker-256 tumor (WT), and Walker-256 tumor supplemented with 2 % L-glutamine (TWG). Walker-256 tumor was induced by inoculation viable tumor cells in the right rear flank. After 10 days, celiotomy was performed and duodenal and jejunal tissues were removed and processed. We evaluated the cachexia index, proliferation index, villus height, crypt depth, total height of the intestinal wall, and number of goblet cells by the technique of periodic acid-Schiff (PAS). Induction of Walker-256 tumor promoted a reduction of metaphase index in the TW group animals, which was accompanied by a reduction in the villous height and crypt depths, resulting in atrophy of the intestinal wall as well as increased PAS-positive goblet cells. Supplementation with L-glutamine reduced the tumor growth and inhibited the development of the cachectic syndrome in animals of the TWG group. Furthermore, amino acid supplementation promoted beneficial effects on the intestinal mucosa in the TWG animals through restoration of the number of PAS-positive goblet cells. Therefore, supplementation with 2 % L-glutamine exhibited a promising role in the prevention of tumor growth and cancer-associated cachexia as well as restoring the intestinal mucosa in the duodenum and jejunum of Walker-256 tumor-bearing rats.

  6. Quantitation of pyridyloxobutyl-DNA adducts in tissues of rats treated chronically with (R)- or (S)-N’-nitrosonornicotine (NNN) in a carcinogenicity study

    PubMed Central

    Zhao, Lijiao; Balbo, Silvia; Wang, Mingyao; Upadhyaya, Pramod; Khariwala, Samir S.; Villalta, Peter W.; Hecht, Stephen S.

    2013-01-01

    We quantified DNA adducts resulting from 2’-hydroxylation of enantiomers of the tobacco-specific nitrosamine N’-nitrosonornicotine (NNN) in tissues of male F-344 rats after 10, 30, 50, and 70 weeks of treatment with 14 ppm in the drinking water. These rats were in subgroups of a carcinogenicity study in which (S)-NNN was highly tumorigenic in the oral cavity and esophagus while (R)-NNN was relatively weakly active. DNA adducts were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry in six tissues – oral mucosa, esophageal mucosa, nasal respiratory mucosa, nasal olfactory mucosa, liver, and lung. O2-[4-(3-Pyridyl)-4-oxobut-1-yl]thymidine (O2-POB-dThd, 7) and 7-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxyguanosine (7-POB-dGuo, 8), the latter as 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine (7-POB-Gua, 11), were detected at each time point in each tissue. In the target tissues for carcinogenicity, oral mucosa and esophageal mucosa, levels of 7-POB-Gua (11) and O2-POB-dThd (7) were similar, or 11 predominated, while in all other tissues at all time points for both enantiomers, 7 was clearly present in greater amounts than 11. Total measured DNA adduct levels in esophageal mucosa and oral mucosa were higher in rats treated with (S)-NNN than (R)-NNN. The highest adduct levels were found in the nasal respiratory mucosa. DNA adducts generally persisted in all tissues without any sign of substantial decreases throughout the 70 week time course. The results of this study suggest that inefficient repair of 7-POB-dGuo (8) in the rat oral cavity and esophagus may be important in carcinogenesis by NNN and support the development of these DNA adducts as potential biomarkers of NNN metabolic activation in people who use tobacco products. PMID:24001146

  7. Sensitive analysis and simultaneous assessment of pharmacokinetic properties of crocin and crocetin after oral administration in rats.

    PubMed

    Zhang, Yue; Fei, Fei; Zhen, Le; Zhu, Xuanxuan; Wang, Jiankun; Li, Sijia; Geng, Jianliang; Sun, Runbin; Yu, Xiaoyi; Chen, Tingting; Feng, Siqi; Wang, Pei; Yang, Na; Zhu, Yejin; Huang, Jingqiu; Zhao, Yuqing; Aa, Jiye; Wang, Guangji

    2017-02-15

    Crocin and crocetin in rat plasma were simultaneously analysed using ultra-performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS), and method was fully validated. For the first time, levels of both crocin and crocetin in plasma were profiled after oral administration of crocin, and this UPLC-MS/MS approach was applied to evaluate pharmacokinetics and relative bioavailability of crocin and crocetin in rats. It was shown that crocin transformed into crocetin quickly in the gastrointestinal tract, and crocetin was 56-81 fold higher exposed in rat plasma than crocin after oral administration of crocin. A comparison study revealed that an oral administration of equal molar crocin achieved higher exposure of crocetin in rat plasma than that of crocetin. It was suggested that oral administration of crocin has the advantages over crocetin, and crocetin may be the active component potentially responsible for the pharmacological effect of crocin.

  8. In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography

    NASA Astrophysics Data System (ADS)

    Lin, Li; Xia, Jun; Wong, Terence T. W.; Zhang, Ruiying; Wang, Lihong V.

    2015-03-01

    We demonstrate, by means of internal light delivery, photoacoustic imaging of the deep brain of rats in vivo. With fiber illumination via the oral cavity, we delivered light directly into the bottom of the brain, much more than can be delivered by external illumination. The study was performed using a photoacoustic computed tomography (PACT) system equipped with a 512-element full-ring transducer array, providing a full two-dimensional view aperture. Using internal illumination, the PACT system provided clear cross sectional photoacoustic images from the palate to the middle brain of live rats, revealing deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

  9. Biological effects caused by low-power laser light in the treatment of the dentition, periodontium, and mucosa of oral cavity, and lip diseases

    NASA Astrophysics Data System (ADS)

    Kunin, Anatoly A.; Erina, Stanislava V.; Kashuba, Victor A.; Pankova, Svetlana N.; Stepanov, Nicolay N.; Kazmina, Svetlana G.; Dergunova, Elvira I.; Buerger, F.; Herdt, Alexander; Podolskaya, Elana E.; Shumilovitch, Bogdan R.; Ippolitov, Yu. A.; Tchernov, V. I.

    1997-12-01

    Nowadays low-power therapy is one of the leading trends in a combined treatment of the oral cavity and lips diseases. The present paper sums up the results of the investigation into the biological effects caused by low-power laser light (LPLL) during its interaction with hard and soft tissues of the oral cavity and lips. A research on the effect of LPLL upon the remineralization processes in the hard dental tissues in the stage in the stage of an initial caries was carried out in 150 patients. The biological effects caused by an interaction of LPLL with the parodontium tissues in the process of treatment of medium degree disease of the parodontium were studied in 140 patients; the effects of the above mentioned character which generated in lips tissues during treatment of a post-radiation chilitis were analyzed in 32 patients. Immunological, biochemical histochemical, morphological, stomatoscopic, bacteriological and other methods were employed while studying the bioeffects caused by LPLL in the parodontium, lips tissues and hard tissues of the tooth.

  10. Decreased oral colonization of Streptococcus mutans during aging of Sprague-Dawley rats.

    PubMed

    Van Houte, J; Upeslacis, V N; Edelstein, S

    1977-04-01

    The colonization by streptomycin-resistant Streptococcus mutans strains of the teeth of conventional and ex-germfree Sprague-Dawley rats of various ages fed either a high-sucrose or a high-glucose diet was studied. Bacterial colonization occurred with increasingly greater difficulty as the rats became older. This was observed in studies of the implantation of the test organism after oral inoculation with different cell numbers as well as its transmission between infected and uninfected rats. With rat fed sucrose diet, the effect of age could not be demonstrated until they were age 3 months or older; the results from rats fed a glucose diet suggest that changes may already have occurred early after weaning. Changes in susceptibility to colonization during aging manifested themselves as a decrease in the proportions of rats which became infected as well as lower population levels in infected rats. The possible mechanism(s) involved as well as the possible significance of the findings was discussed.

  11. Effects of oral exposure to silver nanoparticles on the sperm of rats.

    PubMed

    Lafuente, D; Garcia, T; Blanco, J; Sánchez, D J; Sirvent, J J; Domingo, J L; Gómez, M

    2016-04-01

    It has been demonstrated that exposure to silver nanoparticles (AgNPs) can induce toxicological effects in rodents. In this study, we investigated whether sub-chronic oral exposure to different doses of polyvinil pyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) (50, 100 and 200mg/kg/day) could induce harmful effects on epididymal sperm rat parameters. Sperm motility, viability and morphology were examined. Moreover, a histological evaluation of testis and epididymis was also performed. High doses of PVP-AgNPs showed higher sperm morphology abnormalities, while a progressive, but not significant effect, was observed in other sperm parameters. The current results suggest that oral sub-chronic exposure to PVP-AgNPs induces slight toxicological effects in sperm rat parameters.

  12. Orally bioavailable Syk inhibitors with activity in a rat PK/PD model.

    PubMed

    Thoma, Gebhard; Veenstra, Siem; Strang, Ross; Blanz, Joachim; Vangrevelinghe, Eric; Berghausen, Jörg; Lee, Christian C; Zerwes, Hans-Günter

    2015-10-15

    Design and optimization of benzo- and pyrido-thiazoles/isothiazoles are reported leading to the discovery of the potent, orally bioavailable Syk inhibitor 5, which was found to be active in a rat PK/PD model. Compound 5 showed acceptable overall kinase selectivity. However, in addition to Syk it also inhibited Aurora kinase in enzymatic and cellular settings leading to findings in the micronucleus assay. As a consequence, compound 5 was not further pursued.

  13. Pharmacokinetics of xanthohumol and metabolites in rats after oral and intravenous administration

    PubMed Central

    Legette, LeeCole; Ma, Lian; Reed, Ralph L.; Miranda, Cristobal L.; Christensen, J. Mark; Rodriguez-Proteau, Rosita; Stevens, Jan F.

    2012-01-01

    Scope Xanthohumol (XN), a dietary flavonoid found in hops, may have health protective actions against cardiovascular disease and type 2 diabetes. Yet, there are limited data on the pharmacokinetics (PK) of XN. This study provides PK parameters for XN and its major metabolites in rats. Methods and results A pharmacokinetic study was conducted in male jugular vein-cannulated Sprague-Dawley rats. Rats (n=12/group) received an intravenous (IV) injection (1.86 mg/kg BW) or an oral gavage of a low (1.86 mg/kg BW), medium (5.64 mg/kg BW), or high (16.9 mg/kg BW) dose of XN. Plasma samples were analyzed for XN and its metabolites using LC-MS/MS. The maximum concentration (Cmax) and area under the curve (AUC0-96 h) of total XN (free and conjugated) were 2.9 ± 0.1 mg/L and 2.5 ± 0.3 h*mg/L in the IV group, 0.019 ± 0.002 mg/L and 0.84 ± 0.17 h*mg/L in the oral low group, 0.043 ± 0.002 mg/L and 1.03 ± 0.12 h*mg/L in the oral medium group, and 0.15 ± 0.01 mg/L and 2.49 ± 0.10 h*mg/L in the oral high group. Conclusion The bioavailability of XN is dose-dependent and approximately 0.33, 0.13 and 0.11 in rats, for the low, medium and high dose groups, respectively. PMID:22147307

  14. Enhancement of oscillatory activity in the endopiriform nucleus of rats raised under abnormal oral conditions.

    PubMed

    Yoshimura, Hiroshi; Hasumoto-Honjo, Miho; Sugai, Tokio; Segami, Natsuki; Kato, Nobuo

    2014-02-21

    Endopiriform nucleus (EPN) is located deep to the piriform cortex, and has neural connections with not only neighboring sensory areas but also subcortical areas where emotional and nociceptive information is processed. Well-balanced oral condition might play an important role in stability of brain activities. When the oral condition is impaired, several areas in the brain might be affected. In the present study, we investigated whether abnormal conditions of oral region influence neural activities in the EPN. Orthodontic appliance that generates continuous force and chronic pain-related stress was fixed to maxillary incisors of rats, and raised. Field potential recordings were made from the EPN of brain slices. We previously reported that the EPN has an ability to generate membrane potential oscillation. In the present study, we have applied the same methods to assess activities of neuron clusters in the EPN. In the case of normal rats, stable field potential oscillations were induced in the EPN by application of low-frequency electrical stimulation under the medium with caffeine. In the case of rats with the orthodontic appliance, stable field potential oscillations were also induced, but both duration of oscillatory activities and wavelet number were increased. The enhanced oscillations were depressed by blockade of NMDA receptors. Thus, impairment of oral health under application of continuous orthodontic force and chronic pain-related stress enhanced neural activities in the EPN, in which up-regulation of NMDA receptors may be concerned. These findings suggest that the EPN might be involved in information processing with regard to abnormal conditions of oral region.

  15. GLP-1 secretion in response to oral and luminal palatinose (isomaltulose) in rats.

    PubMed

    Hira, Tohru; Muramatsu, Maya; Okuno, Masahiro; Hara, Hiroshi

    2011-01-01

    Palatinose (isomaltulose), a slowly digested disaccharide, is used as a non-cariogenic sugar and as a sucrose substitute in several foods. Because of its ability to lower postprandial glycemia, palatinose may be beneficial as a treatment for impaired glucose metabolism. Glucagon-like peptide-1 (GLP-1) improves glycemia via enhancing pancreatic beta-cell functions. The secretion of GLP-1 is stimulated by sugars, including glucose and artificial sweeteners. In this study, we examined whether palatinose induced GLP-1 secretion in vivo and in vitro. Firstly, portal GLP-1 and glucose were measured after oral administration of palatinose or sucrose in conscious rats. Secondly, portal GLP-1 and glucose were measured after jejunal or ileal administration of each sugar in anesthetized rats. Finally, GLUTag, a murine GLP-1-producing cell line, was exposed to several sugars, including palatinose and sucrose, to observe the direct effect of these sugars on GLP-1 secretion. Compared with sucrose, palatinose enhanced portal GLP-1 level when administered orally in conscious rats. Both palatinose and sucrose induced a significant increase in portal GLP-1 after jejunal or ileal administration of each sugar in anesthetized rats. Ileal administration triggered a greater response than did jejunal administration. Glycemic responses were higher in sucrose-treated rats than in palatinose-treated rats in every experiment. In GLUTag cells, glucose induced a significant increase in GLP-1 secretion, but neither sucrose nor palatinose had an effect. These data demonstrate that luminal palatinose induces GLP-1 secretion in rats. However, it is likely that GLP-1 secretion is triggered mainly by glucose released in the lumen rather than by palatinose itself.

  16. Oral Prenatal and Postnatal Development Study of WR238605 Succinate in Rats. Volume 1 of 2

    DTIC Science & Technology

    1996-09-18

    0.003 101.8 0 394 ± 0.005 1.144 ± 0.029 96 8 99.6 1.149 ±0.039 95.8 3.646 ±0.131 101.3 3.714 ±0.031 101.9 Page 23 Table 3 0 r- s n ORAL PRENATAL ...Whitney U test (p < 0.05) Page 30 Table 8.1 ORAL PRENATAL AND POSTNATAL DEVELOPMENT STUDY OF WR23 8605 SUCCINATE IN RATS i_.- *.-. L» U...Calculated dai ly food consumption for successive period intervals. "Baseline is GD6. D-2 * I <i •— s n r-i , , ORAL PRENATAL

  17. Anti-Osteoporotic Effects of Angelica sinensis (Oliv.) Diels Extract on Ovariectomized Rats and Its Oral Toxicity in Rats

    PubMed Central

    Lim, Dong Wook; Kim, Yun Tai

    2014-01-01

    Angelica sinensis root is one of the herbs most commonly used in China; it is also often included in dietary supplements for menopause in Europe and North America. In the present study, we examined the anti-osteoporotic effects of A. sinensis extract in an ovariectomized (OVX) rat model of osteoporosis as well as toxicity of the extract after repeated oral administration. The OVX rats were treated with 17β-estradiol (10 μg/kg i.p. once daily) or A. sinensis extract (30, 100, and 300 mg/kg, p.o. once daily) for four weeks. The bone (femur) mineral density (BMD) of rats treated with the extract (300 mg/kg) was significantly higher than that of the OVX-control, reaching BMD of the estradiol group. Markers of bone turnover in osteoporosis, serum alkaline phosphatase, collagen type I C-telopeptide and osteocalcin, were significantly decreased in the extract group. The body and uterus weight and serum estradiol concentration were not affected, and no treatment-related toxicity was observed during extract administration in rats. The results obtained indicate that A. sinensis extract can prevent the OVX-induced bone loss in rats via estrogen-independent mechanism. PMID:25325255

  18. Antimicrobial decapeptide KSL-W attenuates Candida albicans virulence by modulating its effects on Toll-like receptor, human β-defensin, and cytokine expression by engineered human oral mucosa.

    PubMed

    Semlali, A; Leung, K P; Curt, S; Rouabhia, M

    2011-05-01

    We investigated the toxicity of synthetic antimicrobial decapeptide KSL-W on normal human gingival epithelial cell cultures, its effect on Candida albicans adhesion and growth, and the activation of epithelial cell innate immunity. Our results indicate that KSL-W had no toxic effect on cell adhesion or growth, suggesting its safe use with human cells. Pre-treating C. albicans with KSL-W attenuated the yeast's virulence as demonstrated by its reduced adhesion and growth on engineered human oral mucosa epithelium and the subsequent decreased expression of some innate defense molecules by targeted epithelial cells. Indeed, the expression of Toll-like receptors and human β-defensins was reduced in tissues infected with KSL-W-treated Candida. Proinflammatory cytokine secretion (IL-1β and IL-6) by the epithelial cells was also regulated by KSL-W in a manner similar to that of antifungal molecule amphotericin B. These findings therefore show that KSL-W is safe for use with human cells and is able to attenuate Candida virulence by modulating its effects on host innate immunity. This study proposes the potential application of KSL-W peptide as an alternative antifungal agent.

  19. The Role of E-Cadherin in Maintaining the Barrier Function of Corneal Epithelium after Treatment with Cultured Autologous Oral Mucosa Epithelial Cell Sheet Grafts for Limbal Stem Deficiency

    PubMed Central

    Hoft, Richard H.; Wood, Andrew; Oliva, Joan; Niihara, Hope; Makalinao, Andrew; Thropay, Jacquelyn; Pan, Derek; Tiger, Kumar; Garcia, Julio; Laporte, Amanda; French, Samuel W.; Niihara, Yutaka

    2016-01-01

    The role of E-cadherin in epithelial barrier function of cultured autologous oral mucosa epithelial cell sheet (CAOMECS) grafts was examined. CAOMECS were cultured on a temperature-responsive surface and grafted onto rabbit corneas with Limbal Stem Cell Deficiency (LSCD). E-cadherin levels were significantly higher in CAOMECS compared to normal and LSCD epithelium. Beta-catenin colocalized with E-cadherin in CAOMECS cell membranes while phosphorylated beta-catenin was significantly increased. ZO-1, occludin, and Cnx43 were also strongly expressed in CAOMECS. E-cadherin and beta-catenin localization at the cell membrane was reduced in LSCD corneas, while CAOMECS-grafted corneas showed a restoration of E-cadherin and beta-catenin expression. LSCD corneas did not show continuous staining for ZO-1 or for Cnx43, while CAOMECS-grafted corneas showed a positive expression of ZO-1 and Cnx43. Cascade Blue® hydrazide did not pass through CAOMECS. Because E-cadherin interactions are calcium-dependent, EGTA was used to chelate calcium and disrupt cell adhesion. EGTA-treated CAOMECS completely detached from cell culture surface, and E-cadherin levels were significantly decreased. In conclusion, E cadherin high expression contributed to CAOMECS tight and gap junction protein recruitment at the cell membrane, thus promoting cellular adhesion and a functional barrier to protect the ocular surface. PMID:27777792

  20. Toxicokinetics and Oral Bioavailability of Halogenated Acetic Acids Mixtures in Naive and GSTzeta-Depleted Rats

    SciTech Connect

    Saghir, Shakil A.; Schultz, Irv R.

    2005-04-01

    Pharmacokinetics of halogenated acetic acid (HAA) mixtures in native and GSTzeta depleted rats was investigated. Rats were administered orally or i.v. to Mixture-1 (monobromo- dichloro-, chlorodibromo-, tribromo- acetic acids) or Mixture-2 (bromochloro-, dibromo-, trichloro- bromodichloro- acetic acids) at a dose of 25 ?mol/kg HAA and blood samples collected up to 36 h. GSTzeta depleted rats were also orally dosed with each mixture and euthanized at 0.25, 0.5, 1, 2 and 4 h to determine tissue distribution. In Mixture-1, GSTzeta depletion only affected the pharmacokinetics of DCAA, which increased the elimination t? from 9 min to 1.3 h. After oral administration, DCAA exhibited a complex time-course plasma profile with secondary peaks appearing long after completion of the initial absorption phase. This phenomenon coincided with elevated DCA levels in the lower portion of the GI tract compared to CDBAA and TBAA. For Mixture-2, all di-HAAs were eliminated extremely rapidly from plasma in both na?ve and GSTzeta depleted animals (t? was 4-11 min in na?ve and 11-24 min in GSTzeta depleted rats), t? of BDCAA and TCAA was 3.5 and 12 h in na?ve and 2.3 and 7.5 h in GSTzeta depleted rats. The primary difference in the pharmacokinetics among HAAs when administered as mixture was the total body clearance (Clb) which was reduced compared to after individual administration. These results suggest competitive interactions between tri- and di-HAAs beyond what would be predicted from individual HAA studies. For di-HAAs, the total dose is important as clearance is dose dependent due to competition for GSTzeta. When considering HAAs dosimetry, importance should be placed on both the components of the mixture and prior exposure history to di-HAAs.

  1. Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.

    PubMed

    Fabian, E; Bordag, N; Herold, M; Kamp, H; Krennrich, G; Looser, R; Ma-Hock, L; Mellert, W; Montoya, G; Peter, E; Prokudin, A; Spitzer, M; Strauss, V; Walk, T; Zbranek, R; van Ravenzwaay, B

    2016-07-25

    The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome.

  2. Oral administration of d-galactose induces cognitive impairments and oxidative damage in rats.

    PubMed

    Budni, Josiane; Pacheco, Robson; da Silva, Sabrina; Garcez, Michelle Lima; Mina, Francielle; Bellettini-Santos, Tatiani; de Medeiros, Jesiel; Voss, Bruna Constantino; Steckert, Amanda Valnier; Valvassori, Samira da Silva; Quevedo, João

    2016-04-01

    d-Galactose (d-gal) is a reducing sugar that can be used to mimic the characteristics of aging in rodents; however, the effects of d-gal administration by oral route are not clear. Therefore, the aim of this study was to elucidate if the oral administration of d-gal induces cognitive impairments, neuronal loss, and oxidative damage, mimicking an animal model of aging. Male adult Wistar rats (4 months old) received d-gal (100mg/kg) via the oral route for a period of 1, 2, 4, 6 or 8 weeks. The results showed cognitive impairments in the open-field test in the 4th and 6th weeks after d-gal administration, as well as an impairment in spatial memory in the radial maze test after the 6th week of d-gal administration. The results indicated increase of levels of thiobarbituric acid reactive species-TBARS-and carbonyl group content in the prefrontal cortex from the 4th week, and in all weeks of d-gal administration, respectively. An increase in the levels of TBARS and carbonyl group content was observed in the hippocampus over the entire period of d-gal treatment. In the 8th week of d-gal administration, we also observed reductions in synaptophysin and TAU protein levels in the prefrontal cortex. Thus, d-gal given by oral route caused cognitive impairments which were accompanied by oxidative damage. Therefore, these results indicate that orally administered d-gal can induce the behavioral and neurochemical alterations that are observed in the natural aging process. However, oral d-gal effect in rats deserve further studies to be better described.

  3. Pharmacokinetics and therapeutic effects of oltipraz after consecutive or intermittent oral administration in rats with liver cirrhosis induced by dimethylnitrosamine.

    PubMed

    Bae, Soo K; Lee, Shin J; Kim, Taekrho; Kim, Jin W; Lee, Inchul; Kim, Sang G; Lee, Myung G

    2006-05-01

    Pharmacokinetics and therapeutic effects of oltipraz were evaluated after consecutive (once per day at 30 mg/kg/day for 7 and 14 days) or intermittent (once per week at 100 mg/kg/week for 1-3 weeks) oral administration to rats with liver cirrhosis induced by dimethylnitrosamine. The AUC of oltipraz was significantly greater in cirrhotic rats than controls (890 compared with 270 microg . min/mL) due to impaired liver function in cirrhotic rats. However, the AUC values after consecutive 7 (421 compared with 753 microg . min/mL) and 14 (309 compared with 821 microg . min/mL) days oral administration of oltipraz in cirrhotic rats were significantly smaller than those in respective vehicle-treated cirrhotic rats. Moreover, the AUC values after intermittent 2 and 3 weeks in cirrhotic rats were also significantly smaller than that in 1 week vehicle-treated cirrhotic rats (2370 and 1690 compared with 4760 microg . min/mL). This could be due to induction of CYP isozymes and considerably greater numbers of normal liver cells in cirrhotic rats by oral administration of oltipraz. Improved liver function by oltipraz in cirrhotic rats was proved by liver microscopy; livers are free of significant fibrosis, although evidence of bridging necrosis is still present in many rats.

  4. Oral antioxidant therapy for juvenile rats with kaolin-induced hydrocephalus

    PubMed Central

    2014-01-01

    Background Oxidative and nitrosylative changes have been shown to occur in conjunction with the hypoxic changes and cellular/axonal damage in hydrocephalic rodent brains. We hypothesized that antioxidant therapy would improve behavioral, neurophysiological, and/or neurobiochemical outcomes in juvenile rats following induction of hydrocephalus. Methods Three-week old rats received an injection of kaolin (aluminum silicate) into the cisterna magna. Magnetic resonance (MR) imaging was performed two weeks later to assess ventricle size and stratify rats to four treatment conditions. Rats were treated for two weeks daily with sham therapy of either oral canola oil or dextrose or experimental therapy of a low or high dose of an antioxidant mixture containing α-tocopherol, L-ascorbic acid, coenzyme Q10 (CoQ10), reduced glutathione, and reduced lipoic acid. Behavior was examined thrice weekly. Results All hydrocephalic groups lagged in weight gain in comparison to non-hydrocephalic controls, all developed significant ventriculomegaly, and all exhibited white matter destruction. Canola oil with or without the antioxidant mixture normalized antioxidant capacity in brain tissue, and the dextrose-treated rats had the greatest ventricular enlargement during the treatment period. However, there were no significant differences between the four treatment groups of hydrocephalic rats for the various behavioral tasks. Glial fibrillary acidic protein and myelin basic protein quantitation showed no differences between the treatment groups or with control rats. There was increased lipid peroxidation in the hydrocephalic rats compared to controls but no differences between treatment groups. Conclusion The antioxidant cocktail showed no therapeutic benefits for juvenile rats with kaolin-induced hydrocephalus although canola oil might have mild benefit. PMID:25324960

  5. Cardiotoxicity and hypertension in rats after oral lead exposure.

    PubMed

    Lal, B; Murthy, R C; Anand, M; Chandra, S V; Kumar, R; Tripathi, O; Srimal, R C

    1991-01-01

    The rats were exposed to lead (0.25, 0.5 and 1.0 per cent lead acetate through drinking water) for 90 days to study its effect on some physiological and morphological parameters of the cardiovascular system. Blood lead levels increased in a dose dependent manner but heart tissue showed rise at only two higher doses in exposed animals. The two higher doses of lead resulted in an increased arterial blood pressure and calcium influx in atrial trabeculae and papillary muscles. No marked pathological or histochemical changes were observed in heart tissue excepting congestion and slightly reduced activity of succinic dehydrogenase in the highest dosed group. It was concluded that lead exposure through drinking water may produce increased arterial blood pressure and minor changes in the myocardium. Whether these changes are mediated through the effect of lead on the calcium transport needs further investigation.

  6. Oral administration of squid lecithin-transphosphatidylated phosphatidylserine improves memory impairment in aged rats.

    PubMed

    Lee, Bombi; Sur, Bong-Jun; Han, Jeong-Jun; Shim, Insop; Her, Song; Lee, Yang-Seok; Lee, Hye-Jung; Hahm, Dae-Hyun

    2015-01-02

    Recently, lecithin-derived phosphatidylserine (PS), which originates from marine life, has received much attention as a viable alternative to bovine cerebral cortex PS. In this study, the use of squid phosphatidylcholine-transphosphatidylated PS (SQ-PS) was evaluated through examination of its ameliorating effects on age-associated learning and memory deficits in rats. Aged rats were orally administered SQ-PS (10, 20, or 50 mg/kg per day) once a day for seven days 30 min prior to behavioral assessment in a Morris water maze. SQ-PS administration produced significant dose-dependent improvements in escape latency for finding the platform in the Morris water maze in the aged rats even though Soy-PS administration also exhibited comparable improvements with SQ-PS. Biochemical alterations in the hippocampal cholinergic system, including changes in choline acetyltransferase and acetylcholinesterase immunoreactivity, were consistent with the behavioral results. In addition, SQ-PS treatment significantly restored age-associated decreases of choline transporter and muscarinic acetylcholine receptor type 1 mRNA expression in the hippocampus. These results demonstrate that orally administered SQ-PS dose-dependently aids in the improvement of memory deficits that occur during normal aging in rats. This suggests that SQ-PS may be a useful therapeutic agent in the treatment of diminished memory function in elderly people.

  7. Toxicokinetics of cyanide in rats, pigs and goats after oral dosing with potassium cyanide.

    PubMed

    Sousa, Altamir B; Manzano, Helena; Soto-Blanco, Benito; Górniak, Silvana L

    2003-06-01

    The aim of the present study was to determine the effect of the species on the toxicokinetics of cyanide and its main metabolite, thiocyanate. Forty-two rats, six pigs and six goats were dosed orally with 3.0 mg KCN/kg body weight, and cyanide and thiocyanate concentrations in blood were measured within 24 h. After the single oral dose, KCN was rapidly absorbed by rats and goats, with a time of peak concentration ( T(max)) of 15 min. The maximum plasma concentration ( C(max)) of cyanide was observed in goats (93.5 micro mol/l), whereas the C(max) of thiocyanate was higher in rats (58.1 micro mol/l). The elimination half-life ( t(1/2)) and volume of distribution ( Vd(area)) of both cyanide and thiocyanate were higher in goats (1.28 and 13.9 h, and 0.41 and 1.76 l/kg, respectively). Whereas the area under the curve (AUC) of cyanide was significantly higher in goats (234.6 micro mol.l/h), the AUC of thiocyanate was higher in rats (846.5 micro mol.l/h). In conclusion, the results of the present study support the hypothesis that the metabolism of cyanide and its main metabolite, thiocyanate, is species-linked, with the goat being more sensitive to the toxic effects of cyanide/thiocyanate.

  8. Oral supplementation with the rutin improves cardiovagal baroreflex sensitivity and vascular reactivity in hypertensive rats.

    PubMed

    Mendes-Junior, Leônidas das Graças; Monteiro, Matheus Morais de Oliveira; Carvalho, Alynne Dos Santos; de Queiroz, Thyago Moreira; Braga, Valdir de Andrade

    2013-11-01

    The hypothesis that oral supplementation with the flavonoid rutin improves baroreflex sensitivity and vascular reactivity in hypertensive (2-kidney-1-clip (2K1C)) rats was tested. Sixty-four rats were divided in 4 groups: sham + saline; sham + rutin; 2K1C + saline, and 2K1C + rutin. Six weeks after 2K1C surgery, the animals were treated with saline or rutin (40 mg·kg(-1)·day(-1)) by gavage for 7 days. Baroreflex sensitivity test using phenylephrine (8 μg·kg(-1), iv) and sodium nitroprusside (25 μg·kg(-1), iv), vascular reactivity, and thiobarbituric acid reactive substances assay were performed. Baroreflex sensitivity in hypertensive rats was impaired and compared with sham (-2.77 ± 0.15 vs. -1.53 ± 0.27 beats·min(-1)·mm Hg(-1); n = 8; p < 0.05). Oral supplementation with rutin restored baroreflex sensitivity in 2K1C rats (-2.40 ± 0.24 vs. -2.77 ± 0.15 beats·min(-1)·mm Hg(-1); n = 8; p > 0.05). Besides, hypertensive rats have greater contraction to phenylephrine (129.49% ± 4.46% vs. 99.50% ± 11.36%; n = 8; p < 0.05), which was restored by rutin (99.10% ± 1.77% vs. 99.50% ± 11.36%; n = 8; p > 0.05). Furthermore, vasorelaxation to acetylcholine was diminished in hypertensive rats (96.42% ± 2.80% vs. 119.35% ± 5.60%; n = 8; p < 0.05), which was also restored by rutin (117.55% ± 6.94% vs. 119.35% ± 5.60%; n = 8; p > 0.05). Finally, oxidative stress was greater in hypertensive rats (1.54 ± 0.12 vs. 0.53 ± 0.12 nmol MDA·mL(-1); n = 8; p < 0.05) and rutin supplementation significantly decreased oxidative stress in those animals (0.70 ± 0.13 vs. 1.54 ± 0.12 nmol MDA·mL(-1); n = 8; p < 0.05). We concluded that oral supplementation with rutin restores impaired baroreflex sensitivity and vascular reactivity in hypertensive rats by decreasing oxidative stress.

  9. Oral subchronic immunotoxicity study of ethyl tertiary butyl ether in the rat.

    PubMed

    Banton, Marcy I; Peachee, Vanessa L; White, Kimber L; Padgett, Eric L

    2011-01-01

    The potential for immunotoxicological effects of ethyl tertiary butyl ether (ETBE, CAS RN 637-92-3) was studied in young adult female Crl:CD(SD) rats following subchronic oral exposures. Rats were exposed by gavage once daily for 28 consecutive days to 0, 250, 500, or 1000 mg ETBE/kg body weight (BW)/day; a concurrent positive control group received four intraperitoneal injections of at 50 mg cyclophosphamide monohydrate (CPS)/kg/day on study Days 24-27. Immunotoxicity was evaluated using a splenic antibody-forming cell (AFC) assay to assess T-cell-dependent antibody responses in rats sensitized with sheep red blood cells (SRBC). All rats survived to the scheduled necropsy. There were no effects on clinical observations, body weights, feed or water consumption, or macroscopic pathology findings in the ETBE-treated rats. No ETBE-related effects were observed on absolute or relative (to final body weight) spleen or thymus weights, spleen cellularity, or on the specific (AFC/10(6) spleen cells) or total activity (AFC/spleen) of splenic IgM AFC to the T-cell-dependent antigen SRBC. CPS produced expected effects consistent with its known immunosuppressive properties and validated the appropriateness of the AFC assay. Based on the results of this study, ETBE did not suppress the humoral component of the immune system in female rats. The no-observed-effect level for immunotoxicity was the highest dosage tested at 1000 mg/kg/day.

  10. Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats

    PubMed Central

    Castrogiovanni, Daniel; Zuburía, Guillermina; Giovambattista, Andrés

    2015-01-01

    Rats neonatally treated with monosodium L-glutamate (MSG) are deeply dysfunctional in adulthood. We explored the effect of an oral low dose of metformin treatment in male MSG rats on adipoinsular axis and visceral adipose tissue (VAT) dysfunctions, in both basal (nonfasting) and endotoxemia conditions. MSG rats, treated or not treated with metformin (30 days prior to experimentation), and control litter-mates (CTR) were studied at 90 days of age. Peripheral concentrations of glucose, lipids, and hormones were determined in basal and post-lipopolysaccharide (LPS) treatment conditions. Food intake and body weight (BW) were recorded and VAT mass and leptin mRNA levels were evaluated. Data indicated that MSG rats were lighter and displayed hypercorticosteronemia, hypophagia, adipoinsular axis hyperactivity, and enhanced VAT mass associated with an increased leptin gene expression. Interestingly, metformin-treated MSG rats corrected BW catch-up and counteracted VAT (mass and leptin mRNA level) and adipoinsular axis (basal and post-LPS) dysfunctions. Thus metformin treatment in MSG rats is able to correct several VAT and metabolic-endocrine dysfunctions. Our study suggests that a low-dose metformintherapy is effective to correct, at least in part, adipoinsular axis dysfunction in hypertrophic obese phenotypes, such as that of the human Cushing syndrome. PMID:27347514

  11. Rectal mucosa in cows' milk allergy.

    PubMed Central

    Iyngkaran, N; Yadav, M; Boey, C G

    1989-01-01

    Eleven infants who were suspected clinically of having cows' milk protein sensitive enteropathy were fed with a protein hydrolysate formula for six to eight weeks, after which they had jejunal and rectal biopsies taken before and 24 hours after challenge with cows' milk protein. When challenged six infants (group 1) developed clinical symptoms and five did not (group 2). In group 1 the lesions developed in both the jejunal mucosa (four infants at 24 hours and one at three days), and the rectal mucosa, and the injury was associated with depletion of alkaline phosphatase activity. Infants in group 2 were normal. It seems that rectal injury that develops as a direct consequence of oral challenge with the protein in reactive infants may be used as one of the measurements to confirm the diagnosis of cows' milk protein sensitive enteropathy. Moreover, ingestion of such food proteins may injure the distal colonic mucosa without affecting the proximal small gut in some infants. PMID:2817945

  12. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    PubMed

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group).

  13. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    PubMed Central

    Eweka, Andrew Osayame; Eweka, Abieyuwa

    2010-01-01

    Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24), with average weight of 220g were randomly assigned into two treatments (A & B) of (n=16) and Control (c) (n=8) groups. The rats in the treatment groups (A & B) received 0.1g (500mg/kg body weight) and 0.2g (1000mg/kg body weight) of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c) received equal amount of feeds daily without nutmeg added for forty-two days. The growers’ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings. PMID:22624138

  14. Bioelement status with oral administration of fish oil methyl ester and diesel fuel in male rats.

    PubMed

    Aksoy, Laçine; Tütüncü, Hakan; Alper, Yasemin; Büyükben, Ahmet

    2012-10-01

    This paper is a study on the effects on the amounts of trace elements in case of possible repeat accidental or environmental exposure with fish oil biodiesel. For this purpose, 35 male Wistar albino rats were used in the study. Rats were divided into five groups. The first group was determined as the control group. The rats in this group were gavaged orally with 250 mg/kg sunflower oil. The rats in the second and third groups were administered by oral gavage of 250 mg/kg (D1) and 500 mg/kg (D2) diesel fuel mixed with equal amounts of sunflower oil, respectively. The rats in the fourth group were administered by oral gavage of 250 mg/kg fish oil biodiesel (F1) and the rats in the fifth group were administered by oral gavage of 500 mg/kg fish oil biodiesel (F2), both mixed with equal amounts of sunflower oil. At the end of the study, bioelement concentrations in the serum and the kidney, lung, and liver tissues were measured using inductively coupled plasma-optical emission spectroscopy. It was observed that serum Ca, Mg, and Sr concentrations were significantly (p<0.001) higher and Cu concentration was significantly (p<0.01) higher in the control group than in the biodiesel groups. Kidney Mg concentration was significantly (p<0.01) lower in the control group than in the diesel groups. Kidney Mg concentration was significantly (p<0.001) lower in the D2 group than in the F2 group. Kidney Mg concentration was significantly (p<0.01) lower in the control group than in the diesel groups. Lung Cd, Co, Cu, Cr, Na, and Zn concentrations were different significantly higher in the control group than in the other groups. Liver Al concentration was different significantly higher in the control group than in the other groups. Liver Ca concentration was significantly (p<0.05) higher in the control group than in the biodiesel groups. Serum and lung tissue bioelements concentrations were lower in diesel and biodiesel groups than in control group. Due to consumption for biochemical

  15. A comparative study of the pharmacokinetics of propranolol and its major metabolites in the rat after oral and vaginal administration.

    PubMed

    Qureshi, S A; Buttar, H S

    1989-08-01

    1. The concentrations of propranolol (PPL) and its metabolites were monitored by h.p.l.c. in serum of rats during the first 6 h after administering single doses (20 mg/kg) of PPL either orally or intravaginally (i.vg). 2. The results showed that PPL was quickly transferred to the systemic circulation from the rat vagina and the serum concentration profile as substantially altered by the route of administration. Serum concentrations of free PPL were significantly higher in i.vg-dosed animals than their oral dosed counterparts. 3. Inter-animal serum conc. variations of PPL and its metabolites in the i.vg-dosed rats were smaller than those of the orally treated females. 4. In comparison with the i.vg-dosed rats, the levels of PPL metabolites (propranolol glycol, naphthoxylactic acid, naphthoxyacetic acid) were greater by the oral route, though these differences were not statistically significant. 5. The serum elimination half-lives (t1/2)beta of PPL and its metabolites during the beta-phase were not significantly different in the two treatment groups. 6. Following i.vg application, both the AUC and the Cmax values of PPL were significantly greater than those of orally dosed females, while no statistically significant differences were found in the tmax values. 7. Comparison of the AUC values showed that relative bioavailability of PPL was approx. 36 times greater in i.vg-treated animals than those of the orally dosed rats.

  16. Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles.

    PubMed

    Warheit, D B; Brown, S C; Donner, E M

    2015-10-01

    Data generated using standardized testing protocols for toxicity studies generally provide reproducible and reliable results for establishing safe levels and formulating risk assessments. The findings of three OECD guideline-type oral toxicity studies of different duration in rats are summarized in this publication; each study evaluated different titanium dioxide (TiO2) particles of varying sizes and surface coatings. Moreover, each study finding demonstrated an absence of any TiO2 -related hazards. To briefly summarize the findings: 1) In a subchronic 90-day study (OECD TG 408), groups of young adult male and female rats were dosed with rutile-type, surface-coated pigment-grade TiO2 test particles (d50 = 145 nm - 21% nanoparticles by particle number criteria) by oral gavage for 90 days. The no-adverse-effect level (NOAEL) for both male and female rats in this study was 1000 mg/kg bw/day, the highest dose tested. The NOAEL was determined based on a lack of TiO2 particle-related adverse effects on any in-life, clinical pathology, or anatomic/microscopic pathology parameters; 2) In a 28-day repeated-dose oral toxicity study (OECD TG 407), groups of young adult male rats were administered daily doses of two rutile-type, uncoated, pigment-grade TiO2 test particles (d50 = 173 nm by number) by daily oral gavage at a dose of 24,000 mg/kg bw/day. There were no adverse effects measured during or following the end of the exposure period; and the NOAEL was determined to be 24,000 mg/kg bw/day; 3) In an acute oral toxicity study (OECD TG 425), female rats were administered a single oral exposure of surface-treated rutile/anatase nanoscale TiO2 particles (d50 = 73 nm by number) with doses up to 5000 mg/kg and evaluated over a 14-day post-exposure period. Under the conditions of this study, the oral LD50 for the test substance was >5000 mg/kg bw. In summary, the results from these three toxicity studies - each with different TiO2 particulate-types, demonstrated an absence of

  17. Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats-Correlation of HSP72 expression with mucosal protection

    SciTech Connect

    Wada, Isao; Otaka, Michiro . E-mail: otaka@med.akita-u.ac.jp; Jin, Mario; Odashima, Masaru; Komatsu, Koga; Konishi, Noriaki; Matsuhashi, Tamotsu; Horikawa, Youhei; Ohba, Reina; Itoh, Hideaki; Watanabe, Sumio

    2006-10-20

    Background and aim: The real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. Materials and methods: Expression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6 N HCl was compared between control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc L-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. Results: HSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. Conclusion: Our results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist.

  18. Orally supplemented catechin increases heme amounts and catalase activities in rat heart blood mitochondria: a comparison between middle-aged and young rats.

    PubMed

    Cueno, Marni E; Tamura, Muneaki; Imai, Kenichi; Ochiai, Kuniyasu

    2013-11-01

    Orally-administered catechin has long been known to have several beneficial effects on the mammalian host, however, the effects of orally supplemented catechin on the host through gingival tissues have not yet been established. Here, we elucidated the effects of orally supplemented catechin in the rat heart blood mitochondria. We used middle-aged (40 week-old) and young (4 week-old) rats throughout the study. We indirectly verified blood serum catechin levels by measuring O-methyl catechin derivatives using HPLC. Interestingly, we observed higher blood serum O-methyl levels in middle-aged rats as compared to young rats. Subsequently, we isolated blood mitochondria, verified its purity, and measured heme, hydrogen peroxide, and catalase (CAT) levels. We found that catechin induces an increase in blood mitochondrial heme amounts and is associated with an increase in blood mitochondrial CAT activity which is surprisingly higher in middle-aged rats as compared to young rats. This would imply that orally supplemented catechin induces heme increase that preferentially favours CAT activity and is more beneficial to the middle-aged rats.

  19. Enhanced oral bioavailability of docetaxel in rats combined with myricetin: In situ and in vivo evidences.

    PubMed

    Hao, Tianyun; Ling, Yunni; Wu, Meijuan; Shen, Yajing; Gao, Yu; Liang, Shujun; Gao, Yuan; Qian, Shuai

    2017-04-01

    The purpose of this study was to investigate the effect of myricetin on the pharmacokinetics of docetaxel in rats. In comparison to oral docetaxel alone (40mg/kg), the bioavailability of docetaxel could be significantly enhanced by 1.6-2.4-fold via oral co-administration with various flavonoids (apigenin, naringenin, baicalein, quercetin and myricetin) at a dosage of 10mg/kg, and myricetin showed the highest bioavailability improvement. Further pharmacokinetic studies demonstrated that the presence of myricetin (5-20mg/kg) enhanced both Cmax and AUC of docetaxel with the highest Cmax (162ng/mL, 2.3-fold) and relative bioavailability (244%) achieved at 10mg/kg of myricetin, while t1/2 was not influenced. In order to explore the reasons for such bioavailability enhancement of docetaxel, rat in situ single-pass intestinal perfusion model and intravenous docetaxel co-administrated with oral myricetin were carried out. After combining with myricetin, the permeability coefficient (Pblood) of docetaxel based on its appearance in mesenteric blood was significantly increased up to 3.5-fold in comparison to that of docetaxel alone. Different from oral docetaxel, the intravenous pharmacokinetics of docetaxel was not affected by co-administration of myricetin, indicating the limited effect of myricetin on the elimination of docetaxel. The above findings suggested that the oral bioavailability enhancement of docetaxel via co-administration with myricetin might be mainly attributed to the enhanced absorption in gastrointestinal tract rather than modulating the elimination of docetaxel.

  20. Investigation of the rat model for preclinical evaluation of pH-dependent oral absorption in humans.

    PubMed

    Lubach, Joseph W; Chen, Jacob Z; Hau, Jonathan; Imperio, Jose; Coraggio, Melis; Liu, Lichuan; Wong, Harvey

    2013-11-04

    Many pharmaceutically active compounds are weak electrolytes and are ionizable in the pH range experienced throughout the gastrointestinal tract. Changes in protonation state due to pH changes in the gut can have dramatic effects on solubility, dissolution, and permeation through biological barriers. Preclinical assessment of the pH-dependence of oral absorption is critical for compounds possessing pH-dependent solubility. Here we examine pH-dependent solubility and oral exposure in rat for three model compounds, dasatinib, ketoconazole, and mefenamic acid. Dasatinib and ketoconazole are both weak bases, while mefenamic acid is a carboxylic acid. The effects of gastric pH modulators, pentagastrin and famotidine, were investigated in rat PK studies to assess the applicability of using the rat to evaluate the risk of pH-dependent oral exposure for ionizable compounds. Dasatinib showed similar exposure between control and pentagastrin-pretreated groups, and 4.5-fold lower AUC in famotidine-pretreated rats. Ketoconazole showed a 2-fold increase in AUC in pentagastrin-treated rats relative to control, and 4.5-fold lower AUC in famotidine treated rats, relative to the pentagastrin group. Mefenamic acid showed highly similar exposures among control, pentagastrin-pretreated, and famotidine-pretreated groups. The rat model was shown to be useful for compounds displaying pH-dependent solubility and oral absorption that may be affected by gastric pH modulators.

  1. Relationship between host age and susceptibility to oral colonization by Actinomyces viscosus in Sprague-Dawley rats.

    PubMed

    Brecher, S M; van Houte, J

    1979-12-01

    The colonization of Actinomyces viscosus strain Ny-1R on the molar teeth of conventional and ex-germfree rats of various ages fed either a high-sucrose diet, a high-glucose diet, or laboratory chow was studied. Conventional rats directly after weaning and up to 30 days of age are less susceptible to experimental infection by strain Ny-1R than are older rats regardless of the test diet. The relationship between host age and susceptibility to infection is also demonstrable in ex-germfree rats fed a high-sucose diet. Host factors responsible for the differences in susceptibility were investigated. The results from these studies do not implicate host antibodies, host indigenous flora, or host saliva. In other studies, it was demonstrated that within the mouths of rats, strain Ny-1R preferentially colonizes in the pits and fissures of the molar teeth rather than on the dorsum of the tongue or on the vestibular mucosa. In short-term experiments, it was found that strain Ny-1R attaches to the first molars of 40-day-old conventional rats to a greater extent than it attaches to the first molars of 20-day-old rats. The differences in attachment and subsequent colonization of strain Ny-1R in 20- and 40-day-old rats may be related to the varying amounts of the reduced enamel epithelium and connective tissue present in the fissures of the molar teeth.

  2. Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats.

    PubMed

    Nagareddy, Prabhakara Reddy; Vasudevan, Harish; McNeill, John H

    2005-05-01

    Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.

  3. The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate

    PubMed Central

    Kuduban, Ozan; Mazlumoglu, Muhammed Recai; Kuduban, Selma Denktas; Erhan, Ertugrul; Cetin, Nihal; Kukula, Osman; Yarali, Oguzhan; Cimen, Ferda Keskin; Cankaya, Murat

    2016-01-01

    ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX. PMID:27812611

  4. Subchronic oral toxicity of a standardized white kidney bean (Phaseolus vulgaris) extract in rats.

    PubMed

    Chokshi, Dilip

    2007-01-01

    Dietary supplements containing "starch blockers" are believed to reduce carbohydrate-derived calories by interfering with alpha-amylase, the digestive enzyme responsible for conversion of complex carbohydrates to simple, absorbable sugars. The present paper reports the findings of a 28-day oral toxicity study in rats of Phase 2, a standardized extract derived from the common white kidney bean (Phaseolus vulgaris), which has been shown to have alpha-amylase-inhibiting activity. In order to establish safety, eighty male and female Sprague-Dawley rats (10 animals/sex/group) received Phase 2 via oral gavage at doses of 0, 625, 1250, and 2500 mg/kg (7 days/wk) for a period of 31 (males) or 32 (females) days. There were no mortalities, clinical signs, body weight or nutritional effects, gross alterations, clinical or histopathological alterations that were considered attributable to test substance administration. Under conditions of this study and based on toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) of Phase 2 was judged to be 2500 mg/kg/day in each sex for administration by oral gavage of a standardized white kidney bean extract, Phase 2 for 28 days.

  5. A subchronic 90-day oral toxicity study of Origanum vulgare essential oil in rats.

    PubMed

    Llana-Ruiz-Cabello, M; Maisanaba, S; Puerto, M; Pichardo, S; Jos, A; Moyano, R; Cameán, A M

    2017-03-01

    Oregano essential oil (Origanum vulgare L. virens) (OEO) is being used in the food industry due to its useful properties to develop new active packaging systems. In this concern, the safety assessment of this natural extract is of great interest before being commercialized. The European Food Safety Authority requests different in vivo assays to ensure the safety of food contact materials. One of these studies is a 90 days repeated-dose oral assay in rodents. In the present work, 40 male and 40 female Wistar rats were orally exposed to 50, 100 and 200 mg/kg body weight (b.w.) OEO during 90 days following the OECD guideline 408. Data revealed no mortality and no treatment-related adverse effects of the OEO in food/water consumption, body weight, haematology, biochemistry, necropsy, organ weight and histopathology. These findings suggest that the oral no-observed-adverse-effect level (NOAEL) of this OEO is 200 mg/kg b.w. in Wistar rats, the highest dose tested. In conclusion, the use of this OEO in food packaging appears to be safe based on the lack of toxicity during the subchronic study at doses 330-fold higher than those expected to be in contact consumers in the worst scenario of exposure.

  6. Effect of dolomite oral exposure in Wistar rats during organogenesis period of pregnancy.

    PubMed

    Lagarto, Alicia; Bellma, Addis; Tillán, Juana; Gabilondo, Tatiana; Guerra, Isbel; Ocanto, Zuleira; Couret, Micaela; González, Ricardo

    2008-09-01

    The potential of oral exposure to dolomite, a natural product that contains calcium and magnesium, to initiate teratogenesis was analyzed in Wistar rats. Animals received dolomite oral dosages of 500 and 1500mg/kg during the period of gestation from day 6-15 post conceptionem (p.c.). Maternal, embryo and fetal toxicity were evaluated. Dolomite exposure did not produce maternal toxicity assessed by clinical observations, body weight gain, hematology parameters and relative organs weight. Signs of embryo-fetal toxicity were not observed. Skeletal malformations and visceral variations were similar in control and dolomite-treated groups. On the other hand, slight increase was observed in fetal body weight in the dolomite-treated group. Treatment with dolomite resulted in significantly decreased incidences of unossified xiphisternum, incomplete ossification of xiphisternum and sternebrae. These effects could be caused by a beneficial influence of calcium and magnesium salts present in dolomite on ossification process. In conclusion, in this study we found that the oral exposure to rats of up to 1500mg/kg of dolomite during organogenesis did not induce significant maternal and embryo-fetal toxicity.

  7. Drug-drug interaction between voriconazole and oral hypoglycemic agents in diabetic rats

    PubMed Central

    Kumar, Boyina Hemanth; Joshi, Bheemachari; Singh, Jayasingh Chellammal Hanish; Diwan, Prakash V.

    2013-01-01

    Objective: The objective was to study the of drug-drug interaction between voriconazole and oral hypoglycemic agents in normal and alloxan induced diabetic rats. Materials and Methods: The study was designed in two phases. In the first phase, influence of glibenclamide (0.45 mg/kg, p.o.) and pioglitazone (2.7 mg/kg, p.o. once daily) on blood glucose levels in normoglycemic rats was studied and then influence of voriconazole (18 mg/kg, p.o. twice daily.) pre-treatment on the hypoglycemic activity studied. Simultaneously the influence of voriconazole treatment for seven consecutive days (per se effect) on blood glucose levels was also studied in normoglycemic rats. In the second phase of the study alloxan-induced diabetic rats were used to find out the influence of voriconazole pre-treatment on glibenclamide and pioglitazone induced hypoglycemic effect in pathophysiological condition. Blood samples were collected from retro orbital plexus at regular intervals of 0.0, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 18.0 and 24.0 h after drug treatment. All the blood samples were analyzed for plasma glucose by glucose oxidase peroxidase method (GOD/POD). Results: The therapeutic dose of voriconazole potentiates the hypoglycemic activity of glibenclamide and pioglitazone both in normoglycemic and diabetic rats respectively. Conclusion: The results indicate that the dose of oral hypoglycemic agents needs to be adjusted if co-administered with voriconazole. PMID:23716892

  8. Polyethylene glycol-polyvinyl alcohol grafted copolymer: study of the bioavailability after oral administration to rats.

    PubMed

    Heuschmid, Franziska F; Schuster, Paul; Lauer, Birthe; Fabian, Eric; Leibold, Edgar; van Ravenzwaay, Bennard

    2013-07-01

    The absorption, urinary excretion, and the biliary excretion of a single oral dose of 10 or 1000 mg/kg bw of (14)C-polyethylene glycol-polyvinyl alcohol (PEG-PVA) grafted copolymer were studied in adult male and female rats. In a balance/excretion experiment, the total excretion of ingested radioactivity was determined over a period of 168 h and residual radioactivity was detected in selected tissues and the carcass. In a biliary excretion experiment, excretion of radioactivity via the bile duct was determined over a period of 48 h after administration of the substance to cannulated rats. Most, if not all, of the radioactivity (>100%) was excreted within 48 h via the feces regardless of sex or dose. Urinary excretion was very limited: 0.45-0.50% of dose at the low dose and 0.22-0.27% of dose at the high dose. At both dose levels, residual radioactivity in the carcass and all organs and tissues after 168 h was ≤ 0.02% of dose. Biliary excretion was 0.01-0.02% of dose. Based on these findings, the bioavailability of PEG-PVA grafted copolymer was determined to be <1% demonstrating that absorption was virtually negligible following a single oral administration to male and female rats.

  9. Effects of psychological stress and fluoxetine on development of oral candidiasis in rats.

    PubMed

    Núñez, María J; Novío, Silvia; Suárez, Juan Antonio; Balboa, José; Freire-Garabal, Manuel

    2010-04-01

    Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans. Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed experiments to evaluate the effects of fluoxetine on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Stress application and treatment with drugs (placebo or fluoxetine) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, on day 15 postinoculation. Establishment of C. albicans infection was evaluated on days 2 and 15 after inoculation. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results showed that stress exacerbates C. albicans infection in the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by hyphae were found in stressed rats compared to the nonstressed ones. Treatment with fluoxetine significantly reversed these adverse effects of stress. Besides the psychopharmacological properties of fluoxetine against stress, it has consequences for Candida infection.

  10. Topical Aloe Vera (Aloe barbadensis Miller) Extract Does Not Accelerate the Oral Wound Healing in Rats.

    PubMed

    Coelho, Fernanda Hack; Salvadori, Gabriela; Rados, Pantelis Varvaki; Magnusson, Alessandra; Danilevicz, Chris Krebs; Meurer, Luise; Martins, Manoela Domingues

    2015-07-01

    The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re-epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi-quantitative analyses, was performed using the Kruskal-Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats.

  11. Pharmacokinetic alteration of baclofen by multiple oral administration of herbal medicines in rats.

    PubMed

    Kim, Tae Hwan; Park, Gi-Young; Shin, Soyoung; Kwon, Dong Rak; Seo, Won Sik; Shin, Jeong Cheol; Choi, Jin Ho; Joo, Sang Hoon; Weon, Kwon-Yeon; Min, Byung Sun; Baek, Kyung Min; Upadhyay, Mahesh; Zhao, Bing Tian; Woo, Mi Hee; Kwon, So Hee; Shin, Beom Soo

    2014-01-01

    The potential pharmacokinetic (PK) interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY) and Achyranthes bidentata radix (AB) extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW), OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg) was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS. The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed. Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42-4.10 hr, and mostly excreted into urine. The PK of baclofen was not affected by AB extract pretreatment. However, significantly lower maximum plasma concentration (C max) and longer time to reach C max (T max) were observed in OY pretreated rats without changes in the area under the curve (AUC) and the fraction excreted into urine (F urine). The absorption rate (K a ) of baclofen was significantly decreased in OY pretreated rats. These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.

  12. Urinary Trypsin Inhibitor Ameliorates Seawater Immersion-Induced Intestinal Mucosa Injury via Antioxidation, Modulation of NF-κB Activity, and Its Related Cytokines in Rats with Open Abdominal Injury

    PubMed Central

    Zhang, Xing Jian; Wang, Ya Li; Zhou, Song; Xue, Xiaojun; Liu, Qiang; Zhang, Wen Hua; Zheng, Jun

    2014-01-01

    Objective. To investigate the role of oxidative stress, NF-κB activity, and its related cytokines in the pathogenesis of seawater immersion after open abdominal injury (SI-OAI) and whether UTI treatment can attenuate SI-OAI induced IMI. Methods. Wistar rats were randomly divided into three groups: C group, S group, and U group. The rats in C group only suffered from anesthesia and surgical operation, whereas the rats in S group and U group received caudal vein injection of normal saline without/with 50,000 U/kg body weight of UTI. The activities of TNF-α, IL-6, SOD, MDA, ROS, NF-κB, and IκB-β were monitored by ELISA, biochemical methods, EMSA, and Western blot, respectively. Results. The plasma inflammatory mediators and the contents of MDA, ROS, and NF-κB in intestine as well as the pathological scores in ileal mucosa were significantly increased in rats after SI-OAI, accompanied by a reduction in SOD activities and IκB-β levels. UTI treatment significantly attenuated intestinal histopathological changes with evidence of a decrease in all of the parameters, except for upregulation of the levels of SOD and IκB-β protein. Conclusion. UTI can attenuate SI-OAI induced IMI via inhibition of NF-κB activity, subsequently inhibiting the expression of inflammatory cytokines and by combating oxidative stress. PMID:25210512

  13. Influence of PEG coating on the oral bioavailability of gold nanoparticles in rats.

    PubMed

    Alalaiwe, Ahmed; Roberts, Georgia; Carpinone, Paul; Munson, John; Roberts, Stephen

    2017-11-01

    Metallic nanoparticles can be produced in a variety of shapes, sizes, and surface chemistries, making them promising potential tools for drug delivery. Most studies to date have evaluated uptake of metallic nanoparticles from the GI tract with methods that are at best semi-quantitative. This study used the classical method of comparing blood concentration area under the curve (AUC) following intravenous and oral doses to determine the oral bioavailability of 1, 2 and 5 kDa PEG-coated 5 nm gold nanoparticles (AuNPs). Male rats were given a single intravenous dose (0.8 mg/kg) or oral (gavage) dose (8 mg/kg) of a PEG-coated AuNP, and the concentration of gold was measured in blood over time and in tissues (liver, spleen and kidney) at sacrifice. Blood concentrations following oral administration were inversely related to PEG size, and the AUC in blood was significantly greater for the 1 kDa PEG-coated AuNPs than particles coated with 2 or 5 kDa PEG. However, bioavailabilities of all of the particles were very low (< 0.1%). Concentrations in liver, spleen and kidney were similar after the intravenous doses, but kidney showed the highest concentrations after an oral dose. In addition to providing information on the bioavailability of AuNPs coated with PEG in the 1-5 kDa range, this study demonstrates the utility of applying the blood AUC approach to assess the quantitative oral bioavailability of metallic nanoparticles.

  14. Bioavailability and biodistribution of differently charged polystyrene nanoparticles upon oral exposure in rats

    NASA Astrophysics Data System (ADS)

    Walczak, Agata P.; Hendriksen, Peter J. M.; Woutersen, Ruud A.; van der Zande, Meike; Undas, Anna K.; Helsdingen, Richard; van den Berg, Hans H. J.; Rietjens, Ivonne M. C. M.; Bouwmeester, Hans

    2015-05-01

    The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral, positive and negative) using a Caco-2/HT29-MTX in vitro intestinal translocation model. The NPs translocated in a surface charge-dependent manner. The present study aimed to validate this in vitro intestinal model by an in vivo study. For this, rats were orally exposed to a single dose of these polystyrene NPs and the uptake in organs was determined. A negatively charged NP was taken up more than other NPs, with the highest amounts in kidney (37.4 µg/g tissue), heart (52.8 µg/g tissue), stomach wall (98.3 µg/g tissue) and small intestinal wall (94.4 µg/g tissue). This partly confirms our in vitro findings, where the same NPs translocated to the highest extent. The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6-12.3 %). Therefore, the integrated in vitro model cannot be used for a direct prediction of the bioavailability of orally administered NPs. However, the model can be used for prioritizing NPs before further in vivo testing for risk assessment.

  15. Investigation of coco-glucoside as a novel intestinal permeation enhancer in rat models.

    PubMed

    Aguirre, Tanira A S; Rosa, Mónica; Guterres, Sílvia S; Pohlmann, Adriana R; Coulter, Ivan; Brayden, David J

    2014-11-01

    Due to instability in the GI tract and low intestinal permeability, peptides invariably have oral bioavailabilities below 1% and this has prevented the development of oral formulations. A mild plant-derived naturalalkyl polyglycoside (APG), coco-glucoside (CG), was studied for its capacity to enable rat intestinal permeation of the paracellular sugar marker, fluorescein isothiocyanate-dextran 4000 (FD4), across isolated rat jejunal and colonic mucosae mounted in Ussing chambers, as well as the polypeptide, salmon calcitonin (sCT) following intra-intestinal instillations in rats. 0.1% (w/v) CG enabled a 2.9-fold increase in the apparent permeability coefficient (Papp) of FD4 over the basal Papp across colonic mucosae, but it was without effect in jejunal mucosae. In situ intestinal instillations revealed that although sCT was absorbed across rat colonic loops to a greater extent than jejunal, CG still improved sCT absolute bioavailability(F) from both segments. Histopathology of rat intestinal mucosae following exposure to CG indicated only minor perturbation with adequate maintenance of secretory function. High content analysis(HCA) on Caco-2 showed that acute and chronic exposure to a range of concentrations of CG did not cause sub-lethal damage at concentrations at which it was effective as an enhancer. Overall, CG increased bioavailability of sCT across rat jejunal and colonic loops without indication of tissue damage. Thus, CG has potential as a safe and effective intestinal enhancer for oral delivery of proteins and peptides.

  16. ACTIVITY AND ISOZYME CONTENT OF LACTATE DEHYDROGENASE UNDER LONG-TERM ORAL TAURINE ADMINISTRATION TO RATS.

    PubMed

    Ostapiv, R D; Humenyuk, S L; Manko, V V

    2015-01-01

    The effect of long-term oral taurine administration to rats on activity of lactate dehydrogenase (LDH), its isozyme content and activity in the whole blood, liver, thigh muscle, brain and testes tissues were studied in the present work. For this purpose male Wistar rats with body weight 190-220 g were randomly divided into three groups, they were orally administered drinking water (control group) or taurine solution 40 and 100 mg per kg of body weight ( groups I and II, respectively). The total lactate dehydrogenase activity was measured spectrophotometrically, the percentage content of isozymes was determined by electrophoresis in 7.5% poliacrylamide gel withfurther staining according to J. Garbus. It was found that the total lactate dehydrogenase activity increased in all studied tissues. In testes of animals of both groups and in brain of group I animals, the total percentage contents of isozymes that are responsible for lactate production (LDH4+LDH5) increased. In liver of animals of both groups and in whole blood of group II animals, the total percentage content of isozymes that produce pyruvate (LDH1+LDH2) increased. In thigh muscle of both groups and in brain of group II animals the balance between LDH1+LDH2 and LDH4+LDH5 content did not differ from control values, though total lactate dehydrogenase activity was significantly higher, than that in the control group. Thus, the increase in the lactate dehydrogenase activity under long-term oral taurine administration in different rat tissues was found to be tissue- and dose-dependent and was caused by the increase in the content of different isozymes. Such increase in group I animals might be explained by adaptive mechanisms to hypoxia caused by high doses of taurine. For group II animals high doses of taurine were toxic and directly affected metabolic processes in the animal bodies.

  17. Novel montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats.

    PubMed

    Kim, Dong Wuk; Kim, Young Hun; Yousaf, Abid Mehmood; Kim, Dong Shik; Kwon, Taek Kwan; Park, Jung Hee; Kim, Yong Il; Park, Jae-Hyun; Jin, Sung Giu; Kim, Kyung Soo; Cho, Kwan Hyung; Li, Dong Xun; Kim, Jong Oh; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2016-04-01

    To develop a montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats, several montelukast sodium-loaded suspensions were prepared with a suspending agent, stabilizers and anti-aggregation agents, and their stabilities were investigated by visually observing the sedimentation phenomenon and determining the concentration of the degradation product. Moreover, dissolution and pharmacokinetic studies of the optimized formulation were examined in rats compared to commercial montelukast sodium-loaded granules. Avicel RC-591 (Avicel), a suspending agent, prevented the sedimentation of these suspensions at >2.496 (w/v) per cent composition. Amongst the stabilizers tested, fumaric acid provided the lowest concentration of montelukast sulphoxide (a degradation product) in these suspensions at 40 °C, demonstrating its excellent stabilizing activity. Furthermore, as an anti-aggregation agent, glycerin gave lower amounts of degradation product than those with poloxamer 407 and Tween 80. In particular, montelukast-loaded oral suspension, an aqueous suspension containing montelukast sodium/Avicel/fumaric acid/glycerin at a concentration of 312/2496/15.6/62.4 (mg/100 ml), and the commercial granules exhibited similar dissolution profiles in 0.5% (w/v) aqueous solution of sodium lauryl sulphate. Moreover, the pharmacokinetics in rats provided by this suspension was comparable to that of the commercial granules, suggesting that they were bioequivalent. In addition, it was physically and chemically stable at 40 °C for at least 6 months. Thus, this montelukast sodium-loaded oral suspension, with bioequivalence to the commercial granules and excellent stability, could be a prospective dosage form for the treatment of asthma.

  18. Evaluation of a Nanoemulsion Formulation Strategy for Oral Bioavailability Enhancement of Danazol in Rats and Dogs

    PubMed Central

    Devalapally, Harikrishna; Silchenko, Svitlana; Zhou, Feng; McDade, Jessica; Goloverda, Galina; Owen, Albert; Hidalgo, Ismael J.

    2013-01-01

    The objective of this study was to determine whether nanoemulsion formulations constitute a viable strategy to improve the oral bioavailability of danazol, a compound whose poor aqueous solubility limits its oral bioavailability. Danazol-containing oil-in-water nanoemulsions (NE) with and without co-surfactants stearylamine (SA) and deoxycholic acid (DCA) were prepared and characterized. Nanoemulsion droplets size ranging from 238 to 344 nm and with surface charges of −24.8 mV (NE), −26.5 mV (NE-DCA), and +27.8 mV (NE-SA) were reproducibly obtained. Oral bioavailability of danazol in nanoemulsions was compared with other vehicles such as, PEG400, 1% methylcellulose in water (1% MC), Labrafil, and a Labrafil/Tween 80 (9:1) mixture, after intragastric administration to rats and after oral administration of NE-SA, a Labrafil solution, or a Danocrine® tablet to dogs. The absolute bioavailability of danazol was 0.6% (PEG400), 1.2% (1% MC), 6.0% (Labrafil), 7.5% (Labrafil/Tween80), 8.1% (NE-DCA), 14.8% (NE), and 17.4% (NE-SA) in rats, and 0.24% (Danocrine), 6.2% (Labrafil), and 58.7% (NE-SA) in dogs. Overall, danazol bioavailability in any nanoemulsion was higher than any other formulation. Danazol bioavailability from NE and NE-SA was 1.8 to 2.2-fold higher than NE-DCA nanoemulsion and could be due to significant difference in droplet size. PMID:23878097

  19. In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography

    NASA Astrophysics Data System (ADS)

    Lin, Li; Xia, Jun; Wong, Terence T. W.; Li, Lei; Wang, Lihong V.

    2015-01-01

    Using internal illumination with an optical fiber in the oral cavity, we demonstrate, for the first time, photoacoustic computed tomography (PACT) of the deep brain of rats in vivo. The experiment was performed on a full-ring-array PACT system, with the capability of providing high-speed cross-sectional imaging of the brain. Compared with external illumination through the cranial skull, internal illumination delivers more light to the base of the brain. Consequently, in vivo photoacoustic images clearly reveal deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

  20. A fourteen-day repeated dose oral toxicity study of APFO in rats.

    PubMed

    Iwai, Hiroyuki; Yamashita, Kotaro

    2006-01-01

    Ammonium perfluoroocanoate (APFO) was repeatedly administered orally to male Crj:CD(SD)IGS rats for 14 days. Doses of APFO were 0, 0.5, 5, and 50 mg/kg. Significant increases and increasing tendencies in absolute/relative weight of the liver and no change in weight of the spleen were observed in all groups. Although inductions of mitochondrion- and peroxisome-specific enzymes were increased, no decrease was seen in any hematological parameter of lipid metabolism. Red blood cell count, hemoglobin concentration, and hematocrit or these tendencies showed a significant decrease or a tendency to decrease, but no influence on lymphocyte subsets was noted. Secondary inhibition of immunocompetent cells, previously reported for mice, was not seen in this study of rats.

  1. Pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats.

    PubMed

    Kim, H J; Han, K S; Kim, Y G; Chung, Y K; Chang, M S; Lee, M G

    2000-11-01

    The purpose of this study was to investigate the causes for the differences observed in the pharmacokinetics of YJA-20379-8 in 16-week-old spontaneously hypertensive rats (SHRs). To see if the hereditary characteristics of SHRs was the cause, 20 mg/kg of the drug was intravenously infused over 15 min and 50 mg/kg of the drug was orally administered to 6-week-old SHRs and 16-week-old SHRs and their age-matched control Kyoto-Wistar (KW) rats. Also to see if the hypertensive status itself was the cause, the same doses were administered to 16-week-old deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats (DOCA-salt rats) and their age-matched control Sprague-Dawley rats. The areas under the plasma concentration-time curve from time zero to time infinity (for intravenous study) and to the last sampling time in plasma (for oral study) were significantly smaller after both intravenous and oral administration, and the total body clearances of the drug were significantly faster after intravenous administration to 6-week-old SHRs, 16-week-old SHRs, and 16-week-old DOCA-salt rats than those in their respective age-matched control rats. The above pharmacokinetic parameter changes in 16-week-old SHRs were due to both hereditary characteristic of SHRs and the hypertensive status itself.

  2. Beneficial effects of calcium oral coadministration in gentamicin-induced nephrotoxicity in rats.

    PubMed

    Stojiljkovic, Nenad; Stoiljkovic, Milan; Mihailovic, Dragan; Randjelovic, Pavle; Ilic, Sonja; Gocmanac-Ignjatovic, Marija; Veljkovic, Milica

    2012-01-01

    Frequent therapeutical use of an aminoglycoside antibiotic gentamicin (GM) is limited by its nephrotoxic effects often characterized by both morphological and functional alterations of kidney leading to acute renal failure. The aim of this study was to examine the effect of dietary calcium supplementation on GM-induced nephrotoxicity in rats. Experiments were performed on 30 adult male Wistar rats divided into three groups of 10 animals each. G-group received GM intraperitoneally at a dose of 100 mg/kg; GCa-group received the same dose of GM concomitantly with 1 g/kg calcium carbonate given orally; and C-group, serving as control, received 1 mL/day of normal saline. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural and functional changes of kidney was performed by histopathological, morphometrical, and biochemical analyses. Compared with control, G-group of rats were found to have diffusely and unequally thickened glomerular basement membrane with neutrophil cells infiltration. In addition, vacuolization of cytoplasm of proximal tubule cells with coagulation-type necrosis was observed. These GM-induced pathological lesions were significantly reduced in the rats of GCa-group. Morphometric analysis revealed statistically significant differences in the size of glomeruli (area, major and minor axes, perimeter), optical density, and roundness of glomeruli (p < 0.05) between G and GCa groups. Biochemical analysis showed significant elevation in blood urea and serum creatinine concentrations, whereas potassium concentration was lowered in G-group compared with the other groups (p < 0.01). It is concluded that oral supplementation of calcium during treatment with GM resulted in significant reduction of morphological and functional kidney alterations.

  3. Oral exposure to the organophosphorus insecticide, Monocrotophos induces intestinal dysfunction in rats.

    PubMed

    Vismaya; Rajini, P S

    2014-09-01

    There is limited experimental evidence to imply the role of organophosphorus insecticides on intestinal dysfunctions. Residues of Monocrotophos (MCP), above maximum residue limits (MRL), have been reported in fruits and vegetables from various parts of India. Hence, in this study, we investigated the potential of MCP to induce intestinal dysfunction in rats. MCP was administered orally to rats at sublethal doses (0.45, 0.9 and 1.8 mg/kgb.w/d) for 30 days. MCP at the highest dose significantly increased the unit weight of the small intestine. MCP increased the activities of intestinal brush border disaccharidases, intestinal alkaline phosphatase, glycyl-glycine dipeptidase, and Na(+)/K(+)-ATPase while it decreased cholesterol: phospholipid ratio. Histology and scanning electron microscopy of small intestine of MCP treated rats revealed disruption in terms of congestion, increased length of villi, goblet cell hyperplasia, infiltration of inflammatory cells and necrotic villi tip. Further, the intestinal transit rate was found to be increased in MCP treated rats. Collectively, our findings provide evidence that repeated oral intake of MCP has the propensity to alter small intestinal structure and functions, which might lead to intestinal dysfunctions and abnormal nutrient uptake and thereby affect the human health. Although we have employed doses, which are higher than those likely to be encountered as residues, we speculate that further studies should be performed to determine whether MCP residues in foods in the long-term will interfere with the digestive capacity of the small intestine and thus exert adverse effects on the health of human.

  4. Toxicokinetics of acrylamide in rats and humans following single oral administration of low doses

    SciTech Connect

    Kopp, Eva Katharina; Dekant, Wolfgang

    2009-03-01

    The rodent carcinogen acrylamide (AA) is formed during preparation of starch-containing foods. AA is partly metabolized to the genotoxic epoxide glycidamide (GA). After metabolic processing, the mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), rac-N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) and rac-N-acetyl-S-(1-carbamoyl-moyl-2-hydroxyethyl)-L-cysteine (iso-GAMA) are excreted with urine. In humans, AAMA can be sulfoxidized to AAMA-sulfoxide. The aim of this study was to assess potential species-differences in AA-toxicokinetics in rats and humans after single oral administration of doses similar to the daily human dietary exposure. Male Fischer 344 rats (n = 5/dose group) were administered 20 and 100 {mu}g/kg b.w. {sup 13}C{sub 3}-AA in deionized water via oral gavage. Human subjects (n = 3/gender) were orally administered 0.5 and 20 {mu}g/kg b.w. {sup 13}C{sub 3}-AA with drinking water. Urine samples were collected in intervals for 96 and 94 h, respectively. Urinary concentrations of {sup 13}C{sub 3}-AAMA, {sup 13}C{sub 3}-GAMA and {sup 13}C{sub 3}-AAMA-sulfoxide were monitored by liquid chromatography-tandem mass spectrometry. The recovered urinary metabolites accounted for 66.3% and 70.5% of the 20 and 100 {mu}g/kg b.w. doses in rats and for 71.3% and 70.0% of the 0.5 and 20 {mu}g/kg b.w. doses in humans. In rats, {sup 13}C{sub 3}-AAMA accounted for 33.6% and 38.8% of dose and 32.7% and 31.7% of dose was recovered as {sup 13}C{sub 3}-GAMA; {sup 13}C{sub 3}-AAMA-sulfoxide was not detected in rat urine. In humans, {sup 13}C{sub 3}-AAMA, {sup 13}C{sub 3}-GAMA and {sup 13}C{sub 3}-AAMA-sulfoxide accounted for 51.7% and 49.2%, 6.3% and 6.4% and 13.2% and 14.5% of the applied dose, respectively. The obtained results suggest that the extent of AA bioactivation to GA in humans is lower than in rodents.

  5. Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats

    PubMed Central

    Sun, Qiang; Kawamura, Tomohiro; Masutani, Kosuke; Peng, Ximei; Sun, Qing; Stolz, Donna B.; Pribis, John P.; Billiar, Timothy R.; Sun, Xuejun; Bermudez, Christian A.; Toyoda, Yoshiya; Nakao, Atsunori

    2012-01-01

    Aims Arterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia. Methods and results The inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H2O → Mg (OH)2 + H2). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration. Conclusion Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life. PMID:22287575

  6. Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats.

    PubMed

    Kojima, Sayuri; Yoshida, Toshinori; Sasaki, Junya; Takahashi, Naofumi; Kuwahara, Maki; Shutoh, Yasufumi; Saka, Machiko; Nakashima, Nobuaki; Kosaka, Tadashi; Harada, Takanori

    2012-01-01

    Anaemia is a significant prognostic factor in cancer patients receiving anticancer drugs such as methotrexate (MTX). This study focuses on the effects of toxicological changes on the hematopoietic systems in male and female Wistar Hannover rats when MTX is orally administered at a dose of 0, 0.05, 0.15, or 0.45 mg/(kg·day) for a period of 28 days. Both male and female rats receiving 0.45 mg/kg MTX showed a decrease in the haemoglobin concentration (Hb), haematocrit, and erythrocyte count. Female rats showed a decrease in mean corpuscular volume (MCV) and an increase in cell mean Hb (CHCM) in total erythrocytes, including the mature erythrocytes. These results indicate that MTX causes the production of small, mature erythrocytes that contain a high concentration of Hb. MTX reduced the number of peripheral reticulocytes but produced the cells with a large size and a high concentration of Hb, as demonstrated by the reticulocyte MCV and CHCM as well as the content of haemoglobin per reticulocyte (CHr). Consistent with these findings, bone marrow haematopoiesis was impaired by MTX, as there was a reduction in erythroid count in rats of both sexes. The number of cells of the myeloid lineage reduced in female rats, followed by a reduction in the total leukocyte and neutrophil counts in peripheral blood. Thrombocytopenia was detected in a small population of rats. These results indicate that MTX induces hyperchromic microcytic anaemia and pancytopenia, and the use of MCV and CHCM in mature erythrocytes and reticulocytes, along with the CHr, gives a better understanding of the development and nature of anaemia.

  7. Chronic Oral Pelargonidin Alleviates Streptozotocin-Induced Diabetic Neuropathic Hyperalgesia in Rat: Involvement of Oxidative Stress

    PubMed Central

    Mirshekar, Mohammadali; Roghani, Mehrdad; Khalili, Mohsen; Baluchnejadmojarad, Tourandokht; Arab Moazzen, Saiedeh

    2010-01-01

    Background: Diabetes mellitus in some clinical cases is accompanied with hyperalgesia. In this study, we evaluated the possible beneficial effect of chronic pelargonidin (PG) treatment on hyperalgesia in streptozotocin (STZ)-diabetic neuropathic rat. Methods: Male Wistar rats (n = 56) were divided into seven groups, i.e. control, diabetic, PG-treated control, PG (single- and multiple-dose)-treated diabetic, and sodium salicylate-treated control and diabetics. For induction of diabetes, STZ was injected i.p. at a single dose of 60 mg/kg. PG was orally administered at a dose of 10 mg/kg once and/or on alternate days for 8 weeks; 1 week after diabetes induction. After two months, hyperalgesia was assessed using standard formalin and hot tail immersion tests. Meanwhile, markers of oxidative stress in brain were measured. One-way analysis of variance was used for statistical analysis of the data. Results: Diabetic rats showed a marked chemical and thermal hyperalgesia, indicating that development of diabetic neuropathy and PG treatment (especially multiple-doses) significantly ameliorated the alteration in hyperalgesia (P<0.05-0.01) in diabetic rats as compared to untreated diabetics. PG (multiple doses) also significantly decreased diabetes-induced thiobarbituric acid reactive substances formation and non-significantly reversed elevation of nitrite level and reduction of antioxidant defensive enzyme superoxide dismutase. Conclusion: These results clearly suggest that PG prevents diabetic neuropathic hyperalgesia through attenuation of oxidative stress. PMID:20683496

  8. No carcinogenicity of ethyl tertiary-butyl ether by 2-year oral administration in rats.

    PubMed

    Suzuki, Masaaki; Yamazaki, Kazunori; Kano, Hirokazu; Aiso, Shigetoshi; Nagano, Kasuke; Fukushima, Shoji

    2012-01-01

    The carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined by oral administration using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats were given drinking water containing ETBE at doses of 0, 625, 2,500 or 10,000 ppm (w/w) for 104 weeks. No significant increase in the incidence of tumors was detected in any organ of either sex. Rat-specific non-neoplastic lesions were observed in the kidney: An increase in the severity of chronic progressive nephropathy was observed in the male and female 10,000 ppm groups, and increased incidences of urothelial hyperplasia of the pelvis and mineral deposition in the renal papilla were observed in the male 2,500 and 10,000 ppm groups. Besides these lesions, no treatment-related histopathological changes were observed in any organ or tissue in either sex. Thus, the present study demonstrated that a two year administration ETBE in the drinking water did not exert any carcinogenic effects in either male or female rats.

  9. Protective effect of oral L-arginine administration on gentamicin-induced renal failure in rats.

    PubMed

    Can, C; Sen, S; Boztok, N; Tuglular, I

    2000-03-03

    We investigated the effects of orally supplemented L-arginine, the substrate of nitric oxide (NO) and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g/l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or gentamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group developed marked renal failure, characterized by a significantly decreased creatinine clearance and increased blood creatinine, fractional excretion of sodium, fractional excretion of lithium, urine gamma glutamyl transferase, systolic blood pressure and daily urine volume when compared to controls. Renal histological analysis confirmed tubular necrosis. L-arginine administration caused normalization of these parameters, whereas L-NAME led to aggravation of the failure. Concomitant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to the rats receiving gentamicin alone. We conclude that L-arginine supplementation has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME.

  10. Pharmacokinetics of intravenous and oral DA-8159, a new erectogenic, in rats with protein-calorie malnutrition.

    PubMed

    Shim, Hyun J; Kim, Yu C; Lee, Joo H; Ahn, Byung O; Kwon, Jong W; Kim, Won B; Lee, Inchul; Lee, Myung G

    2004-12-01

    Influence of dietary protein deficiency on the pharmacokinetics of DA-8159 and one of its metabolites, DA-8164, was investigated after intravenous and oral administration of DA-8159 at a dose of 30 mg kg(-1) to male Sprague-Dawley rats allowed free access to a 23% (control) or 5% (protein-calorie malnutrition, PCM) casein diet for 4 weeks. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values of DA-8164 were significantly smaller after both intravenous (87.0 vs 162 microg min mL(-1)) and oral (144 vs 319 microg min mL(-1)) administration of DA-8159 to PCM rats. This could be due to the decrease in CYP3A1/2 (50-60%) in the rats because DA-8164 was mainly formed via CYP3A1/2 in rats. This could be supported by significantly slower in-vitro CL(int) (2.04+/-0.646 vs 3.15+/-0.693 microL min(-1) (mg protein)(-1)) for the formation of DA-8164 in hepatic microsomal fraction of PCM rats. After intravenous administration of DA-8159, the AUC values of DA-8159 were not significantly different between the two groups of rats although the AUC of DA-8164 was significantly smaller in PCM rats, and this may be due to the minor metabolic pathway of DA-8164 in rats. However, after oral administration of DA-8159, the AUC of DA-8159 was significantly greater in PCM rats (194 vs 122 microg min mL(-1)). This was not due to enhanced absorption of DA-8159 from the gastrointestinal tract in the rats but may be due to a decreased intestinal first-pass effect of DA-8159 in the rats.

  11. Gene Expression Profile of Colon Mucosa after Cytotoxic Insult in wt and Apc-Mutated Pirc Rats: Possible Relation to Resistance to Apoptosis during Carcinogenesis

    PubMed Central

    Luceri, Cristina; Lodovici, Maura; Crucitta, Stefania; Caderni, Giovanna

    2016-01-01

    Apc-mutated Pirc rats, spontaneously developing intestinal tumours, are resistant to 1,2-dimethylhydrazine- (DMH-) induced colon apoptosis. To understand this phenomenon, we analyzed the expression of genotoxic stress-related genes Mgmt, Gsta1, and Gstp1 in the colon of wt and Pirc rats in basal conditions and 24 h after DMH; plasmatic oxidant/antioxidant status was also evaluated. After DMH, Mgmt expression was increased in both genotypes but significantly only in wt rats; Gsta1 expression was significantly increased in both genotypes. Gstp1 expression did not vary after DMH but was lower in Pirc rats. Moreover, for each genotype, we studied by microarray technique whole gene expression profile after DMH. By unsupervised cluster analysis, 28 genes were differentially modulated between the two genotypes. Among them were interferon-induced genes Irf7, Oas1a, Oasl2, and Isg15 and the transcription factor Taf6l, overexpressed in DMH-treated wt rats and unchanged in Pirc rats. RT-PCR confirmed their overexpression in DMH-treated wt rats and showed a slighter variation in DMH-treated Pirc rats. Taken together, despite a blunted induction of Irf7, Oas1a, and Mgmt, defective apoptosis in Pirc rats 24 h after DMH is not mirrored by major differences in gene expression compared with wt rats. PMID:27840820

  12. Gene Expression Profile of Colon Mucosa after Cytotoxic Insult in wt and Apc-Mutated Pirc Rats: Possible Relation to Resistance to Apoptosis during Carcinogenesis.

    PubMed

    Femia, Angelo Pietro; Luceri, Cristina; Lodovici, Maura; Crucitta, Stefania; Caderni, Giovanna

    2016-01-01

    Apc-mutated Pirc rats, spontaneously developing intestinal tumours, are resistant to 1,2-dimethylhydrazine- (DMH-) induced colon apoptosis. To understand this phenomenon, we analyzed the expression of genotoxic stress-related genes Mgmt, Gsta1, and Gstp1 in the colon of wt and Pirc rats in basal conditions and 24 h after DMH; plasmatic oxidant/antioxidant status was also evaluated. After DMH, Mgmt expression was increased in both genotypes but significantly only in wt rats; Gsta1 expression was significantly increased in both genotypes. Gstp1 expression did not vary after DMH but was lower in Pirc rats. Moreover, for each genotype, we studied by microarray technique whole gene expression profile after DMH. By unsupervised cluster analysis, 28 genes were differentially modulated between the two genotypes. Among them were interferon-induced genes Irf7, Oas1a, Oasl2, and Isg15 and the transcription factor Taf6l, overexpressed in DMH-treated wt rats and unchanged in Pirc rats. RT-PCR confirmed their overexpression in DMH-treated wt rats and showed a slighter variation in DMH-treated Pirc rats. Taken together, despite a blunted induction of Irf7, Oas1a, and Mgmt, defective apoptosis in Pirc rats 24 h after DMH is not mirrored by major differences in gene expression compared with wt rats.

  13. Lack of DNA binding in the rat nasal mucosa and other tissues of the nasal toxicants roflumilast, a phosphodiesterase 4 inhibitor, and a metabolite, 4-amino-3,5-dichloropyridine, in contrast to the nasal carcinogen 2,6-dimethylaniline.

    PubMed

    Jeffrey, Alan M; Luo, Feng-Qi; Amin, Shantilal; Krzeminski, Jacek; Zech, Karl; Williams, Gary M

    2002-02-01

    The phosphodiesterase 4 inhibitor Roflumilast (B9302-107) (RF) and its metabolite 4-amino-3,5-dichloropyridine (ADCP) produced nasal toxicity in preclinical safety studies with rats. The purpose of this study was to assess the possible formation of DNA adducts, by RF and ADCP, in the nasal mucosa, liver and testes of male rats using the 32P-postlabeling assay. For comparison, rats were exposed to the DNA-reactive carcinogens 2,6-dimethylaniline (DMA), also known as 2,6-xylidine, a nasal carcinogen, and the aromatic amine carcinogens 4,4'-methylene-bis(2-chloroaniline) (MOCA), which yields monocyclic DNA adducts, and 2-acetylaminofluorene (2-AAF). In the case of RF, possible sources of DNA adducts include the parent molecule and its ADCP moiety by enzymatic N-hydroxylation and sulfation, reactions typical of carcinogenic aromatic amines. 4-Acetoxylamino-3,5-dichloropyridine (N-acetoxy-ADCP), a chemically activated derivative of ADCP, was prepared and used to modify DNA which was then used to establish the chromatographic conditions with which to reliably detect whether or not such adducts were formed metabolically from RF and ADCP. Similarly, a standard N-hydroxy-DMA was prepared, but the corresponding N-acetoxy derivative was unstable and decomposed during synthesis. Both N-hydroxy-DMA and N-acetoxy-ADCP were mutagenic in the Salmonella typhimurium Ames assay using strain TA100 without an exogenous bioactivation system, with the former being more potent. N-hydroxy-ADCP was essentially inactive in this assay. For the 32P-postlabeling assay, male Wistar rats were exposed to the test substances and carrier control compounds by intragastric instillation at the selected dose levels for 7 days. Subsequently, the nasal mucosa, liver, and testes of the rats exposed to the test or control compounds were extirpated, the DNA extracted and the samples postlabeled. The patterns of adducts formed with the test compounds were compared to those formed in N-acetoxy-ADCP- and N

  14. Formation of epichlorohydrin, a known rodent carcinogen, following oral administration of 1,3-dichloro-2-propanol in rats.

    PubMed

    Waidyanatha, Suramya; Gaudette, Norman F; Hong, Yan; Fennell, Timothy R

    2014-10-20

    The observed toxicity and carcinogenicity of 1,3-dichloro-2-propanol (DCP) in rodents is thought to be due to the formation of reactive metabolites, epichlorohydrin (ECH) and dichloroacetone (DCA). However, there is no direct evidence for the formation of these metabolites from exposure to DCP in rodents due to the challenges of measuring these reactive intermediates directly in vivo. The objective of this work was to investigate the metabolism of DCP to ECH and DCA in vivo by first developing a sensitive analytical method in a suitable biological matrix and analyzing samples from rats administered DCP. DCA reacted rapidly in vitro in rat blood, plasma, and liver homogenate, precluding its detection. Because ECH rapidly disappeared in liver homogenate, but was relatively long-lived in plasma and blood in vitro, blood was selected for analysis of this metabolite. Following a single oral dose of 50 mg/kg DCP in male or female Harlan Sprague-Dawley rats, ECH was detected in blood with a maximum concentration reached at ≤13.7 min. ECH was cleared rapidly with a half-life of ca. 33 and 48 min in males and females, respectively. Following a single oral dose of 25 mg/kg ECH in male and female rats, the elimination half-life of ECH was ca. 34 and 20 min, respectively; the oral bioavailability of ECH was low (males, 5.2%; females, 2.1%), suggesting extensive first pass metabolism of ECH following oral administration. The area under the concentration vs time curve for ECH following oral administration of DCP and intravenous administration of ECH was used to estimate the percent of the DCP dose converted to ECH in rats. On the basis of this analysis, we concluded that in male and female rats following oral administration of 50 mg/kg DCP, ≥1.26% or ≥1.78% of the administered dose was metabolized to ECH, respectively.

  15. Sex Differences in the Physiological and Behavioral Effects of Chronic Oral Methylphenidate Treatment in Rats

    PubMed Central

    Robison, Lisa S.; Michaelos, Michalis; Gandhi, Jason; Fricke, Dennis; Miao, Erick; Lam, Chiu-Yim; Mauceri, Anthony; Vitale, Melissa; Lee, Junho; Paeng, Soyeh; Komatsu, David E.; Hadjiargyrou, Michael; Thanos, Panayotis K.

    2017-01-01

    Methylphenidate (MP) is a psychostimulant prescribed for Attention Deficit Hyperactivity Disorder. Previously, we developed a dual bottle 8-h-limited-access-drinking-paradigm for oral MP treatment of rats that mimics the pharmacokinetic profile of treated patients. This study assessed sex differences in response to this treatment. Male and female Sprague Dawley rats were assigned to one of three treatment groups at 4 weeks of age (n = 12/group): Control (water), low dose (LD) MP, and high dose (HD) MP. Rats drank 4 mg/kg MP (LD) or 30 mg/kg MP (HD) during the first hour, and 10 mg/kg (LD) or 60 mg/kg MP (HD) for the remaining 7 h each day. Throughout 3 months of treatment, rats were monitored for body weight, food intake, and fluid intake; as well as tested for open field behavior, circadian activity, novel object recognition, and social interaction. Chronic MP treated rats exhibited reduced fluid intake during distinct treatment weeks to a greater extent in males, and reduced total fluid intake in males only. HD MP treatment decreased body weight in both sexes, while HD MP increased total food intake in females only, likely to offset energy deficits resulting from MP-induced hyperactivity. LD and HD MP increased locomotor activity in the open field, particularly in females and during later treatment weeks. MP dose-dependently increased activity during the dark cycle of circadian testing in females, while in males hyperactivity was only exhibited by HD rats. HD MP increased center activity to a greater extent in males, while MP increased rearing behavior in females only. MP had no effect on social behavior or novel object recognition in either sex. This study concludes that chronic oral MP treatment at clinically-relevant dosages has significant effects on food intake, body weight, open field behavior, and wake cycle activity. Particularly marked sex differences were apparent for locomotor activity, with females being significantly more sensitive to the

  16. Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in rats.

    PubMed

    Rezvani, Amir H; Cauley, Marty C; Slade, Susan; Wells, Corinne; Glick, Stanley; Rose, Jed E; Levin, Edward D

    The ibogaine derivative 18-methoxycoronaridine (18-MC) has been found to decrease self-administration of morphine, nicotine and alcohol in rats after systemic injection. However oral dosing is the preferred route clinically. The current study evaluated the effect of oral 18-MC dosing in rats on alcohol and nicotine self-administration. For the nicotine study, young adult female Sprague-Dawley rats were fitted with IV jugular infusion catheters and trained for nicotine self-administration in 45min. sessions. At weekly intervals they were administered by oral gavage doses of 18-MC (0, 10, 20 and 40mg/kg) following a repeated measures counterbalanced design twice. Acute oral 18-MC, at the 40mg/kg dosage, significantly reduced nicotine self-administration. There was a differential effect of 18-MC with rats above or below the median level of nicotine self-administration during the pretreatment baseline performance. Rats with lower baseline performance showed a significant reduction in nicotine self-administration with the 40mg/kg dosage, while those in the higher baseline group did not show a significant effect of 18-MC. In alcohol studies, the effects of the same doses of 18-MC were tested in both male and female alcohol preferring (P) rats that had free access to water and alcohol (10% v/v) 6h/day. The results show that 18-MC dose-dependently reduced alcohol intake in both male and female rats. All doses caused significant reductions in alcohol self-administration. These data reinforce previous findings that 18-MC is significantly effective in reducing alcohol intake and nicotine self-administration. The finding that 18-MC is also effective orally makes it advantageous for further development as a possible new therapy for treating alcoholism as well as smoking addiction.

  17. Histological Evaluation of Wound Healing Process after Photodynamic Therapy of Rat Oral Mucosal Ulcer

    PubMed Central

    Deyhimi, Parviz; Khademi, Heidar; Birang, Reza; Akhoondzadeh, Mohammad

    2016-01-01

    Statement of the Problem When the body defense is compromised, wounds can act as a route for entrance and colonization of microorganisms in the body. Photodynamic therapy with methylene blue is known as a promising antimicrobial modality. Purpose The present study aimed to investigate the effects of this procedure on wound healing processes. Materials and Method In this experimental study, 48 male Wistar rats were recruited. Experimental wounds were surgically made on their buccal mucosa. Based on the treatment modality, they were divided into 3 groups (n=16) of control (CG), laser (LG), photosensitizer+ laser (PLG) by methylene blue (MB). The treatment procedure in the two latter groups was done in days 1-4 and 6-9. After sacrificing on 2, 4, 7 and 14-day follow-ups, the microscopic grade of healing of the wounds was assigned on each interval according to histological grading criteria. Results A qualitative result was obtained that showed a healing progression in PLG at day 2 of follow-up. At day 4 of follow-up, no difference was seen in healing stage among the groups. However on day 7 of follow-up, samples of the LG showed a lower degree of healing compared with the other two groups. Likewise, on day 14 of follow- up, both PLG and LG showed lower degree of healing than CG. Conclusion This study qualitatively showed that MB- mediated photodynamic therapy would have an inhibitory effect on healing process after 14 days of the wound creation. PMID:26966708

  18. [Contact allergies of the oral mucosa].

    PubMed

    Pevny, I; Binzenhöfer, A

    1984-02-15

    Patch tests were performed on 132 patients suspected of allergic sensitivity to dentures. Of these, 98 reacted positively to at least one substance. While only 4 patients showed positive reactions to methyl methacrylate, 42 (31,8%) had positive tests with the catalyst benzoyl peroxide, 4 and 5 patients, respectively, were positive to 4 different inhibitors, 7 patients reacted positively to various softeners and 3 to the reducing agent hydrazine sulfate. 43 positive reactions occurred on the commercial products, of these 39,5% on the liquid monomer, 23,2% on the polymer in powder form and 37,2% on the polymer in lamellar form. Among the 132 patients, 111 positive tests on metal allergens could be observed. Cadmium-, copper- and nickel-salts accounted for one half of all reactions. The sensitivity index of cadmium was 18,2% and of copper 13,6%, which indicates a high allergen exposition. Nickel, chrome and cobalt allergies were registered in 9,9; 8,3 and 6,1% of the patients, respectively, what is only slightly below the sensitivity indices of our standard test results in Würzburg.

  19. Excretion of berberine and its metabolites in oral administration in rats.

    PubMed

    Ma, Jing-Yi; Feng, Ru; Tan, Xiang-Shan; Ma, Chao; Shou, Jia-Wen; Fu, Jie; Huang, Min; He, Chi-Yu; Chen, Shuo-Nan; Zhao, Zhen-Xiong; He, Wen-Yi; Wang, Yan; Jiang, Jian-Dong

    2013-11-01

    Berberine (BBR) has been confirmed to show extensive bioactivities for the treatments of diabetes and hypercholesterolemia in clinic. However, there are few pharmacokinetic studies to elucidate the excretions of BBR and its metabolites. Our research studied the excretions of BBR and its metabolites in rats after oral administration (200 mg/kg). Metabolites in bile, urine, and feces were detected by liquid chromatography coupled to ion trap time-of-flight mass spectrometry; meanwhile, a validated liquid chromatography coupled with tandem mass spectrometry method was developed for their quantifications. Sixteen metabolites, including 10 Phase I and six Phase II metabolites were identified and clarified after dosing in vivo. Total recovered rate of BBR was 22.83% (19.07% of prototype and 3.76% of its metabolites) with 9.2 × 10(-6) % in bile (24 h), 0.0939% in urine (48 h), and 22.74% in feces (48 h), respectively. 83% of BBR was excreted as thalifendine (M1) from bile, whereas thalifendine (M1) and berberrubine (M2) were the major metabolites occupying 78% of urine excretion. Most of BBR and its metabolites were found in feces containing 84% of prototype. In summary, we provided excretion profiles of BBR and its metabolites after oral administration in rats in vivo.

  20. Dynamic changes in the gene expression profile during rat oral carcinogenesis induced by 4-nitroquinoline 1-oxide

    PubMed Central

    GE, SHUYUN; ZHANG, JI; DU, YANZHI; HU, BIN; ZHOU, ZENGTONG; LOU, JIANING

    2016-01-01

    The typical progression of oral cancer is from hyperplastic epithelial lesions through dysplasia to invasive carcinoma. It is important to investigate malignant oral cancer progression and development in order to determine useful approaches of prevention of dysplastic lesions. The present study aimed to gain insights into the underlying molecular mechanism of oral carcinogenesis by establishing a rat model of oral carcinogenesis using 4-nitroquino-line 1-oxide. Subsequently, transcription profile analysis using an integrating microarray was performed. The dynamic gene expression changes of the six stages of rat oral carcinogenesis (normal, mild epithelial dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ and oral squamous cell carcinomas) were analyzed using component plane presentations (CPP)-self-organizing map (SOM). Six genes were verified by quantitative polymerase chain reaction, immunohistochemistry and succinate dehydrogenase (SDH) activity assay kit. Numerous differentially expressed genes (DEGs) were identified during rat oral carcinogenesis. CPP-SOM determined that these DEGs were primarily enriched during cell cycle, apoptosis, inflammatory response and tricarboxylic acid cycle, indicating the coordinated regulation of molecular networks. In addition, the expression of specific DEGs, such as janus kinase 3, cyclin-dependent kinase A-1, B-cell chronic lymphocytic leukaemia/lymphoma 2-like 2, nuclear factor-κB, tumor necrosis factor receptor superfamily member 1A, cyclin D1 and SDH were identified to have high concordance with the results from microarray data. The current study demonstrated that oral carcinogenesis is a multi-step and multi-gene process, with a distinct pattern alteration along a continuum of malignant transformation. In addition, this comprehensive investigation provided a theoretical basis for the understanding of the molecular alterations associated with oral carcinogenesis. PMID:26860129

  1. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats.

    PubMed

    Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

    2014-06-01

    Introducción: El kéfir es obtenido por fermentación de la leche con una población microbiana compleja presente en sus granos. Al consumo de kéfir se le atribuyen múltiples efectos beneficiosos sobre la salud. Objetivo: Evaluar la toxicidad subcrónica del kéfir en ratas Wistar, administrado por vía oral en dosis normal (normodosis) y sobredosis. Se evaluaron además, los parámetros de peso corporal, hematología, química sanguínea, translocación bacteriana e integridad de la mucosa intestinal. Métodos: Se conformaron tres grupos de seis animales de manera aleatoria: grupo control, recibió 0,7 mL de agua; grupo kéfir recibió 0,7 mL/día de kéfir (normodosis) y grupo Hkéfir recibió 3,5 mL/día de kéfir (dosis cinco veces superior). La administración se llevó a cabo mediante sonda. Los animales se alojaron individualmente, y se mantuvieron bajo las mismas condiciones de manejo y alimentación durante 4 semanas. Resultados: La administración de kéfir en dosis normal y sobredosis no afectó los parámetros evaluados en los animales, el peso corporal, indicadores hematológicos, de química sanguínea, y la patogenicidad potencial en los tejidos se encontraron dentro de límites normales, lo que demostró que el consumo de kéfir en dosis normal y sobredosis es seguro. Además, se evidenció que la administración de normodosis de kéfir redujo los niveles de colesterol y mejoró la mucosa intestinal de las ratas. Conclusión: Se demostró que el consumo de kéfir es seguro. Destacar que, la administración de sobredosis no evidenció daños, no obstante, se recomienda el consumo de normodosis, debido a los marcados efectos beneficiosos y de seguridad.

  2. Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration

    SciTech Connect

    Voelkel, Wolfgang; Colnot, Thomas; Schauer, Ute M.D.; Broschard, Thomas H.; Dekant, Wolfgang . E-mail: dekant@toxi.uni-wuerzburg.de

    2006-10-15

    3-(4-Methylbenzylidene)camphor (4-MBC) is an UV-filter frequently used in sunscreens and cosmetics. Equivocal findings in some screening tests for hormonal activity initiated a discussion on a possible weak estrogenicity of 4-MBC. In this study, the toxicokinetics and biotransformation of 4-MBC were characterized in rats after oral administration. Male and female Sprague-Dawley rats (n = 3 per group) were administered single oral doses of 25 or 250 mg/kg bw of 4-MBC in corn oil. Metabolites formed were characterized and the kinetics of elimination for 4-MBC and its metabolites from blood and with urine were determined. Metabolites of 4-MBC were characterized by {sup 1}H NMR and LC-MS/MS as 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. After oral administration of 4-MBC, only very low concentrations of 4-MBC were present in blood and the peak concentrations of 3-(4-carboxybenzylidene)camphor were approximately 500-fold above those of 4-MBC; blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection. Blood concentration of 4-MBC and 3-(4-carboxybenzylidene)camphor peaked within 10 h after 4-MBC administration and then decreased with half-lives of approximately 15 h. No major differences in peak blood levels between male and female rats were seen. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine. However, urinary excretion of 4-MBC-metabolites represents only a minor pathway of elimination for 4-MBC, since most of the applied dose was recovered in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor

  3. Effects of cysteine on the pharmacokinetics and pharmacodynamics of intravenous and oral azosemide in rats with protein-calorie malnutrition.

    PubMed

    Kim, Y G; Cho, M K; Kwon, J W; Kim, S G; Kim, S H; Lee, M G

    2001-04-13

    The effects of cysteine on the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous (10 mg/kg) and oral (20 mg/kg) administration to male Sprague-Dawley rats fed on 23% protein diet (control rats), and 5% protein diet with (rats with PCMC) or without (rats with PCM) oral cysteine (250 mg/kg, twice daily for the fourth week) for 4 weeks. After intravenous administration to rats with PCMC, some pharmacokinetic parameters restored fully or more than the level of control rats; the time-averaged nonrenal clearance (2.70 versus 2.32 ml/min/kg) and apparent volume of distribution at steady state (160 versus 189 ml/kg) were comparable to those in control rats, however, the terminal half-life (34.7 versus 57.2 min) and mean residence time (73.3 versus 99.3 min) were significantly shorter, area under the plasma concentration-time curve from time zero to time infinity (AUC, 1930 versus 2680 microg min/ml) was significantly smaller, and time-averaged renal (2.24 versus 1.21 ml/min/kg) and total body (CL, 4.98 versus 3.65 ml/min/kg) clearances were significantly faster than those in control rats. This could be mainly due to significantly faster renal clearance and at least partly due to increased cytochrome P450 1A2 activity by cysteine supplementation. After intravenous administration to rats with PCMC, the total amount of 8-hr urinary excretion of unchanged azosemide was significantly greater (457 versus 305 microg/g body weight), however, the 8-hr urine output (15.3 versus 31.1 ml/g kidney) was not significantly different between control rats and rats with PCMC. This could be due to the fact that urine output seemed to reach an upper plateau from 10 mg/kg dose of azosemide in rats.

  4. The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats.

    PubMed

    Abraham, Premila; Isaac, Bina

    2011-07-01

    Nephrotoxicity is one of the adverse side effects of cyclophosphamide (CP) chemotherapy. In a recent study, we have demonstrated that oxidative stress and glutathione depletion play important roles in CP-induced renal damage. The aim of the study was to verify whether glutamine, the precursor for glutathione synthesis, prevents CP-induced oxidative stress and renal damage using a rat model. Adult male rats were administered a single dose of 150 mg/ kg body weight of CP intraperitoneally. The glutamine-pretreated rats were administered 1 gm/kg body weight of glutamine orally 2 h before the administration of CP. Vehicle/glutamine-treated rats served as controls. All the rats were killed 16 h after the dose of CP/vehicle. The kidneys were removed and used for light microscopic and biochemical studies. The markers of oxidative stress including malondialdehyde content, protein carbonyl content, protein thiol, reduced glutathione and myeloperoxidase activity, a marker of neutrophil infiltration, were measured in kidney homogenates. CP treatment-induced damage to kidney involved the glomeruli and the tubules. Pretreatment with glutamine reduced CP-induced glutathione depletion and increased myeloperoxidase activity. However, it did not prevent CP-induced lipid peroxidation, protein carbonylation and renal damage. The results of the present study suggest that glutamine pretreatment does not prevent CP-induced lipid peroxidation and renal damage, although it prevents CP-induced glutathione depletion and neutrophil infiltration significantly. It is suggested that mechanisms other than oxidative stress may also be involved and/or oxidative stress may be consequence and not the cause of CP induced renal damage.

  5. Oral administration of skin gelatin isolated from Chum salmon (Oncorhynchus keta) enhances wound healing in diabetic rats.

    PubMed

    Zhang, Zhaofeng; Zhao, Ming; Wang, Junbo; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2011-01-01

    Care for diabetic wounds remains a significant clinical problem. The present study was aimed at investigating the effect of skin gelatin from Chum Salmon on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 48 rats, of which 32 were diabetes. The diabetic rats were orally treated daily for 14 days with skin gelatin from Chum Salmon (2 g/kg) or its vehicle. Sixteen non-diabetic control rats received the same amount of water as vehicle-treated non-diabetic rats. Rats were killed to assess the rate of wound closure, microvessel density (MVD), vascular endothelial growth factor (VEGF), hydroxyproline (HP) contents in wound tissues and nitrate in plasma and wound tissue at 7 and 14 days after wounding. Skin gelatin-treated diabetic rats showed a better wound closure, increased MVD, VEGF, hydroxyproline and NO contents and a reduced extent of inflammatory response. All parameters were significant (P < 0.05) in comparison to vehicle-treated diabetic group. In light of our finding that skin gelatin of Chum Salmon promotes skin wound repair in diabetic rats, we propose that oral administration of Chum Salmon skin gelatin might be a beneficial method for treating wound disorders associated with diabetes.

  6. Impact of 30-Day Oral Dosing With N-Acetyl-L-Cysteine on Sprague-Dawley Rat Physiology

    DTIC Science & Technology

    2004-07-01

    A number of studies have demonstrated a protective effect associated with N- acetyl -L- cysteine ( NAC ) against toxic chemical exposure. However, the...impact of long-term oral dosing on tssue pathology has not been determined. In this study, we assessed the impact of long-term oral NAC administration on...SD rats (10 male, 10 female), 8 weeks of age, were dosed daily by oral gavage with deionized H2O (negative controls) or NAC solution at a rate of 600

  7. Oral propylparaben administration to juvenile male Wistar rats did not induce toxicity in reproductive organs.

    PubMed

    Gazin, Vincent; Marsden, Edward; Marguerite, Fabien

    2013-12-01

    Parabens are in widespread use as preservatives in drugs. In the late 1990 s, concerns were raised about their capacity to disrupt endocrine function based on in vitro data and in vivo uterotrophic tests. Studies in juvenile male rats provided conflicting results on pospubertal sperm production. In an exploratory pharmacokinetic study, Wistar male rats received a single dose of propylparaben (PP) at 3, 10, 100, or 1000 mg/kg, orally on postnatal day (PND) 31. Plasma PP concentrations were quantifiable up 8h after dosing with a mean T max value of 15 min. Distribution was 4.8 l/kg, the plasma elimination half-life was 47 min, and clearance was 4.20 (l/h)/kg at 10mg/kg. A sulfoconjugated metabolite was detected. In the juvenile toxicology study, PP was orally administered by gavage to 20 Wistar male rats at doses of 3, 10, 100, or 1000 mg/kg/day in 1% hydroxyethylcellulose for 8 weeks starting on PND21. A first subgroup of 10 males/dose was necropsied immediately after the 8-week exposure period; a second subgroup of 10 males/dose was necropsied after a 26-week washout period. Blood samples were taken from additional satellite animals after dosing on PND21 and PND77 for toxicokinetic analysis. There was no evidence of an effect of PP on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels, or histopathology. The dose of 1000 mg/kg/day was the no-observed adverse effect level, corresponding to a maximum plasma concentration of 12,030 ng/ml and exposure to 47 760 ng · h/ml (AUC0-8 h) at the end of the treatment.

  8. Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse.

    PubMed

    Bhhatarai, Barun; Gramatica, Paola

    2011-05-01

    Quantitative structure-activity relationship (QSAR) analyses were performed using the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD(50) oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC(50) rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted.

  9. Protective effect of Eruca sativa seed oil against oral nicotine induced testicular damage in rats.

    PubMed

    Abd El-Aziz, Gamal Said; El-Fark, Magdy Omar; Hamdy, Raid Mahmoud

    2016-08-01

    Nicotine is a pharmacologically active component of the tobacco that adversely affects the male reproductive system and fertility. Nicotine administration in experimental animals was found to affect spermatogenesis, epididymal sperm count, motility and the fertilizing potential of sperms. The goal of this work is to assess the protective or ameliorative effect of Eruca Sativa seed oil against testicular damage induced by oral administration of nicotine in rats. Male adult Sprague-Dawley rats were used and divided into three groups; control, nicotine treated and nicotine and Eruca seed oil treated groups. After three weeks of treatment, the rats were weighed and sacrificed where testes were removed and weighed then calculating relative testis weights. The testes were processed for routine paraffin embedding and staining and the sections were examined for different morphometric and histopathological changes. The results show that nicotine administration had an effect on the body and testis weight and various morphometric parameters of the testis. It also induced varying degrees of structural damage to the seminiferous tubules, with shrinkage and absence of mature spermatids. Disorganized, vacuolization and loss of germinal cells were noticed in the basement membrane. The co-administration of Eruca Sativa seed oil led to improvement in the morphometric and histopathological changes of the seminiferous tubules. In conclusion, Eruca Sativa seed oil treatment in this study had a protective role by reversing, almost completely, all morphometric and histological changes in the testis induced by nicotine administration.

  10. Oral administration of grape seed polyphenol extract restores memory deficits in chronic cerebral hypoperfusion rats.

    PubMed

    Chen, Chen; Zheng, Yake; Wu, Tianwen; Wu, Chuanjie; Cheng, Xuan

    2017-04-01

    Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer's disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated. Here, CCH-related memory impairment was modeled in rats using permanent bilateral occlusion of the common carotid artery. A Morris water maze task was used to evaluate memory, the levels of acetylcholinesterase, choline acetyltransferase, acetylcholine were used to evaluate cholinergic function, and oxidative stress was assessed by measuring the enzyme activity of superoxide dismutase, glutathione peroxidase, malonic dialdehyde, and catalase. We found that oral administration of GSPE for 1 month can rescue memory deficits. We also found that GSPE restores cholinergic neuronal function and represses oxidative damage in the hippocampus of CCH rats. We propose that GSPE protects memory in CCH rats by reducing ischemia-induced oxidative stress and cholinergic dysfunction. These findings provide a novel application of GSPE in CCH-related memory impairments.

  11. [Research on bioactive ingredients in rat liver after oral administration of different combinations of Wuji pill].

    PubMed

    Zhang, Rui-Jie; Chen, Ying; Gong, Zi-Peng; Dong, Yu; Zhang, Hai-Xian; Yang, Qing; Weng, Xiao-Gang; Li, Yu-Jie; Zhu, Xiao-Xin

    2014-05-01

    A L9 (3(4)) orthogonal design table to be used to get nine combinations of extraction of three herbs of Wuji pill: Coptis chinensis, Tetradium ruticarpum and Paeonia lactiflora Pall., and nine extraction of single herbs correspondingly, altogether eighteen combinations. Quantification of five representative bioactive ingredients: berberine, palmatine, evodiamine, rutaecarpine, paeoniflorin in rat liver by ultra high liquid chromatography-tandem mass spectrometry after oral administration at 2 h time point of eighteen combinations. The result shows the bioactive ingredients have different concentrations betweem different combinations and the single herb with the same dosage significantly as well as the same dose combinations. C. chinensis with evodiamine concentration of low and high dose T. ruticarpum was positively correlated. T. ruticarpum with berberine concentration of low dose C. chinensis was negatively correlated and of meddle dose C. chinensis was correlated positively. T. ruticarpum with paeoniflorin concentration of middle dose P. lactiflora was correlated positively. P. lactiflora with palmatine concentration of middle dose C. chinensis was negatively correlated and with evodiamine and rutaecarpine concentration of middle dose T. ruticarpum was negatively correlated. These shows the three single herbs interactions resulted in the differences of each ingredients concentration in rat liver. The orthogonal analysis indicates the combination 12: 6: 6 make the maximum concentration in rat liver.

  12. Short-term oral toxicity study of FAVOR PAC in rats<