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Sample records for mucosal perfusion experimental

  1. Maintenance of superior mesenteric arterial perfusion prevents increased intestinal mucosal permeability in endotoxic pigs

    SciTech Connect

    Fink, M.P.; Kaups, K.L.; Wang, H.L.; Rothschild, H.R. )

    1991-08-01

    Lipopolysaccharide increases intestinal mucosal permeability to hydrophilic compounds such as chromium 51-labeled edetate (51Cr-EDTA). The authors sought to determine whether this phenomenon is partly mediated by lipopolysaccharide-induced mesenteric hypoperfusion. They assessed permeability in an isolated segment of ileum by measuring plasma-to-lumen clearances (C) for two probes, 51Cr-EDTA and urea, and expressing the results as a ratio (CEDTA/CUREA). In control pigs (n = 6) resuscitated with Ringer's lactate (RL), mucosal permeability was unchanged during the 210-minute period of observation. In pigs (n = 7) infused with lipopolysaccharide (50 micrograms/kg) and similarly resuscitated with RL, mesenteric perfusion (Qsma) decreased significantly and permeability increased progressively and significantly. When endotoxic pigs (n = 6) were resuscitated with a regimen (RL plus hetastarch plus dobutamine) that preserved normal Qsma, lipopolysaccharide-induced mucosal hyperpermeability was prevented. Resuscitation of endotoxic pigs (n = 6) with RL plus hetastarch provided intermediate protection against both mesenteric hypoperfusion and increased permeability. These data suggest that diminished Qsma contributes to impaired ileal mucosal barrier function in experimental endotoxicosis.

  2. 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.

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

    PubMed Central

    2014-01-01

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

  4. Mucosal vaccines

    PubMed Central

    Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis CS; Badoual, Cecile; Tartour, Eric

    2014-01-01

    The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites. PMID:25424921

  5. Mechanisms for inducing nasal mucosal tolerance in experimental autoimmune uveoretinitis.

    PubMed

    Calder, Claudia J; Nicholson, Lindsay B; Dick, Andrew D

    2006-02-01

    Delivering soluble (auto) antigenic peptides via the naso-respiratory route induces tolerance to that peptide and suppression of experimental models of autoimmune disease. In the normal lung, respiratory tract dendritic cells (RTDCs) efficiently endocytose soluble antigens, migrate to regional lymph nodes and present peptide to T cells that subsequently become tolerant. This article describes protocols for inducing tolerance via the naso-respiratory tract in experimental autoimmune uveoretinitis (EAU); for the isolation of RTDCs to facilitate definition of, and conditions for, maturation and activation of cells; and to test RTDC ability to induce tolerance in murine EAU when adoptively transferred.

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

    PubMed

    Gaze, Soraya; McSorley, Henry J; Daveson, James; Jones, Di; Bethony, Jeffrey M; Oliveira, Luciana M; Speare, Richard; McCarthy, James S; Engwerda, Christian R; Croese, John; Loukas, Alex

    2012-02-01

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

  7. Experimental intraocular malignancy: the effect of intracameral perfusion.

    PubMed Central

    Wong, V G; Green, W R; Liu, Y P; Marsden, E R

    1979-01-01

    Transplantable Brown-Pearce carcinoma was adapted successfully in the rabbit anterior chamber. Regression of tumor growth was attained on tri-weekly perfusion of the AC with 10 micromolar of methotrexate. Tumor cyclic nucleotide phosphodiesterase (PDE) and protein activator were found to be markedly depressed during the course of chemotherapy and the PDE cAMP/cGMP ratio was similarly altered. Corroborative light and electron-microscopic studies showed specific alterations of intracellular organelles in relation to MTX and tumor cell death. These findings suggest that metabolic pathways of cyclic nucleotides are important biochemical modulators of neoplastic cells. The method of intraocular perfusion precludes systemic toxic effects and avoids compromising the animals' immunocompetence. Images FIGURE 3 A FIGURE 3 B FIGURE 4 A FIGURE 4 B PMID:232585

  8. Characterization of renal parenchymal perfusion during experimental infrarenal aortic clamping and declamping with enhanced thermodiffusion electrodes.

    PubMed

    Kraus, T; Mehrabi, A; Angelescu, M; Golling, M; Allenberg, J R; Klar, E

    2001-07-01

    Despite multiple previous experimental and clinical investigations, it has not been fully clarified until now whether infrarenal aortic cross-clamping (IRAC) induces a significant disturbance of renal parenchymal perfusion. Most renal cortical flow data collected thus far have been heterogenous because of inherent limitations of available measurement technology. The enhanced thermal diffusion (TD) electrode is a newly developed and previously validated prototype device that allows continuous quantification of parenchymal kidney perfusion after local probe implantation. We monitored renal perfusion during experimental IRAC with TD for the first time, thereby also evaluating the potential applicability of the method in clinical aortic surgery. IRAC (20 min) followed by sudden declamping was performed in pigs under general anesthesia (n = 14). Renal cortical blood flow (RCBF) was continuously quantified by TD, total aortic flow (TABF) and renal artery flow (RABF) were measured by ultrasonic flow probes, and parameters of systemic circulation were determined by Swan-Ganz catheter. Our results showed that kidney perfusion can be continuously quantified using TD electrodes during experimental aortic surgery in a porcine model. IRAC does not lead to a significant impairment of RCBF in young pigs as measured by TD. Renal perfusion appears to be predominantly pressure driven. Consequently, abrubt aortic declamping can bring about prolonged renal ischemia. Transfer of the TD method to RCBF monitoring during clinical aortic surgery appears to be feasible and should be investigated in selected cases.

  9. New methods for monitoring dynamic airway tissue oxygenation and perfusion in experimental and clinical transplantation.

    PubMed

    Khan, Mohammad A; Dhillon, Gundeep; Jiang, Xinguo; Lin, Yu-Chun; Nicolls, Mark R

    2012-11-15

    A dual circulation, supplied by bronchial and pulmonary artery-derived vessels, normally perfuses the airways from the trachea to the terminal bronchioles. This vascular system has been highly conserved through mammalian evolution and is disrupted at the time of lung transplantation. In most transplant centers, this circulation is not restored. The Papworth Hospital Autopsy study has revealed that an additional attrition of periairway vessels is associated with the development of chronic rejection, otherwise known as the bronchiolitis obliterans syndrome (BOS). Experimental studies subsequently demonstrated that airway vessels are subject to alloimmune injury and that the loss of a functional microvascular system identifies allografts that cannot be rescued with immunosuppressive therapy. Therefore, surgical and medical strategies, which preserve the functionality of the existent vasculature in lung transplant patients, may conceivably limit the incidence of BOS. Given these unique anatomic and physiological considerations, there is an emerging rationale to better understand the perfusion and oxygenation status of airways in transplanted lungs. This article describes novel methodologies, some newly developed by our group, for assessing airway tissue oxygenation and perfusion in experimental and clinical transplantation.

  10. Evaluation of subcutaneous versus mucosal (intranasal) allergen-specific rush immunotherapy in experimental feline asthma.

    PubMed

    Lee-Fowler, Tekla M; Cohn, Leah A; DeClue, Amy E; Spinka, Christine M; Reinero, Carol R

    2009-05-15

    Rush immunotherapy (RIT) is effective for the treatment of experimental feline allergic asthma. In humans, the safety profile of immunotherapy is improved by delivering allergen by a mucosal route. We hypothesized that mucosal (intranasal) RIT would have similar efficacy to subcutaneous RIT with improved safety. Twelve cats sensitized and challenged with Bermuda grass allergen (BGA) were randomized to receive subcutaneous (SC) or intranasal (IN) RIT. Increasing doses of BGA (20-200 microg) were administered over 24h followed by 200 microg BGA weekly as maintenance. Adverse reactions were recorded. Clinical respiratory scores after BGA aerosol challenge, bronchoalveolar lavage fluid (BALF) % eosinophils, and cytokine concentrations were measured before RIT (day 1) and at months 1, 3 and 6 (M1, M3, M6). More adverse events were recorded with SC RIT (n=12) compared with IN RIT (n=6). Respiratory scores were lower by M6 compared with D1 in both the groups. The % BALF eosinophils declined significantly after RIT for both groups (mean+/-SEM, SC RIT D1 62+/-12, M6 9+/-4; IN RIT D1 54+/-9, M6 14+/-6). The BALF IL-4:IFN-gamma ratio significantly decreased over time in the IN RIT group (mean+/-SEM, D1 2.4+/-0.2, M6 1.0+/-0.2). While both protocols decreased eosinophilic airway inflammation, the SC RIT protocol did not cause life-threatening adverse events and demonstrated more consistent resolution of clinical signs after allergen challenge. Either protocol could be considered for the treatment of feline allergic asthma.

  11. Oral mucosal desquamation caused by two toothpaste detergents in an experimental model.

    PubMed

    Herlofson, B B; Barkvoll, P

    1996-02-01

    Sodium lauryl sulfate (SLS), the most widely used detergent in toothpastes, has been reported to cause adverse effects on oral soft tissues. This double-blind cross-over study describes the oral mucosal effects of SLS-containing toothpastes and pastes containing a zwitterionic detergent, cocoamidopropyl-betaine (CAPB) in an experimental model in 28 healthy females. Seven toothpastes, differing only in detergent concentration and/or type, were used: SLS (0.5, 1.0, 1.5%), CAPB (0.64, 1.27, 1.90%) and a placebo. Each participant applied 1 cm of assigned test toothpaste via a cap splint to the teeth and the mucosa of the upper jaw. The splints were used twice daily for 2 min during a period of 4 d, after which the participants were examined for oral desquamation. No other oral hygiene was allowed during the test periods. Ten days brushing with a detergent-free toothpaste was performed between each test period. Forty-five desquamative reactions were observed in 21 of 27 subjects (one was excluded) during the trial. Forty-two reactions were recorded during the SLS periods and the remaining three during the CAPB periods. The detergent-free toothpaste did not result in oral desquamation. SLS in toothpastes significantly increased the incidence of desquamation of the oral mucosa compared with toothpastes containing the detergent CAPB. The model used is not directly relevant to normal toothbrushing with toothpaste, but indicates that sensitive patients may contract mucosal irritation through SLS in toothpastes. Less toxic detergents, e.g. CAPB, are desirable in oral hygiene products.

  12. Isolated Liver Perfusion Using Percutaneous Methods:[ql An Experimental Study in the Pig

    SciTech Connect

    Harnek, Jan; Cwikiel, Wojciech; Bergqvist, Lennart; Persson, Bo; Stridbeck, Hans

    1996-11-15

    Purpose: To develop a method for isolated perfusion of the liver using radiological methods. Methods: Twenty-one pigs, weighing about 20 kg, were divided into three groups. By transjugular and transfemoral approaches two occlusion balloons were placed in the inferior vena cava cranial and caudal, respectively, to the origin of the hepatic veins. One occlusion balloon was placed transfemorally in the common hepatic artery. Another occlusion balloon was inserted in the main branch of the portal vein via the transjugular-transhepatic approach in 11 pigs (groups 1 and 2), and in 10 pigs (group 3) by a percutaneous transhepatic route. After inflation of the balloons, patency of the isolated liver circulation was evaluated by recirculation of {sup 99}Tc{sup m}-labelled human albumin during 30 min. Blood tests were obtained after 1, 3, 5, 10, 15, and 30 min to evaluate leakage from the liver to the systemic circulation. Results: Increasing leakage to the systemic circulation from the isolated liver circulation was observed in groups 1 and 2. In the third group the leakage was less than 10%. Conclusion: In an experimental animal model, isolated perfusion of the liver with minor leakage to the systemic circulation may be achieved using radiological methods.

  13. Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation.

    PubMed

    Lofthouse, E M; Perazzolo, S; Brooks, S; Crocker, I P; Glazier, J D; Johnstone, E D; Panitchob, N; Sibley, C P; Widdows, K L; Sengers, B G; Lewis, R M

    2016-02-01

    Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [(14)C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [(14)C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [(14)C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [(14)C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [(14)C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer.

  14. Cytoprotective drugs in the prevention of ethanol-induced experimental gastric mucosal damage: a morphological study.

    PubMed

    Gaudio, E; Carpino, F; Petrozza, V; Bianchi, G; Alberico, P; Melis, M; Carlei, F; Lygidakis, N J

    1993-04-01

    Various so-called "cytoprotective" agents (sucralfate, carbenoxolone, 16,16-dimethyl-PGE2, sulglycotide and Maalox TC) have been tested on rats, with the aim of quantifying their capability to prevent ethanol-induced gastric mucosal damage. Rats fasted for 48 hours received 1 ml of 80% ethanol by oral gavage, after prior oral treatment with placebo or one of the above-mentioned drugs u.i.d. for 5 consecutive days. Six hours after ethanol administration, the animals were sacrificed and the stomach was removed and processed for computerized macroscopic assessment of the damaged surface and for structural (light microscopy) and ultrastructural (scanning and transmission electron microscopy) studies. The results obtained demonstrate that ethanol injury caused extensive mucosal necrosis of the glandular region of the stomach, an event that was effectively reduced in rats treated with 16,16-dm-PGE2, carbenoxolone or sulglycotide. These drugs appeared to preserve the mucosa, with morphology comparable to that of normal noninjured rats - in contrast to the other drugs investigated. These data confirm the cytoprotective properties of sulglycotide in particular, which was the most potent agent for preventing the development of ethanol-induced acute lesions of the gastric mucosa.

  15. Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

    PubMed

    Cheah, Ker Y; Howarth, Gordon S; Yazbeck, Roger; Wright, Tessa H; Whitford, Eleanor J; Payne, Caroline; Butler, Ross N; Bastian, Susan E P

    2009-02-01

    Mucositis is a common side-effect of high-dose chemotherapy regimens. Grape seed extract (GSE) represents a rich source of proanthocyanidins with the potential to decrease oxidative damage and inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of chemotherapy-induced mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by 5-Fluorouracil (5-FU). Cell viability was determined by neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received 5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for myeloperoxidase and sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by 5-FU (p < 0.01). Compared with 5-FU controls, GSE significantly reduced myeloperoxidase activity by 86% and 27% in the proximal jejunum (p < 0.001) and distal ileum (p < 0.05) respectively; decreased qualitative histological scores of damage (p < 0.05) in the proximal jejunum; increased villus height in the proximal jejunum (17%; p < 0.05) and distal ileum (50%; p < 0.01), and attenuated the 5-FU-induced reduction of mucosal thickness by 16% in the jejunum (p < 0.05) and 45% in the ileum (p < 0.01). GSE partially protected IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by 5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis.

  16. Mucosal Tolerance Induced by an Immunodominant Peptide from Rat α3(IV)NC1 in Established Experimental Autoimmune Glomerulonephritis

    PubMed Central

    Reynolds, John; Abbott, Danielle S.; Karegli, Julieta; Evans, David J.; Pusey, Charles D.

    2009-01-01

    Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the α 3 chain of type IV collagen, α3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat α3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 μg had no effect, a dose of 1000 μg resulted in a moderate reduction in EAG severity, and a dose of 3000 μg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of α3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture’s disease and other autoimmune disorders. PMID:19406992

  17. Azadirachta indica Attenuates Colonic Mucosal Damage in Experimental Colitis Induced by Trinitrobenzene Sulfonic Acid

    PubMed Central

    Gautam, M. K.; Goel, Shalini; Ghatule, R. R.; Singh, A.; Joshi, V. K.; Goel, R. K.

    2013-01-01

    Azadirachta indica leaves indicated the presence of active principles with proven antioxidants, antiinflammatory, immunomodulatory, free radical scavenging and healing properties. In the present study we evaluated the healing effects of 50% ethanol extract of dried leaves of Azadirachta indica on trinitrobenzene sulfonic acid-induced colitis in rats. Azadirachta indica extract (500 mg/kg) was administered orally, once daily for 14 days and studied for its effects on diarrhoea, food and water intake, body weight changes, colonic damage and inflammation, histology, antibacterial activity and free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase activities in colonic tissue. Intracolonic trinitrobenzene sulfonic acid increased colonic mucosal damage and inflammation, diarrhea, but decreased body weight which were reversed by Azadirachta indica extract and sulfasalazine (positive control) treatments. Azadirachta indica extract showed antibacterial activity. Azadirachta indica extract and sulfasalazine enhanced the antioxidants but decreased free radicals and myeloperoxidase activities affected in trinitrobenzene sulfonic acid-induced colitis. Azadirachta indica extract, thus seemed to be effective in healing trinitrobenzene sulfonic acid-induced colitis in rats. PMID:24403663

  18. Comparison of laser and ozone treatments on oral mucositis in an experimental model.

    PubMed

    Bayer, Suzan; Kazancioglu, Hakki Oguz; Acar, Ahmet Hüseyin; Demirtas, Nihat; Kandas, Nur Ozten

    2017-02-11

    Oral mucositis (OM) induces severe pain and limits fundamental life behaviors such as eating, drinking, and talking for patients receiving chemotherapy or radiotherapy. In addition, through opportunistic microorganisms, OM frequently leads to systemic infection which then leads to prolonged hospitalization. Severe lesions often adversely affect curative effects in cancer cases. Therefore, the control of OM is important for oral health quality of life and prognosis. Low-level laser therapy (LLLT) and ozone may be useful to accelerate wound healing. In this study, 24 Sprague-Dawley rats were divided into three groups as control, ozone, and laser groups. All groups received 5-fluorouracil intraperitoneally and trauma to the mouth pouch with a needle. After the formation of OM in the mouth, the control group had no treatment; the ozone group was administered ozone, and the laser group, LLLT. Then, all groups were sacrificed and basic fibroblast growth factor (bFGF), transforming growth factor (TGF-β), and platelet-derived growth factor (PDGF) were evaluated in all groups. LLLT was determined to be statistically significantly more effective than ozone on FGF and PDGF. However, in respect of TGF-β, no statistically significant difference was observed between the groups. In conclusion, within the limitations of this study, LLLT is more effective than ozone. However, further studies on this subject are required.

  19. Time-course of cerebral perfusion and tissue oxygenation in the first 6 h after experimental subarachnoid hemorrhage in rats.

    PubMed

    Westermaier, Thomas; Jauss, Alina; Eriskat, Jörg; Kunze, Ekkehard; Roosen, Klaus

    2009-04-01

    Present knowledge about hemodynamic and metabolic changes after subarachnoid hemorrhage (SAH) originates from neuromonitoring usually starting with aneurysm surgery and animal studies that have been focusing on the first 1 to 3 h after SAH. Most patients, however, are referred to treatment several hours after the insult. We examined the course of hemodynamic parameters, cerebral blood flow, and tissue oxygenation (ptiO2) in the first 6 h after experimental SAH. Sixteen Sprague-Dawley rats were subjected to SAH using the endovascular filament model or served as controls (n=8). Bilateral local cortical blood flow, intracranial pressure, cerebral perfusion pressure, and ptiO2 were followed for 6 h after SAH. After induction of SAH, local cortical blood flow rapidly declined to 22% of baseline and returned to 80% after 6 h. The decline of local cortical blood flow markedly exceeded the decline of cerebral perfusion pressure. ptiO2 declined to 57%, recovered after 2 h, and reached > or =140% of baseline after 6 h. Acute vasoconstriction after SAH is indicated by the marked discrepancy of cerebral perfusion pressure and local cortical blood flow. The excess tissue oxygenation several hours after SAH suggests disturbed oxygen utilization and cerebral metabolic depression. Aside from the sudden increase of intracranial pressure at the time of hemorrhage and delayed cerebral vasospasm, the occurrence of acute vasoconstriction and disturbed oxygen utilization may be additional factors contributing to secondary brain damage after SAH.

  20. Do you mind if I vape? Immediate effects of electronic cigarettes on perfusion in buccal mucosal tissue--a pilot study.

    PubMed

    Reuther, William J; Hale, Beverley; Matharu, Jas; Blythe, John N; Brennan, Peter A

    2016-04-01

    The association between smoking and postoperative complications is compounded in patients who have oral and maxillofacial operations by an additional local effect, and patients often continue to smoke after operation despite advice to stop. Recent studies have suggested that nicotine may reduce inflammation and improve angiogenesis, so topical application may be beneficial for smokers. The electronic cigarette is increasing in popularity and more patients ask whether they can vape after operation. We investigated the effect of electronic cigarettes (of which half contained nicotine and half did not) on blood flow in the buccal mucosa in 10 volunteers immediately after vaping. Smokers were excluded as this was considered an additional variable in a small pilot study and our Trust has a no-smoking policy. After vaping for 5 minutes, capillary blood flow was measured in the buccal mucosa at 5-minute intervals using a laser Doppler probe, and the results were expressed as arbitrary perfusion units. There was a wide variation in results and a small but significant rise (p=0.008) as a result of nicotine vaping, but these fell to the same levels as before within 30 minutes. Electronic cigarettes may have an effect on blood flow to the oral mucosa, although further studies are needed to show whether they improve healing time after operation. Additional work is also needed to compare them with cigarettes.

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

    PubMed

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

    2014-08-01

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

  2. Lung Radiofrequency Ablation: In Vivo Experimental Study with Low-Perfusion-Rate Multitined Electrodes

    SciTech Connect

    Crocetti, Laura Lencioni, Riccardo; Bozzi, Elena; Sbrana, Alberto; Bartolozzi, Carlo

    2008-05-15

    The purpose of this study was to investigate the feasibility and safety of lung radiofrequency (RF) ablation by using low-perfusion-rate, expandable, multitined electrodes in an in vivo animal model. Ten New Zealand White rabbits underwent RF ablation using low-perfusion-rate, expandable, multitined electrodes (Starburst Talon; RITA Medical Systems, Mountain View, CA) and a 200-W RF generator. The electrode was positioned under fluoroscopy guidance and a single percutaneous RF ablation was performed. Saline perfusate was doped with nonionic iodinated contrast agent to render it visible on computed tomography (CT). The pump infused the saline doped with contrast agent into the lateral tines at a rate of 0.1ml/min. The planned ablation was of 3 min, with the hooks deployed to 2 cm at a target temperature of 105{sup o}C. An immediate posttreatment CT scan documented the distribution of the doped saline and the presence of immediate complications. The animals were monitored for delayed complications and sacrificed within 72 h (n = 4), 2 weeks (n = 3), or 4 weeks (n = 3). Assessment of ablation zone and adjacent structures was done at autopsy. Major complications consisted of pneumothorax requiring drainage (n = 2) and skin burn (n = 1). Immediately after the procedure the area of ablation was depicted at CT as a round, well-demarcated area, homogeneously opacified by iodinated contrast medium (mean size, 2.3 {+-} 0.8 cm). The presence of a sharply demarcated area of coagulation necrosis (mean size, 2.1 {+-} 0.4 cm) without severe damage to adjacent structures was confirmed at autopsy. In one case, euthanized at 4 weeks, in whom pneumothorax and pleural effusion were depicted, pleural fibrinous adhesions were demonstrated at autopsy. In conclusion, lung RF ablation performed in an in vivo animal model using low-perfusion-rate, expandable, multitined electrodes is feasible and safe. No severe damage to adjacent structures was demonstrated.

  3. Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats

    SciTech Connect

    Bergsland, J.; Carr, E.A. Jr.; Carroll, M.; Feldman, M.J.; Kung, H.; Wright, J.R.

    1989-02-01

    There is a need for a reliable noninvasive marker of rejection in transplanted hearts. Endomyocardial biopsy is now the universally accepted diagnostic method of choice, but the invasiveness of the procedure and the limited size of the sample obtained makes this method far from ideal. As coronary blood flow may be expected to decrease during acute rejection, there has been interest in thallium-201 chloride (T1), a perfusion marker, as an imaging agent for diagnosing cardiac rejection. Hexakis(t-butylisonitrile)-technetium (Tc-TBI) is a representative of a new class of radiopharmaceuticals proposed as perfusion markers. We have compared the uptake of these imaging agents in a rat model of cardiac transplantation. Uptake of Tc-TBI as well as of T1 was significantly lower in rejecting than in nonrejecting hearts. This change was found in both left (LV) and right (RV) ventricles. Allografts in animals treated with cyclosporine (CyA) showed less severe rejection and higher uptakes of both imaging agents as compared to unmodified rejection. Our results suggest that perfusion imaging with these radionuclides is a potentially useful approach to the problem of detecting allograft rejection.

  4. Perfusion, oxygenation status and growth of experimental tumors upon photodynamic therapy with Pd-bacteriopheophorbide.

    PubMed

    Kelleher, Debra K; Thews, Oliver; Scherz, Avigdor; Salomon, Yoram; Vaupel, Peter

    2004-06-01

    The aim of this study was to assess the anti-tumor effect of photodynamic therapy (PDT) using a novel bacteriochlorophyll derivative, palladium-bacteriopheophorbide (TOOKAD) on tumor growth, perfusion and oxygenation. Rat DS-sarcomas were treated with either TOOKAD-PDT (2 mg/kg, i.v., immediate illumination) or one of the control treatments (sham-treatment, illumination without photosensitizer, or photosensitizer without illumination). The light source was an infrared-A irradiator fitted with appropriate filters, so that the wavelengths applied (665-800 nm) included the absorption maximum of TOOKAD at 763 nm. Tumor volume was monitored for 90 days after treatment or until a target volume (3.5 ml) was reached. TOOKAD-PDT dramatically inhibited tumor growth with 92% of tumors not reaching the target volume within the observation period. In further experiments, tumor perfusion was assessed using laser Doppler flowmetry. Upon TOOKAD-PDT treatment, a rapid, pronounced decrease in perfusion was seen, down to levels corresponding to only 3% of initial values. Tumor oxygenation monitoring revealed parallel decreases, with levels corresponding to anoxia being reached. The significant anti-tumor effects presented in this report, taken together with the chemical and pharmacokinetic properties of the novel photosensitizer TOOKAD, underline the therapeutic potential of this approach in which flow stasis and induction of anoxia are key elements.

  5. The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine.

    PubMed

    Good, Misty; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B; Martin, Laura Y; Prindle, Thomas; Nino, Diego F; Zhou, Qinjie; Ma, Congrong; Ozolek, John A; Buck, Rachael H; Goehring, Karen C; Hackam, David J

    2016-10-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2'FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2'FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.

  6. Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy.

    PubMed

    Chen, Chun-Yu; Lee, Jee-Boong; Liu, Bo; Ohta, Shoichiro; Wang, Pin-Yi; Kartashov, Andrey V; Mugge, Luke; Abonia, J Pablo; Barski, Artem; Izuhara, Kenji; Rothenberg, Marc E; Finkelman, Fred D; Hogan, Simon P; Wang, Yui-Hsi

    2015-10-20

    Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin-9 (IL-9). However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9- and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.

  7. Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a clinical and experimental study.

    PubMed

    Ottaviani, Giulia; Gobbo, Margherita; Sturnega, Mauro; Martinelli, Valentina; Mano, Miguel; Zanconati, Fabrizio; Bussani, Rossana; Perinetti, Giuseppe; Long, Carlin S; Di Lenarda, Roberto; Giacca, Mauro; Biasotto, Matteo; Zacchigna, Serena

    2013-12-01

    Oral mucositis (OM) is a serious and acute side effect in patients with cancer who receive chemotherapy or radiotherapy, often leading to the suspension of therapy and a need for opioid analgesic and enteral/parenteral nutrition, with an effect on patient survival. Among the various interventions proposed in OM management, laser therapy is becoming a recommended treatment option but has limitations due to its heterogeneous laser parameters. Here, we report on our successful clinical experience on the use of class IV laser therapy to treat OM induced by different chemotherapy regimens. To shed light on the mechanisms of action of laser therapy in improving OM resolution, we have developed an animal model of chemotherapy-induced OM, in which we compare the efficacy of the standard low-power laser therapy protocol with an innovative protocol, defined as high-power laser therapy. We show that high-power laser therapy is more effective than low-power laser therapy in improving OM lesion healing, reducing the inflammatory burden, and preserving tissue integrity. In addition, high-power laser therapy has been particularly effective in promoting the formation of new arterioles within the granulation tissue. Our results provide important insights into the mechanism of action of biostimulating laser therapy on OM in vivo and pave a way for clinical experimentation with the use of high-power laser therapy.

  8. Experimental Colitis Is Attenuated by Cardioprotective Diet Supplementation That Reduces Oxidative Stress, Inflammation, and Mucosal Damage

    PubMed Central

    Vargas Robles, Hilda; Citalán Madrid, Alí Francisco; García Ponce, Alexander; Silva Olivares, Angelica; Shibayama, Mineko; Betanzos, Abigail; Del Valle Mondragón, Leonardo; Nava, Porfirio; Schnoor, Michael

    2016-01-01

    Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) are multifactorial, relapsing disorders of the gastrointestinal tract. However, the etiology is still poorly understood but involves altered immune responses, epithelial dysfunction, environmental factors, and nutrition. Recently, we have shown that the diet supplement corabion has cardioprotective effects due to reduction of oxidative stress and inflammation. Since oxidative stress and inflammation are also prominent risk factors in IBD, we speculated that corabion also has beneficial effects on experimental colitis. Colitis was induced in male mice by administration of 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for a period of 3 or 7 days with or without daily gavage feeding of corabion consisting of vitamin C, vitamin E, L-arginine, and eicosapentaenoic and docosahexaenoic acid. We found that corabion administration attenuated DSS-induced colon shortening, tissue damage, and disease activity index during the onset of colitis. Mechanistically, these effects could be explained by reduced neutrophil recruitment, oxidative stress, production of proinflammatory cytokines, and internalization of the junctional proteins ZO-1 and E-cadherin leading to less edema formation. Thus, corabion may be a useful diet supplement for the management of chronic inflammatory intestinal disorders such as IBD. PMID:26881044

  9. Double-Balloon Catheter for Isolated Liver Perfusion: An Experimental Study

    SciTech Connect

    Cwikiel, Wojciech; Bergqvist, Lennart; Harnek, Jan

    2001-05-15

    Purpose: Further development of a previously described interventional method for isolated liver perfusion (ILP) with a new double-lumen balloon catheter, and evaluation of the side-effects of such isolation.Methods: In six pigs a double-balloon occlusion catheter was placed via the transjugular approach with its tip in the portal vein. One of the balloons was positioned in the inferior vena cava (IVC), cranial to the origin of the hepatic veins and the other balloon in the portal vein. By the transfemoral approach, a single-balloon occlusion catheter was placed in the IVC caudal to the origin of the hepatic veins. A third catheter was placed by the transfemoral route with the occlusion balloon in the proper hepatic artery. After inflation of all balloons {sup 99}Tc{sup m}-labelled human serum albumin was recirculated through the liver. The isolation was evaluated by repeated measurement of radioactivity levels in peripheral blood. Laboratory tests of liver and pancreas function, and hemoglobin, were taken before, at the end of, and 3 days after the procedure. Blood gases were tested at the beginning and end of the procedure.Results: One pig died during the procedure due to technical failure and was excluded from the study. In the other pigs leakage from the isolated liver to the systemic circulation increased slowly, up to 9.7% (mean) during 30 min of recirculation of the perfusate through the liver. Laboratory tests were normal in all pigs except insignificant acidosis directly after the procedure and the slight elevation of s-ALAT after 3 days.Conclusions: Only minor leakage from the liver to the systemic circulation was noted during ILP performed with a new, double-balloon catheter. There were no serious side effects.

  10. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine

    PubMed Central

    Good, Misty; Sodhi, Chhinder P.; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B.; Martin, Laura Y.; Prindle, Thomas; Nino, Diego F.; Zhou, Qinjie; Ma, Congrong; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Hackam, David J.

    2016-01-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC. PMID:27609061

  11. Beneficial role of the probiotic mixture Ultrabiotique on maintaining the integrity of intestinal mucosal barrier in DSS-induced experimental colitis.

    PubMed

    Toumi, Ryma; Abdelouhab, Katia; Rafa, Hayet; Soufli, Imene; Raissi-Kerboua, Djamila; Djeraba, Zineb; Touil-Boukoffa, Chafia

    2013-06-01

    The etiology of inflammatory bowel diseases which include ulcerative colitis (UC) and Crohn disease has not yet been clarified. Several hypotheses suggest a change in composition of gut microflora along with an impaired mucosal barrier that lead to excessive mucosal immunologic responses. Increased production of nitric oxide (NO) contributes greatly to the tissue injury caused by chronic inflammation. Evidence indicates that the mucus layer covering the epithelium is altered during UC and experimental colitis. Our aim in this study was to investigate the potential therapeutic effect of probiotic during DSS-induced colitis by modulating the immune system and colonic mucus production. For that purpose, the probiotic formulation Ultrabiotique(®) (Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum and Bifidobacterium breve) was administered daily for 7 d to mice with colitis. Probiotic supplementation improved clinical symptoms and histological alterations observed during DSS induced colitis. Ultrabiotique(®) treatment down regulated the NO production by peritoneal macrophages of DSS-treated mice and enhanced mucus production in both DSS-treated and healthy mice. In conclusion, the modification of microflora by the Ultrabiotique(®) played a beneficial role in maintaining the integrity of the intestinal mucosal barrier and promoted tissue repair.

  12. Enhancement of gastric mucosal blood flow with sulglycotide.

    PubMed

    Guslandi, M; Sorghi, M; Tittobello, A

    1994-01-01

    Twelve patients with dyspepsia whose gastric abnormalities ranged from diffuse reddening of the mucosa to multiple erosions were treated for 4 weeks with oral sulglycotide, a sulphated glycopeptide with known gastroprotective and ulcer-healing properties. Before and after treatment, gastric mucosal blood flow was assessed by means of laser Doppler flowmetry. A significant (P < 0.01) increase in mucosal perfusion was observed after sulglycotide treatment, suggesting that enhancement of mucosal blood flow may contribute to the therapeutic properties of the drug.

  13. Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats.

    PubMed

    Funatsu, Toshiyuki; Chono, Koji; Hirata, Takuya; Keto, Yoshihiro; Kimoto, Aishi; Sasamata, Masao

    2007-01-05

    The mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) suppress gastric mucosal blood flow is not fully understood, although the depletion of mucosal prostaglandin E2 has been proposed as one possible explanation. We investigated the role of gastric acid on gastric mucosal blood flow in NSAID-treated rats. A rat stomach was mounted in an ex vivo chamber, and gastric mucosal blood flow was measured sequentially in a 5-mm2 area of the gastric corpus using a scanning laser Doppler perfusion image system. Results showed that diclofenac (5 mg/kg s.c.) and indomethacin (10 mg/kg s.c.) did not affect gastric mucosal blood flow, although both strongly decreased mucosal prostaglandin E2 when saline was instilled into the gastric chamber. On replacement of the saline in the chamber with 100 mM hydrochloric acid, these drugs caused a decrease in gastric mucosal blood flow levels within 30 min. The specific cyclooxygenase (COX)-2 inhibitors celecoxib (50 mg/kg s.c.) and rofecoxib (25 mg/kg s.c.) did not affect mucosal prostaglandin E2 level, nor did they decrease gastric mucosal blood flow, even when hydrochloric acid was added to the chamber. Furthermore, measurement of vasoconstrictive factors present in the mucosa showed that endothelin-1 levels increased after administration of diclofenac s.c. in the presence of intragastric hydrochloric acid. This indicates that the presence of mucosal hydrochloric acid plays an important role in the NSAID-induced decrease in gastric mucosal blood flow, while the COX-1-derived basal prostaglandin E2, which is unlikely to control gastric mucosal blood flow itself, protects microcirculatory systems from mucosal hydrochloric acid.

  14. Reduction of radiochemotherapy-induced early oral mucositis by recombinant human keratinocyte growth factor (palifermin): Experimental studies in mice

    SciTech Connect

    Doerr, Wolfgang . E-mail: doerr@rcs.urz.tu-dresden.de; Baessler, Stefan; Reichel, Sandra; Spekl, Kathrin

    2005-07-01

    Purpose: To study the effect of recombinant human keratinocyte growth factor (rHuKGF or palifermin) on oral mucositis induced by radiochemotherapy in a mouse model. Methods and Materials: Cis-diamminedichloroplatinum (cisplatin) and/or 5-fluorouracil were given before single dose irradiation, combined with palifermin before or after the treatment, or both. Daily fractionated irradiation for 2 weeks was followed by graded test doses. With additional chemotherapy in Week 1, palifermin was given before radiotherapy and at the end of the first week, or additionally at the end of Week 2. Radiochemotherapy in Week 2 was combined with palifermin at the end of Weeks 1 and 2, Weeks 1, 2, and 3, or additionally before radiotherapy. Ulceration of mouse tongue mucosa was analyzed as the endpoint. Results: The dose associated with ulcer induction in 50% of the mice (ED{sub 50}) for single-dose irradiation was 11.5 {+-} 0.7 Gy. Palifermin increased the ED{sub 50} to about 19 Gy in all protocols tested. Similar values were observed when chemotherapy was added before irradiation. With fractionated irradiation, palifermin increased the ED{sub 50} for test irradiation from 5.7 {+-} 1.5 Gy to 12-15 Gy, depending on the administration protocol. With chemotherapy in Week 1, two palifermin injections had no significant effect, but a third injection increased the ED{sub 50} to 13 Gy. With chemotherapy in Week 2, all palifermin protocols resulted in ED{sub 50} values of 13-14 Gy. Conclusion: A marked increase in oral mucosal radiation tolerance by palifermin was found, which was preserved in combinations with chemotherapy using cisplatin and/or 5-fluorouracil.

  15. Experimental verification of bioheat transfer theories: measurement of temperature profiles around large artificial vessels in perfused tissue.

    PubMed

    Crezee, J; Lagendijk, J J

    1990-07-01

    The verification of thermal models for use in hyperthermia treatment planning is essential. We investigated the heat transfer between a single vessel and the surrounding vascularised tissue, comparing the conventional bioheat transfer theory and the recently developed keff model using analytical and numerical methods. A plastic tube inserted into the tissue of an isolated perfused organ served as an artificial vessel. This enabled us to vary the blood flow in the vessel and in the tissue independently. The organ used was a bovine kidney, turned into a perfused tissue phantom using an alcohol fixation technique. The temperature profile within the tissue was mapped with constantan-manganin thermocouple wire sensors with a total diameter of 50 microns. The temperature profile relative to the temperature difference between the vessel and organ was measured; increased perfusion caused a reduction of the vessel wall temperature but did not affect the width of the profile. Studying the transient tissue temperature after a step-wise change of the blood temperature in the vessel revealed a faster diffusion of heat at higher perfusion rates. These facts are in accordance with the keff model, but not with the conventional heat-sink theory.

  16. Lung [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation

    PubMed Central

    Musch, Guido; Winkler, Tilo; Harris, R. Scott; Vidal Melo, Marcos F.; Wellman, Tyler J.; de Prost, Nicolas; Kradin, Richard L.; Venegas, Jose G.

    2014-01-01

    Background Acute lung injury (ALI) occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48 to 72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced ALI. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, we hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of ALI are not yet expected. Methods In five sheep we induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. We used positron emission tomography with: 1) [18F]fluorodeoxyglucose to measure pulmonary inflammatory cell metabolic activity; and 2) [13N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. Results The pulmonary [18F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min−1, P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02, P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01, P < 0.05). Conclusion Using noninvasive imaging we demonstrated that increased pulmonary [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation. PMID:24051392

  17. Denoising and artefact reduction in dynamic flat detector CT perfusion imaging using high speed acquisition: first experimental and clinical results

    NASA Astrophysics Data System (ADS)

    Manhart, Michael T.; Aichert, André; Struffert, Tobias; Deuerling-Zheng, Yu; Kowarschik, Markus; Maier, Andreas K.; Hornegger, Joachim; Doerfler, Arnd

    2014-08-01

    Flat detector CT perfusion (FD-CTP) is a novel technique using C-arm angiography systems for interventional dynamic tissue perfusion measurement with high potential benefits for catheter-guided treatment of stroke. However, FD-CTP is challenging since C-arms rotate slower than conventional CT systems. Furthermore, noise and artefacts affect the measurement of contrast agent flow in tissue. Recent robotic C-arms are able to use high speed protocols (HSP), which allow sampling of the contrast agent flow with improved temporal resolution. However, low angular sampling of projection images leads to streak artefacts, which are translated to the perfusion maps. We recently introduced the FDK-JBF denoising technique based on Feldkamp (FDK) reconstruction followed by joint bilateral filtering (JBF). As this edge-preserving noise reduction preserves streak artefacts, an empirical streak reduction (SR) technique is presented in this work. The SR method exploits spatial and temporal information in the form of total variation and time-curve analysis to detect and remove streaks. The novel approach is evaluated in a numerical brain phantom and a patient study. An improved noise and artefact reduction compared to existing post-processing methods and faster computation speed compared to an algebraic reconstruction method are achieved.

  18. Mucosal vaccines: novel strategies and applications for the control of pathogens and tumors at mucosal sites.

    PubMed

    Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis Cs; Badoual, Cecile; Tartour, Eric

    2014-01-01

    The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites.

  19. Renal perfusion scintiscan

    MedlinePlus

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  20. Oleic acid-induced mucosal injury in developing piglet intestine.

    PubMed

    Velasquez, O R; Henninger, K; Fowler, M; Tso, P; Crissinger, K D

    1993-03-01

    A role for luminal nutrients, in particular products of lipid digestion, in the pathogenesis of mucosal injury to developing intestine has been postulated. We evaluated changes in mucosal permeability and light and electron microscopic histology induced by luminal perfusion with the long-chain fatty acid oleate in developing piglet intestine as a function of age and concentration of the fatty acid. 51Cr-labeled EDTA plasma-to-lumen clearance was measured in jejunum and ileum of 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets during sequential perfusion with saline control (20 min); 0, 1, 5, and 10 mM oleic acid/10 mM taurocholate in saline (20 min); and normal saline (60 min). The jejunum of piglets < or = 2 wk showed significantly greater increases in mucosal permeability compared with 1-mo-old animals after perfusion with oleic acid. This effect was dependent on the luminal concentration of the fatty acid and was associated with mucosal injury evident under light and electron microscopy. In contrast, the overall response in ileum was more attenuated compared with jejunum. Thus oleic acid, a common dietary fatty acid, induces dose- and age-dependent injury in developing piglet intestine. Investigation of the mechanisms of this injury may provide the basis for dietary modifications directed at decreasing the risk of mucosal injury during enteral feeding in neonatal intestine.

  1. Countercurrent transfer of dopamine from venous blood in the cavernous sinus to the arterial blood supplying the brain - the perfused rabbit head as an experimental model.

    PubMed

    Muszak, J; Krzymowski, T; Gilun, P; Stefanczyk-Krzymowska, S

    2014-10-01

    The objective of the current study was to check whether countercurrent transfer of dopamine occurs in the cavernous sinus of the rabbit and whether the rabbit can be used as an animal model to study cavernous sinus function. After exsanguination of the animal, oxygenated and warmed (37°C) Hanseneleit-Krebs buffer with autologous or homologous blood (in a 3:1 or 1:1 ratio) was pumped through both common carotid arteries into the head (60 ml/min; 80-100 mm Hg) and radiolabeled dopamine (3(H)-DA, 10 μCi) was infused into the cavernous sinus through the angular oculi vein. Cerebral blood from the basilar artery was collected from the cannulated vertebral artery during 3(H)-DA infusion and for 10 minutes after completion of infusion. Selected brain tissue samples were collected after completion of the head perfusion. It was demonstrated that dopamine can penetrate from the rabbit's cavernous sinus to the internal carotid artery supplying the brain. Dopamine permeation was greater when the rabbit head was perfused with buffer and blood in a 3:1 ratio than with 1:1 (P<0.01). When the head was perfused with buffer and blood in a 3:1 ratio, significant radioactivity was found in samples collected from the brain basilar artery during and after 3(H)-DA infusion (P<0.001). The radioactivity was identified as 34.13 ± 2.7% unmetabolized 3(H)-DA and 65.9 ± 2.7% its metabolites. Significant radioactivity was also found in some brain tissue samples in both groups (P<0.05). The concentration of free radiolabeled dopamine particles in the dialysate of blood plasma and plasma diluted with buffer did not differ significantly. Because the structures of the cavernous sinus and cavernous fragment of the internal carotid artery of the rabbit are similar to those in humans, it suggests that rabbits can serve as a model for experimental physiological studies of cavernous sinus function and retrograde dopamine transfer in the cavernous sinus should be considered as an important link in

  2. Palliation of radiation-related mucositis

    SciTech Connect

    Rothwell, B.R.; Spektor, W.S.

    1990-01-01

    Oral mucositis associated with head and neck radiotherapy can substantially hinder completion of cancer therapy. Alleviation of this often severe stomatitis can provide enhanced patient comfort and facilitate appropriate care. A double-blind format was used in a pilot project to measure, against a control rinse, the effectiveness of an oral rinse consisting of hydrocortisone, nystatin, tetracycline, and diphenhydramine in controlling radiation-related mucositis. A combination of clinical evaluation and patient responses to a questionnaire was used to judge the results of the topical medications. Patients using the experimental medication developed less mucositis than did patients in the control group.

  3. New generation of oral mucosal vaccines targeting dendritic cells

    PubMed Central

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

    2013-01-01

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

  4. New generation of oral mucosal vaccines targeting dendritic cells.

    PubMed

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

    2013-12-01

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

  5. Oral mucositis - self-care

    MedlinePlus

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

  6. Why mucosal health?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aquaculture species depend more heavily on mucosal barriers than their terrestrial agricultural counterparts as they are continuously interacting with the aquatic microbiota. Unlike classical immune centers, such as the spleen and kidney, the accessibility of mucosal surfaces through immersion/dip t...

  7. Ultrasound perfusion signal processing for tumor detection

    NASA Astrophysics Data System (ADS)

    Kim, MinWoo; Abbey, Craig K.; Insana, Michael F.

    2016-04-01

    Enhanced blood perfusion in a tissue mass is an indication of neo-vascularity and a sign of a potential malignancy. Ultrasonic pulsed-Doppler imaging is a preferred modality for noninvasive monitoring of blood flow. However, the weak blood echoes and disorganized slow flow make it difficult to detect perfusion using standard methods without the expense and risk of contrast enhancement. Our research measures the efficiency of conventional power-Doppler (PD) methods at discriminating flow states by comparing measurement performance to that of an ideal discriminator. ROC analysis applied to the experimental results shows that power Doppler methods are just 30-50 % efficient at perfusion flows less than 1ml/min, suggesting an opportunity to improve perfusion assessment through signal processing. A new perfusion estimator is proposed by extending the statistical discriminator approach. We show that 2-D perfusion color imaging may be enhanced using this approach.

  8. Radiation Induced Oral Mucositis

    PubMed Central

    PS, Satheesh Kumar; Balan, Anita; Sankar, Arun; Bose, Tinky

    2009-01-01

    Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene PMID:20668585

  9. Mucosal immunology of food allergy.

    PubMed

    Berin, M Cecilia; Sampson, Hugh A

    2013-05-06

    Food allergies are increasing in prevalence at a higher rate than can be explained by genetic factors, suggesting a role for as yet unidentified environmental factors. In this review, we summarize the state of knowledge about the healthy immune response to antigens in the diet and the basis of immune deviation that results in immunoglobulin E (IgE) sensitization and allergic reactivity to foods. The intestinal epithelium forms the interface between the external environment and the mucosal immune system, and emerging data suggest that the interaction between intestinal epithelial cells and mucosal dendritic cells is of particular importance in determining the outcome of immune responses to dietary antigens. Exposure to food allergens through non-oral routes, in particular through the skin, is increasingly recognized as a potentially important factor in the increasing rate of food allergy. There are many open questions on the role of environmental factors, such as dietary factors and microbiota, in the development of food allergy, but data suggest that both have an important modulatory effect on the mucosal immune system. Finally, we discuss recent developments in our understanding of immune mechanisms of clinical manifestations of food allergy. New experimental tools, particularly in the field of genomics and the microbiome, are likely to shed light on factors responsible for the growing clinical problem of food allergy.

  10. Cryopreservation of Human Mucosal Leukocytes

    PubMed Central

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

    2016-01-01

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

  11. Mucosal Health in Aquaculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abstract The mucosal surfaces (skin, gill, and intestine) constitute the first line of defense against pathogen invasion while simultaneously carrying out a diverse array of other critical physiological processes, including nutrient absorption, osmoregulation, and waste excretion. Aquaculture specie...

  12. Perfusion decellularization of whole organs.

    PubMed

    Guyette, Jacques P; Gilpin, Sarah E; Charest, Jonathan M; Tapias, Luis F; Ren, Xi; Ott, Harald C

    2014-01-01

    The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo.

  13. Mucosal and systemic adjuvant activity of alphavirus replicon particles

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

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

  14. C. albicans Colonization of Human Mucosal Surfaces

    PubMed Central

    Southern, Peter; Horbul, Julie; Maher, Diane; Davis, Dana A.

    2008-01-01

    Background Candida albicans is a low level commensal organism in normal human populations with the continuous potential to expand and cause a spectrum of clinical conditions. Methodology/Principal Findings Using ex vivo human organ cultures and populations of primary human cells, we have developed several related experimental systems to examine early-stage interactions between C. albicans and mucosal surfaces. Experiments have been conducted both with exogenously added C. albicans and with overtly normal human mucosal surfaces supporting pre-existing infections with natural isolates of Candida. Under different culture conditions, we have demonstrated the formation of C. albicans colonies on human target cells and filament formation, equivalent to tissue invasion. Conclusions/Significance These organ culture systems provide a valuable new resource to examine the molecular and cellular basis for Candida colonization of human mucosal surfaces. PMID:18446191

  15. Influence of NaCl Concentrations on Coagulation, Temperature, and Electrical Conductivity Using a Perfusion Radiofrequency Ablation System: An Ex Vivo Experimental Study

    SciTech Connect

    Aube, Christophe Schmidt, Diethard; Brieger, Jens; Schenk, Martin; Kroeber, Stefan; Vielle, Bruno; Claussen, Claus D.; Goldberg, S. Nahum; Pereira, Philippe L.

    2007-02-15

    Purpose. To determine, by means of an ex vivo study, the effect of different NaCl concentrations on the extent of coagulation obtained during radiofrequency (RF) ablation performed using a digitally controlled perfusion device. Method. Twenty-eight RF ablations were performed with 40 W for 10 min using continuous NaCl infusion in fresh excised bovine liver. For perfusion, NaCl concentrations ranging from 0 (demineralized water) to 25% were used. Temperature, the amount of energy, and the dimensions of thermal-induced white coagulation were assessed for each ablation. These parameters were compared using the nonparametric Mann-Whitney test. Correlations were calculated according to the Spearman test. Results. RF ablation performed with 0.9% to 25% concentrations of NaCl produced a mean volume of coagulation of 30.7 {+-} 3.8 cm{sup 3}, with a mean short-axis diameter of 3.6 {+-} 0.2 cm. The mean amount of energy was 21,895 {+-} 1,674 W and the mean temperature was 85.4 {+-} 12.8 deg. C. Volume of coagulation, short-axis diameter, and amount of energy did not differ significantly among NaCl concentrations (p > 0.5). A correlation was found between the NaCl concentration and the short-axis diameter of coagulation (r = 0.64) and between the NaCl concentration and the mean temperature (r = 0.67), but not between the NaCl concentration and volume of coagulation. Conclusion. In an ex vivo model, continuous perfusion with high NaCl concentrations does not significantly improve the volume of thermal-induced coagulation. This may be because the use of a low-power generator cannot sufficiently exploit the potential advantage of better tissue conductivity provided by NaCl perfusion.

  16. Modulation of gut mucosal biofilms.

    PubMed

    Kleessen, Brigitta; Blaut, Michael

    2005-04-01

    Non-digestible inulin-type fructans, such as oligofructose and high-molecular-weight inulin, have been shown to have the ability to alter the intestinal microbiota composition in such a way that members of the microbial community, generally considered as health-promoting, are stimulated. Bifidobacteria and lactobacilli are the most frequently targeted organisms. Less information exists on effects of inulin-type fructans on the composition, metabolism and health-related significance of bacteria at or near the mucosa surface or in the mucus layer forming mucosa-associated biofilms. Using rats inoculated with a human faecal flora as an experimental model we have found that inulin-type fructans in the diet modulated the gut microbiota by stimulation of mucosa-associated bifidobacteria as well as by partial reduction of pathogenic Salmonella enterica subsp. enterica serovar Typhimurium and thereby benefit health. In addition to changes in mucosal biofilms, inulin-type fructans also induced changes in the colonic mucosa stimulating proliferation in the crypts, increasing the release of mucins, and altering the profile of mucin components in the goblet cells and epithelial mucus layer. These results indicate that inulin-type fructans may stabilise the gut mucosal barrier. Dietary supplementation with these prebiotics could offer a new approach to supporting the barrier function of the mucosa.

  17. Milk supplemented with immune colostrum: protection against rotavirus diarrhea and modulatory effect on the systemic and mucosal antibody responses in calves experimentally challenged with bovine rotavirus.

    PubMed

    Parreño, V; Marcoppido, G; Vega, C; Garaicoechea, L; Rodriguez, D; Saif, L; Fernández, F

    2010-07-01

    Group A bovine rotavirus (BRV) is the major cause of neonatal calf diarrhea worldwide. As a preventive strategy, we evaluated the protection and immunomodulation in two groups of BRV-inoculated calves. All calves received control colostrum (CC; VN=65,536; IgG(1)=16,384) prior to gut closure followed by the milk supplemented with immune colostrum (VN=1,048,576; IgG(1)=262,144), twice a day, for 14 days. Calves received milk supplemented with 0.8% immune colostrum [(Gp 1) VN=16,384; IgG(1)=4096] or milk supplemented with 0.4% immune colostrum [(Gp 2) VN=1024; IgG(1)=1024]. Calves receiving CC or colostrum deprived calves (CD) fed antibody (Ab) free milk served as controls (Gp 3 and 4). Calves were inoculated with virulent BRV IND at 2 days of age. Group 1 calves (milk IgG(1) 4096) showed 80% protection against BRV diarrhea and significantly reduced virus shedding. At 21 post-inoculation days (PID), the antibody secreting cell (ASC) responses of Gp 1 calves were limited mainly to duodenal and jejunal lamina propria (LP) with limited or no responses in systemic sites (spleen and PBL) and mesenteric lymph nodes. The profile of serum and fecal Ab responses as well as the ASC responses was also modulated by the presence of passive IgG(1) Abs and probably other colostrum components, toward higher titers of IgA Ab in serum and feces and a greater number of IgA ASC in the proximal intestine, reflecting positive modulation by colostrum toward this isotype associated with optimal protection of the intestinal mucosa. After challenge, at PID 21, all calves in Gp 1 and 2 were fully protected against diarrhea and only 1 of 5 calves in Gp 1 shed virus asymptomatically, indicating that the passive Ab treatment for 14 days was effective in protecting most of the animals after a first and a second virus exposure. The final outcome was a positive modulation of the mucosal immune responses and a high protection rate against diarrhea and virus shedding during the period of peak

  18. Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.

    PubMed

    Guttu, K; Røsok, B; Gislason, H; Fändriks, L; Svanes, K; Grønbech, J E

    1991-04-01

    In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.

  19. Mucosal melanoma: an update.

    PubMed

    Ballester Sánchez, R; de Unamuno Bustos, B; Navarro Mira, M; Botella Estrada, R

    2015-03-01

    Mucosal melanoma is a rare melanoma subtype that differs from the cutaneous form of the tumor in its biology, clinical manifestations, and management. Diagnosis is usually late due to a lack of early or specific signs and the location of lesions in areas that are difficult to access on physical examination. Surgical excision is the treatment of choice for localized disease. The value of sentinel lymph node biopsy and lymphadenectomy is still unclear. Radiotherapy can be used as adjuvant therapy for the control of local disease. c-KIT mutations are more common than in other types of melanoma and this has led to significant advances in the use of imatinib for the treatment of metastatic mucosal melanoma.

  20. Beneficial Effect of Short Pretransplant Period of Hypothermic Pulsatile Perfusion of the Warm-Ischemic Kidney after Cold Storage: Experimental Study.

    PubMed

    Lázaro, Alberto; Humanes, Blanca; Jado, Juan Carlos; Mojena, Marina; González-Nicolás, María Ángeles; Del Cañizo, Juan Francisco; Tejedor, Alberto; Lledó-García, Enrique

    2016-01-01

    Warm ischemia (WI) produces a significant deleterious effect in potential kidney grafts. Hypothermic machine perfusion (HMP) seems to improve immediate graft function after transplant. Our aim was to analyze the effect of short pretransplant periods of pulsatile HMP on histology and renal injury in warm-ischemic kidneys. Twelve minipigs were used. WI was achieved in the right kidney by applying a vascular clamp for 45 min. After nephrectomy, autotransplant was performed following one of two strategies: cold storage of the kidneys or cold storage combined with perfusion in pulsatile HMP. The graft was removed early to study renal morphology, inflammation (fibrosis), and apoptosis. Proinflammatory activity and fibrosis were less pronounced after cold storage of the kidneys with HMP than after cold storage only. The use of HMP also decreased apoptosis compared with cold storage only. The detrimental effects on cells of an initial and prolonged period of WI seem to improve with a preservation protocol that includes a short period of pulsatile HMP after cold storage and immediately before the transplant, in comparison with cold storage only.

  1. [CT evaluation of extravascular perfusion of contrast medium and its potential to a new method of diagnosis: an experimental study using macro, micro-molecular contrast media].

    PubMed

    Sako, M; Sugimoto, K; Matsumoto, S; Hirota, S; Fujita, Y; Hasegawa, Y; Kuwata, Y; Tomita, M; Murakami, T; Kono, M

    1994-03-25

    To evaluate the dynamics of extravascular perfusion, dynamic CT with two different molecular sized contrast media was performed on VX2 tumor of rabbit. The first dynamic CT was performed with a bolus injection of iopamidol (IP:120 mgI/ml, 5 ml). After ascertaining that the tumor attenuation had returned to the pre-contrast level, the second dynamic CT was performed on the same slice with bolus injection of iodoethylated starch (IES:120 mgI/ml). The time-density (T-D) curves of the same tumor area on the images obtained by two contrast media were compared. The T-D curve with IP showed definitely higher level than that with IES. This occurrence can be explained that IP, 13 A in size, has higher permeability distributing not only in the intravascular space, but also into the extravascular space. On the other hand, IES, 200 A in size, will stay mostly in the intravascular space. From this, we consider that the attenuation difference between the two curves will be an indicator for the dynamics of extravascular perfusion, suggesting to become a new method for CT diagnosis.

  2. Beneficial Effect of Short Pretransplant Period of Hypothermic Pulsatile Perfusion of the Warm-Ischemic Kidney after Cold Storage: Experimental Study

    PubMed Central

    Humanes, Blanca; Jado, Juan Carlos; Mojena, Marina; González-Nicolás, María Ángeles; del Cañizo, Juan Francisco; Lledó-García, Enrique

    2016-01-01

    Warm ischemia (WI) produces a significant deleterious effect in potential kidney grafts. Hypothermic machine perfusion (HMP) seems to improve immediate graft function after transplant. Our aim was to analyze the effect of short pretransplant periods of pulsatile HMP on histology and renal injury in warm-ischemic kidneys. Twelve minipigs were used. WI was achieved in the right kidney by applying a vascular clamp for 45 min. After nephrectomy, autotransplant was performed following one of two strategies: cold storage of the kidneys or cold storage combined with perfusion in pulsatile HMP. The graft was removed early to study renal morphology, inflammation (fibrosis), and apoptosis. Proinflammatory activity and fibrosis were less pronounced after cold storage of the kidneys with HMP than after cold storage only. The use of HMP also decreased apoptosis compared with cold storage only. The detrimental effects on cells of an initial and prolonged period of WI seem to improve with a preservation protocol that includes a short period of pulsatile HMP after cold storage and immediately before the transplant, in comparison with cold storage only. PMID:27556029

  3. Fluorescence endoscopic imaging for evaluation of gastric mucosal blood flow: a preliminary study

    NASA Astrophysics Data System (ADS)

    Bocquillon, Nicolas; Mordon, Serge R.; Mathieu, D.; Maunoury, Vincent; Marechal, Xavier-Marie; Neviere, Remi; Wattel, Francis; Chopin, Claude

    1999-02-01

    Microcirculatory disorders of the gastrointestinal tract appear to be a major compound of the multiple organ dysfunction syndrome secondary to sepsis or septic shock. A better analysis of mucosal hypoperfusion in critically ill patients with sepsis may be helpful for the comprehension of this high mortality-associated syndrome. Fluorescence endoscopy has been recognized as a non-invasive method for both spatial and temporal evaluation of gastrointestinal mucosal perfusion. We performed this imaging technique during routine gastric endoscopy in patients with sepsis criteria. The study included gastric observation and appearance time of gastric fluorescence after an intravenous 10% sodium - fluorescein bolus. Qualitative analysis of high fluorescence areas was compared with mucosal blood flow measurements by laser - Doppler flowmetry. We concluded that the fluorescence endoscopic imaging in critically ill patients with sepsis may reveal spacial and temporal differences in the mucosal microcirculation distribution.

  4. Abdominal perfusion computed tomography.

    PubMed

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-02-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis.

  5. Abdominal Perfusion Computed Tomography

    PubMed Central

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M. Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-01-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis. PMID:25610249

  6. Organizing a mucosal defense.

    PubMed

    Newberry, Rodney D; Lorenz, Robin G

    2005-08-01

    Gastrointestinal associated lymphoid tissue can be divided into loosely organized effector sites, which include the lamina propria and intraepithelial lymphocytes, and more organized structures, such as mesenteric lymph nodes (LNs), Peyer's patches (PPs), isolated lymphoid follicles, and cryptopatches (CPs). These organized structures in the gastrointestinal tract have been hypothesized to play the role of primary lymphoid organ, supporting the extrathymic development of T lymphocytes (CPs), secondary lymphoid organs involved in the induction of the mucosal immune response (PPs), and tertiary lymphoid structures whose function is still under debate (isolated lymphoid follicles). The most widely studied lymphoid structure found in the small intestine is the PP. PPs are secondary lymphoid structures, and their development and function have been extensively investigated. However, single lymphoid aggregates resembling PPs have been also described in humans and in the murine small intestines. These isolated lymphoid follicles have both germinal centers and an overlying follicle-associated epithelium, suggesting that they also can function as inductive sites for the mucosal immune response. This review compares and contrasts the development and function of the four main organized gastrointestinal lymphoid tissues: CPs, isolated lymphoid follicles, PPs, and mesenteric LNs.

  7. Mucosal biofilms of Candida albicans.

    PubMed

    Ganguly, Shantanu; Mitchell, Aaron P

    2011-08-01

    Biofilms are microbial communities that form on surfaces and are embedded in an extracellular matrix. C. albicans forms pathogenic mucosal biofilms that are evoked by changes in host immunity or mucosal ecology. Mucosal surfaces are inhabited by many microbial species; hence these biofilms are polymicrobial. Several recent studies have applied paradigms of biofilm analysis to study mucosal C. albicans infections. These studies reveal that the Bcr1 transcription factor is a master regulator of C. albicans biofilm formation under diverse conditions, though the most relevant Bcr1 target genes can vary with the biofilm niche. An important determinant of mucosal biofilm formation is the interaction with host defenses. Finally, studies of interactions between bacterial species and C. albicans provide insight into the communication mechanisms that endow polymicrobial biofilms with unique properties.

  8. The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils

    PubMed Central

    Driss, V; El Nady, M; Delbeke, M; Rousseaux, C; Dubuquoy, C; Sarazin, A; Gatault, S; Dendooven, A; Riveau, G; Colombel, J F; Desreumaux, P; Dubuquoy, L; Capron, M

    2016-01-01

    Intestinal helminth parasites are potent inducers of T helper type 2 (Th2) response and have a regulatory role, notably on intestinal inflammation. As infection with schistosomes is unlikely to provide a reliable treatment of inflammatory bowel diseases, we have investigated the beneficial effect of a schistosome enzymatic protein, the 28-kDa glutathione S-transferase (P28GST), on the modulation of disease activity and immune responses in experimental colitis. Our results showed that immunization with recombinant P28GST is at least as efficient as established schistosome infection to reduce colitis lesions and expression of pro-inflammatory cytokines. Considering underlying mechanisms, the decrease of inflammatory parameters was associated with the polarization of the immune system toward a Th2 profile, with local and systemic increases of interleukin (IL)-13 and IL-5. Dense eosinophil infiltration was observed in the colons of P28GST-immunized rats and mice. Depletion of eosinophils by treatment with an anti-Siglec-F monoclonal antibody and use of IL-5-deficient mice led to the loss of therapeutic effect, suggesting the crucial role for eosinophils in colitis prevention by P28GST. These findings reveal that immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation through eosinophil-dependent modulation of harmful type 1 responses, representing a new immuno-regulatory strategy against inflammatory bowel diseases. PMID:26174763

  9. 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

  10. The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils.

    PubMed

    Driss, V; El Nady, M; Delbeke, M; Rousseaux, C; Dubuquoy, C; Sarazin, A; Gatault, S; Dendooven, A; Riveau, G; Colombel, J F; Desreumaux, P; Dubuquoy, L; Capron, M

    2016-03-01

    Intestinal helminth parasites are potent inducers of T helper type 2 (Th2) response and have a regulatory role, notably on intestinal inflammation. As infection with schistosomes is unlikely to provide a reliable treatment of inflammatory bowel diseases, we have investigated the beneficial effect of a schistosome enzymatic protein, the 28-kDa glutathione S-transferase (P28GST), on the modulation of disease activity and immune responses in experimental colitis. Our results showed that immunization with recombinant P28GST is at least as efficient as established schistosome infection to reduce colitis lesions and expression of pro-inflammatory cytokines. Considering underlying mechanisms, the decrease of inflammatory parameters was associated with the polarization of the immune system toward a Th2 profile, with local and systemic increases of interleukin (IL)-13 and IL-5. Dense eosinophil infiltration was observed in the colons of P28GST-immunized rats and mice. Depletion of eosinophils by treatment with an anti-Siglec-F monoclonal antibody and use of IL-5-deficient mice led to the loss of therapeutic effect, suggesting the crucial role for eosinophils in colitis prevention by P28GST. These findings reveal that immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation through eosinophil-dependent modulation of harmful type 1 responses, representing a new immuno-regulatory strategy against inflammatory bowel diseases.

  11. Esophageal blood flow in the cat. Normal distribution and effects of acid perfusion

    SciTech Connect

    Hollwarth, M.E.; Smith, M.; Kvietys, P.R.; Granger, D.N.

    1986-03-01

    The radioactive microsphere technique was used to estimate blood flow to different regions of the esophagus and to adjacent regions of the stomach before and after perfusion of the esophagus with hydrochloric acid (pH 1.5) for 5 min. Under resting conditions total blood flow, as well as blood flow to the mucosal-submucosal layer and the muscular layer, to both sphincters was significantly higher than to the esophageal body. Blood flow to the adjacent regions of the stomach was significantly higher than esophageal blood flow. Acid perfusion resulted in a large increase in total blood flow in both sphincters and the lower esophageal body. Gastric blood flow was not altered by acid perfusion. The esophageal hyperemia resulted primarily from an increase in blood flow to the muscular layer; mucosal-submucosal blood flow was increased only in the lower esophageal sphincter. The present study indicates that short periods (5 min) of gastroesophageal reflux may increase esophageal blood flow.

  12. GPU-accelerated voxelwise hepatic perfusion quantification.

    PubMed

    Wang, H; Cao, Y

    2012-09-07

    Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using compute unified device architecture-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, nonlinear least-squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626 400 voxels in a patient's liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10(-6). The method will be useful for generating liver perfusion images in clinical settings.

  13. Quantitative myocardial perfusion SPECT.

    PubMed

    Tsui, B M; Frey, E C; LaCroix, K J; Lalush, D S; McCartney, W H; King, M A; Gullberg, G T

    1998-01-01

    In recent years, there has been much interest in the clinical application of attenuation compensation to myocardial perfusion single photon emission computed tomography (SPECT) with the promise that accurate quantitative images can be obtained to improve clinical diagnoses. The different attenuation compensation methods that are available create confusion and some misconceptions. Also, attenuation-compensated images reveal other image-degrading effects including collimator-detector blurring and scatter that are not apparent in uncompensated images. This article presents basic concepts of the major factors that degrade the quality and quantitative accuracy of myocardial perfusion SPECT images, and includes a discussion of the various image reconstruction and compensation methods and misconceptions and pitfalls in implementation. The differences between the various compensation methods and their performance are demonstrated. Particular emphasis is directed to an approach that promises to provide quantitative myocardial perfusion SPECT images by accurately compensating for the 3-dimensional (3-D) attenuation, collimator-detector response, and scatter effects. With advances in the computer hardware and optimized implementation techniques, quantitatively accurate and high-quality myocardial perfusion SPECT images can be obtained in clinically acceptable processing time. Examples from simulation, phantom, and patient studies are used to demonstrate the various aspects of the investigation. We conclude that quantitative myocardial perfusion SPECT, which holds great promise to improve clinical diagnosis, is an achievable goal in the near future.

  14. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

  15. Parenteral Vaccination Can Be an Effective Means of Inducing Protective Mucosal Responses

    PubMed Central

    Freytag, Lucy C.

    2016-01-01

    The current paradigm in vaccine development is that nonreplicating vaccines delivered parenterally fail to induce immune responses in mucosal tissues. However, both clinical and experimental data have challenged this concept, and numerous studies have shown that induction of mucosal immune responses after parenteral vaccination is not a rare occurrence and might, in fact, significantly contribute to the protection against mucosal infections afforded by parenteral vaccines. While the mechanisms underlying this phenomenon are not well understood, the realization that parenteral vaccination can be an effective means of inducing protective mucosal responses is paradigm-shifting and has potential to transform the way vaccines are designed and delivered. PMID:27122485

  16. [Portable peristaltic perfusion pumps].

    PubMed

    Magallón Pedrera, I; Soto Torres, I

    1999-11-01

    Portable peristaltic perfusion pumps allow one to administer pharmaceuticals in hospitals as well as in primary health care centers and furthermore these pumps present multiple advantages for patients and their families since they make it possible to carry out treatment in a patient's home while at the same time lowering the costs involved. The authors analyze the most out standing aspects of portable peristaltic perfusion pumps along with their characteristics, installation, programming, and how to turn them on; in addition, the authors list the maintenance care which these pumps require.

  17. Gastroduodenal Mucosal Defense Mechanisms

    PubMed Central

    Said, Hyder; Kaji, Izumi; Kaunitz, Jonathan D.

    2015-01-01

    Purpose of Review To highlight recent developments in the field of gastroduodenal mucosal defense with emphasis on lumen-gut interactions. Recent Findings There has been a growing interest in the physiological functions of luminal chemosensors present from tongue to colon that detect organic molecules in the luminal content associated with nutrient ingestion, usually associated with specialized cells, in particular the enteroendocrine cells. These receptors transduce the release of peptide hormones, in particular proglucagon-derived products such as the glucagon-like-peptides (GLPs), which have profound effects on gut function and on metabolism. Luminal chemosensors transduce GLP release in response to changes in the cellular environment, as part of the mechanism of nutrient chemosensing. GLP-2 has important trophic effects on the intestinal mucosa, including increasing the proliferation rate of stem cells and reducing transmucosal permeability to ions and small molecules, in addition to increasing the rate of duodenal bicarbonate secretion. GLP-1, although traditionally considered an incretin that enhances the effect of insulin on peripheral tissues, also has trophic effects on the intestinal epithelium. Summary A better understanding of the mechanisms that mediate GLP release can further illuminate the importance of nutrient chemosensing as an important component of the mechanism that mediates the trophic effects of luminal nutrients. GLP-1 and -2 are already in clinical use for the treatment of diabetes and intestinal failure. Improved understanding of the control of their release and their end-organ effects will identify new clinical indications and interventions that enhance their release. PMID:26376476

  18. Role of endogenous gastric mucosal prostaglandins in the formation of acute gastric mucosal lesions induced by aspirin, ethanol, HCl and CH3COOH.

    PubMed

    Amioka, I; Arima, T; Nagashima, H

    1987-06-01

    The role of endogenous mucosal prostaglandins (PGs) in the production of acute gastric mucosal lesions (AGML) was examined in rats. Aspirin, ethanol or 0.6 N-HCl was given intragastrically and 20% acetic acid was injected into the gastric wall. Endogenous gastric mucosal PG (A + B), PGE and PGF were determined by radioimmunoassay. Their gastric contents were markedly reduced by aspirin administration (p less than 0.001). The level of gastric mucosal PGs still remained low (p less than 0.001) after the aspirin-induced AGML began to heal. Furthermore, rats with AGML induced by ethanol, HCl or acetic acid, showed no decrease in endogenous gastric mucosal PGs compared with the controls. These findings indicated that endogenous PGs are not necessary for either the induction or healing of experimental AGML.

  19. Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo.

    PubMed

    Sommansson, Anna; Saudi, Wan Salman Wan; Nylander, Olof; Sjöblom, Markus

    2013-07-01

    Increased intestinal permeability is often associated with epithelial inflammation, leaky gut, or other pathological conditions in the gastrointestinal tract. We recently found that melatonin decreases basal duodenal mucosal permeability, suggesting a mucosal protective mode of action of this agent. The aim of the present study was to elucidate the effects of melatonin on ethanol-, wine-, and HCl-induced changes of duodenal mucosal paracellular permeability and motility. Rats were anesthetized with thiobarbiturate and a ~30-mm segment of the proximal duodenum was perfused in situ. Effects on duodenal mucosal paracellular permeability, assessed by measuring the blood-to-lumen clearance of ⁵¹Cr-EDTA, motility, and morphology, were investigated. Perfusing the duodenal segment with ethanol (10 or 15% alcohol by volume), red wine, or HCl (25-100 mM) induced concentration-dependent increases in paracellular permeability. Luminal ethanol and wine increased, whereas HCl transiently decreased duodenal motility. Administration of melatonin significantly reduced ethanol- and wine-induced increases in permeability by a mechanism abolished by the nicotinic receptor antagonists hexamethonium (iv) or mecamylamine (luminally). Signs of mucosal injury (edema and beginning of desquamation of the epithelium) in response to ethanol exposure were seen only in a few villi, an effect that was histologically not changed by melatonin. Melatonin did not affect HCl-induced increases in mucosal permeability or decreases in motility. Our results show that melatonin reduces ethanol- and wine-induced increases in duodenal paracellular permeability partly via an enteric inhibitory nicotinic-receptor dependent neural pathway. In addition, melatonin inhibits ethanol-induced increases in duodenal motor activity. These results suggest that melatonin may serve important gastrointestinal barrier functions.

  20. Biology of HIV Mucosal Transmission

    PubMed Central

    Wu, Li

    2008-01-01

    Purpose of review HIV-1 mucosal transmission plays a critical role in HIV-1 infection and AIDS pathogenesis. This review summarizes the latest advances in biological studies of HIV-1 mucosal transmission, highlighting the implications of these studies in the development of microbicides to prevent HIV-1 transmission. Recent findings New studies of initial HIV-1 infection using improved culture models updated the current view of mucosal transmission. Mechanistic studies enhanced our understanding of cell-cell transmission of HIV-1 mediated by the major target cells, including dendritic cells, CD4+ T cells, and macrophages. Increasing evidence indicated the significance of host factors and immune responses in HIV-1 mucosal infection and transmission. Summary Recent progress in HIV-1 mucosal infection and transmission enriches our knowledge of virus-host interactions and viral pathogenesis. Functional studies of HIV-1 interactions with host cells can provide new insights into the design of more effective approaches to combat HIV-1 infection and AIDS. PMID:18802490

  1. Contactless mapping of rhythmical phenomena in tissue perfusion using PPGI

    NASA Astrophysics Data System (ADS)

    Huelsbusch, Markus; Blazek, Vladimir

    2002-04-01

    This paper presents the experimental setup and preliminary results of a near infrared CCD camera based Photoplethysmography Imaging (PPGI) system, which has been shown to be suitable for contactless and spatially resolved assessment of rhythmical blood volume changes in the skin. To visualize the complex rhythmical patterns in the dermal perfusion the Wavelet Transform is utilized. It is able to jointly assess time and frequency behavior of signals and thus allows to analyze instationary oscillations and variabilities in the different human rhythmics. The presented system is expected to provide new insights into the functional sequences of physiological tissue perfusion as well as of the perfusion status in ulcer formation and wound healing.

  2. The mucosal immune system: from fundamental concepts to vaccine development.

    PubMed

    McGhee, J R; Mestecky, J; Dertzbaugh, M T; Eldridge, J H; Hirasawa, M; Kiyono, H

    1992-01-01

    Recent studies in experimental animals and humans have shown that the mucosal immune system, which is characterized by secretory IgA (S-IgA) antibodies as the major humoral defence factor, contains specialized lymphoid tissues where antigens are encountered from the environment, are taken up and induce B- and T-cell responses. This event is followed by an exodus of specific lymphocytes, which home to various effector sites such as the lamina propria regions and glands. These responses are regulated by T cells and cytokines and lead to plasma cell differentiation and subsequent production of S-IgA antibodies in external secretions. This knowledge has led to practical approaches for vaccine construction and delivery into mucosal inductive sites in an effort to elicit host protection at mucosal surfaces where the infection actually occurs.

  3. Sex differences and effects of oestrogen in rat gastric mucosal defence

    PubMed Central

    Shore, Richard; Björne, Håkan; Omoto, Yoko; Siemiatkowska, Anna; Gustafsson, Jan-Åke; Lindblad, Mats; Holm, Lena

    2017-01-01

    AIM To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence. METHODS Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model. Subsequently, sex differences in the distribution of oestrogen receptors and calcitonin gene related peptide in the gastric mucosa of animals exposed to oestrogen in the above experiments was evaluated using immunohistochemistry. RESULTS The absolute blood flow in the GI-tract was generally higher in males, but only significantly different in the corpus part of the stomach (1.12 ± 0.12 mL/min•g in males and 0.51 ± 0.03 mL/min•g in females) (P = 0.002). After removal of the loosely adherent mucus layer the thickness of the firmly adherent mucus layer in males and females was 79 ± 1 µm and 80 ± 3 µm respectively. After 60 min the mucus thickness increased to 113 ± 3 µm in males and 121 ± 3 µm in females with no statistically significant difference seen between the sexes. Following oestrogen administration (0.1 followed by 1 µg/kg•min), mean blood flow in the gastric mucosa decreased by 31% [68 ± 13 perfusion units (PFU)] in males which was significantly different compared to baseline (P = 0.02). In females however, mean blood flow remained largely unchanged with a 4% (5 ± 33 PFU) reduction. The permeability of the gastric mucosa increased to a higher level in females than in males (P = 0.01) after taurocholate challenge. However, the calculated mean clearance increase did not significantly differ between the sexes [0.1 ± 0.04 to 1.1 ± 0.1 mL/min•100 g in males and 0.4 ± 0.3 to 2.1 ± 0.3 mL/min•100 g in females (P = 0.065)]. There were no significant differences between 17

  4. Multiscale modeling of mucosal immune responses

    PubMed Central

    2015-01-01

    Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T cell differentiation and tissue level cell-cell interactions was developed to illustrate the capabilities, power and scope of ENISI MSM. Background Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Implementation Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. Conclusion We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut

  5. Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion.

    PubMed

    Thews, O; Hummel, M; Kelleher, D K; Lecher, B; Vaupel, P

    2002-12-02

    Isolated limb perfusion allows the direct application of therapeutic agents to a tumour-bearing extremity. The present study investigated whether the dihydropyridine-type Ca(2+)-channel blocker nifedipine could improve blood flow and oxygenation status of experimental tumours during isolated limb perfusion. Perfusion was performed by cannulation of the femoral artery and vein in rats bearing DS-sarcoma on the hind foot dorsum. Perfusion rate was adjusted to maintain a perfusion pressure of 100-140 mmHg throughout the experiment. Following equilibration, nifedipine was continuously infused for 30 min (8.3 microg min(-1) kg(-1) BW). During constant-pressure isolated limb perfusion, nifedipine can significantly increase perfusion rate (+100%) and RBC flux (+60%) through experimental leg tumours. "Steal phenomena" in favour of the surrounding normal tissue and oedema formation were not observed. Despite the increased oxygen availability (+63%) seen upon application of this calcium channel blocker, nifedipine does not result in a substantial reduction of tumour hypoxia, most probably due to an increase in O(2) uptake with rising O(2) supply to the tumour-bearing hind limb. Nifedipine application during isolated limb perfusion can enhance tumour microcirculation and may therefore promote the delivery (pharmacokinetics) of anti-cancer drugs to the tumour and by this improve the efficacy of pressure-controlled isolated limb perfusion.

  6. Primary mucosal melanomas: a comprehensive review

    PubMed Central

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

    2012-01-01

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

  7. The Mucosal Immune System of Teleost Fish

    PubMed Central

    Salinas, Irene

    2015-01-01

    Teleost fish possess an adaptive immune system associated with each of their mucosal body surfaces. Evidence obtained from mucosal vaccination and mucosal infection studies reveal that adaptive immune responses take place at the different mucosal surfaces of teleost. The main mucosa-associated lymphoid tissues (MALT) of teleosts are the gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), the gill-associated lymphoid tissue (GIALT) and the recently discovered nasopharynx-associated lymphoid tissue (NALT). Teleost MALT includes diffuse B cells and T cells with specific phenotypes different from their systemic counterparts that have co-evolved to defend the microbe-rich mucosal environment. Both B and T cells respond to mucosal infection or vaccination. Specific antibody responses can be measured in the gills, gut and skin mucosal secretions of teleost fish following mucosal infection or vaccination. Rainbow trout studies have shown that IgT antibodies and IgT+ B cells are the predominant B cell subset in all MALT and respond in a compartmentalized manner to mucosal infection. Our current knowledge on adaptive immunity in teleosts is limited compared to the mammalian literature. New research tools and in vivo models are currently being developed in order to help reveal the great intricacy of teleost mucosal adaptive immunity and help improve mucosal vaccination protocols for use in aquaculture. PMID:26274978

  8. Effect of cardiac dysrhythmia on cerebral perfusion.

    PubMed

    Sand, B J; Rose, H B; Barker, W F

    1976-07-01

    Extracranial carotid arterial obstructive disease has been the entity most commonly associated with transient cerebrovascular insufficiency. A nonobstructive, frequently overlooked cause of cerebral ischemia is cardiac dysrhythmia. We have explored this by observations of experimental animals and of man. Blood flow and pressure in the carotid arteries of dogs were shown to be decreased by mechnically induced premature ventricular contractions. The significance of the cardiogenic contribution to altered cerebrovascular perfusion was studied by ocular and brachial plethysmography in 210 patients suspected by history of having carotid arterial insufficiency. Of the 210 patients, 62 demonstrated abnormal ocular plethysmographic recordings, and of those, nine had dysrhythmias associated with significant deficits of ocular perfusion. Five patients whose recordings were technically suitable for publication are presented to demonstrate the bizarre ocular plethysmographic recordings seen during the dysrhythmic cycle.

  9. Harmonic analysis of perfusion pumps.

    PubMed

    Dougherty, F Carroll; Donovan, F M; Townsley, Mary I

    2003-12-01

    The controversy over the use of nonpulsatile versus pulsatile pumps for maintenance of normal organ function during ex vivo perfusion has continued for many years, but resolution has been limited by lack of a congruent mathematical definition of pulsatility. We hypothesized that the waveform frequency and amplitude, as well as the underlying mean distending pressure are all key parameters controlling vascular function. Using discrete Fourier Analysis, our data demonstrate the complexity of the pulmonary arterial pressure waveform in vivo and the failure of commonly available perfusion pumps to mimic in vivo dynamics. In addition, our data show that the key harmonic signatures are intrinsic to the perfusion pumps, are similar for flow and pressure waveforms, and are unchanged by characteristics of the downstream perfusion circuit or perfusate viscosity.

  10. Mucosal injury induced by ischemia and reperfusion in the piglet intestine: Influences of age and feeding

    SciTech Connect

    Crissinger, K.D.; Granger, D.N. )

    1989-10-01

    The pathogenesis of neonatal necrotizing enterocolitis is unknown, but enteral alimentation, infectious agents, and mesenteric ischemia have been frequently invoked as primary initiators of the disease. To define the vulnerability of the intestinal mucosa to ischemia and reperfusion in the developing piglet, we evaluated changes in mucosal permeability using plasma-to-lumen clearance of chromium 51-labeled ethylenediaminetetraacetic acid in the ileum of anesthetized 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets as a function of (a) duration of intestinal ischemia (20, 40, or 60 min of total superior mesenteric artery occlusion), (b) feeding status (fasted or nursed), and (c) composition of luminal perfusate (balanced salt solution vs. predigested cow milk-based formula). Baseline chromium 51-labeled ethylenediaminetetraacetic acid clearance was not significantly altered by ischemia, irrespective of duration, or feeding in all age groups. However, clearances were significantly elevated during reperfusion after 1 h of total intestinal ischemia in all age groups, whether fasted or fed. Reperfusion-induced increases in clearance did not differ among age groups when the bowel lumen was perfused with a balanced salt solution. However, luminal perfusion with formula resulted in higher clearances in 1-day-old piglets compared with all older animals. Thus, the neonatal intestine appears to be more vulnerable to mucosal injury induced by ischemia and reperfusion in the presence of formula than the intestine of older animals.

  11. Ex vivo lung perfusion

    PubMed Central

    Machuca, Tiago N.

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972

  12. Noncontact blood perfusion mapping in clinical applications

    NASA Astrophysics Data System (ADS)

    Iakovlev, Dmitry; Dwyer, Vincent; Hu, Sijung; Silberschmidt, Vadim

    2016-04-01

    Non-contact imaging photoplethysmography (iPPG) to detect pulsatile blood microcirculation in tissue has been selected as a successor to low spatial resolution and slow scanning blood perfusion techniques currently employed by clinicians. The proposed iPPG system employs a novel illumination source constructed of multiple high power LEDs with narrow spectral emission, which are temporally modulated and synchronised with a high performance sCMOS sensor. To ensure spectrum stability and prevent thermal wavelength drift due to junction temperature variations, each LED features a custom-designed thermal management system to effectively dissipate generated heat and auto-adjust current flow. The use of a multi-wavelength approach has resulted in simultaneous microvascular perfusion monitoring at various tissue depths, which is an added benefit for specific clinical applications. A synchronous detection algorithm to extract weak photoplethysmographic pulse-waveforms demonstrated robustness and high efficiency when applied to even small regions of 5 mm2. The experimental results showed evidences that the proposed system could achieve noticeable accuracy in blood perfusion monitoring by creating complex amplitude and phase maps for the tissue under examination.

  13. Cerebral-Body Perfusion Model

    DTIC Science & Technology

    1990-07-01

    compared to the 0.5g curve) fall in flow. Fig. 9b, showing the 5g case, strongly suggests a possible, so-called, " luxury perfusion ", in which natural...as the luxury perfusion situation which bypasses the flow with the nutrients it carries (through newly opened collaterals) and result in a "blackout...89-0054 CEREBRAL-BODY PERFUSION MODEL S. Sorek’, J. Bear2, and M., Feinsod3 in Collaboration with K. Allen4, L. Bunt5 and S. Ben-IHaiM6 July 1990

  14. Effect of Hymenolepis nana on the mouse ileal mucosal cells: histochemical studies.

    PubMed

    Sanad, M M; Salem, S A; el-Gamal, R L; Darwish, R A; el-Ridi, A M

    1990-12-01

    Histochemical studies of the ileal mucosal cells of mice experimentally infected with H. nana revealed definite increase in mucous secretions indicating increased activity of the goblet cells in response to mucosal irritation. The activity of acid phosphatase was also increased representing a sort of defence mechanism against the attached worms. The activities of ATP-ase and NADH diaphorase enzymes were decreased indicating disturbance in the metabolic and transport processes and in the absorptive function of the intestinal epithelial cells.

  15. The Development of an AIDS Mucosal Vaccine

    PubMed Central

    Tang, Xian; Chen, Zhiwei

    2010-01-01

    It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies. PMID:21994611

  16. Topical therapy for mucosal yeast infections.

    PubMed

    Summers, Paul R

    2011-01-01

    Mucosal yeast infection is best understood as a consequence of compromised mucosal cell-mediated and innate immunity. Defense against oral candidiasis is dominantly cell mediated. The innate immune system may play the main role in regulating vulvovaginal yeast infection. Conditions that compromise cell-mediated immunity such as leukemia, severe illness and HIV infection must be considered as predisposing factors for recurrent oral candidiasis. Compromise of vaginal innate immunity due to mucosal allergy or due to a genetic defect such as mannose-binding lectin deficiency contributes to chronic vulvovaginal yeast infection. Treatment of cofactors must be considered in order to achieve control in recurrent mucosal yeast infection.

  17. The effects of progressive anemia on jejunal mucosal and serosal tissue oxygenation in pigs.

    PubMed

    Haisjackl, M; Luz, G; Sparr, H; Germann, R; Salak, N; Friesenecker, B; Deusch, E; Meusburger, S; Hasibeder, W

    1997-03-01

    Anemia may promote intestinal hypoxia. We studied the effects of progressive isovolemic hemodilution on jejunal mucosal (Po2muc), and serosal tissue oxygen tension (Po2ser, Clark-type surface electrodes), mucosal microvascular hemoglobin oxygen saturation (Hbo2muc), and hematocrit (Hctmuc; tissue reflectance spectophotometry) in a jejunal segment. Twelve domestic pigs were anesthetized, paralyzed, and mechanically ventilated. Laparatomy was performed, arterial supply of a jejunal segment isolated, and constant pressure pump perfused. Seven animals were progressively hemodiluted to systemic hematocrits (Hctsys) of 20%, 15%, 10%, and 6%. Baseline for Po2muc, Po2ser and Hbo2muc was 23.5 +/- 2.1 mm Hg, 57.5 +/- 4 mm Hg, and 47.0% +/- 6.4% which were not different from the five controls. Despite a significant increase in jejunal blood flow, jejunal oxygen delivery decreased and oxygen extraction ratio increased significantly at Hctsys 10% and 6%. Po2ser decreased significantly below or at Hctsys of 15%, whereas Po2muc and Hbo2muc were maintained to Hctsys of 10%, but less than 10% Hbo2muc and mesenteric venous pH decreased significantly, implying that physiological limits of jejunal microvascular adaptation to severe anemia were reached. Decrease of Hctmuc was less pronounced than Hctsys. In conclusion, redistribution of jejunal blood flow and an increase in the ratio of mucosal to systemic hematocrit are the main mechanisms maintaining mucosal oxygen supply during progressive anemia.

  18. Voice Disorders in Mucosal Leishmaniasis

    PubMed Central

    Ruas, Ana Cristina Nunes; Lucena, Márcia Mendonça; da Costa, Ananda Dutra; Vieira, Jéssica Rafael; de Araújo-Melo, Maria Helena; Terceiro, Benivaldo Ramos Ferreira; de Sousa Torraca, Tania Salgado; de Oliveira Schubach, Armando; Valete-Rosalino, Claudia Maria

    2014-01-01

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

  19. Pulmonary ventilation/perfusion scan

    MedlinePlus

    ... JavaScript. A pulmonary ventilation/perfusion scan involves two nuclear scan tests to measure breathing (ventilation) and circulation ( ... In: Mettler FA, Guiberteau MJ, eds. Essentials of Nuclear Medicine Imaging . 6th ed. Philadelphia, PA: Elsevier Saunders; ...

  20. Role of capsaicin sensitive nerves in epidermal growth factor effects on gastric mucosal injury and blood flow

    PubMed Central

    Kang, J; Teng, C; Chen, F; Wee, A

    1998-01-01

    Background—Epidermal growth factor (EGF) and capsaicin protect against experimental gastric mucosal injury. Capsaicin exerts its gastroprotective effect by stimulating afferent neurones leading to release of calcitonin gene related peptide (CGRP) which causes gastric hyperaemia. EGF also causes gastric hyperaemia but whether it acts via capsaicin sensitive neurones is unknown. 
Aims—To assess the influence of: (1) capsaicin desensitisation on EGF effects on gastric mucosal injury and gastric mucosal blood flow; and (2) close arterial infusion of hCGRP8-37, a CGRP antagonist, on EGF effects on gastric mucosal blood flow. 
Methods—The absolute ethanol induced gastric mucosal injury model in the rat was used. Gastric mucosal damage was assessed by planimetry and light microscopy. Gastric mucosal blood flow was measured by laser Doppler flowmetry in a gastric chamber preparation. 
Results—Capsaicin desensitisation abolished the gastroprotective and gastric hyperaemic effects of EGF. Close arterial infusion of hCGRP8-37 antagonised the hyperaemic effect of both capsaicin and EGF. 
Conclusion—Results show that EGF may exert its gastroprotective and gastric hyperaemic effects via capsaicin sensitive afferent neurones. 

 Keywords: capsaicin; epidermal growth factor; gastric mucosal injury; gastric mucosal blood flow; calcitonin gene related peptide antagonist; rat PMID:9577339

  1. Mucosal immunity and probiotics in fish.

    PubMed

    Lazado, Carlo C; Caipang, Christopher Marlowe A

    2014-07-01

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

  2. CAD of myocardial perfusion

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2007-03-01

    Our purpose is in the automated evaluation of the physiological relevance of lesions in coronary angiograms. We aim to extract as much as possible quantitative information about the physiological condition of the heart from standard angiographic image sequences. Coronary angiography is still the gold standard for evaluating and diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. The dimensions of the stenosis can be assessed nowadays successfully with image processing based Quantitative Coronary Angiography (QCA) techniques. Our purpose is to assess the clinical relevance of the pertinent stenosis. We therefore analyze the myocardial perfusion as revealed in standard angiographic image sequences. In a Region-of-Interest (ROI) on the angiogram (without an overlaying major blood vessel) the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In order to minimize motion artifacts we select based on the recorded ECG signal end-diastolic images in both a basal and a hyperemic run in the same projection to position the ROI. We present the development of the algorithms together with results of a small study of 20 patients which have been catheterized following the standard protocol.

  3. Antimicrobials, mucosal coating agents, anesthetics, analgesics, and nutritional supplements for alimentary tract mucositis.

    PubMed

    Barasch, Andrei; Elad, Sharon; Altman, Arnold; Damato, Kathryn; Epstein, Joel

    2006-06-01

    This review focuses on the value of several groups of agents for the prevention and treatment of mucositis. The review refers to alimentary mucositis as a generalized term that includes oral mucositis and gastrointestinal mucositis. This paper is part of the systematic review made by the mucositis study group which operates in the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO). Several new guidelines are suggested in this review as an update to the primary systematic review that was published by the same group in 2004.

  4. Prophylactic and therapeutic modulation of innate and adaptive immunity against mucosal infection of herpes simplex virus.

    PubMed

    Uyangaa, Erdenebileg; Patil, Ajit Mahadev; Eo, Seong Kug

    2014-08-01

    Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are the most common cause of genital ulceration in humans worldwide. Typically, HSV-1 and 2 infections via mucosal route result in a lifelong latent infection after peripheral replication in mucosal tissues, thereby providing potential transmission to neighbor hosts in response to reactivation. To break the transmission cycle, immunoprophylactics and therapeutic strategies must be focused on prevention of infection or reduction of infectivity at mucosal sites. Currently, our understanding of the immune responses against mucosal infection of HSV remains intricate and involves a balance between innate signaling pathways and the adaptive immune responses. Numerous studies have demonstrated that HSV mucosal infection induces type I interferons (IFN) via recognition of Toll-like receptors (TLRs) and activates multiple immune cell populations, including NK cells, conventional dendritic cells (DCs), and plasmacytoid DCs. This innate immune response is required not only for the early control of viral replication at mucosal sites, but also for establishing adaptive immune responses against HSV antigens. Although the contribution of humoral immune response is controversial, CD4(+) Th1 T cells producing IFN-γ are believed to play an important role in eradicating virus from the hosts. In addition, the recent experimental successes of immunoprophylactic and therapeutic compounds that enhance resistance and/or reduce viral burden at mucosal sites have accumulated. This review focuses on attempts to modulate innate and adaptive immunity against HSV mucosal infection for the development of prophylactic and therapeutic strategies. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses. Thus, we summarized the current evidence of various immune mediators in response to mucosal HSV infection, focusing on the importance of innate immune responses.

  5. Localized Pemphigus Vegetans without Mucosal Involvement.

    PubMed

    Jain, Vk; Jindal, N; Imchen, S

    2014-03-01

    Pemphigus vegetans is a rare variant of pemphigus vulgaris. A 62-year-old woman presented with erythematous moist vegetative plaque on the left breast and left groin. There was no mucosal involvement. Histopathological and direct immunofluorescence findings were suggestive of pemphigus vegetans. She showed excellent response to oral steroids. Literature is scarcely available on the limited involvement with pemphigus vegetans without mucosal involvement.

  6. Biology and Mucosal Immunity to Myxozoans

    PubMed Central

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

    2014-01-01

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

  7. Mucosal Wave Measurement and Visualization Techniques

    PubMed Central

    Krausert, Christopher R.; Olszewski, Aleksandra E.; Taylor, Lindsay N.; McMurray, James S.; Dailey, Seth H.; Jiang, Jack J.

    2010-01-01

    Organized vibration of the vocal folds is critical to high quality voice production. When the vocal folds oscillate, the superficial tissue of the vocal fold is displaced in a wave-like fashion, creating the so called “mucosal wave”. Because the mucosal wave is dependent on vocal fold structure, physical alterations of that structure cause mucosal wave abnormalities. Visualization and quantification of mucosal wave properties have become useful parameters in diagnosing and managing vocal fold pathology. Mucosal wave measurement provides information about vocal fold characteristics that cannot be determined with other assessment techniques. Here, we discuss the benefits, disadvantages, and clinical applicability of the different mucosal wave measurement techniques, such as electroglottography (EGG), photoglottography (PGG), and ultrasound and visualization techniques that include videokymography (VKG), stroboscopy, and high-speed digital imaging (HSDI). The various techniques and their specific uses are reviewed with the intention of helping researchers and clinicians choose a method for a given situation and understand its limitations as well as its potential applications. Recent applications of these techniques for quantitative assessment demonstrate that additional research must be conducted to realize the full potential of these tools. Evaluations of existing research and recommendations for future research are given to promote both the quantitative study of the mucosal wave through accurate and standardized measurement of mucosal wave parameters and the development of reliable methods with which physicians can diagnose vocal disorders. PMID:20471798

  8. Vaccination Strategies for Mucosal Immune Responses

    PubMed Central

    Ogra, Pearay L.; Faden, Howard; Welliver, Robert C.

    2001-01-01

    Mucosal administration of vaccines is an important approach to the induction of appropriate immune responses to microbial and other environmental antigens in systemic sites and peripheral blood as well as in most external mucosal surfaces. The development of specific antibody- or T-cell-mediated immunologic responses and the induction of mucosally induced systemic immunologic hyporesponsiveness (oral or mucosal tolerance) depend on complex sets of immunologic events, including the nature of the antigenic stimulation of specialized lymphoid structures in the host, antigen-induced activation of different populations of regulatory T cells (Th1 versus Th2), and the expression of proinflammatory and immunoregulatory cytokines. Availability of mucosal vaccines will provide a painless approach to deliver large numbers of vaccine antigens for human immunization. Currently, an average infant will receive 20 to 25 percutaneous injections for vaccination against different childhood infections by 18 months of age. It should be possible to develop for human use effective, nonliving, recombinant, replicating, transgenic, and microbial vector- or plant-based mucosal vaccines to prevent infections. Based on the experience with many dietary antigens, it is also possible to manipulate the mucosal immune system to induce systemic tolerance against environmental, dietary, and possibly other autoantigens associated with allergic and autoimmune disorders. Mucosal immunity offers new strategies to induce protective immune responses against a variety of infectious agents. Such immunization may also provide new prophylactic or therapeutic avenues in the control of autoimmune diseases in humans. PMID:11292646

  9. Mucosal Immunosenescence In The Gastrointestinal Tract

    PubMed Central

    Sato, Shintaro; Kiyono, Hiroshi; Fujihashi, Kohtaro

    2014-01-01

    It has been shown that pathogen-specific secretory IgA (SIgA) antibody (Ab) is the major player at mucosal surfaces for host defense. However, alterations in the mucosal immune system occur in advanced aging which results in a failure of induction of SIgA Abs for protection from infectious diseases. Signs of mucosal senescence first appear in the gut immune system. Further, changes in the intestinal microbiota most likely influence mucosal immunity. To overcome the immunological aging decline in mucosal immunity, several adjuvant systems including mucosal dendritic cell (DC) targeting have been shown to be attractive and effective immunological strategies. Similarly, antigen (Ag) uptake-M cells are ideal targets for facilitating Ag-specific mucosal immune responses. However, the numbers of M cells are reduced in aged mice. In this regard, Spi-B, an essential transcription factor for the functional and structural differentiation of M cells could be a potent strategy for the induction of effective mucosal immunity in aging. PMID:25531743

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

    PubMed

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

    2015-04-01

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

  11. The effect of royal jelly on oral mucositis in patients undergoing radiotherapy and chemotherapy.

    PubMed

    Erdem, Ozden; Güngörmüş, Zeynep

    2014-01-01

    This study was conducted to evaluate the effect of royal jelly on oral mucositis in patients undergoing radiotherapy and chemotherapy. The study population consisted of 103 patients undergoing radiotherapy and chemotherapy. Oral mucositis was graded according to the World Health Organization criteria, and patients were divided into 2 groups. All patients received mouthwash therapy with benzydamine hydrochloride and nystatin rinses. In addition, patients in the experimental group received royal jelly. The mean resolution time of oral mucositis in the royal jelly group was significantly shorter than that of the control group. As a result, the study results demonstrate that royal jelly administrated by a certain procedure improved the signs and symptoms of oral mucositis and markedly shortened its healing time.

  12. Mucositis management in patients with cancer.

    PubMed

    Keefe, Dorothy M K

    2006-04-01

    Mucositis is an important toxicity to be aware of in anticancer therapy. It contributes to a reduction in cure rates from cancer. Until recently, it has been poorly understood and therefore has not been well managed. It causes patient distress, delays in treatment administration, and reductions in dose intensity, and it costs the health-care system a large amount of money. Mucositis has traditionally been associated more with hematologic malignancies than with solid tumors, because the incidence of severe mucositis has been much higher with the high-dose chemotherapy regimens used in hematologic malignancies. However, the chemotherapy used in solid tumors also causes mucositis and deserves further study. The separation between oral and gastrointestinal mucositis is potentially false and is being removed, with much research now investigating the entire alimentary canal. There are similarities and differences between radiation therapy- and chemotherapy-induced mucositis, and these have implications for treatment and prevention scheduling and type. Risk prediction is another area that requires more work, but there is real hope that, in the future, we might be able to predict who will suffer from mucositis and in which parts of the alimentary canal, thus enabling us to appropriately target the newer antimucotoxic therapies. The Mucositis Study Goup of the Multinational Association for Supportive Care in Cancer has recently published management guidelines for oral and gastrointestinal mucositis and is in the process of updating them. The guidelines serve as an excellent starting place for future mucositis research because they not only review the available treatments but also discuss mechanisms and epidemiology.

  13. Intestinal mucosal atrophy and adaptation.

    PubMed

    Shaw, Darcy; Gohil, Kartik; Basson, Marc D

    2012-11-28

    Mucosal adaptation is an essential process in gut homeostasis. The intestinal mucosa adapts to a range of pathological conditions including starvation, short-gut syndrome, obesity, and bariatric surgery. Broadly, these adaptive functions can be grouped into proliferation and differentiation. These are influenced by diverse interactions with hormonal, immune, dietary, nervous, and mechanical stimuli. It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation. This review will summarize current understanding of the basic science surrounding adaptation, delineate the wide range of potential targets for therapeutic intervention, and discuss how these might be incorporated into an overall treatment plan. Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes.

  14. Intestinal mucosal atrophy and adaptation

    PubMed Central

    Shaw, Darcy; Gohil, Kartik; Basson, Marc D

    2012-01-01

    Mucosal adaptation is an essential process in gut homeostasis. The intestinal mucosa adapts to a range of pathological conditions including starvation, short-gut syndrome, obesity, and bariatric surgery. Broadly, these adaptive functions can be grouped into proliferation and differentiation. These are influenced by diverse interactions with hormonal, immune, dietary, nervous, and mechanical stimuli. It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation. This review will summarize current understanding of the basic science surrounding adaptation, delineate the wide range of potential targets for therapeutic intervention, and discuss how these might be incorporated into an overall treatment plan. Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes. PMID:23197881

  15. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    PubMed

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative.

  16. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    PubMed Central

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative. PMID:8566861

  17. Mucosal Vaccine Development Based on Liposome Technology

    PubMed Central

    Norling, Karin; Bally, Marta; Höök, Fredrik

    2016-01-01

    Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines. PMID:28127567

  18. Treatment of oral mucositis due to chemotherapy

    PubMed Central

    Bagán-Sebastián, José V

    2016-01-01

    Introduction The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the management of oral mucositis caused by chemotherapy in cancer patients. Material and Methods An exhaustive search was made of the PubMed-Medline, Cochrane Library and Scopus databases, crossing the key words “oral mucositis”, “prevention” and “treatment” with the terms “chemotherapy” and “radiotherapy” by means of the boolean operators “AND” and “NOT”. A total of 268 articles were obtained, of which 96 met the inclusion criteria. Results Several interventions for the prevention of oral mucositis, such as oral hygiene protocols, amifostine, benzidamine, calcium phosphate, cryotherapy and iseganan, among others, were found to yield only limited benefits. Other studies have reported a decrease in the appearance and severity of mucositis with the use of cytoprotectors (sucralfate, oral glutamine, hyaluronic acid), growth factors, topical polyvinylpyrrolidone, and low power laser irradiation. Conclusions Very few interventions of confirmed efficacy are available for the management of oral mucositis due to chemotherapy. However, according to the reviewed literature, the use of palifermin, cryotherapy and low power laser offers benefits, reducing the incidence and severity of oral mucositis – though further studies are needed to confirm the results obtained. Key words:Chemotherapy-Induced Oral Mucositis Treatment. PMID:27034762

  19. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

    PubMed

    Becker, Simon; Steinmeyer, Jasmin; Avsar, Murat; Höffler, Klaus; Salman, Jawad; Haverich, Axel; Warnecke, Gregor; Ochs, Matthias; Schnapper, Anke

    2016-01-01

    Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition.

  20. Animal models of mucositis: implications for therapy.

    PubMed

    Bowen, Joanne M; Gibson, Rachel J; Keefe, Dorothy M K

    2011-01-01

    Alimentary mucositis is a major acute complication in the clinical setting, occurring in a large percentage of patients undergoing cytotoxic therapy. One of the major problems with alimentary mucositis is that the underlying mechanisms behind its development are not entirely understood, which makes it extremely difficult to develop effective interventions. Animal models provide a critical source of knowledge when sampling from patients is unavailable or interventions are yet to be fully tested. This review focuses on the animal models used to increase our understanding of the mechanisms of mucositis and translate new antimucotoxic agents into clinical trials.

  1. Viable neurons with luxury perfusion in hydrocephalus.

    PubMed

    Wong, C Y; Luciano, M G; MacIntyre, W J; Brunken, R C; Hahn, J F; Go, R T

    1997-09-01

    A woman with hydrocephalus due to aqueductal stenosis had functional imaging of cerebral perfusion and metabolism to demonstrate the effects of endoscopic third ventriculostomy--a new form of internal surgical shunting. Technetium-99m-ECD SPECT and 18F-FDG PET showed regional luxury perfusion at the left frontal region. Three months after a successful third ventriculostomy, a repeated imaging of cerebral perfusion and metabolism showed resolution of luxury perfusion and global improvement of both perfusion and metabolism. This concurred with postoperative clinical improvement. The paired imaging of cerebral perfusion and metabolism provides more information than just imaging perfusion or metabolism. Thus, the detection of perfusion and metabolism mismatch may open a new window of opportunity for surgical intervention.

  2. Construction and validation of a microprocessor controlled extracorporal circuit in rats for the optimization of isolated limb perfusion.

    PubMed

    Gürtler, Ulrich; Fuchs, Peter; Stangelmayer, Achim; Bernhardt, Günther; Buschauer, Armin; Spruss, Thilo

    2004-12-01

    Although a few experimental approaches to isolated limb perfusion (ILP) are described in the literature, none of these animal models mimics the clinical perfusion techniques adequately to improve the technique of ILP on the basis of valid preclinical data. Therefore, we developed an ILP setup in rats allowing online monitoring of essential perfusion parameters such as temperature (in perfusate, various tissues, and rectum), pH (perfusate), perfusion pressure, and O(2) concentration (in perfusate, tissue), by a tailor-made data acquisition system. This setup permits close supervision of vital parameters during ILP. Various interdependencies, concerning the flow rate and the pressure of perfusate as well as tissue oxygenation were registered. For the measurement of pO(2) values in the perfusate and in different regions of the perfused hind limb, a novel type of microoptode based on quenching of a fluorescent dye was devised. Stable normothermic (37 degrees C) perfusion conditions were maintained at a constant perfusion pressure in the range of 40-60 mm Hg by administration of the spasmo lytic moxaverine (0.5 mg/mL of perfusate as initial dose) at a perfusate flow rate of 0.5 mL/min for 60 min. At the end of an ILP, there were no signs of tissue damage, neither concerning laboratory data (K(+), myoglobin, creatine kinase, lactic dehydrogenase) nor histopathological criteria. The reported ILP model is not only well suited to investigate the effects of hyperthermia but also to assess the efficacy of new antineoplastic approaches, when nude rats, bearing human tumours in the hind limbs, are used.

  3. Targeting Mucosal Healing in Crohn's Disease

    PubMed Central

    Kakkar, Aarti; Wasan, Sharmeel K.

    2011-01-01

    The goal of medical treatment for Crohn's disease includes improving patients' quality of life while reducing the need for hospitalization and surgery. The current medical armamentarium includes 5-aminosalicylates, corticosteroids, immunomodulators, and biologic agents. In the past, response to treatment was measured by clinical improvement in symptoms; however, with the advent of disease-modifying medications, mucosal healing has emerged as an increasingly important goal of therapy. Mucosal healing, or endoscopic remission, is associated with increased rates of clinical remission, fewer hospitalizations, and fewer abdominal surgeries. Both the immunomodulator and biologic classes of medications are effective at inducing mucosal healing. Despite several limitations, mucosal healing has become a desirable and valid measure of disease activity. PMID:21869869

  4. Microbiota and mucosal immunity in amphibians.

    PubMed

    Colombo, Bruno M; Scalvenzi, Thibault; Benlamara, Sarah; Pollet, Nicolas

    2015-01-01

    We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence different aspects of mucosal development and function. Yet, the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: (i) the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and (ii) the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small-animal model to improve the fundamental knowledge on immunological functions of gut microbiota.

  5. A regenerative approach towards mucosal fenestration closure.

    PubMed

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

    2013-06-06

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

  6. Microbiota and Mucosal Immunity in Amphibians

    PubMed Central

    Colombo, Bruno M.; Scalvenzi, Thibault; Benlamara, Sarah; Pollet, Nicolas

    2015-01-01

    We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence different aspects of mucosal development and function. Yet, the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: (i) the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and (ii) the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small-animal model to improve the fundamental knowledge on immunological functions of gut microbiota. PMID:25821449

  7. Mucosal Vaccination against Tuberculosis Using Inert Bioparticles

    PubMed Central

    Reljic, Rajko; Sibley, Laura; Huang, Jen-Min; Pepponi, Ilaria; Hoppe, Andreas; Hong, Huynh A.

    2013-01-01

    Needle-free, mucosal immunization is a highly desirable strategy for vaccination against many pathogens, especially those entering through the respiratory mucosa, such as Mycobacterium tuberculosis. Unfortunately, mucosal vaccination against tuberculosis (TB) is impeded by a lack of suitable adjuvants and/or delivery platforms that could induce a protective immune response in humans. Here, we report on a novel biotechnological approach for mucosal vaccination against TB that overcomes some of the current limitations. This is achieved by coating protective TB antigens onto the surface of inert bacterial spores, which are then delivered to the respiratory tract. Our data showed that mice immunized nasally with coated spores developed humoral and cellular immune responses and multifunctional T cells and, most importantly, presented significantly reduced bacterial loads in their lungs and spleens following pathogenic challenge. We conclude that this new vaccine delivery platform merits further development as a mucosal vaccine for TB and possibly also other respiratory pathogens. PMID:23959722

  8. Effects of long chain fatty acids on solute absorption: perfusion studies in the human jejunum.

    PubMed Central

    Ammon, H V; Thomas, P J; Phillips, S F

    1977-01-01

    Perfusion studies were performed in healthy volunteers to test the hypothesis that net fluid secretion induced by fatty acids is accompanied by parallel reduction in solute transport. Ricinoleic acid provoked a marked net secretion of fluid and concomitantly inhibited the absorption of all solutes tested; these included glucose, xylose, L-leucine, L-lysine, Folic acid, and 2-mono-olein. Oleic acid also reduced net fluid and solute transport, but was less potent in reducing solute absorption than was ricinoleic acid. When fluid secretion was induced osmotically with mannitol, glucose and xylose absorption was not affected. The mechanism for this generalised effect of fatty acids on solute absorption is uncertain, possibly nonspecific, and might be related to mucosal damage and altered mucosal permeability induced by these agents. PMID:590838

  9. Polyamines and Gut Mucosal Homeostasis

    PubMed Central

    Timmons, Jennifer; Chang, Elizabeth T.; Wang, Jian-Ying; Rao, Jaladanki N.

    2012-01-01

    The epithelium of gastrointestinal (GI) mucosa has the most rapid turnover rate of any tissue in the body and its integrity is preserved through the dynamic balance between cell migration, proliferation, growth arrest and apoptosis. To maintain tissue homeostasis of the GI mucosa, the rates of epithelial cell division and apoptosis must be highly regulated by various extracellular and intracellular factors including cellular polyamines. Natural polyamines spermidine, spermine and their precursor putrescine, are organic cations in eukaryotic cells and are implicated in the control of multiple signaling pathways and distinct cellular functions. Normal intestinal epithelial growth depends on the available supply of polyamines to the dividing cells in the crypts, and polyamines also regulate intestinal epithelial cell (IEC) apoptosis. Although the specific molecular processes controlled by polyamines remains to be fully defined, increasing evidence indicates that polyamines regulate intestinal epithelial integrity by modulating the expression of various growth-related genes. In this review, we will extrapolate the current state of scientific knowledge regarding the roles of polyamines in gut mucosal homeostasis and highlight progress in cellular and molecular mechanisms of polyamines and their potential clinical applications. PMID:25237589

  10. Thallium-201 myocardial perfusion imaging in myocarditis

    SciTech Connect

    Tamaki, N.; Yonekura, Y.; Kadota, K.; Kambara, H.; Torizuka, K.

    1985-08-01

    TI-201 myocardial perfusion imaging was performed in six patients with clinically documented myocarditis. Each case manifested electrocardiographic abnormalities with elevation of serum cardiac enzymes and no significant stenosis of the coronary arteries observed on angiogram. Resting TI-201 images were visually assessed by three observers. Focal perfusion defects were observed in three cases (50%), among which two showed multiple perfusion defects. Emission computed tomography using TI-201 clearly delineated multifocal lesions in the first case. On the other hand, no significant perfusion defects were noted in the remaining three cases. Thus, myocarditis should be considered as one of the disease entities that may produce perfusion defects on TI-201 myocardial imaging.

  11. Modeling laser irradiation conditions for mucosal tissues in antimicrobial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zalesskaya, G. A.; Astaf'eva, L. G.; Plavskii, V. Yu.

    2012-05-01

    We use computer modeling to analzye empirically selected conditions for antimicrobial photodynamic therapy of mucosal tissues. We calculate the optical and thermal fields for experimental conditions for low-intensity (cold) laser irradiation used in treatment of lesions in mucosal tissues stained by methylene blue: λ = 670 nm, power density 150-300 mW/cm2, doses 9-18 J/cm2; λ = 632.8 nm, 15 mW/cm2, dose 4.5 J/cm2. For numerical estimates, we used the optical characteristics of methylene blue and three layers of mucosal tissues at the laser radiation wavelengths, and also the thermal characteristics of the tissues. The experimental conditions were optimized using the ratio of the tissue penetration depth for the absorbed optical energy and the penetration depth of methylene blue into the lesion, while maintaining safe tissue heating temperatures.

  12. Three-dimensional optical micro-angiography maps directional blood perfusion deep within microcirculation tissue beds in vivo

    NASA Astrophysics Data System (ADS)

    Wang, Ruikang K.

    2007-12-01

    Optical micro-angiography (OMAG) is a recently developed method of imaging localized blood perfusion at capillary level resolution within microcirculatory beds. This paper reports that the OMAG is capable of directional blood perfusion mapping in vivo. This is achieved simply by translating the mirror located in the reference arm back and forth while 3D imaging is performed. The mirror which moves toward the incident beam gives the blood perfusion that flows away from the beam direction and vice versa. The approach is experimentally demonstrated by imaging of a flow phantom and then cerebro-vascular perfusion of a live mouse with cranium intact.

  13. Does machine perfusion decrease ischemia reperfusion injury?

    PubMed

    Bon, D; Delpech, P-O; Chatauret, N; Hauet, T; Badet, L; Barrou, B

    2014-06-01

    In 1990's, use of machine perfusion for organ preservation has been abandoned because of improvement of preservation solutions, efficient without perfusion, easy to use and cheaper. Since the last 15 years, a renewed interest for machine perfusion emerged based on studies performed on preclinical model and seems to make consensus in case of expanded criteria donors or deceased after cardiac death donations. We present relevant studies highlighted the efficiency of preservation with hypothermic machine perfusion compared to static cold storage. Machines for organ preservation being in constant evolution, we also summarized recent developments included direct oxygenation of the perfusat. Machine perfusion technology also enables organ reconditioning during the last hours of preservation through a short period of perfusion on hypothermia, subnormothermia or normothermia. We present significant or low advantages for machine perfusion against ischemia reperfusion injuries regarding at least one primary parameter: risk of DFG, organ function or graft survival.

  14. Double tracer autoradiographic method for sequential evaluation of regional cerebral perfusion

    SciTech Connect

    Matsuda, H.; Tsuji, S.; Oba, H.; Kinuya, K.; Terada, H.; Sumiya, H.; Shiba, K.; Mori, H.; Hisada, K.; Maeda, T. )

    1989-01-01

    A new double tracer autoradiographic method for the sequential evaluation of altered regional cerebral perfusion in the same animal is presented. This method is based on the sequential injection of two tracers, {sup 99m}Tc-hexamethylpropyleneamine oxime and N-isopropyl-({sup 125}I)p-iodoamphetamine. This method is validated in the assessment of brovincamine effects on regional cerebral perfusion in an experimental model of chronic brain ischemia in the rat. The drug enhanced perfusion recovery in low-flow areas, selectively in surrounding areas of infarction. The results suggest that this technique is of potential use in the study of neuropharmacological effects applied during the experiment.

  15. Early Support of Intracranial Perfusion

    DTIC Science & Technology

    2013-10-01

    automated real-time vital signs monitoring data” was funded by USAF (MSA); UM PI: Deborah Stein  The project, titled “Noninvasive intracranial pressure ...scoring of cerebral perfusion pressure and intracranial pressure provides a Brain Trauma Index that predicts outcome in patients with severe TBI... intracranial pressure dose index: Dynamic 3-D scoring in the assessment of Traumatic Brain Injury Proceedings of American Association for the Surgery of

  16. Modeling of nanotherapeutics delivery based on tumor perfusion

    NASA Astrophysics Data System (ADS)

    van de Ven, Anne L.; Abdollahi, Behnaz; Martinez, Carlos J.; Burey, Lacey A.; Landis, Melissa D.; Chang, Jenny C.; Ferrari, Mauro; Frieboes, Hermann B.

    2013-05-01

    Heterogeneities in the perfusion of solid tumors prevent optimal delivery of nanotherapeutics. Clinical imaging protocols for obtaining patient-specific data have proven difficult to implement. It is challenging to determine which perfusion features hold greater prognostic value and to relate measurements to vessel structure and function. With the advent of systemically administered nanotherapeutics whose delivery is dependent on overcoming diffusive and convective barriers to transport, such knowledge is increasingly important. We describe a framework for the automated evaluation of vascular perfusion curves measured at the single vessel level. Primary tumor fragments, collected from triple-negative breast cancer patients and grown as xenografts in mice, were injected with fluorescence contrast and monitored using intravital microscopy. The time to arterial peak and venous delay, two features whose probability distributions were measured directly from time-series curves, were analyzed using a fuzzy c-mean supervised classifier in order to rank individual tumors according to their perfusion characteristics. The resulting rankings correlated inversely with experimental nanoparticle accumulation measurements, enabling the modeling of nanotherapeutics delivery without requiring any underlying assumptions about tissue structure or function, or heterogeneities contained therein. With additional calibration, these methodologies may enable the investigation of nanotherapeutics delivery strategies in a variety of tumor models.

  17. Limited myocardial perfusion reserve in patients with left ventricular hypertrophy

    SciTech Connect

    Goldstein, R.A.; Haynie, M. )

    1990-03-01

    Experimental studies in animals have suggested that coronary flow reserve may be limited in patients with left ventricular hypertrophy (LVH). Accordingly, to noninvasively determine the effect of LVH on myocardial perfusion reserve, 25 patients, 9 with LVH and 16 controls, underwent positron imaging with rubidium-82 (82Rb) (30-55 mCi) or nitrogen-13 (13N) ammonia (12-19 mCi) at rest and following intravenous dipyridamole and handgrip stress. LVH was documented by echocardiographic and/or electrocardiographic measurements. LVH patients had either no chest pain (n = 8) and/or a normal coronary angiogram (n = 6). Nine simultaneous transaxial images were acquired, and the mean ratio of stress to rest activity (S:R), based on all regions for each heart, was calculated as an estimate of myocardial perfusion reserve. There were no regional differences in activity (i.e., perfusion defects) in any of the studies. S:R averaged 1.41 +/- 0.10 (s.d.) for controls and 1.06 +/- 0.09 for patients with LVH (p less than 0.0001). These data provide support for an abnormality in perfusion reserve in patients with LVH.

  18. Dynamic CT head phantom for perfusion and angiography studies

    NASA Astrophysics Data System (ADS)

    Russell, K.; Blazeski, A.; Dannecker, K.; Lee, Q. Y.; Holscher, C.; Donahue, C.; van Kampen, W.

    2010-03-01

    Contrast imaging is a compelling enhancement for the portable, flat panel-based brain CT scanner currently under development at Xoran. Due to the relative low temporal resolution of flat panel detectors, enabling tomographic imaging on such platform requires optimizing the imaging and injection protocols. A dynamic CT head phantom was designed to facilitate this task. The Dynamic Perfusion and Angiography Model (PAM), mimics tissue attenuation in CT images, provides physiological timing for angiography and perfusion studies, and moves fluid with properties similar to those of blood. The design consists of an arterial system, which contains bifurcating vessels that feed into perfusion chambers, mimicking blood flow through capillaries and smaller vessels, and a venous system, which is symmetrical to the arterial side and drains the perfusion chambers. The variation of geometry and flow rate in the phantom provides the physiological total time that fluid spends in the head, and the difference in material densities correlates to CT numbers for biological tissues. This paper discusses the design of Dynamic PAM and shows experimental results demonstrating its ability to realistically simulate blood flow. Results of dynamic imaging studies of the phantom are also presented.

  19. Intestinal perfusion monitoring using photoplethysmography

    NASA Astrophysics Data System (ADS)

    Akl, Tony J.; Wilson, Mark A.; Ericson, M. Nance; Coté, Gerard L.

    2013-08-01

    In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.

  20. Mucosal Immunity and Candida albicans Infection

    PubMed Central

    Moyes, David L.; Naglik, Julian R.

    2011-01-01

    Interactions between mucosal surfaces and microbial microbiota are key to host defense, health, and disease. These surfaces are exposed to high numbers of microbes and must be capable of distinguishing between those that are beneficial or avirulent and those that will invade and cause disease. Our understanding of the mechanisms involved in these discriminatory processes has recently begun to expand as new studies bring to light the importance of epithelial cells and novel immune cell subsets such as Th17 T cells in these processes. Elucidating how these mechanisms function will improve our understanding of many diverse diseases and improve our ability to treat patients suffering from these conditions. In our voyage to discover these mechanisms, mucosal interactions with opportunistic commensal organisms such as the fungus Candida albicans provide insights that are invaluable. Here, we review current knowledge of the interactions between C. albicans and epithelial surfaces and how this may shape our understanding of microbial-mucosal interactions. PMID:21776285

  1. Oral mucosal diseases: evaluation and management.

    PubMed

    Stoopler, Eric T; Sollecito, Thomas P

    2014-11-01

    Oral mucosal diseases encompass several common conditions that affect the general population. Some of these disorders present with signs and symptoms that are pathognomonic for the condition, whereas others present with similar features that can make clinical diagnosis difficult to achieve. It is important for physicians to have a clear understanding of these disorders to provide appropriate care to patients. This article reviews clinical aspects of common oral mucosal disorders, including candidiasis, herpes simplex viral infections, aphthous stomatitis, lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid.

  2. Concomitant early mucosal and cutaneous leishmaniasis in Brazil.

    PubMed

    Boaventura, Viviane S; Cafe, Virginia; Costa, Jackson; Oliveira, Fabiano; Bafica, Andre; Rosato, Andrea; de Freitas, Luiz A R; Brodskyn, Claudia; Barral-Netto, Manoel; Barral, Aldina

    2006-08-01

    Mucosal leishmaniasis (ML) is often clinically silent until reaching a highly advanced state. In this prospective study, 6 of 220 patients with early cutaneous leishmaniasis were diagnosed with mucosal involvement by otorhinolaryngological examination (a rate similar to the reported rate of late ML). Detection of early ML may represent an important strategy in preventing severe mucosal destruction in human leishmaniasis.

  3. Mucosal melanoma of the head and neck.

    PubMed

    Ascierto, Paolo Antonio; Accorona, Remo; Botti, Gerardo; Farina, Davide; Fossati, Piero; Gatta, Gemma; Gogas, Helen; Lombardi, Davide; Maroldi, Roberto; Nicolai, Piero; Ravanelli, Marco; Vanella, Vito

    2017-04-01

    Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery. Many new treatment options in the last years, in particular targeted therapies (i.e. inhibitors of c-KIT, NRAS/MEK or BRAF) and immunotherapies (anti CTLA-4 and anti PD-1/PD-L1 antibodies), have changed the history of cutaneous melanoma. Despite the different biology, mucosal melanoma is currently treated in the same way as cutaneous melanoma; however, patients with mucosal melanoma were excluded from the majority of recent clinical trials. Recent molecular findings offer new hope for the development of more effective systemic therapy.

  4. Characterization of Mucosal Candida albicans Biofilms

    PubMed Central

    Dongari-Bagtzoglou, Anna; Kashleva, Helena; Dwivedi, Prabhat; Diaz, Patricia; Vasilakos, John

    2009-01-01

    C. albicans triggers recurrent infections of the alimentary tract mucosa that result from biofilm growth. Although the ability of C. albicans to form a biofilm on abiotic surfaces has been well documented in recent years, no information exists on biofilms that form directly on mucosal surfaces. The objectives of this study were to characterize the structure and composition of Candida biofilms forming on the oral mucosa. We found that oral Candida biofilms consist of yeast, hyphae, and commensal bacteria, with keratin dispersed in the intercellular spaces. Neutrophils migrate through the oral mucosa and form nests within the biofilm mass. The cell wall polysaccharide β-glucan is exposed during mucosal biofilm growth and is more uniformly present on the surface of biofilm organisms invading the oral mucosa. We conclude that C. albicans forms complex mucosal biofilms consisting of both commensal bacterial flora and host components. These discoveries are important since they can prompt a shift of focus for current research in investigating the role of Candida-bacterial interactions in the pathogenesis of mucosal infections as well as the role of β-glucan mediated signaling in the host response. PMID:19956771

  5. Tissue perfusion measurements: multiple-exposure laser speckle analysis generates laser Doppler-like spectra.

    PubMed

    Thompson, Oliver B; Andrews, Michael K

    2010-01-01

    Variations in skin perfusion are easily detected by laser speckle contrast maps, but a robust interpretation of the information has been lacking. We show that multiple-exposure laser speckle methods produce the same spectral information as laser Doppler methods when applied to targets with embedded moving scatterers. This enables laser speckle measurements to be interpreted more quantitatively. We do this by using computer simulation of speckle data, and by experimental measurements on Brownian motion and skin perfusion using a laser Doppler system and a multiple-exposure laser speckle system. The power spectral density measurements of the light fluctuations derived using both techniques are exactly equivalent. Dermal perfusion can therefore be measured by laser Doppler or laser speckle contrast methods. In particular, multiexposure laser speckle can be rapidly processed to generate a full-field map of the perfusion index proportional to the concentration and mean velocity of red blood cells.

  6. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids

    PubMed Central

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-01-01

    Background: Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. Methods: We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. Results: HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. Conclusions: We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx. PMID:26867163

  7. Technetium myocardial perfusion agents: an introduction

    SciTech Connect

    English, R.J.; Kozlowski, J.; Tumeh, S.S.; Holman, B.L.

    1987-09-01

    This is the third in a series of four Continuing Education articles on developing radiopharmaceuticals. After reading this article, the reader should be able to: 1) understand the basic concepts of myocardial perfusion imaging; and 2) discuss the advantages of the technetium myocardial perfusion complexes over thallium-201.

  8. Luxury perfusion following anterior ischemic optic neuropathy.

    PubMed

    Friedland, S; Winterkorn, J M; Burde, R M

    1996-09-01

    We present five patients who developed luxury perfusion following anterior ischemic optic neuropathy in whom fluorescein angiography was misinterpreted as "capillary hemangioma" or neovascularization of the disc. In each case, the segment of disc hyperemia corresponded to a spared region of visual field. Luxury perfusion represents a reparative autoregulatory reaction to ischemia.

  9. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  10. Myocardial perfusion with rubidium-82. III. Theory relating severity of coronary stenosis to perfusion deficit

    SciTech Connect

    Mullani, N.A.

    1984-11-01

    The relation between the quantitative perfusion deficit, as measured by emission computerized tomography, and the severity of coronary artery stenosis is important for the noninvasive clinical evaluation of coronary artery disease in man. Positron emission tomography allows direct noninvasive measurement of myocardial perfusion and quantification of the size of the perfusion defect. Given this important imformation, a mathematical model has been derived to gauge the severity of a coronary stenosis from quantitative perfusion measurements in the normal and poststenotic regions of the heart. The theoretical basis is presented for relating regional myocardial perfusion and regional perfusion resistance to total, coronary blood flow and resistance at normal resting flow and during maximal coronary vasodilation. The concept of perfusion reserve is presented as a clinical measure of the severity of a stenosis.

  11. Management of Mucositis During Chemotherapy: From Pathophysiology to Pragmatic Therapeutics.

    PubMed

    Van Sebille, Ysabella Z A; Stansborough, Romany; Wardill, Hannah R; Bateman, Emma; Gibson, Rachel J; Keefe, Dorothy M

    2015-11-01

    Chemotherapy-induced mucositis is a common condition caused by the breakdown of the mucosal barrier. Symptoms can include pain, vomiting and diarrhoea, which can often necessitate chemotherapy treatment breaks or dose reductions, thus compromising survival outcomes. Despite the significant impact of mucositis, there are currently limited clinically effective pharmacological therapies for the pathology. New emerging areas of research have been proposed to play key roles in the development of mucositis, providing rationale for potential new therapeutics for the prevention, treatment or management of chemotherapy-induced mucositis. This review aims to address these new areas of research and to comment on the therapeutics arising from them.

  12. [Compromized myocardial perfusion in arrhythmias (author's transl)].

    PubMed

    Simon, H; Neumann, G; Felix, R; Hedde, H; Schaede, A; Thurn, P; Winkler, C

    1977-09-15

    In 7 patients with arrhythmias of various origin the myocardial scintigram displayed either a diffuse or circumscript defect of the perfusion. The coronary arteriogram was normal in all patients. The localized defect of the perfusion in 2 patients was in the region of the upper part of the interventricular septum. Both had a left bundle brunch block. A correlation between the perfusion defect and the electrophysiological abnormality seems probable. The perfusion defect in one of the patients is most probably caused by a previous myocarditis followed by fibrous changes. In the other 6 patients the cause for the perfusion defect is not obvious. A history of myocarditis is missing. The presence of "small vessel disease" in those patients has however to be considered. Our results point to the relation between an abnormality of the microcirculation and arrhythmias in younger patients.

  13. Increased Mucosal CD4+ T Cell Activation in Rhesus Macaques following Vaccination with an Adenoviral Vector

    PubMed Central

    Bukh, Irene; Calcedo, Roberto; Roy, Soumitra; Carnathan, Diane G.; Grant, Rebecca; Qin, Qiuyue; Boyd, Surina; Ratcliffe, Sarah J.; Veeder, Christin L.; Bellamy, Scarlett L.; Betts, Michael R.

    2014-01-01

    ABSTRACT The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4+ T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4+ T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4+ T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4+ T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination. IMPORTANCE The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4+ T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4+ T cells and potentially increases susceptibility to SIV

  14. Sublingual vaccination with sonicated Salmonella proteins and mucosal adjuvant induces mucosal and systemic immunity and protects mice from lethal enteritis.

    PubMed

    Huang, Ching-Feng; Wu, Tzee-Chung; Wu, Chia-Chao; Lee, Chin-Cheng; Lo, Wen-Tsung; Hwang, Kwei-Shuai; Hsu, Mu-Ling; Peng, Ho-Jen

    2011-07-01

    Salmonella enteritidis is one of the most common pathogens of enteritis. Most experimental vaccines against Salmonella infection have been applied through injections. This is a new trial to explore the effect of sublingual administration of Salmonella vaccines on systemic and mucosal immunity. Adult BALB/c mice were sublingually vaccinated with sonicated Salmonella proteins (SSP) alone, or plus adjuvant CpG DNA (CpG) or cholera toxin (CT). They were boosted 2 weeks later. Saliva specific secretory IgA (SIgA) antibody responses were significantly stimulated in the mice vaccinated with SSP only or together with CpG or CT. Whereas the mice sublingually vaccinated with SSP and CpG had higher spleen cell IFN-γ production and serum specific IgG2a antibody responses, those receiving SSP and CT showed enhanced spleen cell IL-4, IL-5 and IL-6 production, and serum specific IgG1 antibody responses. After oral challenge with live S. enteritidis, the same strain of the source of SSP, immune protection in those sublingually vaccinated with SSP and CpG or CT was found to prevent intestinal necrosis and to render a higher survival rate. In conclusion, sublingual vaccination together with mucosal adjuvant CpG or CT is a simple but effective way against enteric bacterial pathogens.

  15. Saccharomyces cerevisiae UFMG A-905 treatment reduces intestinal damage in a murine model of irinotecan-induced mucositis.

    PubMed

    Bastos, R W; Pedroso, S H S P; Vieira, A T; Moreira, L M C; França, C S; Cartelle, C T; Arantes, R M E; Generoso, S V; Cardoso, V N; Neves, M J; Nicoli, J R; Martins, F S

    2016-09-01

    Indigenous microbiota plays a crucial role in the development of several intestinal diseases, including mucositis. Gastrointestinal mucositis is a major and serious side effect of cancer therapy, and there is no effective therapy for this clinical condition. However, some probiotics have been shown to attenuate such conditions. To evaluate the effects of Saccharomyces cerevisiae UFMG A-905 (Sc-905), a potential probiotic yeast, we investigated whether pre- or post-treatment with viable or inactivated Sc-905 could prevent weight loss and intestinal lesions, and maintain integrity of the mucosal barrier in a mucositis model induced by irinotecan in mice. Only post-treatment with viable Sc-905 was able to protect mice against the damage caused by chemotherapy, reducing the weight loss, increase of intestinal permeability and jejunal lesions (villous shortening). Besides, this treatment reduced oxidative stress, prevented the decrease of goblet cells and stimulated the replication of cells in the intestinal crypts of mice with experimental mucositis. In conclusion, Sc-905 protects animals against irinotecan-induced mucositis when administered as a post-treatment with viable cells, and this effect seems to be related with the reduction of oxidative stress and preservation of intestinal mucosa.

  16. Probiotics as Antifungals in Mucosal Candidiasis.

    PubMed

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections.

  17. [Function and morphology of isolated rat kidney following cellfree perfusion with various plasmaexpanders (author's transl)].

    PubMed

    Franke, H; Sobotta, E E; Witzki, G; Unsicker, K

    1975-05-01

    Isolated arteficially perfused rat kidneys prepared as described by Franke et al. (1971) were perfused for 60 min with solutions of Haemaccel, Dextran 40, Pluronic-F-108, or hydroxy-aethyl starch in a single pass system. The glomerular filtration rate (GFR) of the Haemaccel or Dextran 40 perfused organs amounted during the first 30 min to 0.58 ml X g-1 X min-1 and 0.47 ml X g-1 X min-1 respectively. Using Pluronic-F-108 or hydroxy-aethyl starch GFR rose to 0.94 ml X g-1 X min-1 and to 0.85 ml X G-1 X min-1. With Haemaccel or Dextran 40 solutions a mean tubular Na-reabsorption of 75.4 mumol X g-1 X min-1 and of 59 mumol X g-1 X min-1 respectively was determined. Employing Pluronic-F-108 or hydroxy-aethyl starch a mean sodium net transport of 92.6 mumol X g-1 X min-1 in both experimental groups was obtained. The differences described in the functional capabilities of Haemaccel or Dextran 40 and of Pluronic-F-108 or Hydroxyethyl starch perfused kidneys are in good accordance with morphological changes in the ultrastructure. The most striking morphological deviations were found in proximal tubules of those kidneys perfused with Haemaccel solutions. On the other hand after perfusion with hydroxyethyl starch only very few morphological alterations could be detected.

  18. The Mouse Isolated Perfused Kidney Technique.

    PubMed

    Czogalla, Jan; Schweda, Frank; Loffing, Johannes

    2016-11-17

    The mouse isolated perfused kidney (MIPK) is a technique for keeping a mouse kidney under ex vivo conditions perfused and functional for 1 hr. This is a prerequisite for studying the physiology of the isolated organ and for many innovative applications that may be possible in the future, including perfusion decellularization for kidney bioengineering or the administration of anti-rejection or genome-editing drugs in high doses to prime the kidney for transplantation. During the time of the perfusion, the kidney can be manipulated, renal function can be assessed, and various pharmaceuticals administered. After the procedure, the kidney can be transplanted or processed for molecular biology, biochemical analysis, or microscopy. This paper describes the perfusate and the surgical technique needed for the ex vivo perfusion of mouse kidneys. Details of the perfusion apparatus are given and data are presented showing the viability of the kidney's preparation: renal blood flow, vascular resistance, and urine data as functional, transmission electron micrographs of different nephron segments as morphological readouts, and western blots of transport proteins of different nephron segments as molecular readout.

  19. Parametric imaging of tumor perfusion and neovascular morphology using ultrasound

    NASA Astrophysics Data System (ADS)

    Hoyt, Kenneth

    2015-03-01

    A new image processing strategy is detailed for the simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. A technique for locally mapping tumor perfusion parameters using skeletonized neovascular data is also introduced. Simulated images were used to test the neovascular skeletonization technique and variance (error) of relevant parametric estimates. Preliminary DCE-US image datasets were collected in 6 female patients diagnosed with invasive breast cancer and using a Philips iU22 ultrasound system equipped with a L9-3 MHz transducer and Definity contrast agent. Simulation data demonstrates that neovascular morphology parametric estimation is reproducible albeit measurement error can occur at a lower signal-to-noise ratio (SNR). Experimental results indicate the feasibility of our approach to performing both tumor perfusion and neovascular morphology measurements from DCE-US images. Future work will expand on our initial clinical findings and also extent our image processing strategy to 3-dimensional space to allow whole tumor characterization.

  20. CpG oligodeoxynucleotides as mucosal adjuvants

    PubMed Central

    Iho, Sumiko; Maeyama, Jun-ichi; Suzuki, Fumiko

    2015-01-01

    Bacterial DNA comprising palindromic sequences and containing unmethylated CpG is recognized by toll-like receptor 9 of plasmacytoid dendritic cells (pDCs) and induces the production of interferon-α and chemokines, leading to the activation of a Th1 immune response. Therefore, synthetic equivalents of bacterial DNA (CpG oligodeoxynucleotides) have been developed for clinical applications. They are usually phosphorothioated for in vivo use; this approach also leads to adverse effects as reported in mouse models.Mucosal vaccines that induce both mucosal and systemic immunity received substantial attention in recent years. For their development, phosphodiester-linked oligodeoxynucleotides, including the sequence of a palindromic CpG DNA may be advantageous as adjuvants because their target pDCs are present right there, in the mucosa of the vaccination site. In addition, the probability of adverse effects is believed to be low. Here, we review the discovery of such CpG oligodeoxynucleotides and their possible use as mucosal adjuvants. PMID:25751765

  1. Hitting the mucosal road in tolerance induction.

    PubMed

    Wiedermann, Ursula

    2009-01-01

    Within the last decades a dramatic increase in allergic diseases has been recognized in the Westernized societies, leading to the fact that meanwhile 25-30% of the population is afflicted by allergic disorders. Besides a hereditary disposition, other factors, including a reduced microbial contact early in life or changes in nutrition, might also have influenced this epidemiological development. So far the only causative treatment against type-I allergies is specific immunotherapy. In young and monosensitized patients this treatment is highly efficacious, while there are clear limitations in older or multisensitized patients. Allergy research therefore aims at establishing new and more efficacious treatment strategies in prophylactic as well as therapeutic settings. Our research programs focus on the development of novel allergy vaccines based on the induction of mucosal tolerance. In different mouse models of respiratory allergy mucosal treatment with genetically engineered allergen constructs proved to prevent the development of allergic mono- and multisensitivities. The additional use of mucosal adjuvants seems particularly important to improve therapeutic treatment approaches. Recent studies on the inverse relation of certain parasite infections and the development of allergy prompted us to search for selected parasitic molecules with immunosuppressive properties as potential adjuvant systems for novel allergy vaccines. An overview of our recent studies will be given.

  2. Dermoscopic appearance of an amelanotic mucosal melanoma

    PubMed Central

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

    2016-01-01

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

  3. Oral mucosal manifestations of autoimmune skin diseases.

    PubMed

    Mustafa, Mayson B; Porter, Stephen R; Smoller, Bruce R; Sitaru, Cassian

    2015-10-01

    A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches.

  4. Age, gender, dentures and oral mucosal disorders.

    PubMed

    MacEntee, M I; Glick, N; Stolar, E

    1998-03-01

    The numbers of participants over 75 years of age in previous studies of oral health have not been sufficient to permit a full investigation of the influence of age on the mouth. In this study a disproportionate stratified random sample of 255 independent elders was selected from a list of urban voters to provide similar numbers of men and women in three age groups. The subjects were interviewed and examined, and nearly half of them had mucosal disorders. There was a significant (P < 0.05) association between mucosal lesions and the use of dentures and tobacco, whereas stomatitis, denture-related hyperplasia and angular cheilitis in particular were associated significantly with men and with the use of defective dentures. Logistic regression revealed that neither age alone nor the quality of dentures predispose to mucosal lesions, but that the odds of finding stomatitis, denture-related hyperplasia and angular cheilitis in particular increased about three-fold in denture-users, and almost doubled in men.

  5. Mucosal perforators from the facial artery.

    PubMed

    Coronel-Banda, Mauricio E; Serra-Renom, Jose M; Lorente, Marian; Larrea-Terán, Wendy P

    2014-07-01

    The cutaneous perforators of the facial artery have been well described, but to our knowledge the oral mucosal perforators have not. We studied 10 facial arteries from 10 hemifaces in 5 cadavers. The arteries were injected with latex, and we studied all perforators that extended from the facial artery and headed directly to the oral mucosa. The diameter and length of the facial artery and its mucosal perforators were measured and compared. We found 52 oral mucosal perforators in the 10 facial arteries injected with latex. Their mean (SD) diameter was 0.5 (0.2) mm and the mean (SD) number/facial artery was 5.2 (1.1). Their mean (SD) length was 16.4 (5.3) mm. Most of those to the cheek were localised between the branching-off points of the inferior and superior labial arteries. The facial artery has perforators to the oral mucosa of the cheek, most of them between the points at which the labial arteries emerge.

  6. Cutaneous toxicity of 2-chloroethyl methyl sulfide in isolated perfused porcine skin.

    PubMed

    King, J R; Monteiro-Riviere, N A

    1990-06-01

    Previous research has shown the isolated perfused porcine skin flap (IPPSF) to be a novel in vitro experimental model for investigating xenobiotic percutaneous absorption. In this study, the IPPSF was used to biochemically and morphologically assess the dermatotoxicity of 2-chloroethyl methyl sulfide (CEMS), a monofunctional analog of the vesicant, sulfur mustard. IPPSFs were perfused in a recirculating perfusion system and were treated with 97% CEMS (n = 4) or served as controls (n = 4). Additional IPPSFs were perfused in a nonrecirculating perfusion system and were treated with CEMS (n = 4) or were controls (n = 4). After dosing, each IPPSF was perfused for 8 hr. Cumulative glucose utilization (GU) and lactate production/glucose utilization ratio (L/GU ratio) were used as viability parameters. The average rate of GU for CEMS was significantly lower than control (p less than 0.05) in the recirculating and nonrecirculating IPPSFs. The L/GU ratio for CEMS was not significantly different (p greater than 0.05) from control for either perfusion system. CEMS resulted in a marked increase in vascular resistance versus control in both perfusion systems. Gross vesicles and bullae formation occurred in six of the CEMS-treated IPPSFs. Light microscopy revealed subepidermal vesicle formation above the basement membrane and extensive basal cell pyknosis in all IPPSFs treated with CEMS. No macroscopic or microscopic lesions were noted in the control flaps. Transmission electron microscopy revealed separation between the lamina lucida and the lamina densa of the basal lamina, with intracellular vacuolization and mitochondrial swelling occurring in the stratum basale and stratum spinosum cells of IPPSFs treated with CEMS. These lesions are similar to those described after human exposure to sulfur mustard. Full characterization of the morphological and biochemical changes seen after topical exposure of the IPPSF to vesicants may shed light on the pathogenesis of cutaneous toxicity

  7. Gut permeability and mucosal inflammation: bad, good or context dependent.

    PubMed

    Ahmad, R; Sorrell, M F; Batra, S K; Dhawan, P; Singh, A B

    2017-03-01

    Inflammatory bowel disease (IBD) is a multifactorial disease. A breach in the mucosal barrier, otherwise known as "leaky gut," is alleged to promote mucosal inflammation by intensifying immune activation. However, interaction between the luminal antigen and mucosal immune system is necessary to maintain mucosal homeostasis. Furthermore, manipulations leading to deregulated gut permeability have resulted in susceptibility in mice to colitis as well as to creating adaptive immunity. These findings implicate a complex but dynamic association between mucosal permeability and immune homeostasis; however, they also emphasize that compromised gut permeability alone may not be sufficient to induce colitis. Emerging evidence further supports the role(s) of proteins associated with the mucosal barrier in epithelial injury and repair: manipulations of associated proteins also modified epithelial differentiation, proliferation, and apoptosis. Taken together, the role of gut permeability and proteins associated in regulating mucosal inflammatory diseases appears to be more complex than previously thought. Herein, we review outcomes from recent mouse models where gut permeability was altered by direct and indirect effects of manipulating mucosal barrier-associated proteins, to highlight the significance of mucosal permeability and the non-barrier-related roles of these proteins in regulating chronic mucosal inflammatory conditions.

  8. Ventilation-perfusion imaging in pulmonary papillomatosis

    SciTech Connect

    Espinola, D.; Rupani, H.; Camargo, E.E.; Wagner, H.N. Jr.

    1981-11-01

    Three children with laryngeal papillomas involving the lungs had serial ventilation-perfusion scintigrams to assess results of therapy designed to reduce the bronchial involvement. Different imaging patterns were observed depending on size, number, and location of lesions. In early parenchymal involvement a ventilation-perfusion mismatch was seen. The initial and follow-up studies correlated well with clinical and radiographic findings. This noninvasive procedure is helpful in evaluating ventilatory and perfusion impairment in these patients as well as their response to treatment.

  9. Cochlear perfusion with a viscous fluid.

    PubMed

    Wang, Yi; Olson, Elizabeth S

    2016-07-01

    The flow of viscous fluid in the cochlea induces shear forces, which could provide benefit in clinical practice, for example to guide cochlear implant insertion or produce static pressure to the cochlear partition or wall. From a research standpoint, studying the effects of a viscous fluid in the cochlea provides data for better understanding cochlear fluid mechanics. However, cochlear perfusion with a viscous fluid may damage the cochlea. In this work we studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid. Gerbil cochleae were perfused at a rate of 2.4 μL/min with artificial perilymph (AP) and sodium hyaluronate (Healon, HA) in four different concentrations (0.0625%, 0.125%, 0.25%, 0.5%). The different HA concentrations were applied either sequentially in the same cochlea or individually in different cochleae. The perfusion fluid entered from the round window and was withdrawn from basal scala vestibuli, in order to perfuse the entire perilymphatic space. Compound action potentials (CAP) were measured after each perfusion. After perfusion with increasing concentrations of HA in the order of increasing viscosity, the CAP thresholds generally increased. The threshold elevation after AP and 0.0625% HA perfusion was small or almost zero, and the 0.125% HA was a borderline case, while the higher concentrations significantly elevated CAP thresholds. Histology of the cochleae perfused with the 0.0625% HA showed an intact Reissner's membrane (RM), while in cochleae perfused with 0.125% and 0.25% HA RM was torn. Thus, the CAP threshold elevation was likely due to the broken RM, likely caused by the shear stress produced by the flow of the viscous fluid. Our results and analysis indicate that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Beside these finding, in the 0.125% and 0.25% HA perfusion cases, a temporary CAP threshold shift was observed, perhaps due to the presence and

  10. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: A double-blind, randomized study

    SciTech Connect

    Lin, L.-C. . E-mail: 8508A6@mail.chimei.org.tw; Que, Jenny; Lin, L.-K.; Lin, F.-C.

    2006-07-01

    Purpose: To determine whether zinc supplementation can accelerate the healing of mucositis and dermatitis after radiotherapy. Methods and Materials: In this double-blind study, patients were placed into two randomized groups (experimental and control) of 50 patients each. The groups were homogeneous with respect to medical history, tumor characteristics, and therapeutic details. The experimental group received a standard dose of a zinc supplement, and the control group was given a placebo. Results: Patients in the control group developed Grade 2 mucositis and dermatitis earlier and sooner than patients in the experimental group. There was also a significant difference in the development of Grade 3 mucositis and dermatitis between the two groups. Patients in the experimental group were found to have milder mucositis and dermatitis. Zinc supplementation did not show much benefit in those patients receiving concurrent chemotherapy or make a substantial impact on weight changes. Conclusions: Zinc supplementation used in conjunction with radiotherapy could postpone the development of severe mucositis and dermatitis for patients with cancers of the head and neck. Zinc supplementation can also alleviate the degree of mucositis and dermatitis. The impact of zinc on tumor growth and patient survival is under further investigation.

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

    PubMed

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

    2016-03-01

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

  12. Perceiving nasal patency through mucosal cooling rather than air temperature or nasal resistance.

    PubMed

    Zhao, Kai; Blacker, Kara; Luo, Yuehao; Bryant, Bruce; Jiang, Jianbo

    2011-01-01

    Adequate perception of nasal airflow (i.e., nasal patency) is an important consideration for patients with nasal sinus diseases. The perception of a lack of nasal patency becomes the primary symptom that drives these patients to seek medical treatment. However, clinical assessment of nasal patency remains a challenge because we lack objective measurements that correlate well with what patients perceive. The current study examined factors that may influence perceived patency, including air temperature, humidity, mucosal cooling, nasal resistance, and trigeminal sensitivity. Forty-four healthy subjects rated nasal patency while sampling air from three facial exposure boxes that were ventilated with untreated room air, cold air, and dry air, respectively. In all conditions, air temperature and relative humidity inside each box were recorded with sensors connected to a computer. Nasal resistance and minimum airway cross-sectional area (MCA) were measured using rhinomanometry and acoustic rhinometry, respectively. General trigeminal sensitivity was assessed through lateralization thresholds to butanol. No significant correlation was found between perceived patency and nasal resistance or MCA. In contrast, air temperature, humidity, and butanol threshold combined significantly contributed to the ratings of patency, with mucosal cooling (heat loss) being the most heavily weighted predictor. Air humidity significantly influences perceived patency, suggesting that mucosal cooling rather than air temperature alone provides the trigeminal sensation that results in perception of patency. The dynamic cooling between the airstream and the mucosal wall may be quantified experimentally or computationally and could potentially lead to a new clinical evaluation tool.

  13. Enhancement in gastric mucosal EGF and PDGF receptor expression with ulcer healing by sulglycotide.

    PubMed

    Piotrowski, J; Majka, J; Sano, S; Nowak, P; Murty, V L; Slomiany, A; Slomiany, B L

    1995-07-01

    1. The effect of an antiulcer agent, sulglycotide, on mucosal expression of EGF and PDGF receptors with chronic ulcer healing was investigated. 2. Rats with experimentally-induced gastric ulcers were treated twice daily for 14 consecutive days, either with sulglycotide at 200 mg/kg or vehicle, and at different stages of treatment used for quantitation of gastric mucosal EGF and PDGF receptors. 3. The ulcer healing was accompanied by an increase in mucosal expression of both types of receptors. A 1.8-fold increase in EGF and 3.1-fold increase in PDGF receptors occurred by the 4th day following the development of ulcer and reached a maximum of 2.4-3.9-fold increase by the 10-14th day. 4. Treatment with sulglycotide caused accelerated ulcer healing accompanied by a significant enhancement in the receptors expression. A 2.3- and 3.6-fold increase in EGF and PDGF receptor expression occurred by the 4th day of sulglycotide treatment, reaching a 5.5- and 5.6-fold respective increase by the 10th day when the ulcer essentially healed. 5. The results attest to the ability of sulglycotide to stimulate the gastric mucosal proliferative activities associated with ulcer healing.

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

    PubMed Central

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

    2016-01-01

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

  15. Starter Feeding Supplementation Alters Colonic Mucosal Bacterial Communities and Modulates Mucosal Immune Homeostasis in Newborn Lambs

    PubMed Central

    Liu, Junhua; Bian, Gaorui; Sun, Daming; Zhu, Weiyun; Mao, Shengyong

    2017-01-01

    This study aims to investigate the effect of starter feeding supplementation on colonic mucosal bacterial communities and on mucosal immune homeostasis in pre-weaned lambs. We selected eight pairs of 10-day-old lamb twins. One twin was fed breast milk (M, n = 8), while the other was fed breast milk plus starter (M+S, n = 8). The lambs were sacrificed at 56 days age. Colonic content was collected to determine the pH and the concentrations of volatile fatty acids (VFA) and lactate. The colonic mucosa was harvested to characterize the bacterial communities using Illumina MiSeq sequencing and to determine mRNA expression levels of cytokines and toll-like receptors (TLR) using quantitative real-time PCR. The results show that starter feeding decreased luminal pH and increased the concentrations of acetate, propionate, butyrate, total VFA, and lactate in the colon. The principal coordinate analysis (PCA) and analysis of molecular variance show that starter feeding supplementation significantly affected the colonic mucosal bacterial communities with a higher relative abundance of the dominant taxa unclassified S24-7, Oscillibacter, Prevotella, Parabacteroides, Bifidobacterium, Ruminobacter, and Succinivibrio, and a lower proportion of unclassified Ruminococcaceae, RC9_gut_group, Blautia, Phocaeicola, Phascolarctobacterium, unclassified BS11_gut_group, unclassified family_XIII, and Campylobacter in lambs. Meanwhile, starter feeding decreased mRNA expression of TLR4 and cytokines TNF-α and IFN-γ in colonic tissue. Furthermore, the changes in the colonic mucosal mRNA expression of TLR and cytokines were associated with changes in mucosal bacterial composition. These findings may provide new insights into colonic mucosal bacteria and immune homeostasis in developing lambs. PMID:28382025

  16. Evolution of pulmonary perfusion defects demonstrated with contrast-enhanced dynamic MR perfusion imaging.

    PubMed

    Howarth, N R; Beziat, C; Berthezène, Y

    1999-01-01

    Pulmonary perfusion defects can be demonstrated with contrast-enhanced dynamic MR perfusion imaging. We present the case of a patient with a pulmonary artery sarcoma who presented with a post-operative pulmonary embolus and was followed in the post-operative period with dynamic contrast-enhanced MR perfusion imaging. This technique allows rapid imaging of the first passage of contrast material through the lung after bolus injection in a peripheral vein. To our knowledge, this case report is the first to describe the use of this MR technique in showing the evolution of peripheral pulmonary perfusion defects associated with pulmonary emboli.

  17. Buccal mucosal graft in reconstructive urology: uses beyond urethral stricture.

    PubMed

    Pandey, Abhishek; Dican, Razvan; Beier, Jörn; Keller, Hansjörg

    2014-07-01

    The use of buccal mucosal grafts for the reconstruction of urethral strictures is an established procedure. Because of its robustness, the buccal mucosal graft could also potentially provide an alternative for other indications in reconstructive urology. We report here six consecutive patients who received a buccal mucosal graft for ureteral strictures, glans reconstruction and stoma stenosis. The follow up for all patients ranged from 26 to 50 months. The buccal mucosal graft showed excellent functional results for the ureteral strictures and stenosis from ureterocutaneostomy. For glans reconstructions, the buccal mucosal grafts delivered excellent cosmetic and functional results without causing meatal stenosis. We conclude the buccal mucosal graft can be used in reconstructive surgery beyond the reconstruction of urethral strictures.

  18. Improved exercise myocardial perfusion during lidoflazine therapy

    SciTech Connect

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-11-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise.

  19. Quasi-simultaneous multimodal imaging of cutaneous tissue oxygenation and perfusion

    NASA Astrophysics Data System (ADS)

    Ren, Wenqi; Gan, Qi; Wu, Qiang; Zhang, Shiwu; Xu, Ronald

    2015-12-01

    Simultaneous and quantitative assessment of multiple tissue parameters may facilitate more effective diagnosis and therapy in many clinical applications, such as wound healing. However, existing wound assessment methods are typically subjective and qualitative, with the need for sequential data acquisition and coregistration between modalities, and lack of reliable standards for performance evaluation or calibration. To overcome these limitations, we developed a multimodal imaging system for quasi-simultaneous assessment of cutaneous tissue oxygenation and perfusion in a quantitative and noninvasive fashion. The system integrated multispectral and laser speckle imaging technologies into one experimental setup. Tissue oxygenation and perfusion were reconstructed by advanced algorithms. The accuracy and reliability of the imaging system were quantitatively validated in calibration experiments and a tissue-simulating phantom test. The experimental results were compared with a commercial oxygenation and perfusion monitor. Dynamic detection of cutaneous tissue oxygenation and perfusion was also demonstrated in vivo by a postocclusion reactive hyperemia procedure in a human subject and a wound healing process in a wounded mouse model. Our in vivo experiments not only validated the performance of the multimodal imaging system for cutaneous tissue oxygenation and perfusion imaging but also demonstrated its technical potential for wound healing assessment in clinical practice.

  20. Quasi-simultaneous multimodal imaging of cutaneous tissue oxygenation and perfusion.

    PubMed

    Ren, Wenqi; Gan, Qi; Wu, Qiang; Zhang, Shiwu; Xu, Ronald

    2015-12-01

    Simultaneous and quantitative assessment of multiple tissue parameters may facilitate more effective diagnosis and therapy in many clinical applications, such as wound healing. However, existing wound assessment methods are typically subjective and qualitative, with the need for sequential data acquisition and coregistration between modalities, and lack of reliable standards for performance evaluation or calibration. To overcome these limitations, we developed a multimodal imaging system for quasi-simultaneous assessment of cutaneous tissue oxygenation and perfusion in a quantitative and noninvasive fashion. The system integrated multispectral and laser speckle imaging technologies into one experimental setup. Tissue oxygenation and perfusion were reconstructed by advanced algorithms. The accuracy and reliability of the imaging system were quantitatively validated in calibration experiments and a tissue-simulating phantom test. The experimental results were compared with a commercial oxygenation and perfusion monitor. Dynamic detection of cutaneous tissue oxygenation and perfusion was also demonstrated in vivo by a postocclusion reactive hyperemia procedure in a human subject and a wound healing process in a wounded mouse model. Our in vivo experiments not only validated the performance of the multimodal imaging system for cutaneous tissue oxygenation and perfusion imaging but also demonstrated its technical potential for wound healing assessment in clinical practice.

  1. Evidence for a common mucosal immune system in the pig.

    PubMed

    Wilson, Heather L; Obradovic, Milan R

    2015-07-01

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

  2. Perfusion visualization and analysis for pulmonary embolism

    NASA Astrophysics Data System (ADS)

    Vaz, Michael S.; Kiraly, Atilla P.; Naidich, David P.; Novak, Carol L.

    2005-04-01

    Given the nature of pulmonary embolism (PE), timely and accurate diagnosis is critical. Contrast enhanced high-resolution CT images allow physicians to accurately identify segmental and sub-segmental emboli. However, it is also important to assess the effect of such emboli on the blood flow in the lungs. Expanding upon previous research, we propose a method for 3D visualization of lung perfusion. The proposed method allows users to examine perfusion throughout the entire lung volume at a single glance, with areas of diminished perfusion highlighted so that they are visible independent of the viewing location. This may be particularly valuable for better accuracy in assessing the extent of hemodynamic alterations resulting from pulmonary emboli. The method also facilitates user interaction and may help identify small peripheral sub-segmental emboli otherwise overlooked. 19 patients referred for possible PE were evaluated by CT following the administration of IV contrast media. An experienced thoracic radiologist assessed the 19 datasets with 17 diagnosed as being positive for PE with multiple emboli. Since anomalies in lung perfusion due to PE can alter the distribution of parenchymal densities, we analyzed features collected from histograms of the computed perfusion maps and demonstrate their potential usefulness as a preliminary test to suggest the presence of PE. These histogram features also offer the possibility of distinguishing distinct patterns associated with chronic PE and may even be useful for further characterization of changes in perfusion or overall density resulting from associated conditions such as pneumonia or diffuse lung disease.

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

    NASA Astrophysics Data System (ADS)

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

    1995-12-01

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

  4. Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas.

    PubMed Central

    Suzich, J A; Ghim, S J; Palmer-Hill, F J; White, W I; Tamura, J K; Bell, J A; Newsome, J A; Jenson, A B; Schlegel, R

    1995-01-01

    Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy. Images Fig. 1 PMID:8524802

  5. Gut mucosal immunostimulation by lactic acid bacteria.

    PubMed

    Vitiñi, E; Alvarez, S; Medina, M; Medici, M; de Budeguer, M V; Perdigón, G

    2000-12-01

    The beneficial properties of lactic acid bacteria (LAB) on human health have been frequently demonstrated. The interaction of LAB with the lymphoid cells associated to the gut to activate the mucosal immune system and the mechanisms by which they can exert an adjuvant effect is still unclear, as well as if this property is common for all the LAB. We studied the influence of the oral administration of different geneous of LAB such as Lactobacillus casei, L. acidophilus, L. rhamnosus, L. delbrueckii subsp. bulgaricus, L. plantarum, Lactococcus lactis and Streptococcus thermophilus. We determined if the LAB assayed were able to stimulate the specific, the non-specific immune response (inflammatory response), or both. We demonstrated that all the bacteria assayed were able to increase the number of IgA producing cells associated to the lamina propria of small intestine. This effect was dose dependent. The increase in IgA+ producing cells was not always correlated with an increase in the CD4+ T cell number, indicating that some LAB assayed only induced clonal expansion of B cells triggered to produce IgA. Most of them, induced an increase in the number of cells involved in the inflammatory immune response. CD8+ T cell were diminished or not affected, with exception of L. plantarum that induced an increase at low dose. This fact would mean that LAB are unable to induce cytotoxicity mechanisms. We demonstrated the importance in the selection of LAB to be used as gut mucosal adjuvant. The different behaviours observed among them on the gut mucosal immune response, specially those that induce inflammatory immune response, show that not all the LAB can be used as oral adjuvant and that the beneficial effect of them can not generalized to genous or specie. The immunoadjuvant capacity would be a property of the strain assayed.

  6. Glycerol monolaurate prevents mucosal SIV transmission

    PubMed Central

    Li, Qingsheng; Estes, Jacob D.; Schlievert, Patrick M.; Duan, Lijie; Brosnahan, Amanda J.; Southern, Peter J.; Reilly, Cavan S.; Peterson, Marnie L.; Schultz-Darken, Nancy; Brunner, Kevin G.; Nephew, Karla R.; Pambuccian, Stefan; Lifson, Jeffrey D.; Carlis, John V.; Haase, Ashley T.

    2009-01-01

    While there has been great progress in treating HIV-1 infection1, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission2–4. Nonetheless, studies of vaginal transmission in the SIV-rhesus macaque model point to opportunities in the earliest stages of infection where a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry5, 6. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α, plasmacytoid dendritic cells and CCR5+cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruit CD4+T cells to fuel this obligate expansion. We then show that glycerol monolaurate, a widely used antimicrobial compound 7 with inhibitory activity against production of MIP-3α and other proinflammatory cytokines8, can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This novel approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for development of effective interventions to block HIV-1 mucosal transmission. PMID:19262509

  7. Glycerol monolaurate prevents mucosal SIV transmission.

    PubMed

    Li, Qingsheng; Estes, Jacob D; Schlievert, Patrick M; Duan, Lijie; Brosnahan, Amanda J; Southern, Peter J; Reilly, Cavan S; Peterson, Marnie L; Schultz-Darken, Nancy; Brunner, Kevin G; Nephew, Karla R; Pambuccian, Stefan; Lifson, Jeffrey D; Carlis, John V; Haase, Ashley T

    2009-04-23

    Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)-rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3alpha (also known as CCL20), plasmacytoid dendritic cells and CCR5(+ )cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4(+) T cells to fuel this obligate expansion. We then show that glycerol monolaurate-a widely used antimicrobial compound with inhibitory activity against the production of MIP-3alpha and other proinflammatory cytokines-can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission.

  8. Vitamin D and mucosal immune function

    PubMed Central

    Sun, Jun

    2010-01-01

    Purpose of review Significant advances have been made in the characterization of Vitamin D and the Vitamin D receptor (VDR) in immune function. The studies of signaling pathways involved in the response to infection and inflammation have led to a more detailed understanding of the cellular response to Vitamin D through VDR. This review summarizes recent progress in understanding how Vitamin D contributes to mucosal immune function, particularly in relation to the molecular mechanisms by which Vitamin D and VDR influence mucosal immunity, bacterial infection, and inflammation. Recent findings Recently, it was shown that Vitamin D modulates the T cell antigen receptor, further demonstrating that Vitamin D has a nonclassical role in immunoregulation. The anti-inflammation and anti-infection functions for Vitamin D are newly identified and highly significant activities. Vitamin D/VDR have multiple critical functions in regulating the response to intestinal homeostasis, tight junctions, pathogen invasion, commensal bacterial colonization, antimicrobe peptide secretion, and mucosal defense. Interestingly, microorganisms modulate the VDR signaling pathway. Summary Vitamin D is known as a key player in calcium homeostasis and electrolyte and blood pressure regulation. Recently, important progress has been made in understanding how the noncanonical activities of Vitamin D influence the pathogenesis and prevention of human disease. Vitamin D and VDR are directly involved in T cell antigen receptor signaling. The involvement of Vitamin D/VDR in anti-inflammation and anti-infection represents a newly identified and highly significant activity for VDR. Studies have indicated that the dysregulation of VDR may lead to exaggerated inflammatory responses, raising the possibility that defects in Vitamin D and VDR signaling transduction may be linked to bacterial infection and chronic inflammation. Further characterization of Vitamin D/VDR will help elucidate the pathogenesis of

  9. Oral lichen planus and lichenoid mucositis.

    PubMed

    De Rossi, Scott S; Ciarrocca, Katharine

    2014-04-01

    Oral lichen planus (OLP) is commonly found in middle-aged women. Although the cause is unknown, research points to several complex immunologic events and cells that are responsible for the inflammatory destruction and chronicity of these lesions. Biopsy for histologic diagnosis is recommended. The mainstay of treatment remains topical corticosteroids; however, newer therapies such as immunomodulating agents are available for recalcitrant lesions. In cases of lichenoid mucositis or reactions, treatment should be directed at identifying and removing the presumed cause. Given the apparent risk of squamous cell carcinoma in these patients, frequent follow-up and repeat biopsy are vital.

  10. Peptic activity and gastroduodenal mucosal damage.

    PubMed Central

    Raufman, J. P.

    1996-01-01

    This contribution reviews briefly the history of the discovery and characterization of peptic activity; secretory models and current concepts regarding the regulation of pepsinogen secretion; and evidence that pepsin is a necessary co-factor for gastroduodenal mucosal injury. Several animal studies indicate that peptic activity is required for acid- and nonsteroidal anti-inflammatory drug-induced gastroduodenal ulceration. A more vigorous approach to the development of anti-peptic drugs for the treatment of peptic ulcer disease is encouraged. Images Figure 1 PMID:9041694

  11. Type 2 Diabetes Mellitus Is Associated with More Serious Small Intestinal Mucosal Injuries

    PubMed Central

    Xie, Wen-Rui; Chen, Mei-Hui; He, Xing-Xiang

    2016-01-01

    Background Clinical and experimental research has revealed that diabetes mellitus (DM) is characterized by intestinal hypomotility, gut microbial dysbiosis, increased gut permeability, microcirculation disorders, circulatory changes, and dysfunction of intestinal stem cells, which may be linked to inflammation of intestinal mucosa. However, the relationship between type 2 DM (T2DM) and macroscopic small intestinal mucosal injuries is still unclear. Therefore, we retrospectively studied capsule endoscopy data to determine the relationship between T2DM and small intestinal mucosal injuries. Materials and Methods We compared the records of 38 T2DM patients with those of 152 non-DM patients for small intestinal mucosal injuries. Different types of mucosal injuries and Lewis scores were compared between T2DM and non-DM patients. The relationships between patients with or without different types of diabetic complications and the Lewis score was assessed. Moreover, the relationships between insulin resistance and Lewis score, between HbA1c and Lewis score, were also both assessed. Results The prevalence of a villous edema in subjects with T2DM was significantly higher than in those without DM (P < 0.001), but incidence of ulcers was not different (P = 1.000). With T2DM, the Lewis score was also significantly higher (P = 0.002). In addition, subjects with diabetic nephropathy showed significantly higher Lewis scores than patients without diabetic nephropathy (P = 0.033). In Pearson’s correlation tests, the homeostasis model assessment of insulin resistance (HOMA-IR) value was correlated positively with the Lewis score (γ = 0.175, P = 0.015), but no statistical correlation was found between HbA1c level and Lewis score (γ = 0.039, P = 0.697). Conclusions Subjects with T2DM, especially those with diabetic nephropathy, have higher Lewis scores and more serious small intestinal mucosal lesions. PMID:27598308

  12. A Murine Model of Lipopolysaccharide-Induced Peri-Implant Mucositis and Peri-Implantitis

    PubMed Central

    Pirih, Flavia Q.; Hiyari, Sarah; Leung, Ho-Yin; Barroso, Ana D. V.; Jorge, Adrian C. A.; Perussolo, Jeniffer; Atti, Elisa; Lin, Yi-Ling; Tetradis, Sotirios; Camargo, Paulo M.

    2015-01-01

    Introduction Dental implants are a vastly used treatment option for tooth replacement. Dental implants are however susceptible to inflammatory diseases such as peri-implant mucositis and peri-implantitis, which are highly prevalent and may lead to implant loss. Unfortunately, the understanding of the pathogenesis of peri-implant mucositis and peri-implantitis is fragmented and incomplete. Therefore, the availability of a reproducible animal model to study these inflammatory diseases would facilitate the dissection of their pathogenic mechanisms. The objective of this study is to propose a murine model of experimental peri-implant mucositis and peri-implantitis. Materials and Methods Screw-shaped titanium implants were placed in the upper healed edentulous alveolar ridges of C57BL/6J mice eight weeks after tooth extraction. Following four weeks of osseointegration, Porphyromonas gingivalis-lipolysaccharide (LPS) injections were delivered to the peri-implant soft tissues for six weeks. No-injections and vehicle injections were utilized as controls. Peri-implant mucositis and peri-implantitis were assessed clinically, radiographically (micro-CT) and histologically following LPS-treatment. Results LPS-injections resulted in a significant increase in soft tissue edema around the head of the implants as compared to the control groups. Micro-CT analysis revealed significantly greater bone loss in the LPS-treated implants. Histological analysis of the specimens demonstrated that the LPS-group had increased soft tissue vascularity, which harbored a dense mixed inflammatory cell infiltrate, and the bone exhibited noticeable osteoclast activity. Conclusion The induction of peri-implant mucositis and peri-implantitis in mice via localized delivery of bacterial LPS has been demonstrated. We anticipate that this model will contribute to the development of more effective preventive and therapeutic approaches for these two conditions. PMID:24967609

  13. Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

    PubMed Central

    Bajic, Juliana E; Eden, Georgina L; Lampton, Lorrinne S; Cheah, Ker Y; Lymn, Kerry A; Pei, Jinxin V; Yool, Andrea J; Howarth, Gordon S

    2016-01-01

    AIM To investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats (n = 8/group) were gavaged daily (1 mL) with water, high-dose RE (HDR; 200 mg/kg) or low-dose RE (LDR; 20mg/kg) for eight days. Intestinal mucositis was induced (day 5) with 5-FU (150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase (MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS Bodyweight was significantly reduced in rats administered 5-FU compared to healthy controls (P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels (≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity (by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness (by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats (19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis. CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal

  14. The development of mucosal vaccines for both mucosal and systemic immune induction and the roles played by adjuvants

    PubMed Central

    2017-01-01

    Vaccination is the most successful immunological practice that improves the quality of human life and health. Vaccine materials include antigens of pathogens and adjuvants potentiating the effectiveness of vaccination. Vaccines are categorized using various criteria, including the vaccination material used and the method of administration. Traditionally, vaccines have been injected via needles. However, given that most pathogens first infect mucosal surfaces, there is increasing interest in the establishment of protective mucosal immunity, achieved by vaccination via mucosal routes. This review summarizes recent developments in mucosal vaccines and their associated adjuvants. PMID:28168169

  15. Renal accumulation of /sup 99m/Tc-DMSA in the artificially perfused isolated rat kidney

    SciTech Connect

    Goldraich, N.P.; Alvarenga, A.R.; Goldraich, I.H.; Ramos, O.L.; Sigulem, D.

    1985-12-01

    In order to investigate aspects of the renal handling of /sup 99m/Tc-DMSA, 68 isolated rat kidneys were artificially perfused. The experimental groups were: Group 1 (no. = 32)-oxygenated filtering kidneys; Group 2 (no. = 29)-oxygenated non-filtering kidneys; Group 3 (no. = 7)-anaerobic non-filtering kidneys. The authors conclude that the /sup 99m/Tc-DMSA complex is strongly bound to albumin, is not filtered and is removed from perfusion fluid through the renal peritubular capillary route and that this occurs by an active process which depends upon aerobic metabolism. This process has a high capacity and is not inhibited by probenecid.

  16. Iron medication-induced gastric mucosal injury.

    PubMed

    Zhang, Xuchen; Ouyang, Jie; Wieczorek, Rosemary; DeSoto, Fidelina

    2009-01-01

    Severe gastrointestinal erosion, ulcer, necrosis and strictures after an acute iron overdose are well described. However, gastric mucosal injury in patients receiving therapeutic iron has received only scant recognition despite its wide use. We report a case of iron medication-induced gastric mucosal injury in a 76-year-old male who presented with iron deficiency anemia and had been taking ferrous sulfate tablet for 4 years. Esophagogastroduodenoscopy (EGD) revealed a pale, villous appearing flat lesion along the lesser curvature of gastric body. Histopathologic examination of EGD biopsies of the flat lesion showed brown crystalline materials deposited in the lamina propria of gastric mucosa, which was accompanied with fibrosis, chronic inflammation, and foreign body reaction. The crystalline materials were covered and admixed with gastric epithelium. Prussian blue iron stain confirmed that the brown crystalline materials were iron. The iron and hemosiderin accumulation was also seen in cytoplasm of epithelial cells and lumen of fundic gastric glands. The recognition and reporting by pathologists of iron-induced changes in EGD biopsies will alert clinicians to this underrecognized but easily correctable complication by alternative forms of iron therapy, such as liquid preparation.

  17. Dexmedetomidine decreases the oral mucosal blood flow.

    PubMed

    Kawaai, Hiroyoshi; Yoshida, Kenji; Tanaka, Eri; Togami, Kohei; Tada, Hitoshi; Ganzberg, Steven; Yamazaki, Shinya

    2013-12-01

    There is an abundance of blood vessels in the oral cavity, and intraoperative bleeding can disrupt operations. There have been some interesting reports about constriction of vessels in the oral cavity, one of which reported that gingival blood flow in cats is controlled by sympathetic α-adrenergic fibres that are involved with vasoconstriction. Dexmedetomidine is a sedative and analgesic agent that acts through the α-2 adrenoceptor, and is expected to have a vasoconstrictive action in the oral cavity. We have focused on the relation between the effects of α-adrenoceptors by dexmedetomidine and vasoconstriction in oral tissues, and assessed the oral mucosal blood flow during sedation with dexmedetomidine. The subjects comprised 13 healthy male volunteers, sedated with dexmedetomidine in a loading dose of 6 μg/kg/h for 10 min and a continuous infusion of 0.7 μg/kg/h for 32 min. The mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and palatal mucosal blood flow (PMBF) were measured at 0, 5, 10, 12, 22, and 32 min after the start of the infusion. The HR, CO, and PBMF decreased significantly during the infusion even though there were no differences in the SV. The SVR increased significantly but the PMBF decreased significantly. In conclusion, PMBF was reduced by the mediating effect of dexmedetomidine on α-2 adrenoceptors.

  18. Th17 cells and Mucosal Host Defense

    PubMed Central

    Aujla, Shean J.; Dubin, Patricia J.; Kolls, Jay K.

    2008-01-01

    Th17 cells are a new lineage of T-cells that are controlled by the transcription factor RORγt and develop independent of GATA-3, T-bet, Stat 4 and Stat 6. Novel effector molecules produced by these cells include IL-17A, IL-17F, IL-22, and IL-26. IL-17RA binds IL-17A and IL-17F and is critical for host defense against extracellular planktonic bacteria by regulating chemokine gradients for neutrophil emigration into infected tissue sites as well as host granulopoiesis. Moreover IL-17 and IL-22 regulate the production of antimicrobial proteins in mucosal epithelium. Although TGF-β1 and IL-6 have been shown to be critical for development of Th17 cells from naïve precursors, IL-23 is also important in regulating IL-17 release in mucosal tissues in response to infectious stimuli. Compared to Th1 cells, IL-23 and IL-17 show limited roles in controlling host defense against primary infections with intracellular bacteria such as Mycobacterium tuberculosis suggesting a predominate role of the Th17 lineage in host defense against extracellular pathogens. However in the setting of chronic biofilm infections, as that occurs with Cystic Fibrosis or bronchetctasis, Th17 cells may be key contributors of tissue injury. PMID:18054248

  19. Mucosal Inducible NO Synthase–Producing IgA+ Plasma Cells in Helicobacter pylori–Infected Patients

    PubMed Central

    Mueller, Mattea; Moos, Verena; Heller, Frank; Meyer, Thomas F.; Loddenkemper, Christoph; Bojarski, Christian; Fehlings, Michael; Doerner, Thomas; Allers, Kristina; Aebischer, Toni; Ignatius, Ralf; Schneider, Thomas

    2016-01-01

    The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)–dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infection, but the cellular sources of iNOS are ill defined. Key differences in regulation of iNOS expression impair the translation from mouse models to human medicine. To characterize mucosal iNOS-producing leukocytes, biopsy specimens from H. pylori–infected patients, controls, and participants of a vaccination trial were analyzed by immunohistochemistry, along with flow cytometric analyses of lymphocytes for iNOS expression and activity. We newly identified mucosal IgA-producing plasma cells (PCs) as one major iNOS+ cell population in H. pylori–infected patients and confirmed intracellular NO production. Because we did not detect iNOS+ PCs in three distinct infectious diseases, this is not a general feature of mucosal PCs under conditions of infection. Furthermore, numbers of mucosal iNOS+ PCs were elevated in individuals who had cleared experimental H. pylori infection compared with those who had not. Thus, IgA+ PCs expressing iNOS are described for the first time, to our knowledge, in humans. iNOS+ PCs are induced in the course of human H. pylori infection, and their abundance seems to correlate with the clinical course of the infection. PMID:27456483

  20. Nitric oxide as a mediator of gastrointestinal mucosal injury?—Say it ain't so

    PubMed Central

    Kubes, Paul

    1995-01-01

    Nitric oxide has been suggested as a contributor to tissue injury in various experimental models of gastrointestinal inflammation. However, there is overwhelming evidence that nitric oxide is one of the most important mediators of mucosal defence, influencing such factors as mucus secretion, mucosal blood flow, ulcer repair and the activity of a variety of mucosal immunocytes. Nitric oxide has the capacity to down-regulate inflammatory responses in the gastrointestinal tract, to scavenge various free radical species and to protect the mucosa from injury induced by topical irritants. Moreover, questions can be raised regarding the evidence purported to support a role for nitric oxide in producing tissue injury. In this review, we provide an overview of the evidence supporting a role for nitric oxide in protecting the gastrointestinal tract from injury. PMID:18475671

  1. Mucosal injuries due to ribosome-inactivating stress and the compensatory responses of the intestinal epithelial barrier.

    PubMed

    Moon, Yuseok

    2011-10-01

    Ribosome-inactivating (ribotoxic) xenobiotics are capable of using cleavage and modification to damage 28S ribosomal RNA, which leads to translational arrest. The blockage of global protein synthesis predisposes rapidly dividing tissues, including gut epithelia, to damage from various pathogenic processes, including epithelial inflammation and carcinogenesis. In particular, mucosal exposure to ribotoxic stress triggers integrated processes that are important for barrier regulation and re-constitution to maintain gut homeostasis. In the present study, various experimental models of the mucosal barrier were evaluated for their response to acute and chronic exposure to ribotoxic agents. Specifically, this review focuses on the regulation of epithelial junctions, epithelial transporting systems, epithelial cytotoxicity, and compensatory responses to mucosal insults. The primary aim is to characterize the mechanisms associated with the intestinal epithelial responses induced by ribotoxic stress and to discuss the implications of ribotoxic stressors as chemical modulators of mucosa-associated diseases such as ulcerative colitis and epithelial cancers.

  2. Cannabinoid HU210 protects isolated rat stomach against impairment caused by serum of rats with experimental acute pancreatitis.

    PubMed

    Cao, Ming-hua; Li, Yong-yu; Xu, Jing; Feng, Ya-jing; Lin, Xu-hong; Li, Kun; Han, Tong; Chen, Chang-jie

    2012-01-01

    Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis.

  3. Minimally invasive treatment of oral ranula with a mucosal tunnel.

    PubMed

    Jia, T; Xing, L; Zhu, F; Jin, X; Liu, L; Tao, J; Chen, Y; Gao, Z; Zhang, H

    2015-02-01

    We have developed a new method for minimally-invasive treatment of uncomplicated oral ranulas using a mucosal tunnel, and we report the clinical outcome. We constructed a mucosal tunnel for each of 35 patients who presented with an oral ranula, by making 2 parallel incisions across the top of the protruding ranula 2-3mm apart, and dissected the soft tissue along the incisions to its wall. The fluid was removed and the cavity irrigated with normal saline. The wall of the ranula was not treated. The first mucosal tunnel was made by suturing the base of the mucosal strip to the deepest part of the wall of the ranula. The mucosal base of the tunnel and the deepest part of the base of the ranula were fixed with absorbable sutures. The two external edges of the incisions were sutured together to form the second mucosal tunnel, and apposing sutures were inserted between the two parallel incisions to form two natural mucosal tunnels. The duration of follow-up ranged from 1 to 5 years. One patient was lost to follow-up and 34 patients were cured. Outcomes were satisfactory without relapse during the follow-up period and the patients were satisfied with the outcome. The mucosal tunnel is a safe, effective, simple, and minimally-invasive treatment for oral ranula.

  4. Induction of mucosal immunity through systemic immunization: Phantom or reality?

    PubMed Central

    Su, Fei; Patel, Girishchandra B.; Hu, Songhua; Chen, Wangxue

    2016-01-01

    ABSTRACT Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity. PMID:26752023

  5. OCT visualization of acute radiation mucositis: pilot study

    NASA Astrophysics Data System (ADS)

    Gladkova, Natalia; Maslennikova, Anna; Terentieva, Anna; Fomina, Yulia; Khomutinnikova, Nina; Balalaeva, Irina; Vyseltseva, Yulia; Larin, Roman; Kornoukhova, Natalia; Shakhov, Andrey; Shakhova, Natalia; Gelikonov, Grigory; Kamensky, Vladislav; Feldchtein, Felix

    2005-08-01

    We present pilot results in optical coherence tomography (OCT) visualization of normal mucosa radiation damage. 15 patients undergoing radiation treatment of head and neck cancer were enrolled. OCT was used to monitor the mucositis development during and after treatment. OCT can see stages of radiation mucositis development, including hidden ones, before any clinical manifestations.

  6. [The isolated perfused porcine kidney model for investigations concerning surgical therapy procedures].

    PubMed

    Peters, Kristina; Michel, Maurice Stephan; Matis, Ulrike; Häcker, Axel

    2006-01-01

    Experiments to develop innovative surgical therapy procedures are conventionally conducted on animals, as crucial aspects like tissue removal and bleeding disposition cannot be investigated in vitro. Extracorporeal organ models however reflect these aspects and could thus reduce the use of animals for this purpose fundamentally in the future. The aim of this work was to validate the isolated perfused porcine kidney model with regard to its use for surgical purposes on the basis of histological and radiological procedures. The results show that neither storage nor artificial perfusion led to any structural or functional damage which would affect the quality of the organ. The kidney model is highly suitable for simulating the main aspects of renal physiology and allows a constant calibration of perfusion pressure and tissue temperature. Thus, with only a moderate amount of work involved, the kidney model provides a cheap and readily available alternative to conventional animal experiments; it allows standardised experimental settings and provides valid results.

  7. Effect of specific antibodies on the excitability of internally perfused squid axons.

    PubMed

    Huneeus, F C; Fernandez, H L

    1967-11-01

    Giant axons from the squid Dosidicus gigas were internally perfused with rabbit antiaxoplasm antibodies and their effect upon the action potential and the membrane potential was studied. Necessary requirements for the antibodies to affect these parameters in a consistent manner were: (a) removal of the bulk of axoplasm from the perfused zone, accomplished by initially perfusing with a cysteine-rich (400 mM) solution, and (b) addition of small amounts of cysteine (30 mM) to the antibody-containing solution. When these experimental conditions were met, conduction block ensued generally within 3 hr of the first contact of the axon inner surface with the antibody Antineurofilament antibodies and nonspecific antibodies had no effect. External application of antiaxoplasm antibodies had no effect.

  8. The isolated and perfused working heart of the frog, Rana esculenta: an improved preparation.

    PubMed

    Acierno, R; Gattuso, A; Cerra, M C; Pellegrino, D; Agnisola, C; Tota, B

    1994-05-01

    1. An in vitro preparation of the intact heart of the frog Rana esculenta was set up. 2. The isolated heart, perfused at constant pressure, was spontaneously beating and able to generate physiological values of output pressure, cardiac output, ventricle work and power. It showed the typical phenomenon of the "hypodynamic state" after a relatively constant time from the onset of the perfusion. 3. Perfusion with air-saturated saline and 99.5% oxygen-saturated saline did not show significant differences in the recorded parameters. 4. This experimental model represents a useful tool for physiological and pharmacological studies, especially when the direct analysis of the effects of hormones, mediators or drugs requires an intact heart preparation.

  9. Non-negative constraint for image-based breathing gating in ultrasound hepatic perfusion data

    NASA Astrophysics Data System (ADS)

    Wu, Kaizhi; Ding, Mingyue; Chen, Xi; Deng, Wenjie; Zhang, Zhijun

    2015-12-01

    Images acquired during free breathing using contrast enhanced ultrasound hepatic perfusion imaging exhibits a periodic motion pattern. It needs to be compensated for if a further accurate quantification of the hepatic perfusion analysis is to be executed. To reduce the impact of respiratory motion, image-based breathing gating algorithm was used to compensate the respiratory motion in contrast enhanced ultrasound. The algorithm contains three steps of which respiratory kinetics extracted, image subsequences determined and image subsequences registered. The basic performance of the algorithm was to extract the respiratory kinetics of the ultrasound hepatic perfusion image sequences accurately. In this paper, we treated the kinetics extracted model as a non-negative matrix factorization (NMF) problem. We extracted the respiratory kinetics of the ultrasound hepatic perfusion image sequences by non-negative matrix factorization (NMF). The technique involves using the NMF objective function to accurately extract respiratory kinetics. It was tested on simulative phantom and used to analyze 6 liver CEUS hepatic perfusion image sequences. The experimental results show the effectiveness of our proposed method in quantitative and qualitative.

  10. Human cortical perfusion and the arterial pulse: a near-infrared spectroscopy study

    PubMed Central

    Kwan, Hon C; Cheng, Anita; Liu, Ruth; Borrett, Donald S

    2004-01-01

    Background The pulsatile nature of the arterial pulse induces a pulsatile perfusion pattern which can be observed in human cerebral cortex with non-invasive near-infrared spectroscopy. The present study attempts to establish a quantitative relation between these two events, even in situations of very weak signal-to-noise ratio in the cortical perfusion signal. The arterial pulse pattern was extracted from the left middle finger by means of plethesmographic techniques. Changes in cortical perfusion were detected with a continuous-wave reflectance spectrophotometer on the scalp overlying the left prefrontal cortex. Cross-correlation analysis was performed to provide evidence for a causal relation between the arterial pulse and relative changes in cortical total hemoglobin. In addition, the determination of the statistical significance of this relation was established by the use of phase-randomized surrogates. Results The results showed statistically significant cross correlation between the arterial and perfusion signals. Conclusions The approach designed in the present study can be utilized for a quantitative and continuous assessment of the perfusion states of the cerebral cortex in experimental and clinical settings even in situations of extremely low signal-to-noise ratio. PMID:15113424

  11. Significantly different proliferative potential of oral mucosal epithelial cells between six animal species.

    PubMed

    Kondo, Makoto; Yamato, Masayuki; Takagi, Ryo; Murakami, Daisuke; Namiki, Hideo; Okano, Teruo

    2014-06-01

    There has been an upsurge in regenerative medicine in recent years. In particular, because oral mucosal epithelial cells can be obtained noninvasively, cultured epithelial cell sheets have been used in a number of ectopic transplantations. Additionally, the verification of the properties of experimental animals' cultured cells has accelerated the application of regenerative medicine. In the present study, the properties of oral mucosal epithelial cells were compared between six animal species. The human and pig epithelia were relatively thicker than the epithelia of the other species. The colony-forming efficiency of the rat was the highest, followed by those of the dog, human, rabbit, and pig, whereas the colonies of the mouse cells were all paraclone and uncountable in the colony-forming assay. We also found that the rabbit and pig cells proliferated poorly and were unable to form cell sheets without feeder layers. In contrast, even in the absence of feeder layers and cholera toxin, cultured dog and mouse cells formed contiguous sheets, when the cell seeding density was high. These results indicate that interspecies variation is considerable in oral mucosal epithelial cells and that specific experimental animal or human cells must be chosen according to the intended use.

  12. Recent progress in HIV vaccines inducing mucosal immune responses.

    PubMed

    Pavot, Vincent; Rochereau, Nicolas; Lawrence, Philip; Girard, Marc P; Genin, Christian; Verrier, Bernard; Paul, Stéphane

    2014-07-31

    In spite of several attempts over many years at developing a HIV vaccine based on classical strategies, none has convincingly succeeded to date. As HIV is transmitted primarily by the mucosal route, particularly through sexual intercourse, understanding antiviral immunity at mucosal sites is of major importance. An ideal vaccine should elicit HIV-specific antibodies and mucosal CD8⁺ cytotoxic T-lymphocyte (CTL) as a first line of defense at a very early stage of HIV infection, before the virus can disseminate into the secondary lymphoid organs in mucosal and systemic tissues. A primary focus of HIV preventive vaccine research is therefore the induction of protective immune responses in these crucial early stages of HIV infection. Numerous approaches are being studied in the field, including building upon the recent RV144 clinical trial. In this article, we will review current strategies and briefly discuss the use of adjuvants in designing HIV vaccines that induce mucosal immune responses.

  13. HIV and mucosal barrier interactions: consequences for transmission and pathogenesis.

    PubMed

    Burgener, Adam; McGowan, Ian; Klatt, Nichole R

    2015-10-01

    The mucosal barrier plays an integral function in human health as it is the primary defense against pathogens, and provides a critical transition between the external environment and the human internal body. In the context of HIV infection, the most relevant mucosal surfaces include those of the gastrointestinal (GI) and genital tract compartments. Several components help maintain the effectiveness of this mucosal surface, including the physical anatomy of the barrier, cellular immunity, soluble factors, and interactions between the epithelial barrier and the local microenvironment, including mucus and host microbiota. Any defects in barrier integrity or function can rapidly lead to an increase in acquisition risk, or with established infection may result in increased pathogenesis, morbidities, or mortality. Indeed, a key feature to all aspects of HIV infection from transmission to pathogenesis is disruption and/or dysfunction of mucosal barriers. Herein, we will detail the host-pathogen relationship of HIV and mucosal barriers in both of these scenarios.

  14. Myocardial perfusion scintigraphy: the evidence

    PubMed Central

    Anagnostopoulos, C.; Cerqueira, M.; Ell, P. J.; Flint, E. J.; Harbinson, M.; Kelion, A. D.; Al-Mohammad, A.; Prvulovich, E. M.; Shaw, L. J.; Tweddel, A. C.

    2003-01-01

    This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by

  15. Autologous Transplantation of Oral Mucosal Epithelial Cell Sheets Cultured on an Amniotic Membrane Substrate for Intraoral Mucosal Defects

    PubMed Central

    Amemiya, Takeshi; Nakamura, Takahiro; Yamamoto, Toshiro; Kinoshita, Shigeru; Kanamura, Narisato

    2015-01-01

    The human amniotic membrane (AM) is a thin intrauterine placental membrane that is highly biocompatible and possesses anti-inflammatory and anti-scarring properties. Using AM, we developed a novel method for cultivating oral mucosal epithelial cell sheets. We investigated the autologous transplantation of oral mucosal epithelial cells cultured on AM in patients undergoing oral surgeries. We obtained specimens of AM from women undergoing cesarean sections. This study included five patients without any history of a medical disorder who underwent autologous cultured oral epithelial transplantation following oral surgical procedures. Using oral mucosal biopsy specimens obtained from these patients, we cultured oral epithelial cells on an AM carrier. We transplanted the resultant cell sheets onto the oral mucosal defects. Patients were followed-up for at least 12 months after transplantation. After 2–3 weeks of being cultured on AM, epithelial cells were well differentiated and had stratified into five to seven layers. Immunohistochemistry revealed that the cultured cells expressed highly specific mucosal epithelial cell markers and basement membrane proteins. After the surgical procedures, no infection, bleeding, rejection, or sheet detachment occurred at the reconstructed sites, at which new oral mucous membranes were evident. No recurrence was observed in the long-term follow-up, and the postoperative course was excellent. Our results suggest that AM-cultured oral mucosal epithelial cell sheets represent a useful biomaterial and feasible method for oral mucosal reconstruction. However, our primary clinical study only evaluated their effects on a limited number of small oral mucosal defects. PMID:25915046

  16. Cardiac tissue engineering using perfusion bioreactor systems

    PubMed Central

    Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana

    2009-01-01

    This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955

  17. Imaging of myocardial perfusion with magnetic resonance.

    PubMed

    Barkhausen, Jörg; Hunold, Peter; Jochims, Markus; Debatin, Jörg F

    2004-06-01

    Coronary artery disease (CAD) is currently the leading cause of death in developed nations. Reflecting the complexity of cardiac function and morphology, noninvasive diagnosis of CAD represents a major challenge for medical imaging. Although coronary artery stenoses can be depicted with magnetic resonance (MR) and computed tomography (CT) techniques, its functional or hemodynamic impact frequently remains elusive. Therefore, there is growing interest in other, target organ-specific parameters such as myocardial function at stress and first-pass myocardial perfusion imaging to assess myocardial blood flow. This review explores the pathophysiologic background, recent technical developments, and current clinical status of first-pass MR imaging (MRI) of myocardial perfusion.

  18. Mucosal drug delivery: membranes, methodologies, and applications.

    PubMed

    Song, Yifan; Wang, Yiping; Thakur, Rashmi; Meidan, Victor M; Michniak, Bozena

    2004-01-01

    In recent years, extensive research into novel forms of drug delivery has suggested that mucosal approaches offer a promising therapeutic alternative, especially for systemically acting drugs. Transmucosal drug delivery offers many benefits, including noninvasive administration, convenience, rapid onset, as well as elimination of hepatic first-pass metabolism. The investigated absorptive surfaces consist of the nasal, buccal, ocular, vaginal, and rectal mucosae. Among these, the nasal and buccal routes have proved the most promising to date. The bioavailability achieved mainly depends upon the pathophysiological state of the mucosa and the properties of both the drug and delivery systems. Various agents can increase the efficacy of transmucosal drug delivery. These include cyclodextrins, bile salts, surfactants, fusidic acid derivatives, microspheres, liposomes, and bioadhesive agents. The mechanisms of action, effectiveness, and toxicity profiles of these enhancers have been investigated extensively in both animal and human models.

  19. Cyclosporin metabolism by human gastrointestinal mucosal microsomes.

    PubMed Central

    Webber, I R; Peters, W H; Back, D J

    1992-01-01

    The in vitro metabolism of the immunosuppressant cyclosporin (CsA) by human gastrointestinal mucosal microsomes has been studied. Macroscopically normal intestinal (n = 4) and liver (n = 2) tissue was obtained from kidney transplant donors, and microsomes prepared. Intestinal metabolism was most extensive with duodenal protein (15% conversion to metabolites M1/M17 after 2 h incubation at 37 degrees C; metabolite measurement by h.p.l.c). Western blotting confirmed the presence of P-4503A (enzyme subfamily responsible for CsA metabolism) in duodenum and ileum tissue, but not in colon tissue. The results of this study indicate that the gut wall may play a role in the first-pass metabolism of CsA, and could therefore be a contributory factor to the highly variable oral bioavailability of CsA. PMID:1389941

  20. Mucosal cytokine network in inflammatory bowel disease

    PubMed Central

    Andoh, Akira; Yagi, Yuhki; Shioya, Makoto; Nishida, Atsushi; Tsujikawa, Tomoyuki; Fujiyama, Yoshihide

    2008-01-01

    Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic inflammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina propria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-α clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the biological activities of recently-reported cytokines [Interleukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-α in the pathophysiology of IBD. PMID:18777592

  1. Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.

    PubMed Central

    Konturek, J W; Dembinski, A; Stoll, R; Domschke, W; Konturek, S J

    1994-01-01

    The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth. PMID:7959223

  2. Microbes and mucosal immune responses in asthma.

    PubMed

    Hansel, Trevor T; Johnston, Sebastian L; Openshaw, Peter J

    2013-03-09

    The substantial increase in the worldwide prevalence of asthma and atopy has been attributed to lifestyle changes that reduce exposure to bacteria. A recent insight is that the largely bacterial microbiome maintains a state of basal immune homoeostasis, which modulates immune responses to microbial pathogens. However, some respiratory viral infections cause bronchiolitis of infancy and childhood wheeze, and can exacerbate established asthma; whereas allergens can partly mimic infectious agents. New insights into the host’s innate sensing systems, combined with recently developed methods that characterise commensal and pathogenic microbial exposure, now allow a unified theory for how microbes cause mucosal inflammation in asthma. The respiratory mucosa provides a key microbial interface where epithelial and dendritic cells interact with a range of functionally distinct lymphocytes. Lymphoid cells then control a range of pathways, both innate and specific, which organise the host mucosal immune response. Fundamental to innate immune responses to microbes are the interactions between pathogen-associated molecular patterns and pattern recognition receptors, which are associated with production of type I interferons, proinflammatory cytokines, and the T-helper-2 cell pathway in predisposed people. These coordinated, dynamic immune responses underlie the differing asthma phenotypes, which we delineate in terms of Seven Ages of Asthma. An understanding of the role of microbes in the atopic march towards asthma, and in causing exacerbations of established asthma, provides the rationale for new specific treatments that can be assessed in clinical trials. On the basis of these new ideas, specific host biomarkers might then allow personalised treatment to become a reality for patients with asthma.

  3. The oral mucosal surface and blood vessels

    PubMed Central

    2013-01-01

    Introduction Detailed information about the size of the oral mucosa is scarce in the literature, and those studies that do exist do not take into account the size of the tongue or the enlargement of the surface by the papillae. Because of the various functions of the oral mucosa in the maintenance of oral health, knowledge of its true size may provide a better understanding of the physiology of the oral cavity and some oral diseases and direct future therapeutic strategies. The aim of this study was to determine the total size of the oral mucosa. Methods Five human adult cadaver heads were cut in the median sagittal plane, and the total area of the oral surface was determined using silicon casts. The surface of the tongue was measured with quantitative profilometry. Photographs of oral blood vessels were taken in different areas of the oral mucosa of adult test subjects using intravital microscopy, and the pictures were compared with vessel casts of the oral mucosal capillaries of a maccaca fasciculrais monkey, which was studied using a scanning electron microscope. Results The results showed that the dorsal side of the tongue comprises a large proportion of the total oral mucosal surface. The surface area of the epithelium increases moving from anterior to posterior on the tongue, and the number of underlying blood vessels increases proportionally. Conclusions It can be concluded that the back of the tongue plays an important role in the oral resorption of drugs. Clinical relevance: The results may be of relevance for the delivery and development of oral drug application. PMID:23497446

  4. Ventilation-Perfusion Relationships Following Experimental Pulmonary Contusion

    DTIC Science & Technology

    2007-06-14

    Diffusion limitation, as measured by carbon monoxide rebreathing , did not contribute significantly to hypoxemia (21). Fulton and Peter, in a model of...by the software that involved generation of closed polygons around an image region (52). Air, (1,000 HU), hyperinflated (998 to 900 HU), normally...shunt elevation in patients with flail chest (21). Diffusion limitation, as measured by carbon mon- oxide rebreathing , did not contribute significantly to

  5. Effects of laser acupuncture on blood perfusion rate

    NASA Astrophysics Data System (ADS)

    Wang, Xian-ju; Zeng, Chang-chun; Liu, Han-ping; Liu, Song-hao; Liu, Liang-gang

    2006-09-01

    Based on Pennes equation, the influences of the intensity and the impulse frequency of laser acupuncture on the point tissues' blood flow perfusion rate are discussed. We find that the blood perfusion rate of point tissue increases with the intensity of laser acupuncture increasing. After impulse laser acupuncture the point tissue blood perfusion rate increase little, but after continuum laser acupuncture the point tissues blood perfusion rate increase much.

  6. Gastric HCO3- secretion induced by mucosal acidification: different mechanisms depending on acid concentration.

    PubMed

    Aihara, Eitaro; Hayashi, Masamune; Sasaki, Yoko; Takeuchi, Koji

    2005-01-01

    We compared the HCO3- secretory responses induced by mucosal acidification at different HCl concentrations (100 and 200 mM HCl) in the rat stomach. Under urethane anesthesia, the stomach was mounted on an ex vivo chamber and perfused with saline under inhibition of acid secretion by omeprazole (60 mg/kg, i.p.). TheHCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. The acidification was performed by exposure of the mucosa to 100 mMor 200 mM HCl for 10 min. The secretion of HCO3- was increased by acidification of the mucosa at both 100 and 200 mM of HCl, and the maximal HCO3- response was 1.5-times greater at the latter concentration. The HCO3- responses induced by 100 and 200 mM HCl were both totally inhibited by prior administration of indomethacin, an inhibitor of prostaglandin (PG) production. The HCO3- stimulatory effect of 200 mM HCl was also significantly attenuated by pre-treatment with N(G)-nitro L-arginine methyl ester (L-NAME), the inhibitor of nitric oxide (NO) synthase, as well as chemical ablation of capsaicin-sensitive afferent neurons, whereas that of 100 mM HCl was affected by neither of these treatments. We conclude that the mucosal acidification stimulates gastric HCO3- secretion in different mechanisms, depending on the concentration of acid; the response caused by 100 mM HCl is mediated only by PGs, while that caused by 200 mM HCl is mediated by both capsaicin-sensitive afferent neurons and NO, in addition to PGs.

  7. Temporal and concentration effects of isoflurane anaesthesia on intestinal tissue oxygenation and perfusion in horses.

    PubMed

    Hopster, K; Hopster-Iversen, C; Geburek, F; Rohn, K; Kästner, S B R

    2015-07-01

    The aim of this study was to assess the effect of duration of anaesthesia and concentration of isoflurane on global perfusion as well as intestinal microperfusion and oxygenation. Nine Warmblood horses were premedicated with xylazine; anaesthesia was induced with midazolam and ketamine, and maintained with isoflurane. Horses were ventilated to normocapnia. During 7 h of anaesthesia, mean arterial blood pressures (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration (ETIso) and cardiac output using lithium dilution were measured; cardiac index (CI) was calculated. Intestinal microperfusion and oxygenation were measured using laser Doppler flowmetry and white-light spectrophotometry. Surface probes were placed via median laparotomy on the serosal and mucosal site of the jejunum and the pelvic flexion of the colon. After 3 h of constant ETIso (1.4%), ETIso was increased in 0.2% increments up to 2.4%, followed by a decrease to 1.2% and an increase to 1.4%. The CI and MAP decreased continuously with increasing ETIso to 40 ± 5 mL/kg/min and 52 ± 8 mmHg, respectively. Microperfusion and oxygenation remained unchanged until an ETIso of 2.0% resulted in CI and MAP of 48 ± 5 mL/kg/min and 62 ± 6 mmHg, respectively, and then decreased rapidly. When ETIso decreased back to baseline, CI, MAP, microperfusion and oxygenation recovered to baseline. Isoflurane concentration but not duration of isoflurane anaesthesia influenced central and intestinal oxygenation and perfusion in healthy horses. Under isoflurane, intestinal perfusion appeared to be preserved until a threshold MAP or blood flow was reached.

  8. Contrast-enhanced, real-time volumetric ultrasound imaging of tissue perfusion: preliminary results in a rabbit model of testicular torsion

    NASA Astrophysics Data System (ADS)

    Paltiel, H. J.; Padua, H. M.; Gargollo, P. C.; Cannon, G. M., Jr.; Alomari, A. I.; Yu, R.; Clement, G. T.

    2011-04-01

    Contrast-enhanced ultrasound (US) imaging is potentially applicable to the clinical investigation of a wide variety of perfusion disorders. Quantitative analysis of perfusion is not widely performed, and is limited by the fact that data are acquired from a single tissue plane, a situation that is unlikely to accurately reflect global perfusion. Real-time perfusion information from a tissue volume in an experimental rabbit model of testicular torsion was obtained with a two-dimensional matrix phased array US transducer. Contrast-enhanced imaging was performed in 20 rabbits during intravenous infusion of the microbubble contrast agent Definity® before and after unilateral testicular torsion and contralateral orchiopexy. The degree of torsion was 0° in 4 (sham surgery), 180° in 4, 360° in 4, 540° in 4, and 720° in 4. An automated technique was developed to analyze the time history of US image intensity in experimental and control testes. Comparison of mean US intensity rate of change and of ratios between mean US intensity rate of change in experimental and control testes demonstrated good correlation with testicular perfusion and mean perfusion ratios obtained with radiolabeled microspheres, an accepted 'gold standard'. This method is of potential utility in the clinical evaluation of testicular and other organ perfusion.

  9. Contrast-enhanced, real-time volumetric ultrasound imaging of tissue perfusion: preliminary results in a rabbit model of testicular torsion.

    PubMed

    Paltiel, H J; Padua, H M; Gargollo, P C; Cannon, G M; Alomari, A I; Yu, R; Clement, G T

    2011-04-07

    Contrast-enhanced ultrasound (US) imaging is potentially applicable to the clinical investigation of a wide variety of perfusion disorders. Quantitative analysis of perfusion is not widely performed, and is limited by the fact that data are acquired from a single tissue plane, a situation that is unlikely to accurately reflect global perfusion. Real-time perfusion information from a tissue volume in an experimental rabbit model of testicular torsion was obtained with a two-dimensional matrix phased array US transducer. Contrast-enhanced imaging was performed in 20 rabbits during intravenous infusion of the microbubble contrast agent Definity® before and after unilateral testicular torsion and contralateral orchiopexy. The degree of torsion was 0° in 4 (sham surgery), 180° in 4, 360° in 4, 540° in 4, and 720° in 4. An automated technique was developed to analyze the time history of US image intensity in experimental and control testes. Comparison of mean US intensity rate of change and of ratios between mean US intensity rate of change in experimental and control testes demonstrated good correlation with testicular perfusion and mean perfusion ratios obtained with radiolabeled microspheres, an accepted 'gold standard'. This method is of potential utility in the clinical evaluation of testicular and other organ perfusion.

  10. Mucositis and non-invasive markers of small intestinal function.

    PubMed

    Tooley, Katie L; Howarth, Gordon S; Butler, Ross N

    2009-05-01

    Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H(2) breath tests, serum citrulline tests and the (13)C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.

  11. Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium

    SciTech Connect

    Pratt, A.D.; Clancy, G.; Welsh, M.J.

    1986-08-01

    Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium the authors found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. The observation that mucosal 8-phenyletheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.

  12. The mucosal immune system: From dentistry to vaccine development.

    PubMed

    Kiyono, Hiroshi; Azegami, Tatsuhiko

    2015-01-01

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

  13. The mucosal immune system: From dentistry to vaccine development

    PubMed Central

    KIYONO, Hiroshi; AZEGAMI, Tatsuhiko

    2015-01-01

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

  14. Oral Mucosal Lesions in Indians From Northeast Brazil

    PubMed Central

    Cury, Patricia Ramos; Porto, Lia Pontes Arruda; dos Santos, Jean Nunes; e Ribeiro, Livia Silva Figueiredo; de Aquino Xavier, Flavia Caló; Figueiredo, Andreia Leal; Ramalho, Luciana Maria Pedreira

    2014-01-01

    Abstract The aim of this cross-sectional study was to evaluate the prevalence of oral mucosal lesions, and their risk indicators in adult Kiriri Indians from Northeast Brazil. Clinical oral examination was performed on a representative sample of 223 Indians (age ≥19 years). A systematic evaluation of lips, labial mucosa and sulcus, commissures, buccal mucosa and sulcus, gingiva and alveolar ridge, tongue, floor of the mouth, and soft and hard palate was performed. Bivariate analysis was conducted to assess associations between mucosal conditions and age, gender, income, educational level, diabetic status, and smoking status. Mucosal lesions were found in 50 participants (22.4%). The most prevalent lesions were fistulae (6.2%) and traumatic ulcers (4.48%). Oral mucosal was associated with higher age (≥35 years; odds ratio [OR] = 1.99, 95% confidence interval [CI]: 1.05–3.76, P = 0.03) and lower education level (<9 years; OR = 2.13, 95% CI: 0.96–4.71, P = 0.06). Mucosal conditions are prevalent in Kiriri Indians and the presence of mucosal lesions is associated with advanced age and lower education. A public health program aimed at preventing and treating mucosal lesions and targeted toward the high-risk group is vital to improve the oral health status of this population. PMID:25501053

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

    PubMed Central

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

    2017-01-01

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

  16. Perfusion MRI: The Five Most Frequently Asked Clinical Questions

    PubMed Central

    Essig, Marco; Nguyen, Thanh Binh; Shiroishi, Mark S.; Saake, Marc; Provenzale, James M.; Enterline, David S.; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

    2013-01-01

    OBJECTIVE This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23971482

  17. Role of hypothermic machine perfusion in liver transplantation.

    PubMed

    Schlegel, Andrea; Dutkowski, Philipp

    2015-06-01

    Machine liver perfusion has significantly evolved during the last ten years to optimize extended criteria liver grafts and to address the worldwide organ shortage. This review gives an overview on available ex vivo and in vivo data on hypothermic machine liver perfusion. We discuss also possible protective pathways and show most recent clinical applications of hypothermic machine liver perfusion in human.

  18. Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats

    PubMed Central

    Hassandarvish, Pouya; Abdul Majid, Nazia; Hadi, A. Hamid A.; Nordin, Noraziah; Abdulla, Mahmood A.

    2013-01-01

    The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions. PMID:23781513

  19. Lung Perfusion Scanning in Hepatic Cirrhosis

    PubMed Central

    Stanley, N. N.; Ackrill, P.; Wood, J.

    1972-01-01

    Abnormal lung perfusion scans using radioactive particles were found in five out of six cases of hepatic cirrhosis with arterial hypoxaemia. None had clinical evidence of cardiopulmonary disease or signs of pulmonary embolism on arteriography. The scan defects are probably caused by a disorder of the pulmonary microvasculature, which may show regional variation in severity. ImagesFIG. 1FIG. 2 PMID:4645896

  20. Coupling between resting cerebral perfusion and EEG.

    PubMed

    O'Gorman, R L; Poil, S-S; Brandeis, D; Klaver, P; Bollmann, S; Ghisleni, C; Lüchinger, R; Martin, E; Shankaranarayanan, A; Alsop, D C; Michels, L

    2013-07-01

    While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults (n = 16, ten females, median age: 27 years, range 21-48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13 Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation.

  1. Nuclear cardiology: Myocardial perfusion and function

    SciTech Connect

    Seldin, D.W. )

    1991-08-01

    Myocardial perfusion studies continue to be a major focus of research, with new investigations of the relationship of exercise-redistribution thallium imaging to diagnosis, prognosis, and case management. The redistribution phenomenon, which seemed to be fairly well understood a few years ago, is now recognized to be much more complex than originally thought, and various strategies have been proposed to clarify the meaning of persistent defects. Pharmacologic intervention with dipyridamole and adenosine has become available as an alternative to exercise, and comparisons with exercise imaging and catheterization results have been described. Thallium itself is no longer the sole single-photon perfusion radiopharmaceutical; two new technetium agents are now widely available. In addition to perfusion studies, advances in the study of ventricular function have been made, including reports of studies performed in conjunction with technetium perfusion studies, new insights into cardiac physiology, and the prognostic and case-management information that function studies provide. Finally, work has continued with monoclonal antibodies for the identification of areas of myocyte necrosis. 41 references.

  2. A reappraisal of retrograde cerebral perfusion

    PubMed Central

    2013-01-01

    Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients. PMID:23977600

  3. Asynchronicity of facial blood perfusion in migraine.

    PubMed

    Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A; Kamshilin, Alexei A; Närhi, Matti; Karjalainen, Pasi A; Giniatullin, Rashid

    2013-01-01

    Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology.

  4. Asynchronicity of Facial Blood Perfusion in Migraine

    PubMed Central

    Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A.; Kamshilin, Alexei A.; Närhi, Matti; Karjalainen, Pasi A.; Giniatullin, Rashid

    2013-01-01

    Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology. PMID:24324592

  5. Role of B Cells in Mucosal Vaccine-Induced Protective CD8+ T Cell Immunity against Pulmonary Tuberculosis.

    PubMed

    Khera, Amandeep K; Afkhami, Sam; Lai, Rocky; Jeyanathan, Mangalakumari; Zganiacz, Anna; Mandur, Talveer; Hammill, Joni; Damjanovic, Daniela; Xing, Zhou

    2015-09-15

    Emerging evidence suggests a role of B cells in host defense against primary pulmonary tuberculosis (TB). However, the role of B cells in TB vaccine-induced protective T cell immunity still remains unknown. Using a viral-vectored model TB vaccine and a number of experimental approaches, we have investigated the role of B cells in respiratory mucosal vaccine-induced T cell responses and protection against pulmonary TB. We found that respiratory mucosal vaccination activated Ag-specific B cell responses. Whereas respiratory mucosal vaccination elicited Ag-specific T cell responses in the airway and lung interstitium of genetic B cell-deficient (Jh(-/-) knockout [KO]) mice, the levels of airway T cell responses were lower than in wild-type hosts, which were associated with suboptimal protection against pulmonary Mycobacterium tuberculosis challenge. However, mucosal vaccination induced T cell responses in the airway and lung interstitium and protection in B cell-depleted wild-type mice to a similar extent as in B cell-competent hosts. Furthermore, by using an adoptive cell transfer approach, reconstitution of B cells in vaccinated Jh(-/-) KO mice did not enhance anti-TB protection. Moreover, respiratory mucosal vaccine-activated T cells alone were able to enhance anti-TB protection in SCID mice, and the transfer of vaccine-primed B cells alongside T cells did not further enhance such protection. Alternatively, adoptively transferring vaccine-primed T cells from Jh(-/-) KO mice into SCID mice only provided suboptimal protection. These data together suggest that B cells play a minimal role, and highlight a central role by T cells, in respiratory mucosal vaccine-induced protective immunity against M. tuberculosis.

  6. Mucosal tears at the oesophagogastric junction (the Mallory-Weiss syndrome)

    PubMed Central

    Atkinson, Michael; Bottrill, M. B.; Edwards, A. T.; Mitchell, Winifred M.; Peet, B. Gadsby; Williams, R. E.

    1961-01-01

    This is a re-appraisal of the supposedly rare Mallory-Weiss syndrome in which 11 patients with mucosal tears at the oesophagogastric junction are described. The fact that these cases were collected from general hospitals within a short period suggests that the condition is more common than supposed and may account for a considerable proportion of the 20 to 25% of patients with upper gastrointestinal bleeding in whom no radiological abnormality can subsequently be found. Of the 11 patients, eight presented with gastrointestinal bleeding, two with mediastinitis, and one without relevant symptoms. The classical history of antecedent vomiting before the bleeding was obtained in only four patients, its absence not excluding the diagnosis. The presence of a small hiatal hernia in four patients appeared to predispose to mucosal tears as did mucosal atrophy occurring with advancing age. Some experimental findings pertaining to the mechanism of the tears are presented. ImagesFIG. 1FIG. 2FIG. 3FIGS. 4 and 5FIG. 6FIG. 7FIG. 8FIG. 9FIG. 10 PMID:13684977

  7. 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.

  8. Neurotensin releases norepinephrine differentially from perfused hypothalamus of sated and fasted rat

    SciTech Connect

    Lee, T.F.; Rezvani, A.H.; Hepler, J.R.; Myers, R.D.

    1987-01-01

    The central injection of neurotensin (NT) has been reported to attenuate the intake of food in the fasted animal. To determine whether endogenous norepinephrine (NE) is involved in the satiating effect of NT, the in vivo activity of NE in circumscribed sites in the hypothalamus of the unanesthetized rat was examined. Bilateral guide tubes for push-pull perfusion were implanted stereotaxically to rest permanently above one of several intended sites of perfusion, which included the paraventricular nucleus (PVN), ventromedial nucleus (VMN), and the lateral hypothalamic (LH) area. After endogenous stores of NE at a specific hypothalamic locus were radiolabeled by microinjection of 0.02-0.5 ..mu..Ci of (/sup 3/H)NE, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 ..mu..l/min over successive intervals of 5.0 min. When 0.05 or 0.1 ..mu..g/..mu..l NT was added to the perfusate, the peptide served either to enhance or educe the local release of NE at 50% of the sites of perfusion. In these experiments, the circumscribed effect of NT on the characteristics of catecholamine efflux depended entirely on the state of hunger or satiety of the rat. That is, when NT was perfused in the fully satiated rat, NE release was augmented within the PVn or VMN; conversely, NE release was inhibited in the LH. in the animal fasted for 18-22 h, NT exerted an opposite effect on the activity of NE within the same anatomical loci in that the efflux of NE was enhanced in the LH but attenuated or unaffected in the PVN or VMN. Taken together, these observations provide experimental support for the view-point that NT could act as a neuromodulator of the activity of hypothalamic noradrenergic neurons that are thought to play a functional role in the regulation of food intake.

  9. Mucosal adherent bacterial dysbiosis in patients with colorectal adenomas

    PubMed Central

    Lu, Yingying; Chen, Jing; Zheng, Junyuan; Hu, Guoyong; Wang, Jingjing; Huang, Chunlan; Lou, Lihong; Wang, Xingpeng; Zeng, Yue

    2016-01-01

    Recent reports have suggested that the gut microbiota is involved in the progression of colorectal cancer (CRC). The composition of gut microbiota in CRC precursors has not been adequately described. To characterize the structure of adherent microbiota in this disease, we conducted pyrosequencing-based analysis of 16S rRNA genes to determine the bacterial profile of normal colons (healthy controls) and colorectal adenomas (CRC precursors). Adenoma mucosal biopsy samples and adjacent normal colonic mucosa from 31 patients with adenomas and 20 healthy volunteers were profiled using the Illumina MiSeq platform. Principal coordinate analysis (PCoA) showed structural segregation between colorectal adenomatous tissue and control tissue. Alpha diversity estimations revealed higher microbiota diversity in samples from patients with adenomas. Taxonomic analysis illustrated that abundance of eight phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Chloroflexi, Cyanobacteria, Candidate-division TM7, and Tenericutes) was significantly different. In addition, Lactococcus and Pseudomonas were enriched in preneoplastic tissue, whereas Enterococcus, Bacillus, and Solibacillus were reduced. However, both PCoA and cluster tree analyses showed similar microbiota structure between adenomatous and adjacent non-adenoma tissues. These present findings provide preliminary experimental evidence supporting that colorectal preneoplastic lesion may be the most important factor leading to alterations in bacterial community composition. PMID:27194068

  10. Role of neutrophils in acrylonitrile-induced gastric mucosal damage.

    PubMed

    Hamdy, Nadia M; Al-Abbasi, Fahad A; Alghamdi, Hassan A; Tolba, Mai F; Esmat, Ahmed; Abdel-Naim, Ashraf B

    2012-01-25

    Acrylonitrile (ACN) is a widely used intermediate in the manufacture of plastics, acrylic fibers, synthetic rubbers and resins that are used in a variety of products including food containers and medical devices. ACN is a possible human carcinogen and a documented animal carcinogen, with the stomach being an important target of its toxicity. ACN has been previously reported to require metabolic activation to reactive intermediates and finally to cyanide (CN⁻). The current study aimed at exploring the potential role of neutrophils in ACN-induced gastric damage in rats. Experimental neutropenia was attained by injecting rats with methotrexate. This significantly ameliorated gastric mucosal injury induced by ACN. This is evidenced by protection against the increase in gastric ulcer index, myeloperoxidase (MPO) activity and CN⁻ level. Also, neutropenia guarded against the decrease in prostaglandin E2 (PGE2), induction of oxidative stress and reduction of total nitrites and alleviated histopathological alterations in rat stomachs. These data indicate that neutrophil infiltration is, at least partly, involved in ACN-induced gastric damage in rats.

  11. Targeted inhibition of IL-18 attenuates irinotecaninduced intestinal mucositis in mice

    PubMed Central

    Lima-Júnior, R C P; Freitas, H C; Wong, D V T; Wanderley, C W S; Nunes, L G; Leite, L L; Miranda, S P; Souza, M H L P; Brito, G A C; Magalhães, P J C; Teixeira, M M; Cunha, F Q; Ribeiro, R A

    2014-01-01

    Background and Purpose Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the role of IL-18 in the pathogenesis of irinotecan-induced intestinal mucositis. Experimental Approach Wild type (WT), IL-18 or caspase-1 knockout mice were treated with either saline or irinotecan (60 mg·kg−1 per 4 days, i.p.) or the IL-18 binding protein (IL-18bp, 10 mg·kg−1) before irinotecan. On day 5, diarrhoea was monitored and proximal intestinal strips were obtained for histopathology, in vitro gut contractility, myeloperoxidase (MPO) and inducible NOS (iNOS) activity, and detection of IL-18 expression. Key Results Irinotecan induced severe diarrhoea accompanied by intestinal injury (villi shortening and increased crypt depth). Additionally, irinotecan treatment increased MPO and iNOS activity, iNOS immunostaining and IL-18 expression in WT mice compared with saline treatment. The IL-18 production was associated with macrophages. In vitro, intestinal smooth muscle strips were hyperresponsive to ACh after irinotecan treatment. Increases in MPO and iNOS activity, intestinal contractility and diarrhoea were prevented in caspase-1 knockout and IL-18 knockout mice, and in IL-18bp-treated WT mice. Furthermore, the Survival of irinotecan-treated mice was increased and iNOS immunoexpression and IL-18 production prevented in IL-18 knockout mice. Conclusions and Implications Targeting IL-18 function may be a promising therapeutic approach to decreasing the severity of intestinal mucositis during irinotecan treatment regimens. PMID:24428790

  12. Gastrointestinal mucositis: the role of MMP-tight junction interactions in tissue injury.

    PubMed

    Al-Dasooqi, Noor; Wardill, Hannah R; Gibson, Rachel J

    2014-07-01

    Chemotherapy for cancer causes significant gut toxicity known as mucositis. The pathogenesis of mucositis is ill defined. Recent clinical research guidelines have highlighted epithelial junctional complexes as emerging targets within mucositis research. Given the robust biological evidence linking tight junctions and matrix metalloproteinases, key mediators of mucositis, tight junction proteins have received significant attention. Despite this, the link between tight junctions, matrix metalloproteinases and mucositis development is yet to be established. This critical review therefore aims to describe the role of matrix metalloproteinases in mucositis, and how matrix metalloproteinase-dependent tight junction disruption may contribute to the pathobiology of mucositis.

  13. Physiology and immunology of mucosal barriers in catfish (Ictalurus spp.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mucosal barriers of catfish (Ictalurus spp.) constitute the first line of defense against pathogen invasion while simultaneously carrying out a diverse array of other critical physiological processes, including nutrient adsorption, osmoregulation, waste excretion, and environmental sensing. Catf...

  14. [Mucositis in head and neck cancer patients undergoing radiochemotherapy].

    PubMed

    Santos, Renata Cristina Schmidt; Dias, Rodrigo Souza; Giordani, Adelmo José; Segreto, Roberto Araújo; Segreto, Helena Regina Comodo

    2011-12-01

    The objective of present study was to classify oral mucositis according to the Common Toxicity Criterion (CTC) international parameters in head and neck tumor patients simultaneously treated with radio and chemotherapy, and characterize a patient profile in our area, observing the individuals' habits, tumor characteristics, treatment protocol and acute reaction intensity. Fifty patients undergoing simultaneous 66 to 70 Gy megavoltage radiotherapy and cisplatin/carboplatin chemotherapy were evaluated in this study. Weekly evaluations of the degree of mucositis were perfoemed according to CTC, a four-degree ordinal scale; 36% of all patients and 100% of those with diabetes discontinued treatment due to mucositis, showing that this pathology contributes to the severity of mucositis.

  15. Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis

    PubMed Central

    Deane, Kevin D.; Scher, Jose U.

    2016-01-01

    RA is a complex multifactorial chronic disease that transitions through several stages. Multiple studies now support that there is a prolonged phase in early RA development during which there is serum elevation of RA-related autoantibodies including RF and ACPAs in the absence of clinically evident synovitis. This suggests that RA pathogenesis might originate in an extra-articular location, which we hypothesize is a mucosal site. In discussing this hypothesis, we will present herein the current understanding of mucosal immunology, including a discussion about the generation of autoimmune responses at these surfaces. We will also examine how other factors such as genes, microbes and other environmental toxins (including tobacco smoke) could influence the triggering of autoimmunity at mucosal sites and eventually systemic organ disease. We will also propose a research agenda to improve our understanding of the role of mucosal inflammation in the development of RA. PMID:25539828

  16. Alleviating mucositis: are we on track for a novel therapeutic?

    PubMed

    Lalla, Rajesh V

    2015-02-01

    Oral and gastrointestinal mucositis has emerged as an important toxicity of cancer therapy. In addition to supportive care measures, agents for the prevention or treatment of mucositis in specific patient populations are described in the evidence-based clinical practice guidelines published by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. However, there still remains an unmet clinical need for preventive and therapeutic agents in several patient populations. The successful development of such agents will rely on our improved understanding of the pathogenic mechanisms underlying mucositis. Studies are also underway on novel delivery mechanisms and risk prediction models that can facilitate the selective use of interventions for mucositis in a targeted and cost-effective manner. A large number of agents are at various stages in the clinical development pipeline. Enhanced management of this dose-limiting toxicity will allow the delivery of optimal cancer therapy and improve patient prognosis.

  17. Prevention of acute gastric mucosal lesions by Solcoseryl.

    PubMed

    Brzozowski, T; Radecki, T; Sendur, R; Gustaw, P; Konturek, S J

    1987-04-01

    Solcoseryl, a deproteinized extract from calf blood containing various biologically active substances, has been reported to promote the healing of skin wounds and gastric ulceration In this study, the gastroprotective effects of Solcoseryl vis-a-vis acute gastric mucosal damage were examined in rats. Solcoseryl significantly reduced the formation of acute lesions induced by intragastric application of absolute ethanol or acidified taurocholate and by water immersion and restraint stress, but failed to affect those caused by acidified aspirin. Since Solcoseryl did not offer protection in the absence of mucosal prostaglandins (PG) e.g. in aspirin-induced gastric damage, it is likely that PG may be involved in the observed gastroprotective activity of the drug. Solcoseryl failed to affect gastric acid or pepsin secretion, but increased mucosal blood flow. Thus PG generated by Solcoseryl might contribute to the maintenance of the observed mucosal microcirculation and the prevention of lesion formation by corrosive substances and stress conditions.

  18. Selective cerebral perfusion for cerebral protection: what we do know

    PubMed Central

    Tang, Gilbert H. L.

    2013-01-01

    Selective antegrade cerebral perfusion (SACP) for aortic arch surgery has evolved considerably since it was first reported. Various pressure rates have been investigated through animal models, as has the effect of warmer perfusate temperatures and hematocrit. Clinical research into pH management, the role of unilateral and bilateral perfusion, and core temperatures have further refined the procedure. We recommend the following protocol for SACP: perfusion pressure between 40-60 mmHg, flow rates between 6-10 mL/kg/min, and perfusate temperature of 20-28 °C; core cooling to 18-30 °C contingent on duration of arrest; alpha-stat pH management; hematocrit between 25-30%; near infrared spectroscopy to monitor cerebral perfusion; and bilateral perfusion when prolonged durations of SACP is anticipated. PMID:23977601

  19. A weakly acidic solution containing deoxycholic acid induces esophageal epithelial apoptosis and impairs integrity in an in vivo perfusion rabbit model

    PubMed Central

    Pardon, Nicolas A.; Vicario, Maria; Vanheel, Hanne; Vanuytsel, Tim; Ceulemans, Laurens J.; Vieth, Michael; Jimenez, Marcel; Tack, Jan

    2016-01-01

    Impaired esophageal mucosal integrity may be an important contributor in the pathophysiology of gastroesophageal reflux disease (GERD). Nevertheless, the effect of potentially harmful agents on epithelial integrity is mainly evaluated in vitro for a short period of time and the possible induction of epithelial apoptosis has been neglected. Our objective was to assess the effect of an acidic and weakly acidic solution containing deoxycholic acid (DCA) on the esophageal epithelium in an in vivo rabbit model of esophageal perfusion and to evaluate the role of the epithelial apoptosis. The esophagus of 55 anesthetized rabbits was perfused for 30 min with different solutions at pH 7.2, pH 5.0, pH 1.0, and pH 5.0 containing 200 and 500 μM DCA. Thereafter, animals were euthanized immediately or at 24 or 48 h after the perfusion. Transepithelial electrical resistance, epithelial dilated intercellular spaces, and apoptosis were assessed in Ussing chambers, by transmission electron microscopy, and by TUNEL staining, respectively. No macroscopic or major microscopic alterations were observed after the esophageal perfusions. The acidic and weakly acidic solution containing DCA induced similar long-lasting functional impairment of the epithelial integrity but different ultrastructural morphological changes. Only the solution containing DCA induced epithelial apoptosis in vivo and in vitro in rabbit and human tissue. In contrast to acid, a weakly acidic solution containing DCA induces epithelial apoptosis and a long-lasting impaired mucosal integrity. The presence of apoptotic cells in the esophageal epithelium may be used as a marker of impaired integrity and/or bile reflux exposure. PMID:26797397

  20. Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

    SciTech Connect

    Dowdle, S.C.; Human, D.G.; Mann, M.D. )

    1990-08-01

    Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis.

  1. Human papillomavirus DNA in oral mucosal lesions.

    PubMed

    Giovannelli, Lucia; Campisi, Giuseppina; Lama, Anna; Giambalvo, Ornella; Osborn, John; Margiotta, Valerio; Ammatuna, Pietro

    2002-03-15

    This study determined the presence of human papillomavirus (HPV) DNA in oral mucosa cells from 121 patients with different types of oral mucosal lesions (13 squamous cell carcinomas, 59 potentially malignant lesions, 49 benign erosive ulcerative lesions) and from 90 control subjects. HPV DNA was detected by nested polymerase chain reaction, and genotype was determined by DNA sequencing. HPV prevalence was 61.5% in carcinomas, 27.1% in potentially malignant lesions, 26.5% in erosive ulcerative lesions, and 5.5% in control subjects. The risk of malignant or potentially malignant lesions was associated with HPV and was statistically significant. HPV-18 was found in 86.5% of HPV-positive lesions but was not associated with a particular type of lesion and was found in 80% of the HPV-positive control subjects. HPV infection was related to older age but not to sex, smoking, or alcohol use; the presence of lesions in the oral cavity increased the risk of HPV infection.

  2. Idiopathic mucosal penile squamous papillomas in dogs.

    PubMed

    Cornegliani, Luisa; Vercelli, Antonella; Abramo, Francesca

    2007-12-01

    A new papillomatous clinical entity is described affecting the penile mucosa of dogs. The animals, 11 male dogs of different breeds, ageing from 6 to 13 years, were presented for genital mass and occasional haematuria. Surgical incision of the prepuce skin of the anaesthetized dogs showed the presence of single pedunculated, soft, pink-red, cauliflower-like masses arising from the penile mucosa, with diameter ranging from 2 to 8 cm. In all cases, histopathological examination of the excised masses showed normal epithelial differentiation with digitiform expansion of all the layers and elongated rete ridges slanted towards the periphery of the lesion. Evidence of ballooning degeneration or basophilic intranuclear inclusion bodies was not found. Both immunohistochemistry and polymerase chain reaction techniques failed to reveal papillomavirus. According to the histological World Health Organization classification of papillomatous lesions and due to the lack of evidence of a viral origin the masses were identified as idiopathic mucosal penile squamous papillomas. Urinary problems resolved after surgical excision, haematuria was therefore considered secondary to ulceration of the papillated masses.

  3. Cystic fibrosis: a mucosal immunodeficiency syndrome

    PubMed Central

    Cohen, Taylor Sitarik; Prince, Alice

    2013-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypes—airway inflammation and spontaneous infection—may provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance. PMID:22481418

  4. Mucosal disease series. Number IV. Erythema multiforme.

    PubMed

    Farthing, P; Bagan, J-V; Scully, C

    2005-09-01

    Erythema multiforme (EM) is an acute mucocutaneous hypersensitivity reaction characterised by a skin eruption, with or without oral or other mucous membrane lesions. Occasionally EM may involve the mouth alone. EM has been classified into a number of different variants based on the degree of mucosal involvement and the nature and distribution of the skin lesions. EM minor typically affects no more than one mucosa, is the most common form and may be associated with symmetrical target lesions on the extremities. EM major is more severe, typically involving two or more mucous membranes with more variable skin involvement - which is used to distinguish it from Stevens-Johnson syndrome (SJS), where there is extensive skin involvement and significant morbidity and a mortality rate of 5-15%. Both EM major and SJS can involve internal organs and typically are associated with systemic symptoms. Toxic epidermal necrolysis (TEN) may be a severe manifestation of EM, but some experts regard it as a discrete disease. EM can be triggered by a number of factors, but the best documented is preceding infection with herpes simplex virus (HSV), the lesions resulting from a cell mediated immune reaction triggered by HSV-DNA. SJS and TEN are usually initiated by drugs, and the tissue damage is mediated by soluble factors including Fas and FasL.

  5. Mucosal immune responses following intestinal nematode infection

    PubMed Central

    Zaph, C; Cooper, P J; Harris, N L

    2014-01-01

    In most natural environments, the large majority of mammals harbour parasitic helminths that often live as adults within the intestine for prolonged periods (1–2 years) 1. Although these organisms have been eradicated to a large extent within westernized human populations, those living within rural areas of developing countries continue to suffer from high infection rates. Indeed, recent estimates indicate that approximately 2·5 billion people worldwide, mainly children, currently suffer from infection with intestinal helminths (also known as geohelminths and soil-transmitted helminths) 2. Paradoxically, the eradication of helminths is thought to contribute to the increased incidence of autoimmune diseases and allergy observed in developed countries. In this review, we will summarize our current understanding of host–helminth interactions at the mucosal surface that result in parasite expulsion or permit the establishment of chronic infections with luminal dwelling adult worms. We will also provide insight into the adaptive immune mechanisms that provide immune protection against re-infection with helminth larvae, a process that is likely to be key to the future development of successful vaccination strategies. Lastly, the contribution of helminths to immune modulation and particularly to the treatment of allergy and inflammatory bowel disease will be discussed. PMID:25201407

  6. Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage.

    PubMed

    Yu, Chao; Tan, Shanjun; Zhou, Chunyu; Zhu, Cuilin; Kang, Xin; Liu, Shuai; Zhao, Shuang; Fan, Shulin; Yu, Zhen; Peng, Ai; Wang, Zhen

    2016-11-01

    Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.

  7. Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

    PubMed

    Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Kajiwara, Eiji; Nishida, Ryuichi

    2013-01-01

    Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

  8. Nocifensive Behaviors in Mice with Radiation-Induced Oral Mucositis.

    PubMed

    Nolan, Michael W; Long, C Tyler; Marcus, Karen L; Sarmadi, Shayan; Roback, Donald M; Fukuyama, Tomoki; Baeumer, Wolfgang; Lascelles, B Duncan X

    2017-02-10

    Oral mucositis can result in significant dysphagia, and is the most common dose-limiting acute toxicity in head and neck cancer patients receiving chemoradiotherapy. There is a critical need to determine the cellular and molecular mechanisms that underlie radiotherapy-associated discomfort in patients with mucositis. The objective was to induce oral mucositis in mice, using a clinical linear accelerator, and to quantify resultant discomfort, and characterize peripheral sensitization. A clinical linear accelerator was used to deliver ionizing radiation to the oral cavity of mice. Mucositis severity scoring, and various behavioral assays were performed to quantify bouts of orofacial wiping and scratching, bite force, gnawing behavior and burrowing activity. Calcium imaging was performed on neurons of the trigeminal ganglia. Glossitis was induced with a single fraction of at least 27 Gy. Body weight decreased and subsequently returned to baseline, in concert with development and resolution of mucositis, which was worst at day 10 and 11 postirradiation, however was resolved within another 10 days. Neither bite force, nor gnawing behavior were measurably affected. However, burrowing activity was decreased, and both facial wiping and scratching were increased while mice had visible mucositis lesions. Sensory nerves of irradiated mice were more responsive to histamine, tumor necrosis factor alpha and capsaicin. Radiation-induced glossitis is associated with hyper-reactivity of sensory neurons in the trigeminal ganglia of mice, and is accompanied by several behaviors indicative of both itch and pain. These data validate an appropriate model for cancer treatment related discomfort in humans.

  9. [New routes of administration: epidermal, transcutaneous mucosal ways of vaccination].

    PubMed

    Denis, François; Alain, Sophie; Ploy, Marie-Cécile

    2007-04-01

    A successful vaccine triggers the interaction of various cells of the immune system as does a regular immune response. It is thus necessary to introduce the vaccine antigens into an anatomic site where they will contact immune cells. The route of administration is thus critical for the outcome of vaccination. Intramuscular or subcutaneous injections are the most popular. Antigens injected intramuscularly can form persistent precipitates that are dissolved and re-absorbed relatively slowly. If injecting antigens is a quick, easy and reproducible way to vaccination, it requires trained personnel. Alternatives exist, through non-invasive formulations which allow administration by the patient or a third party with no particular expertise. The skin, especially its epidermal layer, is an accessible and competent immune environment and an attractive target for vaccine delivery, through transcutaneous delivery or immunostimulant patches. Mucosal immunization is another strategy: its major rationale is that organisms invade the body via mucosal surfaces. Therefore, local protection at mucosal surface as well as systemic defense is beneficial. Various formulations of mucosal vaccines have been developed, such as the Sabin oral polio vaccine (OPV), rotavirus vaccines, cold-adapted influenza vaccines or vaccine against typhoid fever. Thus we are entering in an era where mucosal and transcutaneous immunisation will play an important role in disease management. However, it has not been so easy to obtain regulatory approval for mucosal or transcutaneous formulations and needle-based vaccines continue to dominate the market.

  10. Oral mucositis in children suffering from acute lymphoblastic leukaemia

    PubMed Central

    2012-01-01

    Aim of the study Oral mucositis is the most commonly reported side effect observed in neoplastic patients treated with chemotherapy and radiotherapy of the head and neck region as well as in patients who have received a haematopoietic stem cell transplant. The aim of the study was to assess the oral mucosa status in children with acute lymphoblastic leukaemia (ALL) during antineoplastic therapy. Material and methods The clinical examination included 78 children aged 2-18 with ALL. The clinical examination was conducted using the dental preset tray. The condition of the oral mucosa was determined using the WHO scale for oral mucositis. Results In the first period of antineoplastic therapy the pathological lesions of the oral mucosa of the mucositis type were observed among the examined patients. The lesions had various levels of intensity. Pain was found to be the primary symptom of oral mucositis. In this study the following were observed: local erythema of the oral mucosa in 35%, white pseudomembranous lesions in 18%, erosions in 40% and oral ulcerative lesions in 4% of patients who underwent the antineoplastic therapy. Oral mucositis was observed in 3.17% of children after 6 months of chemotherapy. Conclusion Local treatment of oral mucositis with polyantibiotic-antifungal mixture, supporting antifungal systemic treatment, and improving the overall peripheral blood conditions in children suffering from acute lymphoblastic leukaemia improve the condition of the oral mucosa. PMID:23788849

  11. Using Light to Treat Mucositis and Help Wounds Heal

    NASA Technical Reports Server (NTRS)

    Ignatius, Robert W.; Martin, Todd S.; Kirk, Charles

    2008-01-01

    A continuing program of research and development is focusing on the use of controlled illumination by light-emitting diodes (LEDs) to treat mucositis and to accelerate healing of wounds. The basic idea is to illuminate the affected area of a patient with light of an intensity, duration, and wavelength (or combination of wavelengths) chosen to produce a therapeutic effect while generating only a minimal amount of heat. This method of treatment was originally intended for treating the mucositis that is a common complication of chemotherapy and radiation therapy for cancer. It is now also under consideration as a means to accelerate the healing of wounds and possibly also to treat exposure to chemical and radioactive warfare agents. Radiation therapy and many chemotherapeutic drugs often damage the mucosal linings of the mouth and gastrointestinal tract, leading to mouth ulcers (oral mucositis), nausea, and diarrhea. Hyperbaric-oxygen therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowlyhealing problem wounds, including those of oral mucositis. Hyperbaric-oxygen therapy increases such cellular activities as collagen production and angiogenesis, leading to an increased rate of healing. Biostimulation by use of laser light has also been found to be effective in treating mucositis. For hyperbaricoxygen treatment, a patient must remain inside a hyperbaric chamber for an extended time. Laser treatment is limited by laser-wavelength capabilities and by narrowness of laser beams, and usually entails the generation of significant amounts of heat.

  12. The Groningen hypothermic liver perfusion pump: functional evaluation of a new machine perfusion system.

    PubMed

    van der Plaats, A; Maathuis, M H J; 'T Hart, N A; Bellekom, A A; Hofker, H S; van der Houwen, E B; Verkerke, G J; Leuvenink, H G D; Verdonck, P; Ploeg, R J; Rakhorst, G

    2006-12-01

    To improve preservation of donor livers, we have developed a portable hypothermic machine perfusion (HMP) system as an alternative for static cold storage. A prototype of the system was built and evaluated on functionality. Evaluation criteria included 24 h of adequate pressure controlled perfusion, sufficient oxygenation, a maintained 0-4 degrees C temperature and sterile conditions. Porcine livers were perfused with pump pressures that were set at 4 mmHg (continuous, portal vein) and 30/20 mmHg, at 60 BPM (pulsatile, hepatic artery). Control livers were preserved using the clinical golden standard: static cold storage. In the HMP group, pressure, flow and temperature were continuously monitored for 24 h. At time-points t = 0, 2, 4, 8, 12, and 24 h samples of University of Wisconsin machine preservation solution were taken for measurement of partial oxygen pressure (pO(2)) and lacto-dehydrogenase. Biopsies in every lobe were taken for histology and electron microscopy; samples of ice, preservation solution, liver surface, and bile were taken and cultured to determine sterility. Results showed that temperature was maintained at 0-4 degrees C; perfusion pressure was maintained at 4 mmHg and 30/20 mmHg for portal vein and hepatic artery, respectively. Flow was approximately 350 and 80 ml/min, respectively, but decreased in the portal vein, probably due to edema formation. Arterial pO(2) was kept at 100 kPa. Histology showed complete perfusion of the liver with no major damage to hepatocytes, bile ducts, and non-parenchymal cells compared to control livers. The machine perfusion system complied to the design criteria and will have to demonstrate the superiority of machine perfusion over cold storage in transplant experiments.

  13. Effects of different types of hydroxyethyl starch (HES) on microcirculation perfusion and tissue oxygenation in patients undergoing liver surgery.

    PubMed

    Cui, Yinghua; Sun, Bo; Wang, Changsong; Liu, Shujuan; Li, Peng; Shi, Jinghui; Li, Enyou

    2014-01-01

    To compare the effects of hydroxyethyl starch (HES) 130/0.4 and HES 200/0.5, which have different molecular weights and degrees of substitution, on microcirculation perfusion and tissue oxygenation in patients undergoing liver surgery. Thirty patients with an American Society of Anesthesiologists status I/II who were scheduled for liver surgery were randomly divided into two groups: one received an intraoperative HES 130/0.4 infusion equal to the amount of blood loss (HES 130/0.4 group, n=15), and the other received HES 200/0.5 equal to the amount of blood loss (HES 200/0.5 group, n=15). Gastric mucosal perfusion and tissue oxygenation were monitored by measuring the gastric mucosal pH (pHi), which was determined using a carbon dioxide tonometer inserted through a nasogastric tube. Gastric mucosal pHi , hemodynamic parameters, body temperature, and blood gas parameters were recorded upon entering the operating room, before skin incision, one hour and two hours after skin incision, and at the end of surgery. The intraoperative pHi decreased in both groups of patients, but the decline in the HES 130/0.4 group was smaller than that of the HES 200/0.5 group. The pHi of the HES 130/0.4 group was significantly higher than that of the HES 200/0.5 group two hours after skin incision and at the end of surgery (P<0.05). A multivariate analysis showed that the type of colloid used intraoperatively was the only variant that affected pHi (F=0.626, P<0.05). Moreover, there were good correlation between pHi at the end of surgery and the length of postoperative hospital stay (r=-0.536, P<0.05) and the time intervals from surgery to the passage of flatus (r=-0.547, P<0.05). Compared with HES 200/0.5, the use of HES 130/0.4 (with a relatively lower molecular weight and lower degree of substitution) could significantly improve internal organ perfusion and tissue oxygenation in patients undergoing liver surgery with a relatively large amount of blood loss.

  14. Comparison of efficacy of cryotherapy and chlorhexidine to oral nutrition transition time in chemotherapy-induced oral mucositis.

    PubMed

    Erden, Y; Ipekcoban, G

    2016-05-01

    The aim of this study was to compare the efficacy of cryotherapy and chlorhexidine to oral nutrition transition time in chemotherapy-induced oral mucositis. This randomised controlled trial with random assignments to the experimental and control groups was conducted with cancer patients. Study data were collected from 90 cancer patients. The first experimental group (n = 30) received chlorhexidine mouthwash, the second experimental group (n = 30) received oral cryotherapy and the control group (n = 30) received routine care. To collect data we used the 'Mucositis Rating Index'. Changes in patients' oral mucosa in each group were checked and oral feeding transition periods were recorded. There was an important statistical difference between the times of transition to oral nutrition for patients (P < 0.01). Oral nutrition transition time of patients in the first experimental group who had applied chlorhexidine was shorter than in other groups. Following the tests, we detected a significant shortening in oral nutrition transition time of patients in first group who used chlorhexidine gargle as compared to the second group and control group. There was no significant difference between cryotherapy application and control group. In parallel with these findings, we detected that the degree of oral mucositis decreased.

  15. Imaging of drug effects in perfused liver

    NASA Astrophysics Data System (ADS)

    Dammann, Marc; Mahlke, Christine; Kessler, Manfred D.

    2002-06-01

    Various medications affect the systemic circulation and organ oxygenation causing dilatation or constriction of blood vessels. Imminent liver failure can be generated by reduced perfusion of different origins. In this case hepatic vasodilatation would be a therapeutical approach for improving patient's condition. Our examinations have been performed in perfused rat liver using spectrometric methods. Two defined areas of the liver were measured punctually. We compared the influence of Tetramethylpyrazine and Glyceroltrinitrate on hemoglobin oxygenation (HbO2) and concentration (Hb-conc.) in rat liver after application of Norepinephrine, which caused a mid decrease in hemoglobin oxygenation of 47,9 %. Both increased the HbO2, but differed from each other in manner of time and extent. Tetramethylpyrazine indicated a longer effect than Glyceroltrinitrate. Furthermore, HbO2 and Hb-conc. showed a conversed relation. From the shape of the absorption spectra it is possible to derive the oxygenation of hemoglobin.

  16. Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation

    PubMed Central

    Kaths, J. Moritz; Spetzler, Vinzent N.; Goldaracena, Nicolas; Echeverri, Juan; Louis, Kristine S.; Foltys, Daniel B.; Strempel, Mari; Yip, Paul; John, Rohan; Mucsi, Istvan; Ghanekar, Anand; Bagli, Darius; Robinson, Lisa; Selzner, Markus

    2015-01-01

    Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains a serious problem. Therefore, the acceptance criteria for organ donors have been extended leading to the usage of marginal kidney grafts. These marginal organs tolerate cold storage poorly resulting in increased preservation injury and higher rates of delayed graft function. To overcome the limitations of cold storage, extensive research is focused on alternative normothermic preservation methods. Ex vivo normothermic organ perfusion is an innovative preservation technique. The first experimental and clinical trials for ex vivo lung, liver, and kidney perfusions demonstrated favorable outcomes. In addition to the reduction of cold ischemic injury, the method of normothermic kidney storage offers the opportunity for organ assessment and repair. This manuscript provides information about kidney retrieval, organ preservation techniques, and isolated ex vivo normothermic kidney perfusion (NEVKP) in a porcine model. Surgical techniques, set up for the perfusion solution and the circuit, potential assessment options, and representative results are demonstrated. PMID:26275014

  17. Multimodal MRI of experimental stroke

    PubMed Central

    Duong, Timothy Q

    2014-01-01

    Stroke is the fourth leading cause of death and the leading cause of long-term disability in the United States. Brain imaging data from experimental stroke models and stroke patients have shown that there is often a gradual progression of potentially reversible ischemic injury toward infarction. Reestablishing tissue perfusion and/or treating with neuroprotective drugs in a timely fashion are expected to salvage some ischemic tissues. Diffusion-weighted imaging based on magnetic resonance imaging (MRI) in which contrast is based on water motion can detect ischemic injury within minutes after onsets, whereas computed tomography and other imaging modalities fail to detect stroke injury for at least a few hours. Along with quantitative perfusion imaging, the perfusion-diffusion mismatch which approximates the ischemic penumbra could be imaged non-invasively. This review describes recent progresses in the development and application of multimodal MRI and image analysis techniques to study ischemic tissue at risk in experimental stroke in rats. PMID:24323751

  18. Regulation of skeletal muscle perfusion during exercise

    NASA Technical Reports Server (NTRS)

    Delp, M. D.; Laughlin, M. H.

    1998-01-01

    For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.

  19. Inhomogeneity of pulmonary perfusion during sustained microgravity

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim; Guy, Harold J. B.; Elliott, Ann R.; West, John B.

    1994-01-01

    The effects of gravity on the inhomogeneity of pulmonary perfusion in man were studied by performing hyperventilation-breathhold single-breath measurements before, during and after 9 days of continuous exposure to microgravity. In microgravity the indicators of inhomogeneity of perfusion, especially the size of cardiogenic oscillations in expired CO2 and the height of phase 4, were both markedly reduced. Cardiogenic oscillations were reduced to approximately 60 of their preflight standing size, while the height of phase 4 was between 0 and -8% (a terminal fall became a small terminal rise) of preflights standing. The terminal change in CO2 was nearly abolished in microgravity indicating more uniformity of blood flow between lung units that close at the end of expiration and units that remain open. This may result from the disappearance of gravity-dependent topographical inequality of blood flow. The residual cardiographic oscillations in expired CO2 imply a persisting inhomogeneity of perfusion in the absence of gravity at a level larger than acinar.

  20. Vascular perfusion in horses with chronic laminitis.

    PubMed

    Hood, D M; Grosenbaugh, D A; Slater, M R

    1994-05-01

    Vascular perfusion casts were used to define and characterise the macroscopic perfusion defects present in the distal digit of 11 horses affected by chronic laminitis. Five clinically normal horses were used as controls. Based on clinical history and clinical status, horses with chronic laminitis were classified as being potentially treatable or clinically refractory. Eleven macroscopic vascular defects were noted in the casts from horses with laminitis. Four types of lesions were identified in the submural laminar circulation, 3 in the coronary bed and 4 were associated with the solar circulation. Multiple defects were present and a definite trend was noted for the perfusion defects to be worse in the casts of clinically refractory subjects than in those considered treatable. This information suggests that evaluation of circulatory status should add significantly to the ability to separate treatable from clinically refractory patients. Results also indicated that ventral displacement of the third phalanx (sinkers) and compression of the solar vasculature are more prevalent than is presently thought.

  1. Dynamic CT perfusion measurement in a cardiac phantom.

    PubMed

    Ziemer, Benjamin P; Hubbard, Logan; Lipinski, Jerry; Molloi, Sabee

    2015-10-01

    Widespread clinical implementation of dynamic CT myocardial perfusion has been hampered by its limited accuracy and high radiation dose. The purpose of this study was to evaluate the accuracy and radiation dose reduction of a dynamic CT myocardial perfusion technique based on first pass analysis (FPA). To test the FPA technique, a pulsatile pump was used to generate known perfusion rates in a range of 0.96-2.49 mL/min/g. All the known perfusion rates were determined using an ultrasonic flow probe and the known mass of the perfusion volume. FPA and maximum slope model (MSM) perfusion rates were measured using volume scans acquired from a 320-slice CT scanner, and then compared to the known perfusion rates. The measured perfusion using FPA (P(FPA)), with two volume scans, and the maximum slope model (P(MSM)) were related to known perfusion (P(K)) by P(FPA) = 0.91P(K) + 0.06 (r = 0.98) and P(MSM) = 0.25P(K) - 0.02 (r = 0.96), respectively. The standard error of estimate for the FPA technique, using two volume scans, and the MSM was 0.14 and 0.30 mL/min/g, respectively. The estimated radiation dose required for the FPA technique with two volume scans and the MSM was 2.6 and 11.7-17.5 mSv, respectively. Therefore, the FPA technique can yield accurate perfusion measurements using as few as two volume scans, corresponding to approximately a factor of four reductions in radiation dose as compared with the currently available MSM. In conclusion, the results of the study indicate that the FPA technique can make accurate dynamic CT perfusion measurements over a range of clinically relevant perfusion rates, while substantially reducing radiation dose, as compared to currently available dynamic CT perfusion techniques.

  2. Mucosal immunoglobulins and B cells of teleost fish.

    PubMed

    Salinas, Irene; Zhang, Yong-An; Sunyer, J Oriol

    2011-12-01

    As physical barriers that separate teleost fish from the external environment, mucosae are also active immunological sites that protect them against exposure to microbes and stressors. In mammals, the sites where antigens are sampled from mucosal surfaces and where stimulation of naïve T and B lymphocytes occurs are known as inductive sites and are constituted by mucosa-associated lymphoid tissue (MALT). According to anatomical location, the MALT in teleost fish is subdivided into gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), and gill-associated lymphoid tissue (GIALT). All MALT contain a variety of leukocytes, including, but not limited to, T cells, B cells, plasma cells, macrophages and granulocytes. Secretory immunoglobulins are produced mainly by plasmablasts and plasma cells, and play key roles in the maintenance of mucosal homeostasis. Until recently, teleost fish B cells were thought to express only two classes of immunoglobulins, IgM and IgD, in which IgM was thought to be the only one responding to pathogens both in systemic and mucosal compartments. However, a third teleost immunoglobulin class, IgT/IgZ, was discovered in 2005, and it has recently been shown to behave as the prevalent immunoglobulin in gut mucosal immune responses. The purpose of this review is to summarise the current knowledge of mucosal immunoglobulins and B cells of fish MALT. Moreover, we attempt to integrate the existing knowledge on both basic and applied research findings on fish mucosal immune responses, with the goal to provide new directions that may facilitate the development of novel vaccination strategies that stimulate not only systemic, but also mucosal immunity.

  3. Mucosal immunization using recombinant plant-based oral vaccines.

    PubMed

    Streatfield, Stephen J

    2006-02-01

    The induction of mucosal immunity is very important in conferring protection against pathogens that typically invade via mucosal surfaces. Delivery of a vaccine to a mucosal surface optimizes the induction of mucosal immunity. The apparent linked nature of the mucosal immune system allows delivery to any mucosal surface to potentially induce immunity at others. Oral administration is a very straightforward and inexpensive approach to deliver a vaccine to the mucosal lining of the gut. However, vaccines administered by this route are subject to proteolysis in the gastrointestinal tract. Thus, dose levels for protein subunit vaccines are likely to be very high and the antigen may need to be protected from proteolysis for oral delivery to be efficacious. Expression of candidate vaccine antigens in edible recombinant plant material offers an inexpensive means to deliver large doses of vaccines in encapsulated forms. Certain plant tissues can also stably store antigens for extensive periods of time at ambient temperatures, obviating the need for a cold-chain during vaccine storage and distribution, and so further limiting costs. Antigens can be expressed from transgenes stably incorporated into a host plant's nuclear or plastid genome, or from engineered plant viruses infected into plant tissues. Molecular approaches can serve to boost expression levels and target the expressed protein for appropriate post-translational modification. There is a wide range of options for processing plant tissues to allow for oral delivery of a palatable product. Alternatively, the expressed antigen can be enriched or purified prior to formulation in a tablet or capsule for oral delivery. Fusions to carrier molecules can stabilize the expressed antigen, aid in antigen enrichment or purification strategies, and facilitate delivery to effector sites in the gastrointestinal tract. Many antigens have been expressed in plants. In a few cases, vaccine candidates have entered into early phase

  4. Mucosal immunoglobulins and B cells of Teleost fish

    PubMed Central

    Salinas, Irene; Zhang, Yong-An; Sunyer, J. Oriol

    2012-01-01

    As physical barriers that separate teleost fish from the external environment, mucosae are also active immunological sites that protect them against exposure to microbes and stressors. In mammals, the sites where antigens are sampled from mucosal surfaces and where stimulation of naive T and B lymphocytes occurs are known as inductive sites and are constituted by mucosa-associated lymphoid tissue (MALT). According to anatomical location, the MALT in teleost fish is subdivided into gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), and gill-associated lymphoid tissue (GIALT). All MALT contain a variety of leukocytes, including, but not limited to, T cells, B cells, plasma cells, macrophages and granulocytes. Secretory immunoglobulins are produced mainly by plasmablasts and plasma cells, and play key roles in the maintenance of mucosal homeostasis. Until recently, teleost fish B cells were thought to express only two classes of immunoglobulins, IgM and IgD, in which IgM was thought to be the only one responding to pathogens both in systemic and mucosal compartments. However, a third teleost immunoglobulin class, IgT/IgZ, was discovered in 2005, and it has recently been shown to behave as the prevalent immunoglobulin in gut mucosal immune responses. The purpose of this review is to summarise the current knowledge of mucosal immunoglobulins and B cells of fish MALT. Moreover, we attempt to integrate the existing knowledge on both basic and applied research findings on fish mucosal immune responses, with the goal to provide new directions that may facilitate the development of novel vaccination strategies that stimulate not only systemic, but also mucosal immunity. PMID:22133710

  5. Perfusion phantom: An efficient and reproducible method to simulate myocardial first-pass perfusion measurements with cardiovascular magnetic resonance.

    PubMed

    Chiribiri, Amedeo; Schuster, Andreas; Ishida, Masaki; Hautvast, Gilion; Zarinabad, Niloufar; Morton, Geraint; Otton, James; Plein, Sven; Breeuwer, Marcel; Batchelor, Philip; Schaeffter, Tobias; Nagel, Eike

    2013-03-01

    The aim of this article is to describe a novel hardware perfusion phantom that simulates myocardial first-pass perfusion allowing comparisons between different MR techniques and validation of the results against a true gold standard. MR perfusion images were acquired at different myocardial perfusion rates and variable doses of gadolinium and cardiac output. The system proved to be sensitive to controlled variations of myocardial perfusion rate, contrast agent dose, and cardiac output. It produced distinct signal intensity curves for perfusion rates ranging from 1 to 10 mL/mL/min. Quantification of myocardial blood flow by signal deconvolution techniques provided accurate measurements of perfusion. The phantom also proved to be very reproducible between different sessions and different operators. This novel hardware perfusion phantom system allows reliable, reproducible, and efficient simulation of myocardial first-pass MR perfusion. Direct comparison between the results of image-based quantification and reference values of flow and myocardial perfusion will allow development and validation of accurate quantification methods.

  6. Mucosal mast cells and developmental changes in gastric absorption.

    PubMed

    Catto-Smith, A G; Ripper, J L

    1995-01-01

    We aimed to establish whether gastric mucosal mast cells undergo degranulation during normal postnatal development and to correlate this with gastric electrical parameters, paracellular permeability, and macromolecular absorption. Sprague-Dawley rats were studied between 10 and 30 days after birth. Gastric mucosal mast cell degranulation occurred and was maximal on days 15 and 17, measured by histology and gastric and serum levels of rat mast cell protease II. Short-circuit current, transepithelial conductance, and permeability of voltage-clamped glandular stomach were elevated in younger animals, falling with age except for a transient but significant increase in conductance and permeability at 17 days, closely correlated with maximal mast cell degranulation. Macromolecular uptake was significantly increased in animals aged 10-15 days. Concanavalin A and antigen-induced mast cell degranulation increased conductance and permeability in vitro in younger animals. We conclude that 1) gastric mucosal mast cells degranulate during development, 2) the neonatal stomach has increased permeability and uptake of macromolecules, and 3) gastric mucosal mast cell degranulation during development may affect mucosal permeability.

  7. Management of a large mucosal defect after duodenal endoscopic resection

    PubMed Central

    Fujihara, Shintaro; Mori, Hirohito; Kobara, Hideki; Nishiyama, Noriko; Matsunaga, Tae; Ayaki, Maki; Yachida, Tatsuo; Masaki, Tsutomu

    2016-01-01

    Duodenal endoscopic resection is the most difficult type of endoscopic treatment in the gastrointestinal tract (GI) and is technically challenging because of anatomical specificities. In addition to these technical difficulties, this procedure is associated with a significantly higher rate of complication than endoscopic treatment in other parts of the GI tract. Postoperative delayed perforation and bleeding are hazardous complications, and emergency surgical intervention is sometimes required. Therefore, it is urgently necessary to establish a management protocol for preventing serious complications. For instance, the prophylactic closure of large mucosal defects after endoscopic resection may reduce the risk of hazardous complications. However, the size of mucosal defects after endoscopic submucosal dissection (ESD) is relatively large compared with the size after endoscopic mucosal resection, making it impossible to achieve complete closure using only conventional clips. The over-the-scope clip and polyglycolic acid sheets with fibrin gel make it possible to close large mucosal defects after duodenal ESD. In addition to the combination of laparoscopic surgery and endoscopic resection, endoscopic full-thickness resection holds therapeutic potential for difficult duodenal lesions and may overcome the disadvantages of endoscopic resection in the near future. This review aims to summarize the complications and closure techniques of large mucosal defects and to highlight some directions for management after duodenal endoscopic treatment. PMID:27547003

  8. Awareness assessment in Turkish subpopulation with chronic oral mucosal diseases

    PubMed Central

    Okumus, Ozlem; Kalkan, Sevda; Keser, Gaye; Pekiner, Filiz Namdar

    2015-01-01

    Objectives: The aim of this study was to evaluate the awareness of group Turkish patients with chronic oral mucosal diseases by chronic oral mucosal diseases questionnaires (COMDQ). Materials and Methods: Eighty patients with chronic oral mucosal diseases were participated in the study. A detailed medical history of each patient was taken, and all the COMDQ questions, which were translated from English version, were filled out. The data were analyzed with the IBM Statistical Package for Social Sciences Statistics 22.0. Results: The mean ages of patients were 48.91 ± 13.36 years. Of the total 80 cases of chronic oral mucosal diseases identified 52 (65%) were female and 28 (35%) male. The standardized mean scores for COMDQ were 1.72 ± 1.11 for “pain and functional limitation,” 1.09 ± 0.94 for “medication and treatment,” 2.31 ± 1.06 for “social and emotional,” and 2.27 ± 0.83 for “patient support,” respectively. Conclusions: The results of this study indicate that the Turkish version of the COMDQ has the profitable psychometric peculiarity and comfortable to patients with chronic oral mucosal diseases in Turkey. PMID:26929697

  9. Physiology and immunology of mucosal barriers in catfish (Ictalurus spp.)

    PubMed Central

    Peatman, Eric; Lange, Miles; Zhao, Honggang; Beck, Benjamin H

    2015-01-01

    The mucosal barriers of catfish (Ictalurus spp) constitute the first line of defense against pathogen invasion while simultaneously carrying out a diverse array of other critical physiological processes, including nutrient adsorption, osmoregulation, waste excretion, and environmental sensing. Catfish depend more heavily on mucosal barriers than their terrestrial counterparts as they are continuously interacting with the aquatic microbiota. Our understanding of these barriers, while growing, is still limited relative to that of mammalian model systems. Nevertheless, a combination of molecular and cellular studies in catfish over the last few decades, and particularly within the last few years, has helped to elucidate many of the primary actors and pathways critical to their mucosal health. Here we describe aspects of innate and adaptive immune responses in the primary mucosal tissues (skin, gill, and intestine) of catfish, focusing on mucus-driven responses, pathogen recognition, soluble mediators, and immunoglobulin and T-cell derived immunity. Modulation of mucosal barriers will be critical moving forward for crafting better diets, improving vaccine delivery, enhancing water quality, and ensuring sustainable production practices in catfish. PMID:26716071

  10. Prevention and Treatment of Oral Mucositis in Children with Cancer

    PubMed Central

    Miller, Misty M.; Donald, David V.; Hagemann, Tracy M.

    2012-01-01

    Oral mucositis affects more than three-fourths of patients undergoing chemotherapy and represents a significant burden to patients and caregivers. Lesions develop as a result of chemotherapeutic agents attacking the rapidly dividing cells of the gastrointestinal tract. Severity can range from mild, painless tissue changes to bleeding ulcerations that prevent oral intake and require narcotic pain relievers. Oral mucositis also leads to an increased risk of infection and can often delay further chemotherapy treatment. A number of assessment scales have been developed to better qualify the symptoms associated with this condition. Few pharmacologic agents have been approved to either prevent the development or alleviate the symptoms of oral mucositis. Current options include the use of antimicrobial mouthwashes, amino acid rinses, and topical healing agents. Palifermin, a keratinocyte growth factor, may be a future option after its use in children is explored. With achievements in other areas of supportive care in patients undergoing chemotherapy, oral mucositis should represent the forefront of new research. This review will provide a comprehensive examination of available options for children who have oral mucositis. PMID:23413048

  11. Perfusion MRI: The Five Most Frequently Asked Technical Questions

    PubMed Central

    Essig, Marco; Shiroishi, Mark S.; Nguyen, Thanh Binh; Saake, Marc; Provenzale, James M.; Enterline, David; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

    2013-01-01

    OBJECTIVE This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23255738

  12. Perfusion Scintigraphy and Patient Selection for Lung Volume Reduction Surgery

    PubMed Central

    Chandra, Divay; Lipson, David A.; Hoffman, Eric A.; Hansen-Flaschen, John; Sciurba, Frank C.; DeCamp, Malcolm M.; Reilly, John J.; Washko, George R.

    2010-01-01

    Rationale: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS). Objectives: To study the role of perfusion scintigraphy in patient selection for LVRS. Methods: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non–high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non–upper lobe–predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy. Measurements and Main Results: Among 284 of 1,045 patients with upper lobe–predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe–predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non–upper lobe–predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information. Conclusions: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe–predominant emphysema when there is low rather than high perfusion to the upper lung. PMID:20538961

  13. Microvascular Perfusion Changes following Transarterial Hepatic Tumor Embolization

    PubMed Central

    Johnson, Carmen Gacchina; Sharma, Karun V.; Levy, Elliot B.; Woods, David L.; Morris, Aaron H.; Bacher, John D.; Lewis, Andrew L.; Wood, Bradford J.; Dreher, Matthew R.

    2015-01-01

    Purpose To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. Materials and Methods Rabbit Vx2 liver tumors were embolized with 100–300-µm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3–5 per group; 18 total). Results Mean microvascular density was 70 vessels/mm2 ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31+ structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. Conclusions Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy. PMID:26321051

  14. Measurement of continuous distributions of ventilation-perfusion ratios - Theory

    NASA Technical Reports Server (NTRS)

    Wagner, P. D.; Saltzman, H. A.; West, J. B.

    1974-01-01

    The resolution of the technique considered is sufficient to describe smooth distributions containing blood flow to unventilated regions (shunt), ventilation to unperfused regions (dead space), and up to three additional modes over the range of finite ventilation-perfusion ratios. In particular, areas whose ventilation-perfusion ratios are low can be separated from unventilated regions and those whose ventilation-perfusion ratios are high can similarly be distinguished from unperfused areas.

  15. Scintigraphic perfusion patterns in patients with diffuse lung disease

    SciTech Connect

    Newman, G.E.; Sullivan, D.C.; Gottschalk, A.; Putman, C.E.

    1982-04-01

    Perfusion scintigrams of 55 patients with radiographic evidence of diffuse lung disease were reviewed. Thirty-nine had acute and/or chronic changes caused by congestive heart failure, and 16 had diffuse reticulonodular disease. A normal or near-normal perfusion pattern was seen in 40/55 (73%), and this finding was equally common in the two groups. The authors conclude that perfusion scintigraphy is useful in excluding pulmonary embolism in patients with radiographic evidence of diffuse, symmetrical lung disease.

  16. Oral ingestion of Streptococcus thermophilus does not affect mucositis severity or tumor progression in the tumor-bearing rat.

    PubMed

    Tooley, Katie L; Howarth, Gordon S; Lymn, Kerry A; Lawrence, Andrew; Butler, Ross N

    2011-07-15

    Preventative or adjunctive agents for the amelioration of small intestinal chemotherapy-induced mucositis are not currently available for clinical use. We have previously demonstrated that oral ingestion of Streptococcus thermophilus (TH-4) partially attenuated chemotherapy-induced mucositis in the rat. Here we assess the effects of TH-4 on small intestinal damage and tumor progression in tumor-bearing rats with experimentally-induced mucositis. Female Dark Agouti tumor-bearing (mammary adenocarcinoma) rats (n = 36; 139 ± 1 g) had small intestinal damage induced via the administration of methotrexate (MTX). Rats were administered MTX; (1.5 mg/kg intramuscular) or saline at 0 and 24 h; with daily gavage administration of TH-4 (109 cfu/mL) or skim milk from -48 to +96 h post-MTX. Rats were allocated to groups (n=9): saline control, TH-4 control, MTX control or TH-4+MTX. The non-invasive ( 13) C-sucrose breath test (SBT) was conducted prior to tumor inoculation, pre-MTX (-24 h) and prior to sacrifice (96 h) to monitor gut function. At sacrifice small intestinal segments were excised and assessed for sucrase and myeloperoxidase activity as well as histological damage. Irrespective of TH-4 treatment, MTX-treated rats had a significant decrease in bodyweight, SBT levels, sucrase and myeloperoxidase activity, and histological damage score (p < 0.05) compared to saline and TH-4 control rats. TH-4 treatment did not result in tumor progression (p > 0.05) but failed to alleviate mucositis indices. Although TH-4, at a dose of 109 cfu/mL, yielded neither protection nor amelioration of chemotherapy-induced mucositis, progression of mammary adenocarcinoma was unaffected.

  17. Quantitative Tc-99m myocardial perfusion SPECT with 180[degree] acquisition

    SciTech Connect

    Ye, J.

    1992-01-01

    Myocardial perfusion single photon emission computed tomography (SPECT) images using 180[degrees] acquisition are degraded by the effects of scatter, nonuniform attenuation and system geometric resolution variation with source depth. Using a 180[degrees] scan orbit which is closer to the heart may provide higher image resolution, signal-to-noise ratio and defect-to-normal contrast than using a 360[degrees] orbit, however, significant object shape distortion has been observed in the 180[degrees] reconstructed images. A method has been developed that combines filtered back-projection (FBP) with iterative attenuation and three-dimensional (3-D) resolution compensation for Tc-99m myocardial perfusion imaging, data. The non-uniform attenuation coefficient distribution is obtained by a quick transmission scan using a flood source and segmentation of the reconstructed transmission image to define areas of significantly different attenuation. A priori attenuation coefficients are assigned to the areas to form the attenuation distribution map. The 3-D correction is accomplished by including both the non-uniform attenuation and depth-dependent resolution variation in the reprojection procedure of an iterative correction algorithm. The method was evaluated with both simulated and experimental data using clinical protocols with a cardiac phantom. A significant improvement in image resolution was observed with line source images was reduced from approximately 10 mm to 7.l5 mm after 7 iterations of the 3-D correction. The contrast of two perfusion defects to the surrounding normally perfused regions was significantly improved with the correction. Significant improvement in uniformity at different positions in the 100% perfused areas in the myocardium was also observed. The normalized root squared error (NRSE) of one transaxial image from the original source distribution in the simulation study was reduced from 0.8 to 0.2 after 5 iterations of the 3-D correction.

  18. Flat-panel volumetric computed tomography in cerebral perfusion: evaluation of three rat stroke models.

    PubMed

    Juenemann, Martin; Goegel, Sinja; Obert, Martin; Schleicher, Nadine; Ritschel, Nouha; Doenges, Simone; Eitenmueller, Inka; Schwarz, Niko; Kastaun, Sabrina; Yeniguen, Mesut; Tschernatsch, Marlene; Gerriets, Tibo

    2013-09-30

    Flat-panel volumetric computed tomography (fpVCT) is a non-invasive approach to three-dimensional small animal imaging. The capability of volumetric scanning and a high resolution in time and space enables whole organ perfusion studies. We aimed to assess feasibility and validity of fpVCT in cerebral perfusion measurement with impaired hemodynamics by evaluation of three well-established rat stroke models for temporary and permanent middle cerebral artery occlusion (MCAO). Male Wistar rats were randomly assigned to temporary (group I: suture model) and permanent (group II: suture model; III: macrosphere model) MCAO and to a control group. Perfusion scans with respect to cerebral blood flow (CBF) and volume (CBV) were performed 24h post intervention by fpVCT, using a Gantry rotation time of 1s and a total scanning time of 30s. Postmortem analysis included infarct-size calculation by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Infarct volumes did not differ significantly throughout intervention groups. After permanent MCAO, CBF significantly decreased in subcortical regions to 78.2% (group II, p=0.005) and 79.9% (group III, p=0.012) and in total hemisphere to 77.4% (group II, p=0.010) and 82.0% (group III, p=0.049). CBF was less impaired with temporary vessel occlusion. CBV measurement revealed no significant differences. Results demonstrate feasibility of cerebral perfusion quantification in rats with the fpVCT, which can be a useful tool for non-invasive dynamic imaging of cerebral perfusion in rodent stroke models. In addition to methodological advantages, CBF data confirm the macrosphere model as a useful alternative to the suture model for permanent experimental MCAO.

  19. Perfusion lung scanning: differentiation of primary from thromboembolic pulmonary hypertension

    SciTech Connect

    Lisbona, R.; Kreisman, H.; Novales-Diaz, J.; Derbekyan, V.

    1985-01-01

    Of eight patients with pulmonary arterial hypertension, final diagnosis established by autopsy or angiography, four had primary hypertension and four hypertension from thromboembolism. The perfusion lung scan was distinctly different in the two groups. The lung scan in primary pulmonary hypertension was associated with nonsegmental, patchy defects of perfusion, while in thromboembolic hypertensives it was characterized by segmental and/or lobar defects of perfusion with or without subsegmental defects. The perfusion lung scan is a valuable, noninvasive study in the evaluation of the patient with pulmonary hypertension of undetermined cause and in the exclusion of occult large-vessel pulmonary thromboembolism.

  20. New imaging technology: measurement of myocardial perfusion by contrast echocardiography

    NASA Technical Reports Server (NTRS)

    Rubin, D. N.; Thomas, J. D.

    2000-01-01

    Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.

  1. Extracorporeal Free Flap Perfusion in Case of Prolonged Ischemia Time.

    PubMed

    Taeger, C D; Präbst, K; Beier, J P; Meyer, A; Horch, R E

    2016-04-01

    In free flap surgery, a clinically established concept still has to be found for the reduction of ischemia-related cell damage in the case of prolonged ischemia. Although promising results using extracorporeal free flap perfusion in the laboratory have been published in the past, until now this concept has not yet paved its way into clinical routine. This might be due to the complexity of perfusion systems and a lack of standardized tools. Here, we want to present the results of the first extracorporeal free flap perfusion in a clinical setting using a simple approach without the application of a complex perfusion machinery.

  2. The effect of clove-based herbal mouthwash on radiation-induced oral mucositis in patients with head and neck cancer: a single-blind randomized preliminary study

    PubMed Central

    Kong, Moonkyoo; Hwang, Deok-Sang; Yoon, Seong Woo; Kim, Jinsung

    2016-01-01

    Purpose This study was performed to evaluate the efficacy and safety of clove-based herbal mouthwash in ameliorating radiation-induced oral mucositis in patients with head and neck cancer. Methods Fourteen patients were prospectively enrolled in this study and randomized to either an experimental group or a control group. The patients of the experimental group swished their mouths with a clove-based herbal mouthwash during radiotherapy (RT), while the patients of the control group swished with clear water. The primary end point of this study was incidence of radiation-induced oral mucositis. The secondary end points were time to onset of radiation-induced oral mucositis, duration of radiation-induced oral mucositis, incidence of supplemental nutrition through feeding tube, maximum pain score, body weight loss, incidence of RT interruption, and duration of RT interruption. Results The use of clove-based herbal mouthwash shortened the duration of grade ≥2 mucositis (24.3 days vs 37.1 days, P=0.044) and reduced body weight loss during RT (3.1% vs 7.4%, P=0.023) compared with clear water. The use of clove-based herbal mouthwash also reduced the incidence of grade 3 mucositis (28.6% vs 57.1%), supplemental nutrition (0% vs 28.6%), and RT interruption (14.3% vs 28.6%), and reduced the duration of grade 3 mucositis (5.1 days vs 17.7 days) and RT interruption (1 days vs 8.5 days). In addition, clove-based herbal mouthwash delayed the time to onset of mucositis (26.6 days vs 24.5 days) and reduced the maximum pain score (4.1 vs 4.9). However, these differences were not statistically significant. Conclusion Although we could not find significant differences in some end points, this single-blind randomized study showed that a clove-based herbal mouthwash can have a potentially beneficial effect on minimizing or preventing radiation-induced oral mucositis in patients with head and neck cancer. To confirm the results of our study, well-designed randomized studies with large

  3. Immunomodulation by mucosal gene transfer using TGF-beta DNA.

    PubMed Central

    Kuklin, N A; Daheshia, M; Chun, S; Rouse, B T

    1998-01-01

    This report evaluates the efficacy of DNA encoding TGF-beta administered mucosally to suppress immunity and modulate the immunoinflammatory response to herpes simplex virus (HSV) infection. A single intranasal administration of an eukaryotic expression vector encoding TGF-beta1 led to expression in the lung and lymphoid tissue. T cell-mediated immune responses to HSV infection were suppressed with this effect persisting as measured by the delayed-type hypersensitivity reaction for at least 7 wk. Treated animals were more susceptible to systemic infection with HSV. Multiple prophylactic mucosal administrations of TGF-beta DNA also suppressed the severity of ocular lesions caused by HSV infection, although no effects on this immunoinflammatory response were evident after therapeutic treatment with TGF-beta DNA. Our results demonstrate that the direct mucosal gene transfer of immunomodulatory cytokines provides a convenient means of modulating immunity and influencing the expression of inflammatory disorders. PMID:9664086

  4. Potential Benefits of Oral Cryotherapy for Chemotherapy-Induced Mucositis.

    PubMed

    Wodzinski, Amelia

    2016-10-01

    Mucositis is a common side effect of cancer therapies that causes painful, erythematous lesions to develop in the gastrointestinal tract. These lesions can lead to malnutrition, increased risk for serious infection, prolonged hospital stays, and reduced quality of life. Oral cryotherapy, or the use of ice chips to cool the mucous membranes during bolus chemotherapy infusions (e.g., 5-fluorouracil [Adrucil®] and melphalan [Alkeran®]), is the most readily accessible and cost-effective intervention available. Although many factors may contribute to the development of mucositis during cancer treatment, studies have found a reduction in the incidence and the severity of mucositis with the use of oral cryotherapy.


  5. Mucosal vaccination by adenoviruses displaying reovirus sigma 1.

    PubMed

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

    2015-08-01

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

  6. [Myocardial perfusion imaging by digital subtraction angiography].

    PubMed

    Kadowaki, H; Ishikawa, K; Ogai, T; Katori, R

    1986-03-01

    Several methods of digital subtraction angiography (DSA) were compared to determine which could better visualize regional myocardial perfusion using coronary angiography in seven patients with myocardial infarction, two with angina pectoris and five with normal coronary arteries. Satisfactory DSA was judged to be achieved if the shape of the heart on the mask film was identical to that on the live film and if both films were exactly superimposed. To obtain an identical mask film in the shape of each live film, both films were selected from the following three phases of the cardiac cycle; at the R wave of the electrocardiogram, 100 msec before the R wave, and 200 msec before the R wave. The last two were superior for obtaining mask and live films which were similar in shape, because the cardiac motion in these phases was relatively small. Using these mask and live films, DSA was performed either with the continuous image mode (CI mode) or the time interval difference mode (TID mode). The overall perfusion of contrast medium through the artery to the vein was adequately visualized using the CI mode. Passage of contrast medium through the artery, capillary and vein was visualized at each phase using TID mode. Subtracted images were displayed and photographed, and the density of the contrast medium was adequate to display contour lines as in a relief map. Using this DSA, it was found that regional perfusion of the contrast medium was not always uniform in normal subjects, depending on the typography of the coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Mucosal versus muscle pain sensitivity in provoked vestibulodynia

    PubMed Central

    Witzeman, Kathryn; Nguyen, Ruby HN; Eanes, Alisa; As-Sanie, Sawsan; Zolnoun, Denniz

    2015-01-01

    Background An estimated 8.3%—16% of women experience vulvovaginal discomfort during their lifetime. Frequently these patients report provoked pain on contact or with attempted intercourse, commonly referred to as provoked vestibulodynia (PVD). Despite the burden of this condition, little is known about its potential etiologies including pelvic floor muscular dysfunction and mucosal components. This knowledge would be beneficial in developing targeted therapies including physical therapy. Objective To explore the relative contribution of mucosal versus muscle pain sensitivity on pain report from intercourse among women with PVD. Design In this proof of concept study, 54 women with PVD underwent a structured examination assessing mucosal and pelvic muscle sensitivity. Methods We examined three mucosal sites in the upper and lower vestibule. Patients were asked to rate their pain on cotton swab palpation of the mucosa using a 10-point visual analog scale. Muscle pain was assessed using transvaginal application of pressure on right and left puborectalis, and the perineal muscle complex. The Gracely pain scale (0–100) was used to assess the severity of pain with intercourse, with women rating the lowest, average, and highest pain levels; a 100 rating the highest level of pain. Results The lower vestibule’s mucosa 5.81 (standard deviation =2.83) was significantly more sensitive than the upper vestibule 2.52 (standard deviation =2.6) (P<0.01) on exam. However, mucosal sensitivity was not associated with intercourse pain, while muscle sensitivity was moderately associated with both average and highest intensity of intercourse pain (r=−0.46, P=0.01 and r=−0.42, P=0.02), respectively. Conclusion This preliminary study suggests that mucosal measures alone may not sufficiently capture the spectrum of clinical pain report in women with PVD, which is consistent with the empirical success of physical therapy in this population. PMID:26316805

  8. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    SciTech Connect

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

    1987-09-01

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

  9. Oral cryotherapy reduced oral mucositis in patients having cancer treatments.

    PubMed

    Spivakovsky, Sylvia

    2016-09-01

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

  10. Is correction necessary when clinically determining quantitative cerebral perfusion parameters from multi-slice dynamic susceptibility contrast MR studies?

    PubMed

    Salluzzi, M; Frayne, R; Smith, M R

    2006-01-21

    Several groups have modified the standard singular value decomposition (SVD) algorithm to produce delay-insensitive cerebral blood flow (CBF) estimates from dynamic susceptibility contrast (DSC) perfusion studies. However, new dependences of CBF estimates on bolus arrival times and slice position in multi-slice studies have been recently recognized. These conflicting findings can be reconciled by accounting for several experimental and algorithmic factors. Using simulation and clinical studies, the non-simultaneous measurement of arterial and tissue concentration curves (relative slice position) in a multi-slice study is shown to affect time-related perfusion parameters, e.g. arterial-tissue-delay measurements. However, the current clinical impact of relative slice position on amplitude-related perfusion parameters, e.g. CBF, can be expected to be small unless any of the following conditions are present individually or in combination: (a) high concentration curve signal-to-noise ratios, (b) small tissue mean transit times, (c) narrow arterial input functions or (d) low temporal resolution of the DSC image sequence. Recent improvements in magnetic resonance (MR) technology can easily be expected to lead to scenarios where these effects become increasingly important sources of inaccuracy for all perfusion parameter estimates. We show that using Fourier interpolated (high temporal resolution) residue functions reduces the systematic error of the perfusion parameters obtained from multi-slice studies.

  11. Inorganic nitrogen transformations in the bed of the Shingobee River, Minnesota: Integrating hydrologic and biological processes using sediment perfusion cores

    USGS Publications Warehouse

    Sheibley, R.W.; Duff, J.H.; Jackman, A.P.; Triska, F.J.

    2003-01-01

    Inorganic N transformations were examined in streambed sediments from the Shingobee River using sediment perfusion cores. The experimental design simulated groundwater-stream water mixing within sediment cores, which provided a well-defined one-dimensional representation of in situ hydrologic conditions. Two distinct hydrologic and chemical settings were preserved in the sediment cores: the lowermost sediments, perfused with groundwater, remained anaerobic during the incubations, whereas the uppermost sediments, perfused with oxic water pumped from the overlying water column, simulated stream water penetration into the bed. The maintenance of oxic and anoxic zones formed a biologically active aerobic-anaerobic interface. Ammonium (NH4+) dissolved in groundwater was transported conservatively through the lower core zone but was removed as it mixed with aerated recycle water. Concurrently, a small quantity of nitrate (NO3-) equaling ???25% of the NH4+ loss was produced in the upper sediments. The NH4+ and NO3- profiles in the uppermost sediments resulted from coupled nitrification-denitrification, because assimilation and sorption were negligible. We hypothesize that anaerobic microsites within the aerated upper sediments supported denitrification. Rates of nitrification and denitrification in the perfusion cores ranged 42-209 and 53-160 mg N m-2 day-1, respectively. The use of modified perfusion cores permitted the identification and quantification of N transformations and verified process control by surface water exchange into the shallow hyporheic zone of the Shingobee River.

  12. Mucosal wrinkling in animal antra induced by volumetric growth

    NASA Astrophysics Data System (ADS)

    Li, Bo; Cao, Yan-Ping; Feng, Xi-Qiao; Yu, Shou-Wen

    2011-04-01

    Surface wrinkling of animal mucosas is crucial for the biological functions of some tissues, and the change in their surface patterns is a phenotypic characteristic of certain diseases. Here we develop a biomechanical model to study the relationship between morphogenesis and volumetric growth, either physiological or pathological, of mucosas. Theoretical analysis and numerical simulations are performed to unravel the critical characteristics of mucosal wrinkling in a spherical antrum. It is shown that the thicknesses and elastic moduli of mucosal and submucosal layers dictate the surface buckling morphology. The results hold clinical relevance for such diseases as inflammation and gastritis.

  13. Targeting early infection to prevent HIV-1 mucosal transmission.

    PubMed

    Haase, Ashley T

    2010-03-11

    Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.

  14. Improved Techniques for Endoscopic Mucosal Resection (EMR) in Colorectal Adenoma

    PubMed Central

    Sold, Moritz; Kähler, Georg

    2014-01-01

    Summary Background Endoscopic therapy of colorectal adenomas and early cancers is a standard method. Besides oncological criteria, the method is limited by polyp location, size, and texture. Method Based on the current literature, technical modifications and developments in endoscopic mucosal resection are described. Results Numerous approaches exist to improve the conditions of resection, including optimisation of mucosal elevation and modification of techniques, tools, and devices. Conclusion Endoscopic therapy of sessile and flat colorectal polyps remains a challenge. Some of the presented modifications can help to address this challenge. PMID:26286120

  15. A case of unexpected regeneration of small intestinal mucosal necrosis.

    PubMed

    Kim, Dong Wook; Park, Youn Joon

    2012-01-01

    If full-thickness mucosa, including the mucosal crypt, has been almost denuded, mucosa cannot regenerate as has been shown by animal models. The authors experienced an unusual mucosal regeneration exceed denuded bowel that occur in midgut volvulus of duration 2 days in a 6-day-old infant. Santulli's jejunostomy was performed using seriously denuded small bowel to prevent short bowel syndrome, despite the risks of leakage or stricture. Subsequently, stomal mucosa was fully regenerated when grossly identified 19 days after the second operation without any surgical complications.

  16. Impact of dose and volume on radiation-induced mucositis.

    PubMed

    Mantini, Giovanna; Manfrida, Stefania; Cellini, Francesco; Giammarino, Daniela; Petrone, Adelina; Vitucci, Pasquale; Cellini, Numa

    2005-01-01

    There is a relationship between a given radiation dose and the resulting biological effect in the management of head and neck cancer. Radiation mucositis represents a frequent complication in cancer chemoradiation. Its prevention and treatment are major goals in radiation therapy schedules. Critical tissues can be spared using high conformal radiation therapy (3DCRT) based on consensus guidelines for target volume. Current approaches to radiation mucositis with respect to the dose and volume impact are illustrated. The monitoring system of late toxicity used by the authors is presented.

  17. Rotating cylindrical filters used in perfusion cultures: CFD simulations and experiments.

    PubMed

    Figueredo-Cardero, Alvio; Martínez, Edel; Chico, Ernesto; Castilho, Leda R; Medronho, Ricardo A

    2014-01-01

    The particle and fluid dynamics in a rotating cylindrical filtration (RCF) system used for animal cell retention in perfusion processes was studied. A validated CFD model was used and the results gave numerical evidence of phenomena that had been earlier claimed, but not proven for this kind of application under turbulent and high mesh permeability conditions, such as bidirectional radial exchange flow (EF) through the filter mesh and particle (cells) lateral migration. Taylor vortices were shown to cause EF 10-100 times higher than perfusion flow, indicating that EF is the main drag source, at least in early stages of RCF operation. Particle lateral migration caused a cell concentration reduction (CCR) near the filter surface of approximately 10%, contributing significantly to cell separation in RCF systems and giving evidence that the mesh sieving effect is not the sole phenomenon underlying cell retention in RCF systems. Filter rotation rate was shown to significantly affect both EF and CCR. A higher separation efficiency (measured experimentally at 2,000-L bioreactor scale) and an enhanced CCR (predicted by the numerical simulations) were found for the same rotation rate range, indicating that there is an optimal operational space with practical consequences on RCF performance. Experimental data of a large-scale perfusion run employing the simulated RCF showed high cell viabilities for over 100 days, which is probably related to the fact that the computed shear stress level in the system was shown to be relatively low (below 20 Pa under all tested conditions).

  18. Drug perfusion enhancement in tissue model by steady streaming induced by oscillating microbubbles.

    PubMed

    Oh, Jin Sun; Kwon, Yong Seok; Lee, Kyung Ho; Jeong, Woowon; Chung, Sang Kug; Rhee, Kyehan

    2014-01-01

    Drug delivery into neurological tissue is challenging because of the low tissue permeability. Ultrasound incorporating microbubbles has been applied to enhance drug delivery into these tissues, but the effects of a streaming flow by microbubble oscillation on drug perfusion have not been elucidated. In order to clarify the physical effects of steady streaming on drug delivery, an experimental study on dye perfusion into a tissue model was performed using microbubbles excited by acoustic waves. The surface concentration and penetration length of the drug were increased by 12% and 13%, respectively, with streaming flow. The mass of dye perfused into a tissue phantom for 30s was increased by about 20% in the phantom with oscillating bubbles. A computational model that considers fluid structure interaction for streaming flow fields induced by oscillating bubbles was developed, and mass transfer of the drug into the porous tissue model was analyzed. The computed flow fields agreed with the theoretical solutions, and the dye concentration distribution in the tissue agreed well with the experimental data. The computational results showed that steady streaming with a streaming velocity of a few millimeters per second promotes mass transfer into a tissue.

  19. Gastric invasion by Trypanosoma cruzi and induction of protective mucosal immune responses.

    PubMed Central

    Hoft, D F; Farrar, P L; Kratz-Owens, K; Shaffer, D

    1996-01-01

    Trypanosoma cruzi is an intracellular parasite transmitted from a reduviid insect vector to humans by exposure of mucosal surfaces to infected insect excreta. We have used an oral challenge murine model that mimics vector-borne transmission to study T. cruzi mucosal infection. Although gastric secretions have microbicidal activity against most infectious pathogens, we demonstrate that T. cruzi can invade and replicate in the gastric mucosal epithelium. In addition, gastric mucosal invasion appears to be the unique portal of entry for systemic T. cruzi infection after oral challenge. The mucosal immune responses stimulated by T. cruzi gastric infection are protective against a secondary mucosal parasite challenge. This protective mucosal immunity is associated with increased numbers of lymphocytes that secrete parasite-specific immunoglobulin A. Our results document the first example of systemic microbial invasion through gastric mucosa and suggest the feasibility of a mucosal vaccine designed to prevent infection with this important human pathogen. PMID:8751932

  20. Cyclo-oxygenase isozymes in mucosal ulcerogenic and functional responses following barrier disruption in rat stomachs

    PubMed Central

    Hirata, Takuya; Ukawa, Hideki; Yamakuni, Hisashi; Kato, Shinichi; Takeuchi, Koji

    1997-01-01

    We examined the effects of selective and nonselective cyclo-oxygenase (COX) inhibitors on various functional changes in the rat stomach induced by topical application of taurocholate (TC) and investigated the preferential role of COX isozymes in these responses. Rat stomachs mounted in ex vivo chambers were perfused with 50 mM HCl and transmucosal potential difference (p.d.), mucosal blood flow (GMBF), luminal acid loss and luminal levels of prostaglandin E2 (PGE2) were measured before, during and after exposure to 20 mM TC. Mucosal application of TC in control rats caused a reduction in p.d., followed by an increase of luminal acid loss and GMBF, and produced only minimal damage in the mucosa 2 h later. Pretreatment with indomethacin (10 mg kg−1, s.c.), a nonselective COX-1 and COX-2 inhibitor, attenuated the gastric hyperaemic response caused by TC without affecting p.d. and acid loss, resulting in haemorrhagic lesions in the mucosa. In contrast, selective COX-2 inhibitors, such as NS-398 and nimesulide (10 mg kg−1, s.c.), had no effect on any of the responses induced by TC and did not cause gross damage in the mucosa. Luminal PGE2 levels were markedly increased during and after exposure to TC and this response was significantly inhibited by indomethacin but not by either NS-398 or nimesulide. The expression of COX-1-mRNA was consistently detected in the gastric mucosa before and after TC treatment, while a faint expression of COX-2-mRNA was detected only 2 h after TC treatment. Both NS-398 and nimesulide significantly suppressed carrageenan-induced rat paw oedema, similar to indomethacin. These results confirmed a mediator role for prostaglandins in the gastric hyperaemic response following TC-induced barrier disruption, and suggest that COX-1 but not COX-2 is a key enzyme in maintaining ‘housekeeping' functions in the gastric mucosa under both normal and adverse conditions. PMID:9351500

  1. Challenges in machine perfusion preservation for liver grafts from donation after circulatory death

    PubMed Central

    2013-01-01

    Donation after circulatory death (DCD) is a promising solution to the critical shortage of donor graft tissue. Maintaining organ viability after donation until transplantation is essential for optimal graft function and survival. To date, static cold storage is the most widely used form of preservation in clinical practice. However, ischemic damage present in DCD grafts jeopardizes organ viability during cold storage, and whether static cold storage is the most effective method to prevent deterioration of organ quality in the increasing numbers of organs from DCD is unknown. Here we describe the historical background of DCD liver grafts and a new preservation method for experimental and clinical transplantation. To prevent ischemia-reperfusion injury in DCD liver grafts, a hypothermic machine perfusion (HMP) technique has recently been developed and may be superior to static cold preservation. We present evidence supporting the need for improving liver perfusion performance and discuss how doing so will benefit liver transplantation recipients. PMID:24283383

  2. Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice

    PubMed Central

    Margolis, Kara G.; Li, Zhishan; Gershon, Michael D.

    2014-01-01

    Enteric neurons express oxytocin (OT); moreover, enteric neurons and enterocytes express developmentally regulated OT receptors (OTRs). Although OT (with secretin) opposes intestinal inflammation, physiological roles played by enteric OT/OTR signaling have not previously been determined. We tested hypotheses that OT/OTR signaling contributes to enteric nervous system (ENS)-related gastrointestinal (GI) physiology. GI functions and OT effects were compared in OTR-knockout (OTRKO) and wild-type (WT) mice. Stool mass and water content were greater in OTRKO mice than in WT. GI transit time in OTRKO animals was faster than in WT; OT inhibited in vitro generation of ENS-dependent colonic migrating motor complexes in WT but not in OTRKO mice. Myenteric neurons were hyperplastic in OTRKO animals, and mucosal exposure to cholera toxin (CTX) in vitro activated Fos in more myenteric neurons in OTRKO than WT than in WT mice; OT inhibited the CTX response in WT but not in OTRKO mice. Villi and crypts were shorter in OTRKO than in WT mice, and transit-amplifying cell proliferation in OTRKO crypts was deficient. Macromolecular intestinal permeability in OTRKO was greater than WT mice, and experimental colitis was more severe in OTRKO mice; moreover, OT protected WT animals from colitis. Observations suggest that OT/OTR signaling acts as a brake on intestinal motility, decreases mucosal activation of enteric neurons, and promotes enteric neuronal development and/or survival. It also regulates proliferation of crypt cells and mucosal permeability; moreover OT/OTR signaling is protective against inflammation. Oxytocinergic signaling thus appears to play an important role in multiple GI functions that are subject to neuronal regulation. PMID:25147234

  3. Separate effects of irradiation and of graft-versus-host reaction on rat mucosal mast cells.

    PubMed Central

    Cummins, A G; Munro, G H; Huntley, J F; Miller, H R; Ferguson, A

    1989-01-01

    T cell mediated immune responses in the gut can produce enteropathy and malabsorption. We have investigated the relevance of mucosal mast cells (MMC) to the mechanisms of this enteropathy by using graft-versus-host reaction (GvHR) in the rat as a model of mucosal delayed type hypersensitivity. Measurements of mucosal architecture, intraepithelial lymphocytes (IEL) and MMC counts were performed in control and experimental rats, and release of rat mast cell protease II (RMCPII) into the bloodstream was used as an index of MMC activation. In unirradiated rats, jejunal MMC count was increased on day 14 of the GvHR (mean 272/mm2 v 182 in controls, p less than 0.01), as was serum RMCPII (p less than 0.01). Irradiated rats (4.5 Gy, reconstituted with isogeneic spleen cells) had low counts of IEL and crypt hyperplasia seven to 14 days after irradiation. Irradiated rats with GvHR (induced by ip injection of parental strain spleen cells) and studied on days 7, 10 and 14, had significant enteropathy with longer crypts and higher CCPR than matched irradiated animals (p less than 0.05 on day 14 when compared with irradiation alone). Intraepithelial lymphocytes counts, however, reflected only the effect of radiation. Irradiation, with or without GvHR, led to the virtual disappearance of jejunal MMC, undetectable jejunal RMCPII and very low levels of RMCPII in serum (all p less than 0.01 when compared with unirradiated controls). These experiments show that there is a modest expansion in jejunal MMC in unirradiated rats with semiallogeneic GvHR, whereas irradiation, alone or associated with GvHR, profoundly depletes MMC for at least two weeks. The enteropathy of GvHR can evolve in the virtual absence of MMC. PMID:2707634

  4. Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats.

    PubMed

    Arslan, Aynur; Ozcicek, Adalet; Suleyman, Bahadir; Coban, Taha Abdulkadir; Cimen, Ferda Keskin; Nalkiran, Hatice Sevim; Kuzucu, Mehmet; Altuner, Durdu; Cetin, Nihal; Suleyman, Halis

    2016-11-01

    Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide.

  5. Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats

    PubMed Central

    Arslan, Aynur; Ozcicek, Adalet; Suleyman, Bahadir; Coban, Taha Abdulkadir; Cimen, Ferda Keskin; Nalkiran, Hatice Sevim; Kuzucu, Mehmet; Altuner, Durdu; Cetin, Nihal; Suleyman, Halis

    2016-01-01

    Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide. PMID:27333839

  6. The pediatric template of brain perfusion

    PubMed Central

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7–18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development. PMID:25977810

  7. The pediatric template of brain perfusion.

    PubMed

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7-18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development.

  8. Prolonged cerebral "luxury perfusion" after removal of a convexity meningioma.

    PubMed

    Lunsford, L D; Selker, R G

    1979-04-01

    Following total removal of a convexity meningioma, serial computerized tomographic scans disclosed massive hemispheric contrast enhancement compatible with "luxury perfusion". Maximum enhancement occurred one month following the operation and resolved two months postoperatively. Luxury perfusion appeared to be associated with slowly resolving cerebral edema.

  9. Magnetic Resonance Perfusion Imaging in the Study of Language

    ERIC Educational Resources Information Center

    Hillis, Argye E.

    2007-01-01

    This paper provides a brief review of various uses of magnetic resonance perfusion imaging in the investigation of brain/language relationships. The reviewed studies illustrate how perfusion imaging can reveal areas of brain where dysfunction due to low blood flow is associated with specific language deficits, and where restoration of blood flow…

  10. Perfusion Electronic Record Documentation Using Epic Systems Software.

    PubMed

    Riley, Jeffrey B; Justison, George A

    2015-12-01

    The authors comment on Steffens and Gunser's article describing the University of Wisconsin adoption of the Epic anesthesia record to include perfusion information from the cardiopulmonary bypass patient experience. We highlight the current-day lessons and the valuable quality and safety principles the Wisconsin-Epic model anesthesia-perfusion record provides.

  11. Free flap rescue using an extracorporeal perfusion device.

    PubMed

    Fichter, Andreas M; Ritschl, Lucas M; Rau, Andrea; Schwarzer, Claudia; von Bomhard, Achim; Wagenpfeil, Stefan; Wolff, Klaus-Dietrich; Mücke, Thomas

    2016-12-01

    The warm ischaemia time of microvascular free flaps is limited. Incalculable events, such as lack of adequate recipient vessels or intraoperative medical emergencies, can lead to prolonged ischaemia and potentially to flap loss. In this study, critically perfused ischaemic or congested flaps were temporarily perfused with an extracorporeal perfusion system until anastomosis could be commenced. Temporary extracorporeal perfusion was performed in 8 radial forearm flaps for 147 ± 52 (range 77-237) minutes. Flap perfusion was assessed using Indocyanine Green fluorescence angiography and combined laser Doppler flowmetry and remission spectroscopy. Results were compared with those of 30 patients who underwent conventional reconstruction with radial forearm flaps. Flap survival, flap microcirculation, postoperative complications, and hospital stay did not differ between groups. We report successful free flap transfer after short-term extracorporeal perfusion for up to 4 h in 8 patient cases. Temporary extracorporeal free flap perfusion reduces the warm ischaemia time in emergency situations and can help to prevent flap failure in critically perfused or congested flaps. The trial is registered with ClinicalTrials.gov, number NCT02449525.

  12. Hepatic perfusion abnormalities during CT angiography: Detection and interpretation

    SciTech Connect

    Freeny, P.C.; Marks, W.M.

    1986-06-01

    Twenty-seven perfusion abnormalities were detected in 17 of 50 patients who underwent computed tomographic angiography (CTA) of the liver. All but one of the perfusion abnormalities occurred in patients with primary or metastatic liver tumors. Perfusion abnormalities were lobar in nine cases, segmental in 11, and subsegmental in seven; 14 were hypoperfusion and 13 were hyperperfusion abnormalities. The causes for the abnormalities included nonperfusion of a replaced hepatic artery (n = 11), cirrhosis and nodular regeneration (n = 3), altered hepatic hemodynamics (e.g., siphoning, laminar flow) caused by tumor (n = 7), contrast media washout from a nonperfused vessel (n = 1), compression of adjacent hepatic parenchyma (n = 1), and unknown (n = 4). Differentiation of perfusion abnormalities from tumor usually can be made by comparing the morphology of the known tumor with the suspected perfusion abnormality, changes of each on delayed CTA scans, and review of initial angiograms and other imaging studies.

  13. [Ocular perfusion pressure and its relevance for glaucoma].

    PubMed

    Schmidl, D; Werkmeister, R; Garhöfer, G; Schmetterer, L

    2015-02-01

    Ocular perfusion pressure is defined as the difference between arterial and venous pressure in ocular vessels. In practice, mean arterial pressure is used to substitute for arterial pressure in ocular vessels while intraocular pressure gives an estimate for ocular venous pressure. This results in a value that is easy to calculate and which is of importance since several studies have shown that it is correlated to the prevalence, incidence and progression of primary open angle glaucoma. Today, ocular perfusion pressure is used to estimate individual risks. Since no target value for ocular perfusion pressure can be defined, direct therapeutic intervention is difficult. Still, it has to be kept in mind that lowering intraocular pressure automatically leads to an increase in ocular perfusion pressure. The present article also points out problems and limitations in the concept of ocular perfusion pressure and suggests possible solutions for these problems in the future.

  14. Automated quantitative analysis of ventilation-perfusion lung scintigrams

    SciTech Connect

    Burton, G.H.; Vernon, P.; Seed, W.A.

    1984-05-01

    An automated computer analysis of ventilation (Kr-81m) and perfusion (Tc-99m) lung images has been devised that produces a graphical image of the distribution of ventilation and perfusion, and of ventilation-perfusion ratios. The analysis has overcome the following problems: the identification of the midline between two lungs and the lung boundaries, the exclusion of extrapulmonary radioactivity, the superimposition of lung images of different sizes, and the format for presentation of the data. Therefore, lung images of different sizes and shapes may be compared with each other. The analysis has been used to develop normal ranges from 55 volunteers. Comparison of younger and older age groups of men and women show small but significant differences in the distribution of ventilation and perfusion, but no differences in ventilation-perfusion ratios.

  15. Impedance plethysmography: a new method for continuous muscle perfusion monitoring.

    PubMed

    Concannon, M J; Stewart, D H; Welsh, C F; Puckett, C L

    1991-08-01

    Vigilant postoperative monitoring of the buried muscle flap is critical after free transfer because early diagnosis of vascular insufficiency is essential to allow prompt correction. We have identified a monitoring method utilizing needle electrodes and impedance plethysmography that gives a beat-to-beat representation of muscular perfusion. In 25 New Zealand White rabbits the gastrocnemius muscle was isolated on its vascular pedicle, and two intramuscular needle electrodes were placed. The instantaneous impedance changes of the muscle (corresponding to the pulsatile volume changes of perfusion) were measured and recorded. Using this representation of perfusion, an independent judge was able to correctly diagnose muscular ischemia 100 percent of the time (n = 25). Further, the judge was able to correctly distinguish the ischemia as arterial (n = 10) or venous (n = 10) in origin 100 percent of the time. Additionally, we monitored muscle perfusion transcutaneously in five free muscle flaps and demonstrated a reliable impedance signal that correlated with perfusion.

  16. Lipid microparticles for mucosal immunization against hepatitis B.

    PubMed

    Saraf, Surbhi; Mishra, Dinesh; Asthana, Abhay; Jain, Renu; Singh, Surinder; Jain, N K

    2006-01-09

    Parenteral administration of vaccines often does not lead to optimal or long lasting protection against disease causing organisms particularly those that are inhaled, ingested or sexually transmitted. For optimal mucosal protection induction of immune response via mucosal routes is therefore highly desirable. Double emulsion-solvent evaporation (w/o/w) method best suited for water-soluble bioactives was selected for the preparation of hepatitis B surface antigen (HBsAg) loaded lipid microparticles. Intranasal route was considered for mucosal administration and hence to prepare the delivery system biocompatible and least irritable, soyalecithin (phospholipid) was taken instead of polymer because phosphatidylcholine is the major component of endogenous lung surfactant. The studies performed in present work included antigen characterization, development of lipid microparticles, stability studies of the prepared lipid microparticle formulations, percent mucoadhesion, ex vivo cellular uptake studies and in vivo studies. The general order obtained from in vivo studies for mucosal immune response (IgA) followed the sequence: LMST-HBsAg (IN)>LM-HBsAg (IN)>alum-HBsAg (IN)>LMST-HBsAg (IM)>alum-HBsAg (IM)>or=LM-HBsAg (IM)>plain HBsAg (IN)>plain HBsAg (IM).

  17. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey.

    PubMed

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian; Drzewiecki, Krzysztof T; Prause, Jan U; Heegaard, Steffen

    2016-06-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma).

  18. Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis

    SciTech Connect

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

    2012-07-15

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

  19. Management and treatment of mucosal melanoma of the genital tract.

    PubMed

    Vaccari, Sabina; Barisani, Alessia; Dika, Emi; Fanti, Pier A; DE Iaco, Pierandrea; Gurioli, Carlotta; Tosti, Giulio

    2017-01-24

    Melanoma of the genital mucosa is a rare melanocytic neoplasm that affects both sexes. The diagnosis is often delayed; a useful diagnostic tool may be represented by videodermatoscopy, The treatment is complex and multidisciplinary. We report the main diagnostic features and therapeutic approaches for mucosal melanoma of the genital tract.

  20. Enhancing the buccal mucosal uptake and retention of triamcinolone acetonide.

    PubMed

    Nicolazzo, Joseph A; Reed, Barry L; Finnin, Barrie C

    2005-07-20

    In this study, the buccal mucosal uptake and retention of triamcinolone acetonide (TAC) were assessed in the presence of the skin penetration enhancer, Azone (AZ). Porcine buccal mucosa was excised, mounted in modified Ussing chambers, and pretreated with ethanolic solutions of AZ. After 2 h, the rate of TAC disappearance from the donor chamber and TAC appearance in the receptor chamber was monitored, and the mucosal retention of TAC was determined at the completion of the experiment. The permeability and mucosal uptake of TAC was also determined using the TAC-containing proprietary product, Kenalog in Orabase (KO), in the presence and absence of AZ. Pretreatment of the buccal mucosa with AZ increased the TAC disappearance permeability coefficient from 4.78+/-0.31x10(-5) cm/s to 7.12+/-0.53x10(-5) cm/s. While the TAC appearance permeability coefficient was also enhanced 3.8-fold, a 4.4-fold increase in the tissue concentration of TAC was observed. Incorporation of AZ into KO did not result in an enhanced tissue concentration of TAC, however, when the tissue was pretreated with AZ, significantly higher amounts of TAC accumulated in the tissue. Pretreatment of the buccal mucosa with AZ results in increased tissue concentrations of TAC, which may be of clinical benefit in the treatment of oral mucosal inflammatory conditions.

  1. The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra

    PubMed Central

    Schröder, Katja

    2016-01-01

    ABSTRACT Historically, mucosal immunity—i.e., the portion of the immune system that protects an organism’s various mucous membranes from invasion by potentially pathogenic microbes—has been studied in single-cell epithelia in the gastrointestinal and upper respiratory tracts of vertebrates. Phylogenetically, mucosal surfaces appeared for the first time about 560 million years ago in members of the phylum Cnidaria. There are remarkable similarities and shared functions of mucosal immunity in vertebrates and innate immunity in cnidarians, such as Hydra species. Here, we propose a common origin for both systems and review observations that indicate that the ultimately simple holobiont Hydra provides both a new perspective on the relationship between bacteria and animal cells and a new prism for viewing the emergence and evolution of epithelial tissue-based innate immunity. In addition, recent breakthroughs in our understanding of immune responses in Hydra polyps reared under defined short-term gnotobiotic conditions open up the potential of Hydra as an animal research model for the study of common mucosal disorders. PMID:27803185

  2. Canine gastric mucosal vasodilation with prostaglandins and histamine analogs

    SciTech Connect

    Gerber, J.G.; Nies, A.S.

    1982-10-01

    The effect of direct intragastric artery infusion of prostaglandins E2 and I2, arachidonic acid, dimaprit (histamine H2 agonist), and 2',2'-pyridylethylamine (histamine H1 agonist) on gastric mucosal blood flow was examined in dogs to elucidate the relationship between gastric secretory state and mucosal blood flow in dogs. These compounds were chosen because of their diverse effect on gastric acid secretion. Gastric fundus blood flow was measured both electromagnetically with a flow probe around the left gastric artery which supplies the fundus almost exclusively, and by the radioactive microsphere technique. Intraarterial infusion of all the compounds resulted in gastric mucosal vasodilation even though PGE2, PGI2, and arachidonic acid inhibit gastric acid secretion, dimaprit stimulated gastric acid secretion, and 2',2'-pyridylethylamine does not affect gastric acid secretion. There was total agreement in the blood flow measurements by the two different techniques. Our data suggest that gastric acid secretion and gastric vasodilation are independently regulated. In addition, the validity of the studies in which the aminopyrine clearance indicates that prostaglandins are mucosal vasoconstrictors needs to be questioned because of the reliance of those measurements on the secretory state of the stomach.

  3. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    SciTech Connect

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

    2015-08-15

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

  4. Individual mammalian mucosal glucosidase subunits digest various starch structures differently

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch digestion in the human body requires two luminal enzymes,salivary and pancreatic alpha-amylase (AMY), and four small intestinal mucosal enzyme activities related to the maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) complexes. Starch consists of two polysaccharides, amylose (AM) and ...

  5. The Mucosal Immune System and Its Regulation by Autophagy

    PubMed Central

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

    2016-01-01

    The gastrointestinal tract presents a unique challenge to the mucosal immune system, which has to constantly monitor the vast surface for the presence of pathogens, while at the same time maintaining tolerance to beneficial or innocuous antigens. In the intestinal mucosa, specialized innate and adaptive immune components participate in directing appropriate immune responses toward these diverse challenges. Recent studies provide compelling evidence that the process of autophagy influences several aspects of mucosal immune responses. Initially described as a “self-eating” survival pathway that enables nutrient recycling during starvation, autophagy has now been connected to multiple cellular responses, including several aspects of immunity. Initial links between autophagy and host immunity came from the observations that autophagy can target intracellular bacteria for degradation. However, subsequent studies indicated that autophagy plays a much broader role in immune responses, as it can impact antigen processing, thymic selection, lymphocyte homeostasis, and the regulation of immunoglobulin and cytokine secretion. In this review, we provide a comprehensive overview of mucosal immune cells and discuss how autophagy influences many aspects of their physiology and function. We focus on cell type-specific roles of autophagy in the gut, with a particular emphasis on the effects of autophagy on the intestinal T cell compartment. We also provide a perspective on how manipulation of autophagy may potentially be used to treat mucosal inflammatory disorders. PMID:27446072

  6. Photobiomodulation reduces oral mucositis by modulating NF-kB

    NASA Astrophysics Data System (ADS)

    Curra, Marina; Pellicioli, Ana Carolina Amorim; Filho, Nélson Alexandre Kretzmann; Ochs, Gustavo; Matte, Úrsula; Filho, Manoel Sant'Ana; Martins, Marco Antonio Trevizani; Martins, Manoela Domingues

    2015-12-01

    The aim of this study was to evaluate NF-kB during 5-fluorouracil (FU)-induced oral mucositis and ascertain whether photobiomodulation (PBM), as a preventive and/or therapeutic modality, influences this transcription factor. Ninety-six male golden Syrian hamsters were allocated into four groups: control (no treatment); PBM therapeutic, PBM preventive, and PBM combined. Animals received an injection of 5-FU on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched. Irradiation was carried out using a 660-nm, 40-mW diode laser at 6 J/cm2 during 6 s/point, 0.24 J/point, for a total dose of 1.44 J/day of application. Animals were euthanized on days 0, 5, 10, and 15 (n=6). Buccal mucosa was removed for protein quantification by Western blot. Clinical analysis revealed that PBM groups exhibited less mucositis than controls on day 10. Control animals exhibited lower levels of NF-kB during mucositis development and healing. The preventive and combined protocols were associated with higher NF-kB levels at day 5; however, the therapeutic group had higher levels at days 10 and 15. These findings suggest that the preventive and/or therapeutic PBM protocols reduced the severity of oral mucositis by activating the NF-kB pathway.

  7. The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra.

    PubMed

    Schröder, Katja; Bosch, Thomas C G

    2016-11-01

    Historically, mucosal immunity-i.e., the portion of the immune system that protects an organism's various mucous membranes from invasion by potentially pathogenic microbes-has been studied in single-cell epithelia in the gastrointestinal and upper respiratory tracts of vertebrates. Phylogenetically, mucosal surfaces appeared for the first time about 560 million years ago in members of the phylum Cnidaria. There are remarkable similarities and shared functions of mucosal immunity in vertebrates and innate immunity in cnidarians, such as Hydra species. Here, we propose a common origin for both systems and review observations that indicate that the ultimately simple holobiont Hydra provides both a new perspective on the relationship between bacteria and animal cells and a new prism for viewing the emergence and evolution of epithelial tissue-based innate immunity. In addition, recent breakthroughs in our understanding of immune responses in Hydra polyps reared under defined short-term gnotobiotic conditions open up the potential of Hydra as an animal research model for the study of common mucosal disorders.

  8. Photobiomodulation reduces oral mucositis by modulating NF-kB.

    PubMed

    Curra, Marina; Pellicioli, Ana Carolina Amorim; Filho, Nélson Alexandre Kretzmann; Ochs, Gustavo; Matte, Úrsula; Filho, Manoel Sant'Ana; Martins, Marco Antonio Trevizani; Martins, Manoela Domingues

    2015-01-01

    The aim of this study was to evaluate NF-kB during 5-fluorouracil (FU)-induced oral mucositis and ascertain whether photobiomodulation (PBM), as a preventive and/or therapeutic modality, influences this transcription factor. Ninety-six male golden Syrian hamsters were allocated into four groups: control (no treatment); PBM therapeutic, PBM preventive, and PBM combined. Animals received an injection of 5-FU on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched. Irradiation was carried out using a 660-nm, 40-mW diode laser at 6  J/cm(2) during 6  s/point, 0.24  J/point, for a total dose of 1.44  J/day of application. Animals were euthanized on days 0, 5, 10, and 15 (n=6). Buccal mucosa was removed for protein quantification by Western blot. Clinical analysis revealed that PBM groups exhibited less mucositis than controls on day 10. Control animals exhibited lower levels of NF-kB during mucositis development and healing. The preventive and combined protocols were associated with higher NF-kB levels at day 5; however, the therapeutic group had higher levels at days 10 and 15. These findings suggest that the preventive and/or therapeutic PBM protocols reduced the severity of oral mucositis by activating the NF-kB pathway.

  9. Why Chitosan? From properties to perspective of mucosal drug delivery.

    PubMed

    Kumar, Ashwini; Vimal, Archana; Kumar, Awanish

    2016-10-01

    Non-parenteral drug delivery routes primarily remove the local pain at the injection site. The drugs administered through the oral route encounter the process of hepatic first pass metabolism. Among the alternative delivery routes, mucosal route is being investigated as the most preferred route. Different mucosal routes include the gastrointestinal tract (oral), vagina, buccal cavity and nasal cavity. Novel formulations are being developed using natural and synthetic polymers that could increase the residence time of the drug at mucosal surface in order to facilitate permeation and reduce (or bypass) the first pass metabolism. For recombinant drugs, the formulations are accompanied by enzyme inhibitors and penetration enhancers. Buccal cavity (buccal and sublingual mucosa) has smaller surface area than the gastrointestinal tract but the drugs can easily escape the first pass metabolism. Chitosan is the most applied natural polymer while synthetic polymers include Carbopol and Eudragit. Chitosan has inherent properties of mucoadhesion and penetration enhancement apart from biodegradability and efflux pump inhibition. This review hoards the important research purview of chitosan as a compatible drug carrier macromolecule for mucosal delivery on single platform.

  10. Perfusion and diffusion limitations in middle ear gas exchange: the exchange of CO2 as a test case.

    PubMed

    Marcusohn, Yael; Ar, Amos; Dirckx, Joris J J

    2010-06-14

    A long standing debate on perfusion/diffusion limitations in the context of middle ear (ME) gas exchange was revisited using data obtained from previous iso-pressure gas-exchange measurements in different mammals. We tried to determine whether the exchange of CO(2) in the ME is limited by perfusion or by diffusion by comparing the mass specific cardiac output (msQ) and the mass specific initial CO(2) flow rate into air-washed MEs (msV(i) CO(2)) of rabbits and rats. Based on previously published allometry at rest, the msQ was 0.154 mL/(min g) in rabbits (mean body weight: 2800 g) and 0.259 mL/(min g) in rats (mean body weight: 179.1 g); msV(i) CO(2) (Delta t=0) was 0.109+/-0.047 microL/(h g) in rabbits (n=16) and 0.170+/-0.094 microL/(h g) in rats (n=9). Similar ratios were found when an allometric comparison was made between the ratio of msV(i) CO(2) (Delta t=0) (approximately 0.64), and the ratio of msQs (approximately 0.59) in rabbits and rats. If the active mucosal surface areas of MEs of rabbits and rats are directly proportional to their masses as are the masses of their hearts and if their msQs are proportional to the rates of blood flows in the ME mucosa, these results support the assumption that the exchange of CO(2) in the ME of mammals is mainly perfusion (and not diffusion) dependent.

  11. Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis

    SciTech Connect

    Kahan, A.; Devaux, J.Y.; Amor, B.; Menkes, C.J.; Weber, S.; Nitenberg, A.; Venot, A.; Guerin, F.; Degeorges, M.; Roucayrol, J.C.

    1986-05-29

    Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.

  12. Transport of benzo[alpha]pyrene in the dually perfused human placenta perfusion model: effect of albumin in the perfusion medium.

    PubMed

    Mathiesen, Line; Rytting, Erik; Mose, Tina; Knudsen, Lisbeth E

    2009-09-01

    Transport of benzo[alpha]pyrene (BaP) across the placenta was examined because it is a ubiquitous and highly carcinogenic substance found in tobacco smoke, polluted air and certain foods. Foetal exposure to this substance is highly relevant but is difficult to estimate. The human placenta is unique compared to other species; since it is available without major ethical obstacles, we have used the human placenta perfusion model to study transport from mother to foetus. Placentas were donated after births at Rigshospitalet in Copenhagen from pregnant mothers who signed an informed consent. BaP is lipophilic and studies using cell culture medium in 6-hr placenta perfusions showed minimal transport through the placenta. To increase the solubility of BaP in perfusion medium and to increase physiological relevance, perfusions were also performed with albumin added to the perfusion medium [2 and 30 mg/ml bovine serum albumin (BSA) and 30 mg/ml human serum albumin (HSA)]. The addition of albumin resulted in increased transfer of BaP from maternal to foetal reservoirs. The transfer was even higher in the presence of an HSA formulation containing acetyltryptophanate and caprylate, resulting in a foetal-maternal concentration (FM) ratio of 0.71 +/- 0.10 after 3 hr and 0.78 +/- 0.11 after 6 hr, whereas the FM ratio in perfusions without albumin was only 0.05 +/- 0.03 after 6 hr of perfusion. Less BaP accumulated in placental tissue in perfusions with added albumin. This shows that transplacental transport of the pro-carcinogenic substance BaP occurs, and emphasizes the importance of adding physiological concentrations of albumin when studying the transport of lipophilic substances.

  13. Developments in the production of mucosal antibodies in plants.

    PubMed

    Vasilev, Nikolay; Smales, C Mark; Schillberg, Stefan; Fischer, Rainer; Schiermeyer, Andreas

    2016-01-01

    Recombinant mucosal antibodies represent attractive target molecules for the development of next generation biopharmaceuticals for passive immunization against various infectious diseases and treatment of patients suffering from mucosal antibody deficiencies. As these polymeric antibodies require complex post-translational modifications and correct subunit assembly, they are considered as difficult-to-produce recombinant proteins. Beside the traditional, mammalian-based production platforms, plants are emerging as alternative expression hosts for this type of complex macromolecule. Plant cells are able to produce high-quality mucosal antibodies as shown by the successful expression of the secretory immunoglobulins A (IgA) and M (IgM) in various antibody formats in different plant species including tobacco and its close relative Nicotiana benthamiana, maize, tomato and Arabidopsis thaliana. Importantly for biotherapeutic application, transgenic plants are capable of synthesizing functional IgA and IgM molecules with biological activity and safety profiles comparable with their native mammalian counterparts. This article reviews the structure and function of mucosal IgA and IgM antibodies and summarizes the current knowledge of their production and processing in plant host systems. Specific emphasis is given to consideration of intracellular transport processes as these affect assembly of the mature immunoglobulins, their secretion rates, proteolysis/degradation and glycosylation patterns. Furthermore, this review provides an outline of glycoengineering efforts that have been undertaken so far to produce antibodies with homogenous human-like glycan decoration. We believe that the continued development of our understanding of the plant cellular machinery related to the heterologous expression of immunoglobulins will further improve the production levels, quality and control of post-translational modifications that are 'human-like' from plant systems and enhance the

  14. 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

  15. Low-dose irradiation affects the functional behavior of oral microbiota in the context of mucositis.

    PubMed

    Vanhoecke, Barbara W A; De Ryck, Tine R G; De boel, Kevin; Wiles, Siouxsie; Boterberg, Tom; Van de Wiele, Tom; Swift, Simon

    2016-01-01

    The role of host-microbe interactions in the pathobiology of oral mucositis is still unclear; therefore, this study aimed to unravel the effect of irradiation on behavioral characteristics of oral microbial species in the context of mucositis. Using various experimental in vitro setups, the effects of irradiation on growth and biofilm formation of two Candida spp., Streptococcus salivarius and Klebsiella oxytoca in different culture conditions were evaluated. Irradiation did not affect growth of planktonic cells, but reduced the number of K. oxytoca cells in newly formed biofilms cultured in static conditions. Biofilm formation of K. oxytoca and Candida glabrata was affected by irradiation and depended on the culturing conditions. In the presence of mucins, these effects were lost, indicating the protective nature of mucins. Furthermore, the Galleria melonella model was used to study effects on microbial virulence. Irradiated K. oxytoca microbes were more virulent in G. melonella larvae compared to the nonirradiated ones. Our data indicate that low-dose irradiation can have an impact on functional characteristics of microbial species. Screening for pathogens like K. oxytoca in the context of mucosits could be useful to allow early detection and immediate intervention.

  16. Microbial Activation of Gut Dendritic Cells and the Control of Mucosal Immunity

    PubMed Central

    Owen, Jennifer L.

    2013-01-01

    Current data support a role for gut colonization in maintaining balanced mucosal and systemic immune responses and have suggested aberrant innate immune recognition of enteric bacteria as an initiator of the adaptive immune damage associated with inflammatory bowel disease (Crohn's disease and ulcerative colitis). In fact, data from human studies and experimental mouse models have implicated transformation of the gut microbiota from a beneficial symbiotic state to one of imbalance or “dysbiosis” in the pathogenesis of several autoinflammatory diseases, including allergic skin and respiratory disorders, rheumatoid arthritis, type I diabetes, and colorectal cancer. The host has evolved to co-exist and maintain a mutualistic relationship with the commensal microbes of the gut, and it is the function of the host innate immune system to initiate and maintain this homeostasis, while retaining the ability to respond appropriately to pathogenic organisms. In this review, we discuss the molecular and cellular interactions of the mucosal immune system that decide this delicate balance of mutualism. Furthermore, we will highlight the role of dendritic cells in preserving this precarious balance and how gene products of commensal microbes may play an integral role in re-establishing this balance once it has gone awry. PMID:23962004

  17. VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer

    PubMed Central

    Arthur, Janelle C.; Gharaibeh, Raad Z.; Uronis, Joshua M.; Perez-Chanona, Ernesto; Sha, Wei; Tomkovich, Sarah; Mühlbauer, Marcus; Fodor, Anthony A.; Jobin, Christian

    2013-01-01

    Although probiotics have shown success in preventing the development of experimental colitis-associated colorectal cancer (CRC), beneficial effects of interventional treatment are relatively unknown. Here we show that interventional treatment with VSL#3 probiotic alters the luminal and mucosally-adherent microbiota, but does not protect against inflammation or tumorigenesis in the azoxymethane (AOM)/Il10−/− mouse model of colitis-associated CRC. VSL#3 (109 CFU/animal/day) significantly enhanced tumor penetrance, multiplicity, histologic dysplasia scores, and adenocarcinoma invasion relative to VSL#3-untreated mice. Illumina 16S sequencing demonstrated that VSL#3 significantly decreased (16-fold) the abundance of a bacterial taxon assigned to genus Clostridium in the mucosally-adherent microbiota. Mediation analysis by linear models suggested that this taxon was a contributing factor to increased tumorigenesis in VSL#3-fed mice. We conclude that VSL#3 interventional therapy can alter microbial community composition and enhance tumorigenesis in the AOM/Il10−/− model. PMID:24100376

  18. Analytical estimation of ultrasound properties, thermal diffusivity, and perfusion using magnetic resonance-guided focused ultrasound temperature data

    PubMed Central

    Dillon, C R; Borasi, G; Payne, A

    2016-01-01

    For thermal modeling to play a significant role in treatment planning, monitoring, and control of magnetic resonance-guided focused ultrasound (MRgFUS) thermal therapies, accurate knowledge of ultrasound and thermal properties is essential. This study develops a new analytical solution for the temperature change observed in MRgFUS which can be used with experimental MR temperature data to provide estimates of the ultrasound initial heating rate, Gaussian beam variance, tissue thermal diffusivity, and Pennes perfusion parameter. Simulations demonstrate that this technique provides accurate and robust property estimates that are independent of the beam size, thermal diffusivity, and perfusion levels in the presence of realistic MR noise. The technique is also demonstrated in vivo using MRgFUS heating data in rabbit back muscle. Errors in property estimates are kept less than 5% by applying a third order Taylor series approximation of the perfusion term and ensuring the ratio of the fitting time (the duration of experimental data utilized for optimization) to the perfusion time constant remains less than one. PMID:26741344

  19. Analytical estimation of ultrasound properties, thermal diffusivity, and perfusion using magnetic resonance-guided focused ultrasound temperature data

    NASA Astrophysics Data System (ADS)

    Dillon, C. R.; Borasi, G.; Payne, A.

    2016-01-01

    For thermal modeling to play a significant role in treatment planning, monitoring, and control of magnetic resonance-guided focused ultrasound (MRgFUS) thermal therapies, accurate knowledge of ultrasound and thermal properties is essential. This study develops a new analytical solution for the temperature change observed in MRgFUS which can be used with experimental MR temperature data to provide estimates of the ultrasound initial heating rate, Gaussian beam variance, tissue thermal diffusivity, and Pennes perfusion parameter. Simulations demonstrate that this technique provides accurate and robust property estimates that are independent of the beam size, thermal diffusivity, and perfusion levels in the presence of realistic MR noise. The technique is also demonstrated in vivo using MRgFUS heating data in rabbit back muscle. Errors in property estimates are kept less than 5% by applying a third order Taylor series approximation of the perfusion term and ensuring the ratio of the fitting time (the duration of experimental data utilized for optimization) to the perfusion time constant remains less than one.

  20. A comparative study of lingual mucosal graft urethroplasty with buccal mucosal graft urethroplasty in urethral stricture disease: An institutional experience

    PubMed Central

    Pal, Dilip Kumar; Gupta, Depak Kumar; Ghosh, Bastab; Bera, Malay Kumar

    2016-01-01

    Aims: A prospective study to compare the outcomes of lingual versus buccal mucosal graft urethroplasty in patients with long segment anterior urethral strictures disease. Materials and Methods: The study included 30 patients for buccal mucosal graft urethroplasty (group I) and 30 patients for lingual mucosal graft urethroplasty (group II) for treatment of long segment (>3 cm) incomplete anterior urethral stricture disease using single-stage dorsal onlay free oral mucosal graft urethroplasty by Barbagli's technique between February 2013 to September 2014. All patients underwent complete evaluation of the stricture including inspection of the oral cavity. Results: The results of urethroplasty in between two group were not significant (P > 0.05) in terms of Qmax (P = 0.63), mean postoperative AUA symptom score (P = 0.83), operative time (P = 0.302) intra operative blood loss (P = 0.708), duration of postoperative hospitalization (P = 0.83), but slurring of speech complications was seen in group II, but not in group I. Long-term complications of salivary disturbance, tightness of the mouth, persistent pain at graft site, perioral numbness, seen only in group I (BMGU). Conclusion: LMG urethroplasty is an excellent alternative to BMG urethroplasty with comparable results of urethroplasty and minimal donor site complications. PMID:27141184

  1. Intra-Arterial MR Perfusion Imaging of Meningiomas: Comparison to Digital Subtraction Angiography and Intravenous MR Perfusion Imaging

    PubMed Central

    Martin, Alastair J.; Alexander, Matthew D.; McCoy, David B.; Cooke, Daniel L.; Lillaney, Prasheel; Moftakhar, Parham; Amans, Matthew R.; Settecase, Fabio; Nicholson, Andrew; Dowd, Christopher F.; Halbach, Van V.; Higashida, Randall T.; McDermott, Michael W.; Saloner, David; Hetts, Steven W.

    2016-01-01

    Background and Purpose To evaluate the ability of IA MR perfusion to characterize meningioma blood supply. Methods Studies were performed in a suite comprised of an x-ray angiography unit and 1.5T MR scanner that permitted intraprocedural patient movement between the imaging modalities. Patients underwent intra-arterial (IA) and intravenous (IV) T2* dynamic susceptibility MR perfusion immediately prior to meningioma embolization. Regional tumor arterial supply was characterized by digital subtraction angiography and classified as external carotid artery (ECA) dural, internal carotid artery (ICA) dural, or pial. MR perfusion data regions of interest (ROIs) were analyzed in regions with different vascular supply to extract peak height, full-width at half-maximum (FWHM), relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and mean transit time (MTT). Linear mixed modeling was used to identify perfusion curve parameter differences for each ROI for IA and IV MR imaging techniques. IA vs. IV perfusion parameters were also directly compared for each ROI using linear mixed modeling. Results 18 ROIs were analyzed in 12 patients. Arterial supply was identified as ECA dural (n = 11), ICA dural (n = 4), or pial (n = 3). FWHM, rCBV, and rCBF showed statistically significant differences between ROIs for IA MR perfusion. Peak Height and FWHM showed statistically significant differences between ROIs for IV MR perfusion. RCBV and MTT were significantly lower for IA perfusion in the Dural ECA compared to IV perfusion. Relative CBF in IA MR was found to be significantly higher in the Dural ICA region and MTT significantly lower compared to IV perfusion. PMID:27802268

  2. Neutrophil gelatinase-associated lipocalin, a new biomarker candidate in perfusate of machine-perfused kidneys: a porcine pilot experiment.

    PubMed

    Jochmans, I; Monbaliu, D; Pirenne, J

    2011-11-01

    The enduring kidney graft shortage has led to the increasing use of expanded-criteria donors as well as kidneys donated after cardiac death, triggering the revival of machine perfusion preservation. Indeed, machine perfusion not only preserves these kidneys better than static cold storage, but also has the potential to evaluate them. The presence of certain biomarkers, among them aspartate aminotransferase (AST) and heart-type fatty acid binding protein (H-FABP), has been demonstrated in the perfusate of human kidneys, making them potentially useful as biomarkers of graft quality. Neutrophil gelatinase-associated lipocalin (NGAL) which is believed to be released upon renal tubular cell injury is another biomarker candidate. However, because it is also released from neutrophils, it is currently unclear whether NGAL is a direct or indirect, inflammatory-mediated marker of kidney injury. To resolve this issue we established a pilot experiment to study the concentrations of AST, H-FABP, and NGAL in the perfusates of 6 porcine kidneys that were exposed to incremental periods of warm ischemia before machine perfusion for 22 hours. An ex vivo porcine model was chosen because preclinical large animal work remains necessary to refine machine perfusion technology and because the presence of these markers in perfusates of porcine kidneys had not been shown previously. All 3 biomarkers were detectable in the cold acellular perfusate; their release seemed to be proportionate to the degree of warm injury, albeit that this must be confirmed in a larger sample. In conclusion, NGAL is directly released by ischemically damaged kidneys, independent of neutrophil activation. In addition to NGAL, the determination of AST and H-FABP in perfusates of machine-perfused porcine kidneys is also feasible. Determination of these markers may be added to the arsenal of research tools for preclinical preservation research.

  3. Evaluation of Perfusion Quantification Methods with Ultrasound Contrast Agents in a Machine-Perfused Pig Liver.

    PubMed

    Averkiou, M; Keravnou, C P; Izamis, M L; Leen, E

    2016-05-03

    Purpose: To evaluate dynamic contrast-enhanced ultrasound (DCEUS) as a tool for measuring blood flow in the macro- and microcirculation of an ex-vivo machine-perfused pig liver and to confirm the ability of DCEUS to accurately detect induced flow rate changes so that it could then be used clinically for monitoring flow changes in liver tumors. Materials and Methods: Bolus injections of contrast agents in the hepatic artery (HA) and portal vein (PV) were administered to 3 machine-perfused pig livers. Flow changes were induced by the pump of the machine perfusion system. The induced flow rates were of clinical relevance (150 - 400 ml/min for HA and 400 - 1400 ml/min for PV). Quantification parameters from time-intensity curves [rise time (RT), mean transit time (MTT), area under the curve (AUC) and peak intensity (PI)] were extracted in order to evaluate whether the induced flow changes were reflected in these parameters. Results: A linear relationship between the image intensity and the microbubble concentration was confirmed first, while time parameters (RT and MMT) were found to be independent of concentration. The induced flow changes which propagated from the larger vessels to the parenchyma were reflected in the quantification parameters. Specifically, RT, MTT and AUC correlated with flow rate changes. Conclusion Machine-perfused pig liver is an excellent test bed for DCEUS quantification approaches for the study of the hepatic vascular networks. DCEUS quantification parameters (RT, MTT, and AUC) can measure relative flow changes of about 20 % and above in the liver vasculature. DCEUS quantification is a promising tool for real-time monitoring of the vascular network of tumors.

  4. Measuring perfusion with light (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jansen, Sanne M. A.; de Bruin, Daniel M.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-03-01

    There is no gold standard test for perfusion evaluation in surgery. Optical Imaging techniques are able to image tissue at high resolution and in real-time. Laser Speckle Contrast Imaging, Optical Coherence Tomography, Sidestream Darkfield and Incident Darkfield all use the interaction of light with tissue to create an image. To test their feasibility and explore validity in a controlled setting, we created a phantom with the optical properties of tissue and microvascular channels of 30-400 micrometer. With a Hamilton Syringe Pump we mimicked blood flow velocities of 0-20 mm/sec. Images of all different modalities at different blood flow velocities were compared in terms of imaging depth, resoluation and hemodynamic parameters.

  5. Hydrogels for Engineering of Perfusable Vascular Networks.

    PubMed

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S P; Machens, Hans-Günther; Schilling, Arndt F

    2015-07-14

    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation.

  6. Hydrogels for Engineering of Perfusable Vascular Networks

    PubMed Central

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.

    2015-01-01

    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

  7. Adenosine thallium 201 myocardial perfusion scintigraphy

    SciTech Connect

    Verani, M.S. )

    1991-07-01

    Pharmacologic coronary vasodilation as an adjunct to myocardial perfusion imaging has become increasingly important in the evaluation of patients with coronary artery disease, in view of the large number of patients who cannot perform an adequate exercise test or in whom contraindications render exercise inappropriate. Adenosine is a very potent coronary vasodilator and when combined with thallium 201 scintigraphy produces images of high quality, with the added advantages of a very short half-life (less than 10 seconds) and the ability to adjust the dose during the infusion, which may enhance safety and curtail the duration of side effects. The reported sensitivity and specificity of adenosine thallium 201 scintigraphy for the detection of coronary artery disease are high and at least comparable with imaging after exercise or dipyridamole administration. 23 refs.

  8. Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture.

    PubMed

    Huang, Song-Bin; Chou, Dean; Chang, Yu-Han; Li, Ke-Cing; Chiu, Tzu-Keng; Ventikos, Yiannis; Wu, Min-Hsien

    2015-12-16

    Before microfluidic-based cell culture models can be practically utilized for bioassays, there is a need for a transitional cell culture technique that can improve conventional cell culture models. To address this, a hybrid cell culture system integrating an active cover lid and a multi-well microplate was proposed to achieve perfusion 3-D cell culture. In this system, a microfluidic-based pneumatically-driven liquid transport mechanism was integrated into the active cover lid to realize 6-unit culture medium perfusion. Experimental results revealed that the flow of culture medium could be pneumatically driven in a flow-rate uniform manner. We used the system to successfully perform a perfusion 3-D cell culture of mesenchymal stem cells (MSCs) for up to 16 days. Moreover, we investigated the effects of various cell culture models on the physiology of MSCs. The physiological nature of MSCs can vary with respect to the cell culture model used. Using the perfusion 3-D cell culture format might affect the proliferation and osteogenic differentiation of MSCs. Overall, we have developed a cell culture system that can achieve multi-well microplate-based perfusion 3-D cell culture in an efficient, cost-effective, and user-friendly manner. These features could facilitate the widespread application of perfusion cell culture models for cell-based assays.

  9. Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture

    NASA Astrophysics Data System (ADS)

    Huang, Song-Bin; Chou, Dean; Chang, Yu-Han; Li, Ke-Cing; Chiu, Tzu-Keng; Ventikos, Yiannis; Wu, Min-Hsien

    2015-12-01

    Before microfluidic-based cell culture models can be practically utilized for bioassays, there is a need for a transitional cell culture technique that can improve conventional cell culture models. To address this, a hybrid cell culture system integrating an active cover lid and a multi-well microplate was proposed to achieve perfusion 3-D cell culture. In this system, a microfluidic-based pneumatically-driven liquid transport mechanism was integrated into the active cover lid to realize 6-unit culture medium perfusion. Experimental results revealed that the flow of culture medium could be pneumatically driven in a flow-rate uniform manner. We used the system to successfully perform a perfusion 3-D cell culture of mesenchymal stem cells (MSCs) for up to 16 days. Moreover, we investigated the effects of various cell culture models on the physiology of MSCs. The physiological nature of MSCs can vary with respect to the cell culture model used. Using the perfusion 3-D cell culture format might affect the proliferation and osteogenic differentiation of MSCs. Overall, we have developed a cell culture system that can achieve multi-well microplate-based perfusion 3-D cell culture in an efficient, cost-effective, and user-friendly manner. These features could facilitate the widespread application of perfusion cell culture models for cell-based assays.

  10. Low dose CT perfusion using k-means clustering

    NASA Astrophysics Data System (ADS)

    Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

    2016-03-01

    We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.

  11. Humoral immune responses among mucosal and cutaneous leishmaniasis patients caused by Leishmania braziliensis.

    PubMed

    Valli, L C; Passos, V M; Dietze, R; Callahan, H L; Berman, J D; Grogl, M

    1999-12-01

    Mucosal leishmaniasis is arguably the most morbid sequelae of cutaneous leishmaniasis. The importance of early diagnosis for effective therapy, coupled with the difficulty of diagnosing the disease parasitologically, prompted this investigation of humoral immune markers of mucosal disease. Promastigote soluble antigens of Leishmania braziliensis, isolated from cutaneous and mucosal lesions, were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis; antigens were identified by immunoblotting with parasite-specific IgG antibody-positive sera of patients with mucosal disease (n = 18) and cutaneous disease (n = 23). For antigens of the cutaneous parasite WR 2095, mucosal sera generally reacted intensely to antigens of 75, 66, and 45 kDa and weakly to 48-50-kDa antigens, whereas cutaneous sera generally detected weakly the first 3 antigens and intensely the latter doublet. The data suggest that the transition from the cutaneous antigenic profile to a mucosal antigenic profile could be used to predict mucosal disease in approximately half of mucosal patients. An additional finding was that antibodies present in the sera of patients with mucosal disease labeled a 66-kDa peptide of normal human lip mucosa more intensely than did cutaneous sera. Autoimmune processes stimulated by the reaction of IgG, originally directed against the 66-kDa of L. braziliensis, to the 66-kDa antigen of mucosal tissue may contribute to the clinical presentation of mucosal leishmaniasis.

  12. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

    SciTech Connect

    Myllynen, Paeivi . E-mail: paivi.k.myllynen@oulu.fi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-09-01

    Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure.

  13. Plasmid pVAX1-NH36 purification by membrane and bead perfusion chromatography.

    PubMed

    Franco-Medrano, Diana Ivonne; Guerrero-Germán, Patricia; Montesinos-Cisneros, Rosa María; Ortega-López, Jaime; Tejeda-Mansir, Armando

    2017-03-01

    The demand for plasmid DNA (pDNA) has increased in response to the rapid advances in vaccines applications to prevent and treat infectious diseases caused by virus, bacteria or parasites, such as Leishmania species. The immunization protocols require large amounts of supercoiled plasmid DNA (sc-pDNA) challenging the development of efficient and profitable processes for capturing and purified pDNA molecules from large volumes of lysates. A typical bioprocess involves four steps: fermentation, primary recovery, intermediate recovery and final purification. Ion-exchange chromatography is one of the key operations in the purification schemes of pDNA owing the chemical structure of these macromolecules. The goal of this research was to compare the performance of the final purification step of pDNA using ion-exchange chromatography on columns packed with Mustang Q membranes or perfusive beads POROS 50 HQ. The experimental results showed that both matrixes could separate the plasmid pVAX1-NH36 (3936 bp) from impurities in clarified Escherichia coli lysates with an adequate resolution. In addition, a 24- and 21-fold global purification factor was obtained. An 88 and 63% plasmid recuperation was achieved with ion-exchange membranes and perfusion beads, respectively. A better understanding of perfusion-based matrices for the purification of pDNA was developed in this research.

  14. Multiphysics simulation of a microfluidic perfusion chamber for brain slice physiology.

    PubMed

    Caicedo, Hector H; Hernandez, Maximiliano; Fall, Christopher P; Eddington, David T

    2010-10-01

    Understanding and optimizing fluid flows through in vitro microfluidic perfusion systems is essential in mimicking in vivo conditions for biological research. In a previous study a microfluidic brain slice device (microBSD) was developed for microscale electrophysiology investigations. The device consisted of a standard perfusion chamber bonded to a polydimethylsiloxane (PDMS) microchannel substrate. Our objective in this study is to characterize the flows through the microBSD by using multiphysics simulations of injections into a pourous matrix to identify optimal spacing of ports. Three-dimensional computational fluid dynamic (CFD) simulations are performed with CFD-ACE + software to model, simulate, and assess the transport of soluble factors through the perfusion bath, the microchannels, and a material that mimics the porosity, permeability and tortuosity of brain tissue. Additionally, experimental soluble factor transport through a brain slice is predicted by and compared to simulated fluid flow in a volume that represents a porous matrix material. The computational results are validated with fluorescent dye experiments.

  15. LOW DOSE NITRITE ENHANCES PERFUSION AFTER FLUID RESUSCITATION FROM HEMORRHAGIC SHOCK

    PubMed Central

    Cabrales, Pedro

    2010-01-01

    This study determines the systemic and microvascular hemodynamic consequences of administering a low dose sodium nitrite after fluid resuscitation from hemorrhagic shock. Hemodynamic responses to hemorrhagic shock and resuscitation were studied in the hamster window chamber model. Moderated hemorrhage was induced by arterial controlled bleeding of 50% of the blood volume (BV) and the hypovolemic state was maintained for one hour. Volume restitution was performed by infusion of 25% of BV using Hextend® (6% Hetastarch 670 kDa in lactated electrolyte solution) 10 min after fluid resuscitation 100μl of specific concentrations of sodium nitrite were infused. The experimental groups were named based on the nitrite concentration used, namely: 0 μM, 10 μM and 50 μM. Systemic parameters, microvascular hemodynamics and capillary perfusion (functional capillary density, FCD) were followed during entire protocol. Exogenous 10 μM nitrite maintained systemic and microhemodynamic conditions post fluid resuscitation from hemorrhagic shock, compared to 50 μM or no nitrite. A moderated increase in plasma nitrite during the early phase of resuscitation reversed arteriolar vasoconstriction and increased capillary perfusion and venous return, improving central cardiac function. Nitrite effects on resistance vessels, directly influenced intravascular pressure redistribution, sustained blood flow, and prevented tissue ischemia. In conclusion, increasing nitrite plasma bioavailability after fluid resuscitation from hemorrhagic shock can be a potential therapy to enhance microvascular perfusion and to improve overall outcome. PMID:19804938

  16. Measurement of cerebrospinal fluid formation and absorption by ventriculo-cisternal perfusion: what is really measured?

    PubMed Central

    Orešković, Darko; Klarica, Marijan

    2014-01-01

    The generally accepted hypothesis on cerebrospinal fluid (CSF) hydrodynamics suggests that CSF is actively formed mainly by choroid plexuses, circulates unidirectionally along the brain ventricles and subarachnoid space, and is passively absorbed mainly into the dural venous sinuses. CSF formation rate (Vf) has been extensively studied using the ventriculo-cisternal perfusion technique and the results have been used as the key evidence confirming the mentioned hypothesis. This method and the equation for Vf calculation are based on the assumption that the dilution of the indicator substance is a consequence of the newly formed CSF, ie, that a higher CSF formation rate will result in a higher degree of dilution. However, it has been experimentally shown that the indicator substance dilution inside the CSF system does not occur because of a “newly formed” CSF, but as consequence of a number of other factors (departure of substances into the surrounding tissue, flowing around the collecting cannula into the cortical and spinal subarachnoid space, departure into the contralateral ventricle, etc). This technique allows “calculation” of the CSF formation even in dead animals, in an in vitro model, and in any other part of the CSF system outside the ventricles that is being perfused. Therefore, this method is indirect and any dilution of the indicator substance in the perfusate caused by other reasons would result in questionable and often contradictory conclusions regarding CSF formation rates. PMID:25165046

  17. Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit.

    PubMed

    Leung, F W; Guth, P H; Scremin, O U; Golanska, E M; Kauffman, G L

    1984-07-01

    Hydrogen gas clearance using 3% hydrogen in air and platinum contact electrodes was employed for measuring antral and corpus mucosal blood flow in anesthetized animals. Significantly greater antral than corpus mucosal blood flow was consistently demonstrated. Corpus but not antral mucosal blood flow showed a significant dose-related increase with intravenous pentagastrin. Vasopressin induced a significant dose-related decrease in both antral and corpus mucosal blood flow. Simultaneous measurement of basal corpus mucosal blood flow by hydrogen gas clearance and of gastric mucosal blood flow by aminopyrine clearance gave similar values, but the changes with intravenous pentagastrin or vasopressin measured by aminopyrine clearance were of a much higher order of magnitude. Hydrogen gas clearance, however, reflected changes in left gastric artery blood flow much more closely than did aminopyrine clearance. Therefore, we conclude that the hydrogen gas clearance technique as described is valid for measuring regional gastric mucosal blood flow. It is safe and has potential application in human studies.

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2015-01-01

    Mucositis is a major oncological problem. The entire gastrointestinal and genitourinary tract and also other mucosal surfaces can be affected in recipients of radiotherapy, and/or chemotherapy. Major progress has been made in recent years in understanding the mechanisms of oral and small intestinal mucositis, which appears to be more prominent than colonic damage. This progress is largely due to the development of representative laboratory animal models of mucositis. This review focuses on the development and establishment of the Dark Agouti rat mammary adenocarcinoma model by the Mucositis Research Group of the University of Adelaide over the past 20 years to characterize the mechanisms underlying methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to summarize the results from studies using different animal model systems to identify new molecular and cellular markers of mucositis. PMID:25966981

  20. Impact of colonic mucosal lipoxin A4 synthesis capacity on healing in rats with dextran sodium sulfate-induced colitis.

    PubMed

    Ağış, Erol R; Savaş, Berna; Melli, Mehmet

    2015-09-01

    Ulcerative colitis is a chronic inflammatory disease of the colon. This study evaluates the role of colonic mucosal lipoxin A4 (LXA4) synthesis in an experimental rat model of dextran sodium sulfate (DSS)-induced colitis. Wistar rats were randomly assigned to four groups: healthy controls, DSS-induced colitis with no or vehicle therapy, misoprostol or 5-aminosalicylic acid (5-ASA) therapy groups. Disease severity and colonic mucosal LXA4 synthesis was assessed specifically during the acute phase (day 5), chronic phase (day 15) and healing phases (day 19). Both misoprostol and 5-ASA reduced histopathologic score during the acute phase and reduced disease activity score at the healing phase. In addition, misoprostol reduced histopathologic score and colon weight/length ratio during the healing phase. Only misoprostol therapy increased colonic mucosal LXA4 synthesis. Furthermore, LXA4 levels correlated negatively with disease progression (R=-0.953). Collectively, our findings suggest that misoprostol-induced LXA4 synthesis may be favorable for the healing of ulcerative colitis.

  1. Luxury perfusion phenomenon in acute herpes simplex virus encephalitis.

    PubMed

    Tanaka, M; Uesugi, M; Igeta, Y; Kondo, S; Sun, X; Hirai, S

    1995-02-01

    In a patient with acute herpes simplex virus (HSV) encephalitis, positron emission tomography (PET) demonstrated increased cerebral blood flow in the affected temporal lobe accompanied by reduction in the cerebral oxygen extraction fraction and the cerebral metabolic rate of oxygen, i.e., luxury perfusion. Follow-up PET studies showed reduction in cerebral perfusion until it was more closely coupled with oxygen metabolism after the resolution of the acute inflammation. These findings support previous single photon emission computed tomographic data and provide a pathophysiological background for the occurrence of hyperperfusion in HSV encephalitis. This is an interesting example of the luxury perfusion phenomenon occurring in a disease other than cerebral ischemia.

  2. A new apex-ejecting perfused rat heart preparation: relation between coronary flow and loading conditions.

    PubMed

    Wikman-Coffelt, J; Coffelt, R J; Rapcsak, M; Sievers, R; Rouleau, J L; Parmley, W W

    1983-12-01

    The isolated perfused rat heart is an important experimental preparation for both mechanical and biochemical studies. In order to define better the relationship between coronary flow and loading conditions, a new preparation was developed in which the left ventricle ejected through the apex, while the aortic perfusion pressure could be separately controlled at a higher level than the apex afterload. Results were compared with a standard aortic perfused and ejecting preparation. All analyses were made at low calcium concentration (1.6 mmol X litre-1) for reducing cardiac performance. Coronary flow was related to perfusion pressure in the aortic ejecting preparation when the aortic afterload chamber was between 6.0 and 9.3 kPa (45 and 70 mmHg). Coronary autoregulation was demonstrable in the apex ejecting preparation irrespective of the height of the apex afterload chamber and the aortic ejecting preparation when the aortic chamber was between 11.0 and 16.0 kPa (83 and 120 mmHg). Following the addition of 10(-6) mol X litre-1 adenosine, there was significant coronary vasodilatation, and flow became pressure dependent in all cases. In the apex-ejecting preparation, with a high aortic pressure, coronary flow remained at relatively fixed level, and increases in oxygen demand were met by increasing oxygen extraction. Thus, in this preparation oxygen extraction was directly related to workload. With abrupt increases in afterload, going from 6.0 to 9.3 kPa (45 to 70 mmHg) to a higher level, there was evidence of transient hypoxia with the aortic ejecting but not the apex ejecting preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. First steps in membrane oxygenation and prolonged extracorporeal perfusion in Duesseldorf using the Bramson membrane lung.

    PubMed

    Schulte, Hagen D

    2003-05-01

    After a shortened history of conventional closed and open heart surgery, including hypothermia by surface cooling and extracorporeal circulation, the first application of a new membrane oxygenator developed by ML Bramson with an integrated temperature exchange system and a heart-lung machine (HLM) was reported in 1972. The aim was to have an efficient oxygenating and gas exchange artificial lung that allowed prolonged perfusions in patients with cardiogenic shock or acute respiratory insufficiency. After in vitro closed recirculation studies comparing different bubble, vertical screen, and the new membrane oxygenators, the Bramson HLM was used in dog experiments before starting clinical cardiac surgery with routine interventions (closure of an atrial septal defect). The first clinically prolonged support for more than three hours after a double valve replacement in a NYHA class IV patient failed. A partial venoarterial prolonged perfusion for 42 hours and 43 minutes in a 10-year-old girl after surgical correction of a partial av canal defect and postoperative development of consistent lung edema caused by myocardial failure after an ischemic time of 43 minutes was the first successful long-term perfusion case in Europe. These first experiences with the Bramson membrane lung formed the basis, in our group, for further investigations of different perfusion routes and cannulations in animal experiments. Also, scanning electron microscopy studies could be performed with experimentally and clinically used membranes. The development of disposable membrane lung devices, for instance, Lande-Edwards, Kolobow Scimed, and General Electric Peirce membrane lungs, ameliorated and improved the use of these devices considerably. Also, BRAMSON had developed a disposable membrane lung device that had proved to be very effective in animal experiments by 1972, but, unfortunately, this device did not become commercially available.

  4. Maximizing kidneys for transplantation using machine perfusion: from the past to the future

    PubMed Central

    Hameed, Ahmer M.; Pleass, Henry C.; Wong, Germaine; Hawthorne, Wayne J.

    2016-01-01

    Abstract Background: The two main options for renal allograft preservation are static cold storage (CS) and machine perfusion (MP). There has been considerably increased interest in MP preservation of kidneys, however conflicting evidence regarding its efficacy and associated costs have impacted its scale of clinical uptake. Additionally, there is no clear consensus regarding oxygenation, and hypo- or normothermia, in conjunction with MP, and its mechanisms of action are also debated. The primary aims of this article were to elucidate the benefits of MP preservation with and without oxygenation, and/or under normothermic conditions, when compared with CS prior to deceased donor kidney transplantation. Methods: Clinical (observational studies and prospective trials) and animal (experimental) articles exploring the use of renal MP were assessed (EMBASE, Medline, and Cochrane databases). Meta-analyses were conducted for the comparisons between hypothermic MP (hypothermic machine perfusion [HMP]) and CS (human studies) and normothermic MP (warm (normothermic) perfusion [WP]) compared with CS or HMP (animal studies). The primary outcome was allograft function. Secondary outcomes included graft and patient survival, acute rejection and parameters of tubular, glomerular and endothelial function. Subgroup analyses were conducted in expanded criteria (ECD) and donation after circulatory (DCD) death donors. Results: A total of 101 studies (63 human and 38 animal) were included. There was a lower rate of delayed graft function in recipients with HMP donor grafts compared with CS kidneys (RR 0.77; 95% CI 0.69–0.87). Primary nonfunction (PNF) was reduced in ECD kidneys preserved by HMP (RR 0.28; 95% CI 0.09–0.89). Renal function in animal studies was significantly better in WP kidneys compared with both HMP (standardized mean difference [SMD] of peak creatinine 1.66; 95% CI 3.19 to 0.14) and CS (SMD of peak creatinine 1.72; 95% CI 3.09 to 0.34). MP improves renal

  5. In-vivo quantitative evaluation of perfusion zones and perfusion gradient in the deep inferior epigastric artery perforator flap

    NASA Astrophysics Data System (ADS)

    Saint-Cyr, Michel; Lakhiani, Chrisovalantis; Cheng, Angela; Mangum, Michael; Liang, Jinyang; Teotia, Sumeet; Livingston, Edward H.; Zuzak, Karel J.

    2013-03-01

    The selection of well-vascularized tissue during DIEP flap harvest remains controversial. While several studies have elucidated cross-midline perfusion, further characterization of perfusion to the ipsilateral hemiabdomen is necessary for minimizing rates of fat necrosis or partial fat necrosis in bilateral DIEP flaps. Eighteen patients (29 flaps) underwent DIEP flap harvest using a prospectively designed protocol. Perforators were marked and imaged with a novel system for quantitatively measuring tissue oxygenation, the Digital Light Hyperspectral Imager. Images were then analyzed to determine if perforator selection influenced ipsilateral flap perfusion. Flaps based on a single lateral row perforator (SLRP) were found to have a higher level of hemoglobin oxygenation in Zone I (mean %HbO2 = 76.1) compared to single medial row perforator (SMRP) flaps (%HbO2 = 71.6). Perfusion of Zone III relative to Zone I was similar between SLRP and SMRP flaps (97.4% vs. 97.9%, respectively). These differences were not statistically significant (p>0.05). Perfusion to the lateral edge of the flap was slightly greater for SLRP flaps compared SMRP flaps (92.1% vs. 89.5%, respectively). SMRP flaps had superior perfusion travelling inferiorly compared to SLRP flaps (88.8% vs. 83.9%, respectively). Overall, it was observed that flaps were better perfused in the lateral direction than inferiorly. Significant differences in perfusion gradients directed inferiorly or laterally were observed, and perforator selection influenced perfusion in the most distal or inferior aspects of the flap. This suggests broader clinical implications for flap design that merit further investigation.

  6. Development of Mucosal Vaccines Based on Lactic Acid Bacteria

    NASA Astrophysics Data System (ADS)

    Bermúdez-Humarán, Luis G.; Innocentin, Silvia; Lefèvre, Francois; Chatel, Jean-Marc; Langella, Philippe

    Today, sufficient data are available to support the use of lactic acid bacteria (LAB), notably lactococci and lactobacilli, as delivery vehicles for the development of new mucosal vaccines. These non-pathogenic Gram-positive bacteria have been safely consumed by humans for centuries in fermented foods. They thus constitute an attractive alternative to the attenuated pathogens (most popular live vectors actually studied) which could recover their pathogenic potential and are thus not totally safe for use in humans. This chapter reviews the current research and advances in the use of LAB as live delivery vectors of proteins of interest for the development of new safe mucosal vaccines. The use of LAB as DNA vaccine vehicles to deliver DNA directly to antigen-presenting cells of the immune system is also discussed.

  7. Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys.

    PubMed

    Barouch, Dan H; Ghneim, Khader; Bosche, William J; Li, Yuan; Berkemeier, Brian; Hull, Michael; Bhattacharyya, Sanghamitra; Cameron, Mark; Liu, Jinyan; Smith, Kaitlin; Borducchi, Erica; Cabral, Crystal; Peter, Lauren; Brinkman, Amanda; Shetty, Mayuri; Li, Hualin; Gittens, Courtney; Baker, Chantelle; Wagner, Wendeline; Lewis, Mark G; Colantonio, Arnaud; Kang, Hyung-Joo; Li, Wenjun; Lifson, Jeffrey D; Piatak, Michael; Sekaly, Rafick-Pierre

    2016-04-21

    The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-β pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.

  8. Novel ways for immune intervention in immunotherapy: mucosal allergy vaccines.

    PubMed

    Mascarell, Laurent; Van Overtvelt, Laurence; Moingeon, Philippe

    2006-05-01

    Allergen-specific immunotherapy is currently the only curative treatment for allergy. Subcutaneous immunotherapy (SCIT) has been successfully used to treat patients who are allergic to insect venom, house dust mites, or tree or grass pollens. In the context of potentially severe, albeit infrequent, side effects associated with SCIT, mucosal routes of administration are being investigated to conduct allergenic desensitization. This article reviews recent developments in the field of nasal, oral, and sublingual immunotherapy as they relate to safety, clinical efficacy, and immune mechanisms of action. Implications for the design and development of improved allergy vaccines that could be used through such nonparenteral routes are discussed. Specifically, allergen presentation platforms and adjuvants facilitating the targeting of immune cells at mucosal surfaces to promote tolerance induction are reviewed.

  9. Induction of allergen-specific tolerance via mucosal routes.

    PubMed

    Mascarell, Laurent; Zimmer, Aline; Van Overtvelt, Laurence; Tourdot, Sophie; Moingeon, Philippe

    2011-01-01

    Allergen-specific immunotherapy is the only curative treatment of allergies against insect venom, house dust mites, tree/grass pollens, or cat dander. Subcutaneous immunotherapy is successful to reorient the immune system and re-establish long-term tolerance. However, major drawbacks for using this route include: repeated injections, as well as the risk of anaphylaxis. In this context, alternative mucosal routes of administration are being considered together with the combined use of adjuvants/vector systems and recombinant allergens or peptide fragments. Herein, we review the current status in the use of mucosal routes (i.e., sublingual, oral, intranasal) for allergen-specific immunotherapy, as well as the latest understanding with respect to underlying mechanisms of action.

  10. Mucosal Immunity in the Female Genital Tract, HIV/AIDS

    PubMed Central

    Reis Machado, Juliana; da Silva, Marcos Vinícius; Cavellani, Camila Lourencini; Antônia dos Reis, Marlene; Monteiro, Maria Luiza Gonçalves dos Reis; Teixeira, Vicente de Paula Antunes; Rosa Miranda Corrêa, Rosana

    2014-01-01

    Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs. PMID:25313360

  11. Mucosal Schwann cell “Hamartoma”: A new entity?

    PubMed Central

    Pasquini, Paola; Baiocchini, Andrea; Falasca, Laura; Annibali, Dante; Gimbo, Guido; Pace, Francesco; Nonno, Franca Del

    2009-01-01

    Schwannoma is a well-described, benign nerve sheath tumor of the soft tissue, but is rare in the gastrointestinal tract. Gastrointestinal schwannomas are often incidentally discovered as small polypoid intraluminal lesions. In this report, we describe the clinicopathologic and immunohistochemical features of a distinctive neural mucosal polyp composed of a diffuse cellular proliferation of uniform bland spindled cells in the lamina propria that entraps the colonic crypts. Immunohistochemical analysis revealed strong and diffuse positivity for the S-100 protein. To avoid confusion of these solitary colorectal polyps containing pure spindled Schwann cell proliferation in the lamina propria with neural lesions that have significant association with inherited syndromes, it is better to use the designation “mucosal Schwann hamartoma”. PMID:19437573

  12. [Miltefosine versus meglumine antimoniate in the treatment of mucosal leishmaniasis].

    PubMed

    Garcia Bustos, Maria F; Barrio, Alejandra; Parodi, Cecilia; Beckar, Josefina; Moreno, Sonia; Basombrio, Miguel A

    2014-01-01

    The conventional treatment for tegumentary leishmaniasis is meglumine antimoniate, which needs parenteral administration, has increased therapeutic failure, and produces serious adverse effects, justifying the search for therapeutic alternatives. We report here the preliminary results of a phase II clinical trial in patients with mucosal leishmaniasis, in which the efficacy of oral miltefosine versus the antimonial compound was assessed. The evaluation of response to the treatment was performed by monitoring with nasopharyngeal video-fibroscopy, using a score of mucosal injury severity for patients at each follow-up point. We found no significant differences so far between the number of patients cured with miltefosine or conventional chemotherapy. The favorable results of this study suggest that miltefosine could be an effective and safe oral therapeutic alternative in the region.

  13. The role of Th17 cytokines in primary mucosal immunity

    PubMed Central

    Kolls, Jay K.; Khader, Shabaana A.

    2010-01-01

    The T helper type 17 (Th17) lineage of CD4+ T-cells produce several effector molecules including IL-17A, IL-17F, IL-21, and IL-22. In addition to CD4+, αβ T-cells, these cytokines can be produced by natural killer and γδ T-cells. These effector cytokines can be produced rapidly upon infection at mucosal sites and evidence to date strongly implicates that this arm of the immune system plays a critical role in mucosal immunity to many extracellular pathogens. Moreover these cytokines can also coordinate adaptive immunity to some intracellular pathogens. In this review, we will highlight recent progress in our understanding of these cytokines, and mechanisms of their effector function in the mucosa. PMID:21095154

  14. [Mucosal healling: a realistic aim or marketing myth?].

    PubMed

    García-Sánchez, Valle; Iglesias-Flores, Eva

    2011-12-01

    The classical aim of the treatment of ulcerative colitis is to induce and maintain remission. However, this aim has not been shown to prevent long-term complications. Current treatment goals attempt to prevent complications. In some studies, healing of the intestinal mucosa has been shown to improve long-term outcomes. In ulcerative colitis, mucosal healing reduces recurrence, the risk of colorectal cancer and the need for surgery, and improves patients' quality of life. The drugs for which there is greatest evidence of their efficacy in inducing and maintaining mucosal healing are salicylates and biological agents. In the near future, endoscopic monitoring may be required to evaluate response to the treatment and decisions may have to be taken according to the persistence or disappearance of these lesions.

  15. Cultivation of Human Oral Mucosal Explants on Contact Lenses.

    PubMed

    Zsebik, Barbara; Ujlaky-Nagy, László; Losonczy, Gergely; Vereb, György; Takács, Lili

    2017-03-24

    Purpose/Aim: Autologous cultivated oral mucosal (OM) epithelial transplantation has been successfully used as corneal epithelial replacement in bilateral limbal stem cell deficiency. Recently, lotrafilcon A contact lens (CL) surface was described as a suitable carrier for cultured stem cells in corneal epithelial transplantation. Our aim was to establish explant cultures from human OM on CL carriers that are free of animal-derived materials and feeder cells.

  16. What interactions drive the salivary mucosal pellicle formation?

    PubMed Central

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

    2014-01-01

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

  17. Metabolism of 7-ethyoxycoumarin by Isolated Perfused Rainbow Trout Livers

    EPA Science Inventory

    Isolated trout livers were perfused using methods designed to preserve tissue viability and function. Liver performance was evaluated by measuring O2 consumption, vascular resistance, K+ leakage, glucose flux, lactate flux, alanine aminotransferase leakage, and metabolic clearanc...

  18. Hemangioma of the tongue demonstrating a perfusion blood pool mismatch

    SciTech Connect

    Front, D.; Groshar, D.; Israel, O.; Robinson, E.

    1986-02-01

    Perfusion blood pool mismatch using Tc-99m labeled red blood cells (RBCs) in a hemangioma of the tongue is described. The method is useful in the evaluation of size of the residual blood pool after irradiation of the tumor.

  19. JAM-related proteins in mucosal homeostasis and inflammation.

    PubMed

    Luissint, Anny-Claude; Nusrat, Asma; Parkos, Charles A

    2014-03-01

    Mucosal surfaces are lined by epithelial cells that form a physical barrier protecting the body against external noxious substances and pathogens. At a molecular level, the mucosal barrier is regulated by tight junctions (TJs) that seal the paracellular space between adjacent epithelial cells. Transmembrane proteins within TJs include junctional adhesion molecules (JAMs) that belong to the cortical thymocyte marker for Xenopus family of proteins. JAM family encompasses three classical members (JAM-A, JAM-B, and JAM-C) and related molecules including JAM4, JAM-like protein, Coxsackie and adenovirus receptor (CAR), CAR-like membrane protein and endothelial cell-selective adhesion molecule. JAMs have multiple functions that include regulation of endothelial and epithelial paracellular permeability, leukocyte recruitment during inflammation, angiogenesis, cell migration, and proliferation. In this review, we summarize the current knowledge regarding the roles of the JAM family members in the regulation of mucosal homeostasis and leukocyte trafficking with a particular emphasis on barrier function and its perturbation during pathological inflammation.

  20. Small intestinal mucosal abnormalities in post-perinatal deaths.

    PubMed Central

    Variend, S; Sunderland, R

    1984-01-01

    Examination of small intestinal mucosa from cases of post-perinatal death in Sheffield between September 1980 and September 1981 showed mucosal changes before death in 18 of 78 cases (20%). There was no significant difference in prevalence between explained and unexplained deaths, nor was there any positive association with viral isolation from the small intestine. The lesion was much more common in males than females and showed a strong association with bottle feeding--no infant wholly breast fed showed an enteropathy. There was a low incidence of symptoms referrable to the gastrointestinal tract among affected infants, and no appreciable evidence of failure to thrive, as reflected by the postmortem body weight, was present. Mucosal changes of the small intestine in cases of sudden infant death syndrome have previously been reported and attributed to heatstroke. Although the finding of similar lesions in infants who died explicably does not appear to support this view, overheating is difficult to exclude as most of the explained deaths with a mucosal lesion occurred at home. Images PMID:6699191

  1. Oral complications of cancer therapies. Management of mucositis during therapy

    SciTech Connect

    Miaskowski, C. )

    1990-01-01

    This paper reviews the purposes of an oral care protocol, the major components of an oral care regimen, and oral care protocols and studies done to date. Many questions remain in the area of optimal oral care for the patient experiencing mucositis as a sequela of cancer treatment. Research is needed on types and use of mouth rinses, effective, harmless, and pleasant lip lubricants, appropriate analgesic and anti-inflammatory combinations, and the effectiveness of a variety of devices for oral cleansing, to name a few areas. As outpatient oncology services grow, oral care protocols must be developed to meet the needs of ambulatory patient populations. Oral care regimens must be safe, easy to use, and economical as well as effective to ensure patient and staff compliance. Research on the management of mucositis must be conducted in both inpatient and outpatient settings. Finally, in order to obtain sufficient sample sizes and optimize data collection, these studies will need to be conducted by multidisciplinary teams (including dentists, oncologists, radiation therapists, and nurses) across multiple sites. Not until large-scale clinical trials are done on the treatment of mucositis will we be able to optimize the therapeutic regimen for the patient. 43 references.

  2. Enhancing the buccal mucosal delivery of peptide and protein therapeutics.

    PubMed

    Caon, Thiago; Jin, Liang; Simões, Cláudia M O; Norton, Raymond S; Nicolazzo, Joseph A

    2015-01-01

    With continuing advances in biotechnology and genetic engineering, there has been a dramatic increase in the availability of new biomacromolecules, such as peptides and proteins that have the potential to ameliorate the symptoms of many poorly-treated diseases. Although most of these macromolecular therapeutics exhibit high potency, their large molecular mass, susceptibility to enzymatic degradation, immunogenicity and tendency to undergo aggregation, adsorption, and denaturation have limited their ability to be administered via the traditional oral route. As a result, alternative noninvasive routes have been investigated for the systemic delivery of these macromolecules, one of which is the buccal mucosa. The buccal mucosa offers a number of advantages over the oral route, making it attractive for the delivery of peptides and proteins. However, the buccal mucosa still exhibits some permeability-limiting properties, and therefore various methods have been explored to enhance the delivery of macromolecules via this route, including the use of chemical penetration enhancers, physical methods, particulate systems and mucoadhesive formulations. The incorporation of anti-aggregating agents in buccal formulations also appears to show promise in other mucosal delivery systems, but has not yet been considered for buccal mucosal drug delivery. This review provides an update on recent approaches that have shown promise in enhancing the buccal mucosal transport of macromolecules, with a major focus on proteins and peptides.

  3. Cancer patients with oral mucositis: challenges for nursing care1

    PubMed Central

    Araújo, Sarah Nilkece Mesquita; Luz, Maria Helena Barros Araújo; da Silva, Grazielle Roberta Freitas; Andrade, Elaine Maria Leite Rangel; Nunes, Lívio César Cunha; Moura, Renata Oliveira

    2015-01-01

    OBJECTIVE: to analyze nursing care provided to cancer patients with oral mucositis based on the Nursing Process (NP). METHOD: this exploratory, descriptive, cross-sectional and quantitative study was conducted with 213 patients undergoing chemotherapy and/or radiotherapy in two cancer facilities: one philanthropic and one private service. RESULTS: the participants were mainly female, aged 45.8 years old on average, with up to 11 years of schooling and income of up to one times the minimum wage. Severe mucositis was related to chemotherapy associated with radiotherapy. Only 25.3% of the patients reported having received guidance from nurses during their treatment concerning self-care. The perceptions of patients regarding quality of care did not significantly differ between the private and public facilities. The basic human needs mainly affected were comfort, eating, and hygiene. Based on this finding, one NP was established listing the diagnoses, interventions and expected results to establish an ideal, though individualized, standard of nursing care to be provided to these patients. CONCLUSION: to understand oral mucositis is crucial to establish nursing care that includes prevention based on the implementation of an oral care plan. PMID:26039297

  4. Intestinal epithelial cells and their role in innate mucosal immunity.

    PubMed

    Maldonado-Contreras, A L; McCormick, Beth A

    2011-01-01

    The mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts are covered by a layer of epithelial cells that are responsible for sensing and promoting a host immune response in order to establish the limits not only for commensal microorganisms but also for foreign organisms or particles. This is a remarkable task as the human body represents a composite of about 10 trillion human-self cells plus non-self cells from autochthonous or indigenous microbes that outnumber human cells 10:1. Hence, the homeostasis of epithelial cells that line mucosal surfaces relies on a fine-tuned immune system that patrols the boundaries between human and microbial cells. In the case of the intestine, the epithelial layer is composed of at least six epithelial cell lineages that act as a physiological barrier in addition to aiding digestion and the absorption of nutrients, water and electrolytes. In this review, we highlight the immense role of the intestinal epithelium in coordinating the mucosal innate immune response.

  5. Strategies for Preventing Mucosal Cell-Associated HIV Transmission

    PubMed Central

    Whaley, Kevin J.; Mayer, Kenneth H.

    2014-01-01

    Human immunodeficiency virus (HIV) may be transmitted through either cell-free virions or leukocytes harboring intracellular HIV in bodily fluids. In recent years, the early initiation of combination antiretroviral therapy leading to virological suppression has resulted in decreased HIV transmission to uninfected partners. Additionally, the efficacy of primary chemoprophylaxis with oral or topical antiretroviral regimens containing tenofovir (with or without emtricitabine) has been demonstrated. However, the efficacy of these approaches may be compromised by suboptimal adherence, decreased drug concentrations in mucosal compartments in women, and genital inflammation. Furthermore, in vitro studies on the effects of tenofovir on cell-associated HIV transmission have produced conflicting results. Preclinical studies suggest that combination preventive approaches may be most effective in stopping the transmission of HIV after mucosal exposure. Since the development of antibodies were found to correlate with protection in the only effective HIV vaccine trial, the administration of preformed mucosal and systemic antibodies may inform the development of safe and effective antibody-based oral, topical, and/or systemic preexposure prophylaxis agents and provide guidance in the development of HIV vaccines that effectively block cell-associated HIV transmission. PMID:25414423

  6. JAM related proteins in mucosal homeostasis and inflammation

    PubMed Central

    Luissint, Anny-Claude; Nusrat, Asma; Parkos, Charles A.

    2014-01-01

    Mucosal surfaces are lined by epithelial cells that form a physical barrier protecting the body against external noxious substances and pathogens. At a molecular level, the mucosal barrier is regulated by tight junctions (TJs) that seal the paracellular space between adjacent epithelial cells. Transmembrane proteins within TJs include Junctional Adhesion Molecules (JAMs) that belong to the CTX (Cortical Thymocyte marker for Xenopus) family of proteins. JAM family encompasses three classical members (JAM-A, -B and –C) and related molecules including JAM4, JAM-Like protein (JAM-L), Coxsackie and Adenovirus Receptor (CAR), CAR-Like Membrane Protein (CLMP) and Endothelial cell-Selective Adhesion Molecule (ESAM). JAMs have multiple functions that include regulation of endothelial and epithelial paracellular permeability, leukocyte recruitment during inflammation, angiogenesis, cell migration and proliferation. In this review, we summarize the current knowledge regarding the roles of the JAM family members in the regulation of mucosal homeostasis and leukocyte trafficking with a particular emphasis on barrier function and its perturbation during pathological inflammation. PMID:24667924

  7. Feline immunodeficiency virus clade C mucosal transmission and disease courses.

    PubMed

    Obert, L A; Hoover, E A

    2000-05-01

    The transmissibility and pathogenicity of a clade C feline immunodeficiency virus (FIV-C) was examined via the oral-nasal, vaginal, or rectal mucosa. FIV-C was transmissible by all three mucosal routes. Vaginal transmission was most efficient (100%), oral exposure resulted in a 80% infection rate, and rectal transmission was least effective (44%). In contrast to previous intravenous passage studies, a broader range of host-virus relationships was observed after mucosal exposure. Three categories of FIV-C infection were defined: (1) rapidly progressive infection marked by high virus burdens and rapid CD4+ cell depletion (43% of vaginally exposed animals); (2) conventional (typical) infection featuring slowly progressive CD4+ cell decline (61% of all exposed animals); and (3) regressive (transient) infection marked by low and then barely detectable virus burdens and no CD4+ cell alterations (22% of rectally inoculated cats). These disease courses appear to have parallels in mucosal HIV and SIV infections, emphasizing the importance of the virus-mucosa interface in lentiviral pathogenesis.

  8. Plausibility of HIV-1 Infection of Oral Mucosal Epithelial Cells

    PubMed Central

    Herzberg, M.C.; Vacharaksa, A.; Gebhard, K.H.; Giacaman, R.A.; Ross, K.F.

    2011-01-01

    The AIDS pandemic continues. Little is understood about how HIV gains access to permissive cells across mucosal surfaces, yet such knowledge is crucial to the development of successful topical anti-HIV-1 agents and mucosal vaccines. HIV-1 rapidly internalizes and integrates into the mucosal keratinocyte genome, and integrated copies of HIV-1 persist upon cell passage. The virus does not appear to replicate, and the infection may become latent. Interactions between HIV-1 and oral keratinocytes have been modeled in the context of key environmental factors, including putative copathogens and saliva. In keratinocytes, HIV-1 internalizes within minutes; in saliva, an infectious fraction escapes inactivation and is harbored and transferable to permissive target cells for up to 48 hours. When incubated with the common oral pathogen Porphyromonas gingivalis, CCR5− oral keratinocytes signal through protease-activated receptors and Toll-like receptors to induce expression of CCR5, which increases selective uptake of infectious R5-tropic HIV-1 into oral keratinocytes and transfer to permissive cells. Hence, oral keratinocytes—like squamous keratinocytes of other tissues—may be targets for low-level HIV-1 internalization and subsequent dissemination by transfer to permissive cells. PMID:21441479

  9. Cell-associated HIV mucosal transmission: the neglected pathway.

    PubMed

    Anderson, Deborah J; Le Grand, Roger

    2014-12-15

    This supplement to The Journal of Infectious Diseases is devoted to the important and understudied topic of cell-associated human immunodeficiency virus Type 1 (HIV) mucosal transmission. It stems from a workshop held in Boston, Massachusetts, in October 2013, in which scientists discussed their research and insights regarding cell-associated HIV mucosal transmission. The 10 articles in this supplement present the case for cell-associated HIV transmission as an important element contributing to the HIV epidemic, review evidence for the efficacy of current HIV prevention strategies against cell-associated HIV transmission and opportunities for further development, and describe in vitro, ex vivo, and animal cell-associated transmission models that can be used to further elucidate the molecular mechanisms of cell-associated HIV mucosal transmission and test HIV prevention strategies. We hope that these articles will help to inform and invigorate the HIV prevention field and contribute to the development of more-effective vaccine, treatment, and microbicide strategies for HIV prevention.

  10. Arterial Perfusion Imaging-Defined Subvolume of Intrahepatic Cancer

    PubMed Central

    Wang, Hesheng; Farjam, Reza; Feng, Mary; Hussain, Hero; Ten Haken, Randall K.; Lawrence, Theodore S.; Cao, Yue

    2014-01-01

    Purpose To assess whether an increase in a subvolume of intrahepatic tumor with elevated arterial perfusion during radiation therapy (RT) predicts tumor progression post RT. Methods and Materials Twenty patients with unresectable intrahepatic cancers undergoing RT were enrolled in a prospective IRB-approved study. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) were performed prior to RT (pre-RT), after delivering ~60% of the planned dose (mid-RT) and one month after completion of RT to quantify hepatic arterial perfusion. The arterial perfusions of the tumors at pre-RT were clustered into low-normal and elevated perfusion by a fuzzy clustering-based method, and the tumor subvolumes with elevated arterial perfusion were extracted from the hepatic arterial perfusion images. The percentage changes in the tumor subvolumes and means of arterial perfusion over the tumors from pre-RT to mid-RT were evaluated for predicting tumor progression post-RT. Results Of the 24 tumors, 6 tumors in 5 patients progressed 5–21 months after RT completion. Neither tumor volumes nor means of tumor arterial perfusion at pre-RT were predictive of treatment outcome. The mean arterial perfusion over the tumors increased significantly at mid-RT in progressive tumors comparing to the responsive ones (p=0.006). From pre-RT to mid-RT, the responsive tumors had a decrease in the tumor subvolumes with elevated arterial perfusion (median: −14%, range: −75% – 65%), while the progressing tumors had an increase of the subvolumes (median: 57%, range: −7% – 165%) (p=0.003). Receiver operating characteristic (ROC) analysis of the percentage change in the subvolume for predicting tumor progression post-RT had an area under the curve (AUC) of 0.90. Conclusion The increase in the subvolume of the intrahepatic tumor with elevated arterial perfusion during RT has the potential to be a predictor for tumor progression post-RT. The tumor subvolume could be a radiation boost candidate

  11. Effects of physical training on myocardial vascularity and perfusion.

    PubMed

    Scheuer, J

    1982-09-01

    Physical training is thought to be a stimulus for coronary vascular growth and coronary collateral development. This report is a summary of knowledge in the area. Studies in experimental animals with normal hearts indicate that physical training promotes increased myocardial capillary density and also causes enlargement of the surface coronary vessels. The physiologic effect of these changes on coronary vascular reserve and protection of segments of the heart against myocardial ischemia has not been established. Physically trained dogs and pigs do not appear to be protected against the effects of coronary occlusion, in that the ischemic area appears to be as large in trained animals as in untrained animals for any given coronary lesion. One study in physically trained rats appears to show protection against myocardial infarction, but whether this is related to coronary vascular changes has not been established. Experiments in dogs subjected to chronic narrowing or gradual occlusion demonstrate that physical training in these models does promote collateral blood flow as measured by retrograde flow in open-chest experiments. Studies using the microsphere technique in closed-chest animals confirms increased collateral flow to ischemic areas in some animals, but the magnitude of the increases appears to be small and varies greatly from animal to animal. Studies in athletes suggest that myocardial blood flow is lower at any submaximal level of training in athletes than in sedentary persons. Studies in patients with coronary artery disease have generally failed to show an increase in coronary blood flow or in perfusion of ischemic areas after physical training programs, but the techniques used might not have been sensitive enough to detect changes. The evidence in the experimental animals is sufficiently promising to indicate that the search should be continued to define physical training programs that will most stimulate myocardial vascularity and coronary collaterals

  12. Diurnal Curve of the Ocular Perfusion Pressure

    PubMed Central

    Moreira, TCA; Bezerra, BSP; Vianello, MP; Corradi, J; Dorairaj, SK; Prata, TS

    2016-01-01

    ABSTRACT Purpose: To describe the diurnal variation of the ocular perfusion pressure (OPP) in normal, suspects and glaucoma patients. Materials and methods: Seventy-nine subjects were enrolled in a prospective study. The diurnal curve of intraocular pressure (IOP) was performed and blood pressure measurements were obtained. Each participant was grouped into one of the following based upon the clinical evaluation of the optic disk, IOP and standard achromatic perimetry (SAP): 18 eyes were classified as normal (normal SAP, normal optic disk evaluation and IOP < 21 mm Hg in two different measurements), 30 eyes as glaucoma suspect (GS) (normal SAP and mean deviation (MD), C/D ration > 0.5 or asymmetry > 0.2 and/or ocular hypertension), 31 eyes as early glaucoma (MD < -6 dB, glaucomatous optic neuropathy and SAP and MDs on SAP. Standard achromatic perimetry was performed with the Octopus 3.1.1 Dynamic 24-2 program. Intraocular pressure and blood pressure measurements were taken at 6 am, 9 am, 12, 3 and 6 pm. The patients stayed in the seated position for 5 minutes prior to blood pressure measurements. Results: The mean IOP values in all groups did not follow any regular pattern. The peak IOP was found to be greater in suspect [18.70 ± 3.31 (mm Hg ± SD)] and glaucoma (18.77 ± 4.30 mm Hg) patients as compared to normal subjects (16.11 ± 2.27 mm Hg). In studying the diurnal variation of the OPP, we found lower values at 3 pm in normals (34.21 ± 2.07 mm Hg), at 9 am in suspects (54.35 ± 3.32 mm Hg) and at 12 pm in glaucoma patients (34.84 ± 1.44 mm Hg). Conclusion: Each group has a specific OPP variation during the day with the most homogeneous group being the suspect one. It is important to keep studying the IOP and OPP variation for increased comprehension of the pathophysiology of glaucomatous optic neuropathy. How to cite this article: Kanadani FN, Moreira TCA, Bezerra BSP, Vianello MP, Corradi J, Dorairaj SK, Prata TS. Diurnal Curve of the Ocular Perfusion

  13. Perfusion Electronic Record Documentation Using Epic Systems Software.

    PubMed

    Steffens, Thomas G; Gunser, John M; Saviello, George M

    2015-12-01

    This paper describes the design and use of Epic Systems software for documentation of perfusion activities as part of the patient electronic medical record. The University of Wisconsin Hospital and Clinics adapted the Anesthesia software module and developed an integrated perfusion/anesthesia record for the documentation of cardiac and non-cardiac surgical procedures. This project involved multiple committees, approvals, and training to successfully implement. This article will describe our documentation options, concepts, design, challenges, training, and implementation during our initial experience.

  14. Perfusion characteristics of preserved canine kidneys subjected to warm ischaemia.

    PubMed

    Modgill, V K; Wiggins, P A; Giles, G R

    1978-02-01

    Canine kidneys were subjected to 0, 15 or 30 min of warm ischaemia followed by 24 hours preservation by perfusion. Changes in perfusate concentration of acid radicles, lactate, free fatty acid and lactice dehydrogenase were assessed at 1 hour and 24 hours. With the exception of LDH concentration at 1 hour, no single parameter was capable of detecting kidneys which were so damaged as to be non-life supporting.

  15. Assessment of lung tumor response by perfusion CT.

    PubMed

    Coche, E

    2013-01-01

    Perfusion CT permits evaluation of lung cancer angiogenesis and response to therapy by demonstrating alterations in lung tumor vascularity. It is advocated that perfusion CT performed shortly after initiating therapy may provide a better evaluation of physiological changes rather than the conventional size assessment obtained with RECIST. The radiation dose,the volume of contrast medium delivered to the patient and the reproducibility of blood flow parameters remain an issue for this type of investigation.

  16. Predictive Computational Modeling of the Mucosal Immune Responses during Helicobacter pylori Infection

    PubMed Central

    Carbo, Adria; Bassaganya-Riera, Josep; Pedragosa, Mireia; Viladomiu, Monica; Marathe, Madhav; Eubank, Stephen; Wendelsdorf, Katherine; Bisset, Keith; Hoops, Stefan; Deng, Xinwei; Alam, Maksudul; Kronsteiner, Barbara; Mei, Yongguo; Hontecillas, Raquel

    2013-01-01

    T helper (Th) cells play a major role in the immune response and pathology at the gastric mucosa during Helicobacter pylori infection. There is a limited mechanistic understanding regarding the contributions of CD4+ T cell subsets to gastritis development during H. pylori colonization. We used two computational approaches: ordinary differential equation (ODE)-based and agent-based modeling (ABM) to study the mechanisms underlying cellular immune responses to H. pylori and how CD4+ T cell subsets influenced initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN) on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamics of effector and regulatory pathways in the gastric lamina propria (LP) in silico. Simulation results show the induction of a Th17 response and a dominant Th1 response, together with a regulatory response characterized by high levels of mucosal Treg) cells. We also investigated the potential role of peroxisome proliferator-activated receptor γ (PPARγ) activation on the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPARγ knockout system when compared to the wild-type simulation. Spatio-temporal, object-oriented ABM approaches suggested similar dynamics in induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, sensitivity analysis predicted a crucial contribution of Th1 and Th17 effector responses as mediators of histopathological changes in the gastric mucosa during chronic stages of infection, which were experimentally validated in mice. These integrated immunoinformatics approaches characterized the

  17. Predictive computational modeling of the mucosal immune responses during Helicobacter pylori infection.

    PubMed

    Carbo, Adria; Bassaganya-Riera, Josep; Pedragosa, Mireia; Viladomiu, Monica; Marathe, Madhav; Eubank, Stephen; Wendelsdorf, Katherine; Bisset, Keith; Hoops, Stefan; Deng, Xinwei; Alam, Maksudul; Kronsteiner, Barbara; Mei, Yongguo; Hontecillas, Raquel

    2013-01-01

    T helper (Th) cells play a major role in the immune response and pathology at the gastric mucosa during Helicobacter pylori infection. There is a limited mechanistic understanding regarding the contributions of CD4+ T cell subsets to gastritis development during H. pylori colonization. We used two computational approaches: ordinary differential equation (ODE)-based and agent-based modeling (ABM) to study the mechanisms underlying cellular immune responses to H. pylori and how CD4+ T cell subsets influenced initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN) on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamics of effector and regulatory pathways in the gastric lamina propria (LP) in silico. Simulation results show the induction of a Th17 response and a dominant Th1 response, together with a regulatory response characterized by high levels of mucosal Treg) cells. We also investigated the potential role of peroxisome proliferator-activated receptor γ (PPARγ) activation on the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPARγ knockout system when compared to the wild-type simulation. Spatio-temporal, object-oriented ABM approaches suggested similar dynamics in induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, sensitivity analysis predicted a crucial contribution of Th1 and Th17 effector responses as mediators of histopathological changes in the gastric mucosa during chronic stages of infection, which were experimentally validated in mice. These integrated immunoinformatics approaches characterized the

  18. Risk analysis, diagnosis and management of gastrointestinal mucositis in pediatric cancer patients.

    PubMed

    Kuiken, Nicoline S S; Rings, Edmond H H M; Tissing, Wim J E

    2015-04-01

    Mucositis is a complex inflammatory reaction of the mucous membranes of the alimentary tract upon chemotherapy and radiotherapy treatment in oncology patients. Mucositis can be subdivided in oral and gastrointestinal mucositis (GI mucositis). The damage to the gastrointestinal tract compromises the intestinal function and thereby the nutritional status and the quality of life, and eventually affects survival. The literature on GI mucositis focuses mainly on adults. This review focuses on data available on GI mucositis in pediatric cancer patients. An evaluation of the clinical presentation and consequences of GI mucositis in children is outlined. The review summarizes key issues for clinicians with respect to risk analysis for developing mucositis and the diagnosis of this condition in children. Information on these issues is obtained from clinical trials in children and adults, and from animal models. Diagnostic tools and assessment of severity of GI mucositis in children is elaborated on. Furthermore, the clinical management of the symptoms and consequences of GI mucositis in children, with specific focus on nutritional support, are discussed.

  19. An Overview of Challenges Limiting the Design of Protective Mucosal Vaccines for Finfish

    PubMed Central

    Munang’andu, Hetron Mweemba; Mutoloki, Stephen; Evensen, Øystein

    2015-01-01

    Research in mucosal vaccination in finfish has gained prominence in the last decade in pursuit of mucosal vaccines that would lengthen the duration of protective immunity in vaccinated fish. However, injectable vaccines have continued to dominate in the vaccination of finfish because they are perceived to be more protective than mucosal vaccines. Therefore, it has become important to identify the factors that limit developing protective mucosal vaccines in finfish as an overture to identifying key areas that require optimization in mucosal vaccine design. Some of the factors that limit the success for designing protective mucosal vaccines for finfish identified in this review include the lack optimized protective antigen doses for mucosal vaccines, absence of immunostimulants able to enhance the performance of non-replicative mucosal vaccines, reduction of systemic antibodies due to prolonged exposure to oral vaccination and the lack of predefined correlates of protective immunity for use in the optimization of newly developed mucosal vaccines. This review also points out the need to develop prime-boost vaccination regimes able to induce long-term protective immunity in vaccinated fish. By overcoming some of the obstacles identified herein, it is anticipated that future mucosal vaccines shall be designed to induce long-term protective immunity in finfish. PMID:26557121

  20. Quantitative measurement of tissue perfusion and diffusion in vivo.

    PubMed

    Chenevert, T L; Pipe, J G; Williams, D M; Brunberg, J A

    1991-01-01

    Magnetic resonance imaging techniques designed for sensitivity to microscopic motions of water diffusion and blood flow in the capillary network are also exceptionally sensitive to bulk motion properties of the tissue, which may lead to contrast artifact and large quantitative errors. The magnitude of bulk motion error that exists in human brain perfusion/diffusion imaging and the inability of cardiac gating to adequately control this motion are demonstrated by direct measurement of phase stability of voxels localized in the brain. Two methods are introduced to reduce bulk motion phase error. The first, a postprocessing phase correction algorithm, reduces coarse phase error but is inadequate by itself for quantitative perfusion/diffusion MRI. The second method employs orthogonal slice selection gradients to define a column of tissue in the object, from which echoes may be combined in a phase-insensitive manner to measure more reliably the targeted signal attenuation. Applying this acquisition technique and a simplistic model of perfusion and diffusion signal attenuations yields an estimated perfusion fraction of 3.4 +/- 1.1% and diffusion coefficient of 1.1 +/- 0.2 x 10(-5) cm2/s in the white matter of one normal volunteer. Successful separation of perfusion and diffusion effects by this technique is supported in a dynamic study of calf muscle. Periods of normal blood flow, low flow, and reactive hyperemia are clearly distinguished in the quantitative perfusion results, whereas measured diffusion remained nearly constant.

  1. Goal-directed-perfusion in neonatal aortic arch surgery

    PubMed Central

    Purbojo, Ariawan; Muench, Frank; Juengert, Joerg; Rueffer, André

    2016-01-01

    Reduction of mortality and morbidity in congenital cardiac surgery has always been and remains a major target for the complete team involved. As operative techniques are more and more standardized and refined, surgical risk and associated complication rates have constantly been reduced to an acceptable level but are both still present. Aortic arch surgery in neonates seems to be of particular interest, because perfusion techniques differ widely among institutions and an ideal form of a so called “total body perfusion (TBP)” is somewhat difficult to achieve. Thus concepts of deep hypothermic circulatory arrest (DHCA), regional cerebral perfusion (RCP/with cardioplegic cardiac arrest or on the perfused beating heart) and TBP exist in parallel and all carry an individual risk for organ damage related to perfusion management, chosen core temperature and time on bypass. Patient safety relies more and more on adequate end organ perfusion on cardiopulmonary bypass, especially sensitive organs like the brain, heart, kidney, liver and the gut, whereby on adequate tissue protection, temperature management and oxygen delivery should be visualized and monitored. PMID:27709094

  2. Quantitative Analysis of Peripheral Tissue Perfusion Using Spatiotemporal Molecular Dynamics

    PubMed Central

    Lee, Jungsul; Koh, Gou Young; Kwon, Kihwan; Choi, Chulhee

    2009-01-01

    Background Accurate measurement of peripheral tissue perfusion is challenging but necessary to diagnose peripheral vascular insufficiency. Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging. Methodology/Principal Findings We developed a new optical imaging-based strategy for quantitative measurement of peripheral tissue perfusion by time-series analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green (ICG). Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model. Mathematical modeling and computational simulations were used for translating time-series ICG images into quantitative pixel perfusion rates and a perfusion map. We could successfully predict the prognosis of ischemic hindlimbs based on the perfusion profiles obtained immediately after surgery, which were dependent on the preexisting collaterals. This method also reflected increases in perfusion and improvements in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial growth factor and COMP-angiopoietin-1. Conclusions/Significance We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis. PMID:19169354

  3. Myocardial perfusion echocardiography and coronary microvascular dysfunction

    PubMed Central

    Barletta, Giuseppe; Del Bene, Maria Riccarda

    2015-01-01

    Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking. PMID:26730291

  4. Perfusion Angiography in Acute Ischemic Stroke

    PubMed Central

    Liebeskind, David S.

    2016-01-01

    Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and Tmax, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232

  5. Chemosaturation Percutaneous Hepatic Perfusion: A Systematic Review.

    PubMed

    Vogel, Arndt; Gupta, Sanjay; Zeile, Martin; von Haken, Rebecca; Brüning, Roland; Lotz, Gösta; Vahrmeijer, Alexander; Vogl, Thomas; Wacker, Frank

    2017-01-01

    The Hepatic CHEMOSAT(®) Delivery System is an innovative medical device for the treatment of patients with unresectable primary liver tumors or unresectable hepatic metastases from solid organ malignancies. This system is used to perform chemosaturation percutaneous hepatic perfusion (CS-PHP), a procedure in which a high dose of the chemotherapeutic agent melphalan is delivered directly to the liver while limiting systemic exposure. In a clinical trial program, CS-PHP with melphalan significantly improved hepatic progression-free survival in patients with unresectable hepatic metastases from ocular or cutaneous melanoma. Clinically meaningful hepatic responses were also observed in patients with hepatocellular carcinoma or neuroendocrine tumors. Furthermore, the results of published studies and case reports demonstrated that CS-PHP with melphalan resulted in favorable tumor response rates in a range of tumor histologies (ocular or cutaneous melanoma, colorectal cancer, and hepatobiliary tumors). Analyses of the safety profile of CS-PHP revealed that the most common adverse effects were hematologic events (thrombocytopenia, anemia, and neutropenia), which were clinically manageable. Taken together, these findings indicate that CS-PHP is a promising locoregional therapy for patients with primary and secondary liver tumors and has a acceptable safety profile.

  6. New Trends in Radionuclide Myocardial Perfusion Imaging

    PubMed Central

    Hung, Guang-Uei; Wang, Yuh-Feng; Su, Hung-Yi; Hsieh, Te-Chun; Ko, Chi-Lun; Yen, Ruoh-Fang

    2016-01-01

    Radionuclide myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) has been widely used clinically as one of the major functional imaging modalities for patients with coronary artery disease (CAD) for decades. Ample evidence has supported the use of MPI as a useful and important tool in the diagnosis, risk stratification and treatment planning for CAD. Although popular in the United States, MPI has become the most frequently used imaging modality among all nuclear medicine tests in Taiwan. However, it should be acknowledged that MPI SPECT does have its limitations. These include false-positive results due to certain artifacts, false-negative due to balanced ischemia, complexity and adverse reaction arising from current pharmacological stressors, time consuming nature of the imaging procedure, no blood flow quantitation and relatively high radiation exposure. The purpose of this article was to review the recent trends in nuclear cardiology, including the utilization of positron emission tomography (PET) for MPI, new stressor, new SPECT camera with higher resolution and higher sensitivity, dynamic SPECT protocol for blood flow quantitation, new software of phase analysis for evaluation of LV dyssynchrony, and measures utilized for reducing radiation exposure of MPI. PMID:27122946

  7. Myocardial perfusion assessment with contrast echocardiography

    NASA Astrophysics Data System (ADS)

    Desco, Manuel; Ledesma-Carbayo, Maria J.; Santos, Andres; Garcia-Fernandez, Miguel A.; Marcos-Alberca, Pedro; Malpica, Norberto; Antoranz, Jose C.; Garcia-Barreno, Pedro

    2001-05-01

    Assessment of intramyocardial perfusion by contrast echocardiography is a promising new technique that allows to obtain quantitative parameters for the assessment of ischemic disease. In this work, a new methodology and a software prototype developed for this task are presented. It has been validated with Coherent Contrast Imaging (CCI) images acquired with an Acuson Sequoia scanner. Contrast (Optison microbubbles) is injected continuously during the scan. 150 images are acquired using low mechanical index U/S pulses. A burst of high mechanical index pulses is used to destroy bubbles, thus allowing to detect the contrast wash-in. The stud is performed in two conditions: rest and pharmacologically induced stress. The software developed allows to visualized the study (cine) and to select several ROIs within the heart wall. The position of these ROIs along the cardiac cycle is automatically corrected on the basis of the gradient field, and they can also be manually corrected in case the automatic procedure fails. Time curves are analyzed according to a parametric model that incorporates both contrast inflow rate and cyclic variations. Preliminary clinical results on 80 patients have allowed us to identify normal and pathological patterns and to establish the correlation of quantitative parameters with the real diagnosis.

  8. Color-Doppler sonographic tissue perfusion measurements reveal significantly diminished renal cortical perfusion in kidneys with vesicoureteral reflux

    PubMed Central

    Scholbach, T. M.; Sachse, C.

    2016-01-01

    Vesicoureteral reflux (VUR) and its sequelae may lead to reduced renal perfusion and loss of renal function. Methods to describe and monitor tissue perfusion are needed. We investigated dynamic tissue perfusion measurement (DTPM) with the PixelFlux-software to measure microvascular changes in the renal cortex in 35 children with VUR and 28 healthy children. DTPM of defined horizontal slices of the renal cortex was carried out. A kidney was assigned to the “low grade reflux”-group if the reflux grade of the voiding cystourethrogram was 1 to 3 and to the “high grade reflux”-group if the reflux grade was 4 to 5. Kidneys with VUR showed a significantly reduced cortical perfusion. Compared to healthy kidneys, this decline reached in low and high grade refluxes within the proximal 50% of the cortex: 3% and 12 %, in the distal 50% of the cortex: 21% and 44 % and in the most distal 20 % of the cortex 41% and 44%. DTPM reveals a perfusion loss in kidneys depending on the degree of VUR, which is most pronounced in the peripheral cortex. Thus, DTPM offers the tool to evaluate microvascular perfusion, to help planning treatment decisions in children with VUR. PMID:27051133

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

    PubMed Central

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

    2004-01-01

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

  10. Chemotherapy-induced mucositis: the role of mucin secretion and regulation, and the enteric nervous system.

    PubMed

    Thorpe, Daniel; Stringer, Andrea; Butler, Ross

    2013-09-01

    Alimentary mucositis is a severe, dose-limiting, toxic side effect of cytotoxic chemotherapy and radiotherapy. Patients with mucositis often have reductions or breaks imposed on cytotoxic therapy, which may lead to reduced survival. Furthermore, there is an increased risk of infection and hospitalization, compounding the cost of treatment. There are currently limited therapeutic options for mucositis, and no effective prevention available. Mucin expression and secretion have been shown to be associated with mucositis. Furthermore, mucins exhibit protective effects on the alimentary tract through reducing mechanical and chemical stress, preventing bacterial overgrowth and penetration, and digestion of the mucosa. Additionally, a number of studies have implicated some key neurotransmitters in both mucositis and mucin secretion, suggesting that the enteric nervous system may also play a key role in the development of mucositis.

  11. Perfusion MRI Indexes Variability in the Functional Brain Effects of Theta-Burst Transcranial Magnetic Stimulation

    PubMed Central

    Gratton, Caterina; Lee, Taraz G.; Nomura, Emi M.; D’Esposito, Mark

    2014-01-01

    Transcranial Magnetic Stimulation (TMS) is an important tool for testing causal relationships in cognitive neuroscience research. However, the efficacy of TMS can be variable across individuals and difficult to measure. This variability is especially a challenge when TMS is applied to regions without well-characterized behavioral effects, such as in studies using TMS on multi-modal areas in intrinsic networks. Here, we examined whether perfusion fMRI recordings of Cerebral Blood Flow (CBF), a quantitative measure sensitive to slow functional changes, reliably index variability in the effects of stimulation. Twenty-seven participants each completed four combined TMS-fMRI sessions during which both resting state Blood Oxygen Level Dependent (BOLD) and perfusion Arterial Spin Labeling (ASL) scans were recorded. In each session after the first baseline day, continuous theta-burst TMS (TBS) was applied to one of three locations: left dorsolateral prefrontal cortex (L dlPFC), left anterior insula/frontal operculum (L aI/fO), or left primary somatosensory cortex (L S1). The two frontal targets are components of intrinsic networks and L S1 was used as an experimental control. CBF changes were measured both before and after TMS on each day from a series of interleaved resting state and perfusion scans. Although TBS led to weak selective increases under the coil in CBF measurements across the group, individual subjects showed wide variability in their responses. TBS-induced changes in rCBF were related to TBS-induced changes in functional connectivity of the relevant intrinsic networks measured during separate resting-state BOLD scans. This relationship was selective: CBF and functional connectivity of these networks were not related before TBS or after TBS to the experimental control region (S1). Furthermore, subject groups with different directions of CBF change after TBS showed distinct modulations in the functional interactions of targeted networks. These results suggest

  12. Parametric perfusion imaging based on low-cost ultrasound platform.

    PubMed

    Gu, Xiaolin; Zhong, Hui; Wan, Mingxi; Hu, Xiaowen; Lv, Dan; Shen, Liang; Zhang, Xiaomei

    2010-01-01

    In this study, we attempted to implement parametric perfusion imaging to quantify blood perfusion based on modified low-cost ultrasound platform. A novel ultrasound contrast-specific imaging method called pulse-inversion harmonic sum-squared-differences (PIHSSD) was proposed for improving the sensitivity for detecting contrast agents and the accuracy of parametric perfusion imaging, which combined pulse-inversion harmonic (PIH) with pulse-inversion sum-squared-differences (PISSD) threshold-based decision. PIHSSD method just involved simple operations including addition and multiplication and was easy to realize. The sequences of contrast images without logarithmic compression were used to acquire time intensity curves (TICs) from numerous equal-sized regions-of-interest (ROI) covering the entire image plane. Parametric perfusion images were obtained based on the parameters extracted from the TICs, including peak value (PV), area under curve (AUC), mean transit time (MTT), peak value time (PVT), peak width (PW) and climbing rate (CR). Flow phantom was used for validation and the results suggested that PIHSSD method provided 9.6 to 20.3 dB higher contrast-to-tissue ratio (CTR) than PIH method. The results of the experiments of rabbit kidney also showed that the CTR of PIHSSD images was higher than that of PIH images, and the parametric perfusion images based on PIHSSD method provided more accurate quantification of blood perfusion compared with those based on PIH and PISSD methods. It demonstrated that the parametric perfusion imaging achieved good performance though implemented on low-cost ultrasound platform. (E-mail: mxwan@mail.xjtu.edu.cn).

  13. Renal disposition of colistin in the isolated perfused rat kidney.

    PubMed

    Ma, Zheng; Wang, Jiping; Nation, Roger L; Li, Jian; Turnidge, John D; Coulthard, Kingsley; Milne, Robert W

    2009-07-01

    Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 microg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA], glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different concentrations. When perfused alone, the renal clearances (CL(R)) for colistin A and B (the major components of colistin) in control kidneys were constant and low (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios [CR, defined as CL(R)/(f(u) x GFR), where f(u) is the fraction of drug unbound in perfusate and GFR is the glomerular filtration rate] were significantly less than 1. It was concluded that there is net tubular reabsorption of colistin, and this exceeded the reabsorption of water. Less than 10% eliminated from perfusate was recovered in urine, suggesting considerable renal accumulation of colistin. The CR values for colistin were significantly increased when perfused with TEA (500 microM), Gly-Gly (833 microM), and HCl (2,500, 5,000, and 10,000 microM). It is proposed that renal reabsorption of colistin may involve organic cation transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly) and that the process is sensitive to the pH of urine.

  14. Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD: a randomised clinical trial

    PubMed Central

    Buggeskov, Katrine B; Sundskard, Martin M; Jonassen, Thomas; Andersen, Lars W; Secher, Niels H; Ravn, Hanne B; Steinbrüchel, Daniel A; Jakobsen, Janus C; Wetterslev, Jørn

    2016-01-01

    Introduction Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. Methods 90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital. Results 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes. Discussion Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing

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

    PubMed Central

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

    2016-01-01

    The human gut microbiota plays a pivotal role in the maintenance of health, but how the microbiota interacts with the host at the colorectal mucosa is poorly understood. We proposed that confocal laser endomicroscopy (CLE) might help to untangle this relationship by providing in vivo physiological information of the mucosa. We used CLE to evaluate the in vivo physiology of human colorectal mucosa, and the mucosal microbiota was quantified using 16 s rDNA pyrosequencing. The human mucosal microbiota agglomerated to three major clusters dominated by Prevotella, Bacteroides and Lactococcus. The mucosal microbiota clusters did not significantly correlate with the disease status or biopsy sites but closely correlated with the mucosal niche physiology, which was non-invasively revealed by CLE. Inflammation tilted two subnetworks within the mucosal microbiota. Infiltration of inflammatory cells significantly correlated with multiple components in the predicted metagenome, such as the VirD2 component of the type IV secretory pathway. Our data suggest that a close correlation exists between the mucosal microbiota and the colorectal mucosal physiology, and CLE is a clinically available tool that can be used to facilitate the study of the in vivo correlation between colorectal mucosal physiology and the mucosal microbiota. PMID:26916597

  16. Mucosal HIV transmission and vaccination strategies through oral compared to vaginal and rectal routes

    PubMed Central

    Yu, Mingke; Vajdy, Michael

    2010-01-01

    Importance of the field There are currently over thirty million people infected with HIV and there are no vaccines available to prevent HIV infections or disease. The genitourinary, rectal and oral mucosa are the mucosal HIV transmission routes. An effective vaccine that can induce both systemic and local mucosal immunity is generally accepted as a major means of protection against mucosal HIV transmission and AIDS. What the reader will gain Structure and cells that comprise the oral, vaginal and rectal mucosa pertaining to HIV transmission and vaccination strategies through each mucosal route to prevent mucosal and systemic infection will be discussed. Areas covered in this review Covering publications from 1980’s through 2010, mucosal transmission of HIV and current and previous approaches to vaccinations are discussed. Take home message Although oral transmission of HIV is far less common than vaginal and rectal transmissions, infections through this route do occur through oral sex as well as vertically from mother to child. Mucosal vaccination strategies against oral and other mucosal HIV transmissions are under intense research but the lack of consensus on immune correlates of protection and lack of safe and effective mucosal adjuvants and delivery systems hamper progress towards a licensed vaccine. PMID:20624114

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

    PubMed

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

    2017-03-01

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

  18. Mucosal Immunization with Liposome-Nucleic Acid Adjuvants Generates Effective Humoral and Cellular Immunity

    PubMed Central

    Henderson, Angela; Propst, Katie; Kedl, Ross; Dow, Steven

    2012-01-01

    Development of effective new mucosal vaccine adjuvants has become a priority with the increase in emerging viral and bacterial pathogens. We previously reported that cationic liposomes complexed with non-coding plasmid DNA (CLDC) were effective parenteral vaccine adjuvants. However, little is known regarding the ability of liposome-nucleic acid complexes to function as mucosal vaccine adjuvants, or the nature of the mucosal immune responses elicited by mucosal liposome-nucleic acid adjuvants. To address these questions, antibody and T cell responses were assessed in mice following intranasal immunization with CLDC-adjuvanted vaccines. The effects of CLDC adjuvant on antigen uptake, trafficking, and cytokine responses in the airways and draining lymph nodes were also assessed. We found that mucosal immunization with CLDC-adjuvanted vaccines effectively generated potent mucosal IgA antibody responses, as well as systemic IgG responses. Notably, mucosal immunization with CLDC adjuvant was very effective in generating strong and sustained antigen-specific CD8+ T cell responses in the airways of mice. Mucosal administration of CLDC vaccines also induced efficient uptake of antigen by DCs within the mediastinal lymph nodes. Finally, a killed bacterial vaccine adjuvanted with CLDC induced significant protection from lethal pulmonary challenge with Burkholderia pseudomallei. These findings suggest that liposome-nucleic acid adjuvants represent a promising new class of mucosal adjuvants for non-replicating vaccines, with notable efficiency at eliciting both humoral and cellular immune responses following intranasal administration. PMID:21600950

  19. Current Trends in the Management of Oral Mucositis Related to Cancer Treatment

    PubMed Central

    Biswal, Biswa Mohan

    2008-01-01

    Oral mucositis is one of the most common toxicities observed during radiotherapy and chemotherapy treatment for cancers. Mucositis results in sore mouth, altered taste sensation, pain and dysphagia leading to malnutrition. Left untreated, oral mucositis leads to ulceration, orodental infection, bleeding and discontinuation of effective radiotherapy or chemotherapy. Frequent hospitalization, enteral or parenteral nutrition, increased demand for analgesics ultimately account for increased cost of healthcare. Quantification of oral mucositis using standardized grading system is important for appropriate evaluation, reporting and management. In the recent past there is a paradigm shift in the pathobiology of cancer therapy related mucositis. Clear understanding of its pathogenesis is essential for the formulation of effective mucositis care. Numerous drug therapies, radiation techniques and oral care protocols have been tried in the past to reduce oral mucositis, None have proven to be consistently effective. Current trends for the prevention and treatment of oral mucositis is multi-targeted treatment supplemented by aggressive oral hygiene, reactive oxygen species (ROS) inhibitors, growth factors and use of specific topical agents to improve treatment of oral mucositis in future. PMID:22570584

  20. Fluid absorption in isolated perfused colonic crypts.

    PubMed Central

    Singh, S K; Binder, H J; Boron, W F; Geibel, J P

    1995-01-01

    A spatial segregation of ion transport processes between crypt and surface epithelial cells is well-accepted and integrated into physiological and pathophysiological paradigms of small and large intestinal function: Absorptive processes are believed to be located in surface (and villous) cells, whereas secretory processes are believed to be present in crypt cells. Validation of this model requires direct determination of fluid movement in intestinal crypts. This study describes the adaptation of techniques from renal tubule microperfusion to hand-dissect and perfuse single, isolated crypts from rat distal colon to measure directly fluid movement. Morphologic analyses of the isolated crypt preparation revealed no extraepithelial cellular elements derived from the lamina propria, including myofibroblasts. In the basal state, crypts exhibited net fluid absorption (mean net fluid movement = 0.34 +/- 0.01 nl.mm-1.min-1), which was Na+ and partially HCO3- dependent. Addition of 1 mM dibutyryl-cyclic AMP, 60 nM vasoactive intestinal peptide, or 0.1 mM acetylcholine to the bath (serosal) solution reversibly induced net fluid secretion (net fluid movement approximately -0.35 +/- 0.01 nl.mm-1.min-1). These observations permit speculation that absorption is a constitutive transport function in crypt cells and that secretion by crypt cells is regulated by one or more neurohumoral agonists that are released in situ from lamina propria cells. The functional, intact polarized crypt described here that both absorbs and secretes will permit future studies that dissect the mechanisms that govern fluid and electrolyte movement in the colonic crypt. Images PMID:7593625

  1. Myocardial Perfusion SPECT 2015 in Germany

    PubMed Central

    Burchert, Wolfgang; Schäfer, Wolfgang; Hacker, Marcus

    2016-01-01

    Summary Aim The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 7th survey of myocardial perfusion SPECT (MPS) of the reporting year 2015. Method 268 questionnaires (173 practices [PR], 67 hospitals [HO], 28 university hospitals [UH]) were evaluated. Results of the last survey from 2012 are set in squared brackets. Results MPS of 121 939 [105 941] patients were reported. 98 % [95 %] of all MPS were performed with Tc-99m radiopharmaceuticals and 2 % [5 %] with Tl-201. 78 % [79 %] of all patients were studied in PR, 14 % [15 %] in HO, and 8 % [6 %] in UH. A pharmacological stress test was performed in 43 % [39 %] (22 % [24 %] adenosine, 20 % [9 %] regadenoson, 1% [6 %] dipyridamole or dobutamine). Attenuation correction was applied in 25 % [2009: 10 %] of MPS. Gated SPECT was performed in 78 % [70 %] of all rest MPS, in 80 % [73 %] of all stress and in 76 % [67 %] of all stress and rest MPS. 53 % [33 %] of all nuclear medicine departments performed MPS scoring by default, whereas 24 % [41 %] did not apply any quantification. 31 % [26 %] of all departments noticed an increase in their counted MPS and 29 % [29 %] no changes. Data from 89 departments which participated in all surveys showed an increase in MPS count of 11.1 % (PR: 12.2 %, HO: 4.8 %, UH: 18.4 %). 70 % [60 %] of the MPS were requested by ambulatory care cardiologists. Conclusion The 2015 MPS survey reveals a high-grade adherence of routine MPS practice to current guidelines. The positive trend in MPS performance and number of MPS already observed in 2012 continues. Educational training remains necessary in the field of SPECT scoring. PMID:27909712

  2. Perfusion imaging with non-contrast ultrasound

    NASA Astrophysics Data System (ADS)

    Tierney, Jaime E.; Dumont, Douglas M.; Byram, Brett C.

    2016-04-01

    A Doppler ultrasound clutter filter that enables estimation of low velocity blood flow could considerably improve ultrasound as a tool for clinical diagnosis and monitoring, including for the evaluation of vascular diseases and tumor perfusion. Conventional Doppler ultrasound is currently used for visualizing and estimating blood flow. However, conventional Doppler is limited by frame rate and tissue clutter caused by involuntary movement of the patient or sonographer. Spectral broadening of the clutter due to tissue motion limits ultrasound's ability to detect blood flow less than about 5mm/s at an 8MHz center frequency. We propose a clutter filtering technique that may increase the sensitivity of Doppler measurements to at least as low as 0.41mm/s. The proposed filter uses an adaptive demodulation scheme that decreases the bandwidth of the clutter. To test the performance of the adaptive demodulation method at removing sonographer hand motion, six volunteer subjects acquired data from a basic quality assurance phantom. Additionally, to test initial in vivo feasibility, an arterial occlusion reactive hyperemia study was performed to assess the efficiency of the proposed filter at preserving signals from blood velocities 2mm/s or greater. The hand motion study resulted in initial average bandwidths of 577Hz (28.5mm/s), which were decreased to 7.28Hz (0.36mm/s) at -60 dB at 3cm using our approach. The in vivo power Doppler study resulted in 15.2dB and 0.15dB dynamic ranges between the lowest and highest blood flow time points for the proposed filter and conventional 50Hz high pass filter, respectively.

  3. Ventilation-perfusion matching during exercise

    NASA Technical Reports Server (NTRS)

    Wagner, P. D.

    1992-01-01

    In normal subjects, exercise widens the alveolar-arterial PO2 difference (P[A-a]O2) despite a more uniform topographic distribution of ventilation-perfusion (VA/Q) ratios. While part of the increase in P(A-a)O2 (especially during heavy exercise) is due to diffusion limitation, a considerable amount is caused by an increase in VA/Q mismatch as detected by the multiple inert gas elimination technique. Why this occurs is unknown, but circumstantial evidence suggests it may be related to interstitial pulmonary edema rather than to factors dependent on ventilation, airway gas mixing, airway muscle tone, or pulmonary vascular tone. In patients with lung disease, the gas exchange consequences of exercise are variable. Thus, arterial PO2 may increase, remain the same, or fall. In general, patients with advanced chronic obstructive pulmonary disease (COPD) or interstitial fibrosis who exercise show a fall in PO2. This is usually not due to worsening VA/Q relationships but mostly to the well-known fall in mixed venous PO2, which itself results from a relatively smaller increase in cardiac output than VO2. However, in interstitial fibrosis (but not COPD), there is good evidence that a part of the fall in PO2 on exercise is caused by alveolar-capillary diffusion limitation of O2 transport; in COPD (but not interstitial fibrosis), a frequent additional contributing factor to the hypoxemia of exercise is an inadequate ventilatory response, such that minute ventilation does not rise as much as does CO2 production or O2 uptake, causing arterial PCO2 to increase and PO2 to fall.

  4. [Model of intraluminal perfusion of the guinea pig ileum in vitro in the study of the antidiarrheal properties of the guava (Psidium guajava)].

    PubMed

    Lozoya, X; Becerril, G; Martínez, M

    1990-01-01

    An experimental in vitro model was developed for the study of plant extracts reported by traditional medicines in the treatment of diarrhea. The guinea-pig isolated ileum is perfused with the plant extract using an intraluminal approach. The peristaltic reflex is induced by electrical stimulation while the plant extract is perfused. The spasmolytic effects of Psidium guajava leaf methanol, hexane and water extracts were demonstrated suggesting the existence of two different types of active components. The results obtained allow to propose this in vitro method as a useful model to reproduce some of the characteristics of the oral way of administration of plant extracts.

  5. In vitro studies of ferric carboxymaltose on placental permeability using the dual perfusion model of human placenta.

    PubMed

    Malek, Antoine

    2010-01-01

    An in vitro perfusion model of human placenta was used to study the transplacental passage of iron applied in the form of the drug compound ferric carboxymaltose (FCM) which had been radio-labelled with 59Fe. In four placental perfusion experiments, two simulated circuits for the maternal and fetal sides of the placenta were set up with two experimental phases each lasting 3 h. FCM was added to the maternal circuit at the beginning of each phase to a final iron concentration of 11 mM, which is at least 10 times higher than the maximal predicted level in blood after an administration of 200 mg iron as FCM. The effects of adding transferrin at a physiological concentration of 1.67 mg/ ml were also tested. The concentration profiles of 59Fe showed a 10% decrease within the first 30 min of perfusion on the maternal side. Thereafter the radioactivity levels remained unchanged. The addition of transferrin had no effect on the tissue uptake of 59Fe-FCM. No transferred iron radioactivity could be detected in the fetal circuit. Despite a loss of approximately 10% of the radio-labelled iron observed on the maternal side, only 0.5-2% of the radioactivity was detected in the placental tissue after perfusion. No free iron could be detected at the end of perfusion on the maternal side using ultrafiltration or acid precipitation methods. In addition, the production of transferrin receptor remained unchanged, with similar concentrations in placental tissue before and after perfusion. No effects of FCM on placental viability were observed in terms of energy metabolism (glucose consumption and lactate production), hormone release or placental permeability (assessed by the transfer rates of creatinine and antipyrine). However, two additional observations were made: firstly, a significant reduction in the rate of cell death compared to control conditions was observed in the presence of FCM; secondly, the integrity of the fetal capillary system was improved on the fetal side of the

  6. Alginate-based hybrid aerogel microparticles for mucosal drug delivery.

    PubMed

    Gonçalves, V S S; Gurikov, P; Poejo, J; Matias, A A; Heinrich, S; Duarte, C M M; Smirnova, I

    2016-10-01

    The application of biopolymer aerogels as drug delivery systems (DDS) has gained increased interest during the last decade since these structures have large surface area and accessible pores allowing for high drug loadings. Being biocompatible, biodegradable and presenting low toxicity, polysaccharide-based aerogels are an attractive carrier to be applied in pharmaceutical industry. Moreover, some polysaccharides (e.g. alginate and chitosan) present mucoadhesive properties, an important feature for mucosal drug delivery. This feature allows to extend the contact of DDS with biological membranes, thereby increasing the absorption of drugs through the mucosa. Alginate-based hybrid aerogels in the form of microparticles (<50μm) were investigated in this work as carriers for mucosal administration of drugs. Low methoxyl pectin and κ-carrageenan were co-gelled with alginate and further dried with supercritical CO2 (sc-CO2). Spherical mesoporous aerogel microparticles were obtained for alginate, hybrid alginate/pectin and alginate/κ-carrageenan aerogels, presenting high specific surface area (370-548m(2)g(-1)) and mucoadhesive properties. The microparticles were loaded with ketoprofen via adsorption from its solution in sc-CO2, and with quercetin via supercritical anti-solvent precipitation. Loading of ketoprofen was in the range between 17 and 22wt% whereas quercetin demonstrated loadings of 3.1-5.4wt%. Both the drugs were present in amorphous state. Loading procedure allowed the preservation of antioxidant activity of quercetin. Release of both drugs from alginate/κ-carrageenan aerogel was slightly faster compared to alginate/pectin. The results indicate that alginate-based aerogel microparticles can be viewed as promising matrices for mucosal drug delivery applications.

  7. Mucosal microbiome in patients with recurrent aphthous stomatitis.

    PubMed

    Hijazi, K; Lowe, T; Meharg, C; Berry, S H; Foley, J; Hold, G L

    2015-03-01

    Recurrent aphthous stomatitis (RAS) is the most common disease affecting oral mucosae. Etiology is unknown, but several factors have been implicated, all of which influence the composition of microbiota residing on oral mucosae, which in turn modulates immunity and thereby affects disease progression. Although no individual pathogens have been conclusively shown to be causative agents of RAS, imbalanced composition of the oral microbiota may play a key role. In this study, we sought to determine composition profiles of bacterial microbiota in the oral mucosa associated with RAS. Using high-throughput 16S rRNA gene sequencing, we characterized the most abundant bacterial populations residing on healthy and ulcerated mucosae in patients with RAS (recruited using highly stringent criteria) and no associated medical conditions; we also compared these to the bacterial microbiota of healthy controls (HCs). Phylum-level diversity comparisons revealed decreased Firmicutes and increased Proteobacteria in ulcerated sites, as compared with healthy sites in RAS patients, and no differences between RAS patients with healthy sites and HCs. Genus-level analysis demonstrated higher abundance of total Bacteroidales in RAS patients with healthy sites over HCs. Porphyromonadaceae comprising species associated with periodontal disease and Veillonellaceae predominated in ulcerated sites over HCs, while no quantitative differences of these families were observed between healthy sites in RAS patients and HCs. Streptococcaceae comprising species associated with oral health predominated in HCs over ulcerated sites but not in HCs over healthy sites in RAS patients. This study demonstrates that mucosal microbiome changes in patients with idiopathic RAS--namely, increased Bacteroidales species in mucosae of RAS patients not affected by active ulceration. While these changes suggest a microbial role in initiation of RAS, this study does not provide data on causality. Within this limitation

  8. Airway cooling and mucosal injury during cold weather exercise.

    PubMed

    Davis, M S; Lockard, A J; Marlin, D J; Freed, A N

    2002-09-01

    In human subjects that exercise strenuously in cold weather, there is evidence that hyperventilation with cold air leads to peripheral airway cooling, desiccation and mucosal injury. Our hypothesis was that hyperventilation with cold air can result in penetration of unconditioned air (air that is not completely warmed and humidified) into the peripheral airways of exercising horses, resulting in peripheral airway mucosal injury. To test this hypothesis, a thermister-tipped catheter was inserted through the midcervical trachea and advanced into a sublobar bronchus in three horses that cantered on a treadmill at 6.6 m/s while breathing cold (5 degrees C) air. The mean (+/- s.e.) intra-airway temperature during cantering was 33.3 +/- 0.4 degrees C, a value comparable to the bronchial lumen temperatures measured in man during maximal exercise while breathing subfreezing dry air. In a second experiment, 6 fit Thoroughbred racehorses with satisfactory performance were used to determine whether strenuous exercise in cold conditions can produce airway injury. Horses were assigned to Exercise (E) or Control (C) groups in a random crossover design. Samples of bronchoalveolar lavage fluid (BALF) in the E treatment were recovered within 30 min of galloping exercise in 4 degrees C, 100% relative humidity (E), while in C BALF samples were obtained when the horses had not performed any exercise for at least 48 h prior. Ciliated epithelial cells in BALF were higher in E than in the C treatment. Similar results have been found in human athletes and laboratory animal models of cold weather exercise. These results support the hypothesis that, similar to man, horses that exercise in cold weather experience peripheral airway mucosal injury due to the penetration of unconditioned air. Furthermore, these results suggest that airway cooling and desiccation may be a factor in airway inflammation commonly found in equine athletes.

  9. [Malignant mucosal melanoma of the head and neck].

    PubMed

    Slavícek, A; Astl, J; Válková, D; Betka, J; Petruzelka, L

    2000-01-01

    Mucosal melanoma comparison to cutaneous melanoma of the head and neck are rare and do poorly. Approximately 0.5-2% of all melanomas occur from the mucous membranes of aerodigestive tract. Most common site of the tumor are the nasal cavity and paranasal sinuses but melanoma of the oral cavity are described too. Therapy usually consists of surgical resection with or without postoperative radiotherapy and immunochemotherapy eventually. The definite role of a kind of therapy in the treatment of mucosal melanoma is not remains to be defined as the small number of cases make prospective study challenging. This article reviews 19 patients with mucosal melanoma of the head and neck treated at the Department of ENT and Head and Neck Surgery Charles University of Prague since 1980 to 1999. Clinical data were obtained from the patient's charts. Analysis of the metastatic disease, type of therapy and follow-up was retrospectively reviewed. The site of the tumor was the lateral wall of the nasal cavity (five cases), nasal septum (four cases), maxilar cavity (two cases), and ethmoidal cavity, orbitoethmoidal complex, nasopharynx, saccus lacrimalis to ethmoidal sinuses diffused, tonsilla (one case each) and hypopharynx (two cases). Primary treatment was surgical resection in ten cases, in one case with radiation therapy, and in seven cases chemotherapy. In three cases were diagnostic surgery only and one patient was without therapy. Three patients received radical neck dissection more. Four patients were treated radiation therapy and three chemotherapy after surgery. In two cases were surgery after primary radiotherapy. For nine cases of recurrence of the disease were surgery (in five cases) and chemotherapy (in four cases). Overal and disease free interval was from 2 to 22 month, approximately 9.3 month and 3-year survival was 41.18%.

  10. Mucosal Microbiome in Patients with Recurrent Aphthous Stomatitis

    PubMed Central

    Hijazi, K.; Lowe, T.; Meharg, C.; Berry, S.H.; Foley, J.; Hold, G.L.

    2015-01-01

    Recurrent aphthous stomatitis (RAS) is the most common disease affecting oral mucosae. Etiology is unknown, but several factors have been implicated, all of which influence the composition of microbiota residing on oral mucosae, which in turn modulates immunity and thereby affects disease progression. Although no individual pathogens have been conclusively shown to be causative agents of RAS, imbalanced composition of the oral microbiota may play a key role. In this study, we sought to determine composition profiles of bacterial microbiota in the oral mucosa associated with RAS. Using high-throughput 16S rRNA gene sequencing, we characterized the most abundant bacterial populations residing on healthy and ulcerated mucosae in patients with RAS (recruited using highly stringent criteria) and no associated medical conditions; we also compared these to the bacterial microbiota of healthy controls (HCs). Phylum-level diversity comparisons revealed decreased Firmicutes and increased Proteobacteria in ulcerated sites, as compared with healthy sites in RAS patients, and no differences between RAS patients with healthy sites and HCs. Genus-level analysis demonstrated higher abundance of total Bacteroidales in RAS patients with healthy sites over HCs. Porphyromonadaceae comprising species associated with periodontal disease and Veillonellaceae predominated in ulcerated sites over HCs, while no quantitative differences of these families were observed between healthy sites in RAS patients and HCs. Streptococcaceae comprising species associated with oral health predominated in HCs over ulcerated sites but not in HCs over healthy sites in RAS patients. This study demonstrates that mucosal microbiome changes in patients with idiopathic RAS—namely, increased Bacteroidales species in mucosae of RAS patients not affected by active ulceration. While these changes suggest a microbial role in initiation of RAS, this study does not provide data on causality. Within this limitation

  11. Activation of rat intestinal mucosal mast cells by fat absorption.

    PubMed

    Ji, Yong; Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick

    2012-06-01

    Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D(2) (PGD(2)) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD(2), ∼20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent.

  12. Duct-associated lymphoid tissue (DALT) of minor salivary glands and mucosal immunity.

    PubMed Central

    Nair, P N; Schroeder, H E

    1986-01-01

    Minor salivary glands (MSG) play a substantial role in the secretory immunoglobulin A (sIgA)-mediated immunity of the oral cavity. There are two possibilities for the induction of this immunity: (i) an explicitly local antigenic stimulus, or (ii) a remote stimulus as part of the so-called 'common mucosal immune system'. This communication is an attempt to consolidate available evidence in support of both possibilities and to address the former in detail. Although there is strong circumstantial evidence supporting the feasibility of MSG functioning as a part of the common mucosal immune system, direct experimental evidence is yet to emerge. On the other hand, there is increasing structural and physiological evidence in support of MSG serving as a local immunological organ. The purely local response is attributed to the presence of MSG duct-associated lymphoid tissue (DALT), which is comparable to gut- or bronchial-associated lymphoid tissue (GALT or BALT) in origin, tissue organization and function. DALT is accessible to oral antigens by retrograde passage through MSG ducts. Repeated topical antigenic challenging via the oral mucosa may result in the appearance of interacinar plasma cells carrying specific homologous antibodies in MSG. Gut or enteric priming of the same antigen, by passing the oral mucosa by gastric intubation, need not evoke a remote immune response in MSG. Since DALT is more likely to occur in healthy, young growing individuals, who are less likely to undergo bioptic examination of MSG, it has not yet been documented in humans. The physiologically induced DALT is apt to be confused with focal accumulations of lymphoid tissue in pathologically altered MSG, as a consequence of local and some systemic autoimmune diseases. An attempt is made to demarcaate healthy and pathological MSG on the basis of currently available clinical, serological, immunological and genetic evidence. Images Figure 1 Figure 2 PMID:3512423

  13. A Molecular Link Between Interleukin 22 and Intestinal Mucosal Wound Healing

    PubMed Central

    Sun, Xiaoyan; Chalmers, Laura; Fu, Xiaobing; Zhao, Min

    2012-01-01

    Background Interleukin 22 (IL-22) and signal transducer and activator of transcription 3 (STAT3) are two important regulators of inflammation. Crohn's disease and ulcerative colitis are considered inflammatory bowel diseases (IBDs), due to the belief that these diseases result from dysregulated responses of the intestinal immune system to bacteria present in the commensal flora. The Problem It is debated whether a breakdown of immune tolerance is the primary cause of these diseases or occurs downstream of an initial defect of the intestinal barrier and intestinal epithelial cells (IECs). Basic/Clinical Science Advances Recent reports suggest a crucial role for IL-22 in the regulation of gut inflammation as well as epithelial barrier integrity. Local IL-22 gene delivery enhances expression of its downstream effector, STAT3, within colonic epithelial cells and induces both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. IEC-specific deletion of STAT3 results in significant susceptibility to experimental colitis with a striking defect in epithelial restitution. STAT3 activation, thus, may regulate immune homeostasis in the gut by promoting IL-22-dependent mucosal wound healing. Clinical Care Relevance The importance of IL-22/STAT3 signaling in IEC wound healing suggests a critical role for epithelial homeostasis in IBDs. Conclusion Effective healing of the IECs could be considered a primary target in the development of treatments for IBDs. IL-22/STAT3 signaling exerts a protective role in the process of intestinal mucosal wound healing and may thereby provide a promising therapeutic approach to the treatment of IBDs. PMID:24527311

  14. Characterization of a Surface Glycoprotein from Echinococcus multilocularis and Its Mucosal Vaccine Potential in Dogs

    PubMed Central

    Kouguchi, Hirokazu; Matsumoto, Jun; Nakao, Ryo; Yamano, Kimiaki; Oku, Yuzaburo; Yagi, Kinpei

    2013-01-01

    Alveolar echinococcosis is a refractory disease caused by the metacestode stage of Echinococcus multilocularis. The life cycle of this parasite is maintained primarily between foxes and many species of rodents; thus, dogs are thought to be a minor definitive host except in some endemic areas. However, dogs are highly susceptible to E. multilocularis infection. Because of the close contact between dogs and humans, infection of dogs with this parasite can be an important risk to human health. Therefore, new measures and tools to control and prevent parasite transmission required. Using 2-dimensional electrophoresis followed by western blot (2D-WB) analysis, a large glycoprotein component of protoscoleces was identified based on reactivity to intestinal IgA in dogs experimentally infected with E. multilocularis. This component, designated SRf1, was purified by gel filtration using a Superose 6 column. Glycosylation analysis and immunostaining revealed that SRf1 could be distinguished from Em2, a major mucin-type antigen of E. multilocularis. Dogs (n = 6) were immunized intranasally with 500 µg of SRf1 with cholera toxin subunit B by using a spray syringe, and a booster was given orally using an enteric capsule containing 15 mg of the same antigen. As a result, dogs immunized with this antigen showed an 87.6% reduction in worm numbers compared to control dogs (n = 5) who received only PBS administration. A weak serum antibody response was observed in SRf1-immunized dogs, but there was no correlation between antibody response and worm number. We demonstrated for the first time that mucosal immunization using SRf1, a glycoprotein component newly isolated from E. multilocularis protoscoleces, induced a protection response to E. multilocularis infection in dogs. Thus, our data indicated that mucosal immunization using surface antigens will be an important tool to facilitate the development of practical vaccines for definitive hosts. PMID:23894545

  15. Repeat perfusion imaging may differentiate airways obstruction from pulomonary embolic disease: report of two cases

    SciTech Connect

    Greenspon, L.W.; LaManna, M.M.; Dhand, S.

    1987-06-01

    Two cases are presented in which patients with obstructive lung disease were considered to have a pulmonary embolism (PE). Emergency lung perfusion scans supported the diagnosis of PE in both cases. However, rapid resolution of the symptoms and perfusion defects by repeat ventilation-perfusion scanning at 24 hr suggested that PE was unlikely. In selected cases of wheezing patients, repeat perfusion scans may obviate the need for pulmonary angiography. The authors report two cases in which repeat perfusion scans almost normalized by 24 hr. Review of the literature indicates that the rate of resolution of perfusion defects would have been much slower had pulmonary embolism occurred.

  16. Oral mucosal precancer and cancer: A helpful discriminating clinical tool.

    PubMed

    Scully, Crispian; Sciubba, James J; Bagan, Jose V

    2015-09-01

    The authors have collaborated with many colleagues in several countries in formulating a useful and practical clinical tool for evaluating oral mucosal findings on routine examination. Consideration of several factors including history, evolution of positive findings and clinical information allows placement of examination results into one of three categories which are graded by a color scheme along a spectrum of concerns (green to red, or no concern to serious concern). Afforded to the clinician is a straightforward grading system as a starting point for office end clinic use for all patients.

  17. Oral mucosal precancer and cancer: A helpful discriminating clinical tool

    PubMed Central

    Scully, Crispian; Bagan, Jose V.

    2015-01-01

    The authors have collaborated with many colleagues in several countries in formulating a useful and practical clinical tool for evaluating oral mucosal findings on routine examination. Consideration of several factors including history, evolution of positive findings and clinical information allows placement of examination results into one of three categories which are graded by a color scheme along a spectrum of concerns (green to red, or no concern to serious concern). Afforded to the clinician is a straightforward grading system as a starting point for office end clinic use for all patients. Key words:Oral, precancer, cancer, clinical tool. PMID:26241449

  18. Thalidomide induces mucosal healing in postoperative Crohn disease endoscopic recurrence

    PubMed Central

    Hu, Huiqin; Wang, Xinying; Liu, Side

    2016-01-01

    Abstract Background: Thalidomide has been successful use in patients with refractory Crohn disease (CD) in recent years. Methods: We collected the data of a postoperative CD patient who was prescribed thalidomide to induce remission and reviewed the relevant literatures. Results: A 51-year-old female was diagnosed as CD after an urgent terminal intestinal resection and presented endoscopic recurrence despite the prophylactic treatment with azathioprine (AZA). Fortunately, she achieved mucosal healing (MH) at a low dose of thalidomide for 15 months. Conclusion: Thalidomide is effective to induce MH in the postoperative CD endoscopic recurrence. PMID:27603389

  19. Isoniazid Induced Lupus Presenting as Oral Mucosal Ulcers with Pancytopenia

    PubMed Central

    Ankale, Padmaraj; Sinha, Kanishk; Iyer, Aparna; Jayalakshmi, T.K

    2016-01-01

    Drug Induced Lupus Erythematous (DILE) is a rare adverse reaction to a large variety of drugs including Isoniazid (INH), with features resembling idiopathic Systemic Lupus Erythematosus (SLE). Diagnosis require identification of a temporal relationship between drug administered and symptom. It is an idiosyncratic reaction, with no pre-existing lupus. Our case highlights a rare presentation of isoniazid induced lupus with profound pancytopenia and mucosal ulcers, thus posing a diagnostic challenge. The patient was on multidrug treatment for pulmonary and knee joint tuberculosis. DILE was diagnosed on basis of strongly positive Anti Nuclear Antibodies (ANA), anti ds DNA and antihistone antibodies with clinical response to cessation of INH. PMID:27891378

  20. Dynamic metabolic flux analysis using a convex analysis approach: Application to hybridoma cell cultures in perfusion.

    PubMed

    Fernandes de Sousa, Sofia; Bastin, Georges; Jolicoeur, Mario; Vande Wouwer, Alain

    2016-05-01

    In recent years, dynamic metabolic flux analysis (DMFA) has been developed in order to evaluate the dynamic evolution of the metabolic fluxes. Most of the proposed approaches are dedicated to exactly determined or overdetermined systems. When an underdetermined system is considered, the literature suggests the use of dynamic flux balance analysis (DFBA). However the main challenge of this approach is to determine an appropriate objective function, which remains valid over the whole culture. In this work, we propose an alternative dynamic metabolic flux analysis based on convex analysis, DMFCA, which allows the determination of bounded intervals for the fluxes using the available knowledge of the metabolic network and information provided by the time evolution of extracellular component concentrations. Smoothing splines and mass balance differential equations are used to estimate the time evolution of the uptake and excretion rates from this experimental data. The main advantage of the proposed procedure is that it does not require additional constraints or objective functions, and provides relatively narrow intervals for the intracellular metabolic fluxes. DMFCA is applied to experimental data from hybridoma HB58 cell perfusion cultures, in order to investigate the influence of the operating mode (batch and perfusion) on the metabolic flux distribution.

  1. Understanding and modeling alternating tangential flow filtration for perfusion cell culture.

    PubMed

    Kelly, William; Scully, Jennifer; Zhang, Di; Feng, Gang; Lavengood, Mathew; Condon, Jason; Knighton, John; Bhatia, Ravinder

    2014-01-01

    Alternating tangential flow (ATF) filtration has been used with success in the Biopharmaceutical industry as a lower shear technology for cell retention with perfusion cultures. The ATF system is different than tangential flow filtration; however, in that reverse flow is used once per cycle as a means to minimize fouling. Few studies have been reported in the literature that evaluates ATF and how key system variables affect the rate at which ATF filters foul. In this study, an experimental setup was devised that allowed for determination of the time it took for fouling to occur for given mammalian (PER.C6) cell culture cell densities and viabilities as permeate flow rate and antifoam concentration was varied. The experimental results indicate, in accordance with D'Arcy's law, that the average resistance to permeate flow (across a cycle of operation) increases as biological material deposits on the membrane. Scanning electron microscope images of the post-run filtration surface indicated that both cells and antifoam micelles deposit on the membrane. A unique mathematical model, based on the assumption that fouling was due to pore blockage from the cells and micelles in combination, was devised that allowed for estimation of sticking factors for the cells and the micelles on the membrane. This model was then used to accurately predict the increase in transmembane pressure during constant flux operation for an ATF cartridge used for perfusion cell culture.

  2. BOLD-Perfusion Coupling during Monocular and Binocular Stimulation

    PubMed Central

    Gauthier, Claudine; Hoge, Richard D.

    2008-01-01

    Previous studies have suggested that during selective activation of a subset of the zones comprising a columnar system in visual cortex, perfusion increases uniformly in all columns of the system, while increases in oxidative metabolism occur predominantly in the activated columns. This could lead to disproportionately large blood oxygenation level-dependent (BOLD) signal increases for a given flow increase during monocular (relative to binocular) stimulation, due to contributions from columns which undergo large increases in perfusion with little or no change in oxidative metabolism. In the present study, we sought to test this hypothesis by measuring BOLD-perfusion coupling ratios in spatially averaged signals over V1 during monocular and binocular visual stimulation. It was found that, although withholding input to one eye resulted in statistically significant decreases in BOLD and perfusion signals in primary visual cortex, the ratio between BOLD and perfusion increases did not change significantly. These results do not support a gross mismatch between spatial patterns of flow and metabolism response during monocular stimulation. PMID:18350120

  3. Inert gas analysis of ventilation-perfusion matching during hemodialysis.

    PubMed Central

    Ralph, D D; Ott, S M; Sherrard, D J; Hlastala, M P

    1984-01-01

    The mechanism of hypoxemia during hemodialysis was investigated by the multiple inert gas elimination technique in anesthetized, paralyzed, mechanically ventilated dogs. Profound leukopenia occurred in the first hour of a 2-h hemodialysis with a cuprophan membrane and dialysate that contained acetate. Arterial partial pressure of O2 and CO2 and oxygen consumption remained unchanged during dialysis. Pulmonary carbon dioxide elimination and lung respiratory exchange ratio decreased with the initiation of dialysis, remained depressed throughout the duration of dialysis, and returned to predialysis levels after the cessation of dialysis. Cardiac output diminished during dialysis but did not return to base-line levels after dialysis. Multiple indices calculated from inert gas analysis revealed no ventilation-perfusion mismatching during dialysis. The shunt and perfusion to regions of low alveolar ventilation-to-perfusion ratio (VA/Q) were unchanged during dialysis. There was no change in the mean or standard deviation of the profile of the percentage of total perfusion to regions of the lung that had VA/Q near 1.0; nor was there any increase in the directly calculated arterial-alveolar partial pressure differences for the inert gases during dialysis. Dead space became mildly elevated during dialysis. These results show that during dialysis with controlled ventilation there is no ventilation-perfusion mismatching that leads to hypoxemia. During spontaneous ventilation any hypoxemia must occur due to hypoventilation secondary to the CO2 exchange by the dialyzer and subsequent reduction in pulmonary CO2 exchange. PMID:6715542

  4. Modelling of temperature and perfusion during scalp cooling.

    PubMed

    Janssen, F E M; Van Leeuwen, G M J; Van Steenhoven, A A

    2005-09-07

    Hair loss is a feared side effect of chemotherapy treatment. It may be prevented by cooling the scalp during administration of cytostatics. The supposed mechanism is that by cooling the scalp, both temperature and perfusion are diminished, affecting drug supply and drug uptake in the hair follicle. However, the effect of scalp cooling varies strongly. To gain more insight into the effect of cooling, a computer model has been developed that describes heat transfer in the human head during scalp cooling. Of main interest in this study are the mutual influences of scalp temperature and perfusion during cooling. Results of the standard head model show that the temperature of the scalp skin is reduced from 34.4 degrees C to 18.3 degrees C, reducing tissue blood flow to 25%. Based upon variations in both thermal properties and head anatomies found in the literature, a parameter study was performed. The results of this parameter study show that the most important parameters affecting both temperature and perfusion are the perfusion coefficient Q10 and the thermal resistances of both the fat and the hair layer. The variations in the parameter study led to skin temperature ranging from 10.1 degrees C to 21.8 degrees C, which in turn reduced relative perfusion to 13% and 33%, respectively.

  5. Modelling of temperature and perfusion during scalp cooling

    NASA Astrophysics Data System (ADS)

    Janssen, F. E. M.; Van Leeuwen, G. M. J.; Van Steenhoven, A. A.

    2005-09-01

    Hair loss is a feared side effect of chemotherapy treatment. It may be prevented by cooling the scalp during administration of cytostatics. The supposed mechanism is that by cooling the scalp, both temperature and perfusion are diminished, affecting drug supply and drug uptake in the hair follicle. However, the effect of scalp cooling varies strongly. To gain more insight into the effect of cooling, a computer model has been developed that describes heat transfer in the human head during scalp cooling. Of main interest in this study are the mutual influences of scalp temperature and perfusion during cooling. Results of the standard head model show that the temperature of the scalp skin is reduced from 34.4 °C to 18.3 °C, reducing tissue blood flow to 25%. Based upon variations in both thermal properties and head anatomies found in the literature, a parameter study was performed. The results of this parameter study show that the most important parameters affecting both temperature and perfusion are the perfusion coefficient Q10 and the thermal resistances of both the fat and the hair layer. The variations in the parameter study led to skin temperature ranging from 10.1 °C to 21.8 °C, which in turn reduced relative perfusion to 13% and 33%, respectively.

  6. Validation of Histologic Bone Analysis Following Microfil Vessel Perfusion

    PubMed Central

    Sarhaddi, D; Poushanchi, B; Merati, M; Tchanque-Fossuo, C; Donneys, A; Baker, J; Buchman, SR

    2015-01-01

    The ability to examine bone vascularity using Micro-Computed Tomography (μCT) following vessel perfusion with Microfil® and to subsequently perform histologic bone analysis in the same specimen would provide an efficient method by which the vascular and cellular environment of bone can be examined simultaneously. The purpose of this report is to determine if the administration of Microfil® precludes accurate histologic assessment of bone quality via osteocyte count and empty lacunae count. Sprague-Dawley rats (n=6) underwent perfusion with Microfil®. Left hemi-mandibles were harvested, decalcified and underwent vascular analysis via μCT prior to sectioning and staining with Gomori's Trichrome. Quantitative Histomorphometric evaluation was performed. Ninety-five percent confidence intervals were used to determine statistical differences from an established set of controls (n=12). Histologic analyses were successfully performed on specimens that had undergone previous perfusion. Quantitative measures of bone cellularity of perfused versus control specimens revealed no statistical difference in osteocyte count per high-power field (95.33 versus 94.66; 95 percent CI,-7.64 to 6.30) or empty lacunae per high-power field (2.73 versus 1.89, 95 percent CI, -1.81 to 0.13). Here we report a statistical validation allowing for histological analysis of cell counts in specimens in which Microfil® perfusion has previously been performed. PMID:26207077

  7. Magnetic resonance cardiac perfusion imaging-a clinical perspective.

    PubMed

    Hunold, Peter; Schlosser, Thomas; Barkhausen, Jörg

    2006-08-01

    Coronary artery disease (CAD) with its clinical appearance of stable or unstable angina and acute myocardial infarction is the leading cause of death in developed countries. In view of increasing costs and the rising number of CAD patients, there has been a major interest in reliable non-invasive imaging techniques to identify CAD in an early (i.e. asymptomatic) stage. Since myocardial perfusion deficits appear very early in the "ischemic cascade", a major breakthrough would be the non-invasive quantification of myocardial perfusion before functional impairment might be detected. Therefore, there is growing interest in other, target-organ-specific parameters, such as relative and absolute myocardial perfusion imaging. Magnetic resonance (MR) imaging has been proven to offer attractive concepts in this respect. However, some important difficulties have not been resolved so far, which still causes uncertainty and prevents the broad application of MR perfusion imaging in a clinical setting. This review explores recent technical developments in MR hardware, software and contrast agents, as well as their impact on the current and future clinical status of MR imaging of first-pass myocardial perfusion imaging.

  8. Cyanide-induced injury to the isolated perfused rat liver.

    PubMed

    Younes, M; Strubelt, O

    1988-11-01

    In order to study the events that follow cyanide-induced inhibition of oxidative metabolism and produce cellular injury, isolated, haemoglobin-free perfused rat livers from fasted rats were exposed to KCN (100 mg/l). KCN reduced the oxygen consumption of the livers by about 80%. Hepatotoxicity was evident by a marked release of enzymes (LDH, SDH) and of glutathione (mainly GSSG) into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. Cyanide-induced hepatotoxicity could be prevented completely by feeding the rats before preparing the liver as well as by addition of fructose to the perfusate of fasted livers. Both treatments resulted in an increased energy supply from anaerobic glycolysis as evidenced by a large release of lactate + pyruvate into the perfusate. The toxic actions of cyanide were markedly attenuated by deferrioxamine as well as by allopurinol. These antitoxic actions occurred without changes in anaerobic glycolysis. Omission of calcium from the perfusate, however, did not influence cyanide toxicity. Thus, energy supply from anaerobic glycolysis seems to be sufficient for the basic functions of the liver to occur, when oxidative metabolism is inhibited by cyanide. The effects of deferrioxamine and allopurinol indicate the involvement of radical intermediates and/or Fe2+ in cyanide-induced cellular toxicity. An influx of calcium from the extracellular to the intracellular space is not involved in cyanide-induced hepatocellular injury.

  9. Perfused multiwell plate for 3D liver tissue engineering.

    PubMed

    Domansky, Karel; Inman, Walker; Serdy, James; Dash, Ajit; Lim, Matthew H M; Griffith, Linda G

    2010-01-07

    In vitro models that capture the complexity of in vivo tissue and organ behaviors in a scalable and easy-to-use format are desirable for drug discovery. To address this, we have developed a bioreactor that fosters maintenance of 3D tissue cultures under constant perfusion and we have integrated multiple bioreactors into an array in a multiwell plate format. All bioreactors are fluidically isolated from each other. Each bioreactor in the array contains a scaffold that supports formation of hundreds of 3D microscale tissue units. The tissue units are perfused with cell culture medium circulated within the bioreactor by integrated pneumatic diaphragm micropumps. Electronic controls for the pumps are kept outside the incubator and connected to the perfused multiwell by pneumatic lines. The docking design and open-well bioreactor layout make handling perfused multiwell plates similar to using standard multiwell tissue culture plates. A model of oxygen consumption and transport in the circulating culture medium was used to predict appropriate operating parameters for primary liver cultures. Oxygen concentrations at key locations in the system were then measured as a function of flow rate and time after initiation of culture to determine oxygen consumption rates. After seven days of culture, tissue formed from cells seeded in the perfused multiwell reactor remained functionally viable as assessed by immunostaining for hepatocyte and liver sinusoidal endothelial cell (LSEC) phenotypic markers.

  10. Perfusion calorimetry in the characterization of solvates forming isomorphic desolvates.

    PubMed

    Baronsky, Julia; Preu, Martina; Traeubel, Michael; Urbanetz, Nora Anne

    2011-09-18

    In this study, the potential of perfusion calorimetry in the characterization of solvates forming isomorphic desolvates was investigated. Perfusion calorimetry was used to expose different hydrates forming isomorphic desolvates (emodepside hydrates II-IV, erythromycin A dihydrate and spirapril hydrochloride monohydrate) to stepwise increasing relative vapour pressures (RVP) of water and methanol, respectively, while measuring thermal activity. Furthermore, the suitability of perfusion calorimetry to distinguish the transformation of a desolvate into an isomorphic solvate from the adsorption of solvent molecules to crystal surfaces as well as from solvate formation that is accompanied by structural rearrangement was investigated. Changes in the samples were confirmed using FT-Raman and FT-IR spectroscopy. Perfusion calorimetry indicates the transformation of a desolvate into an isomorphic solvate by a substantial exothermic, peak-shaped heat flow curve at low RVP which reflects the rapid incorporation of solvent molecules by the desolvate to fill the structural voids in the lattice. In contrast, adsorption of solvent molecules to crystal surfaces is associated with distinctly smaller heat changes whereas solvate formation accompanied by structural changes is characterized by an elongated heat flow. Hence, perfusion calorimetry is a valuable tool in the characterization of solvates forming isomorphic desolvates which represents a new field of application for the method.

  11. Real-time vascular mechanosensation through ex vivo artery perfusion

    PubMed Central

    2014-01-01

    Background Cell-based perfusion studies have provided great insight into fluid-sensing mechanisms, such as primary cilia in the renal and vascular systems. However, the intrinsic limitations of in vitro cell culture, such as the inability to reflect cellular organization within tissues, has distanced observed paradigms from possible clinical developments. Here we describe a protocol that applies ex vivo artery perfusion and calcium imaging to observe real-time cellular responses to fluid-shear stress. Results Through our ex vivo artery perfusion method, we were able to simulate physiological flow and initiate distinct fluid shear stress mechanosensory responses, as well as induced acetylcholine responses in mouse aortic tissue. The observed calcium profiles confirm results found through previous in vitro cell culture experiments. The overall procedure, including dissection, sample preparation and perfusion, takes around 3 hours to complete. Conclusion Through our unique method, we are able to induce laminar flow within intact mouse aortic tissue and illicit subsequent cellular responses. This method of ex vivo artery perfusion provides the opportunity to bridge the novel findings of in vitro studies with subsequent physiological models of fluid-shear stress mechanosensation in vascular tissues. PMID:24685068

  12. Brain perfusion asymmetry in patients with oral somatic delusions.

    PubMed

    Umezaki, Yojiro; Katagiri, Ayano; Watanabe, Motoko; Takenoshita, Miho; Sakuma, Tomomi; Sako, Emi; Sato, Yusuke; Toriihara, Akira; Uezato, Akihito; Shibuya, Hitoshi; Nishikawa, Toru; Motomura, Haruhiko; Toyofuku, Akira

    2013-06-01

    Oral cenesthopathy is a somatic delusion or hallucination involving the oral area and is categorized as a delusional disorder, somatic type. The pathophysiology of this intractable condition remains obscure. In this study, we clarified the pathophysiology of oral cenesthopathy by evaluating regional brain perfusion. We performed single photon emission computed tomography (SPECT) using (99m)Tc-ethylcysteinate dimer in 16 subjects (cenesthopathy:control = 8:8). The SPECT images were visually assessed qualitatively, and quantitative analyses were also performed using a three-dimensional stereotactic region-of-interest template. The visual assessment revealed a right > left perfusion asymmetry in broad areas of the brain among the patients. The quantitative analysis confirmed that the regional cerebral blood flow values on the right side were significantly larger than those on the left side for most areas of the brain in the patients. A comparison of the R/(R + L) ratios in both groups confirmed the significant brain perfusion asymmetry between the two sides in the callosomarginal, precentral, and temporal regions in the patients. Qualitative evaluation of the SPECT images revealed right > left brain perfusion asymmetry in broad regions of the brain. Moreover, the quantitative analyses confirmed the perfusion asymmetry between the two sides in the frontal and temporal areas. Those may provide the key for elucidation of the pathophysiology of oral cenesthopathy.

  13. Numerical simulation of blood flow in femoral perfusion: comparison between side-armed femoral artery perfusion and direct femoral artery perfusion.

    PubMed

    Kitamura, Shingo; Shirota, Minori; Fukuda, Wakako; Inamura, Takao; Fukuda, Ikuo

    2016-12-01

    Computational numerical analysis was performed to elucidate the flow dynamics of femoral artery perfusion. Numerical simulation of blood flow was performed from the right femoral artery in an aortic model. An incompressible Navier-Stokes equation and continuity equation were solved using computed flow dynamics software. Three different perfusion models were analyzed: a 4.0-mm cannula (outer diameter 15 French size), a 5.2-mm cannula (18 French size) and an 8-mm prosthetic graft. The cannula was inserted parallel to the femoral artery, while the graft was anastomosed perpendicular to the femoral artery. Shear stress was highest with the 4-mm cannula (172 Pa) followed by the graft (127 Pa) and the 5.2-mm cannula (99 Pa). The cannula exit velocity was high, even when the 5.2-mm cannula was used. Although side-armed perfusion with an 8-mm graft generated a high shear stress area near the point of anastomosis, flow velocity at the external iliac artery was decreased. The jet speed decreased due to the Coanda effect caused by the recirculation behind sudden expansion of diameter, and the flow velocity maintains a constant speed after the reattachment length of the flow. This study showed that iliac artery shear stress was lower with the 5.2-mm cannula than with the 4-mm cannula when used for femoral perfusion. Side-armed graft perfusion generates a high shear stress area around the anastomotic site, but flow velocity in the iliac artery is slower in the graft model than in the 5.2-mm cannula model.

  14. Retinal research using the perfused mammalian eye.

    PubMed

    Niemeyer, G

    2001-05-01

    applied transiently. This process is monitored histochemically using FITC-albumin and with electrophysiological parameters. Changes in vitreo-scleral resistance and in the amplitude of the EOG-light peak appear to reflect the open/closed status of the barrier. This overview of the uses of the isolated perfused mammalian eye in retinal research concludes with a discussion of potential implications for clinically relevant topics.

  15. Testosterone biotransformation by the isolated perfused canine pancreas

    SciTech Connect

    Fernandez-del Castillo, C.; Diaz-Sanchez, V.; Varela-Fascinetto, G.; Altamirano, A.; Odor-Morales, A.; Lopez-Medrano, R.M.; Robles-Diaz, G. )

    1991-01-01

    There is strong evidence indicating that the pancreas is under the influence of sex steroid hormones, and that it may even participate in their biosynthesis and metabolism. In the present study, (3H)testosterone was perfused into the isolated canine pancreas, and measured in the effluent with several of its metabolites (5 alpha-dihydrotestosterone, androstenedione, and estradiol). Results show that testosterone is readily transformed by the canine pancreas. The main product found in the effluent is androstenedione. The testis and spleen were also perfused with (3H)testosterone and used as controls. In both cases, this hormone appeared mostly unchanged in the effluent as compared to the pancreatic perfusion (p less than 0.0001). From our data, we conclude that the canine pancreas has the capacity to transform sex steroid hormones, and could be considered an extragonadal site of sex steroid biosynthesis.

  16. Complete inhibition of creatine kinase in isolated perfused rat hearts

    SciTech Connect

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.

  17. Delayed redistribution in thallium 201 SPECT myocardial perfusion studies

    SciTech Connect

    Ziessman, H.A.; Keyes, J.W. Jr.; Fox, L.M.; Green, C.E.; Fox, S.M. )

    1989-11-01

    Stress {sup 201}Tl myocardial perfusion studies are useful in differentiating viable, reversibly ischemic from infarcted myocardium. A perfusion defect that shows redistribution 2 to 4 h after {sup 201}Tl injection is diagnostic of ischemia, while a fixed defect suggests infarction. However, occasional patients with a fixed defect at 4 h have redistribution at 24 h. This study evaluates the frequency and significance of this delayed redistribution with SPECT {sup 201}Tl. Patients with either no or incomplete redistribution at 4 h had repeat imaging 18 to 48 h later. Delayed redistribution was seen in 8/26 (31 percent). Four had incomplete and four had no redistribution at 4 h. Delayed redistribution with SPECT {sup 201}Tl is more common than generally appreciated, and we recommend delayed images in patients with fixed perfusion defects or incomplete redistribution at 4-h imaging, particularly in patients with previous infarctions for whom a revascularization procedure is being considered.

  18. Regional pulmonary perfusion following human heart-lung transplantation

    SciTech Connect

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  19. Monitoring tissue perfusion, oxygenation, and metabolism in critically ill patients.

    PubMed

    Ekbal, Nasirul J; Dyson, Alex; Black, Claire; Singer, Mervyn

    2013-06-01

    Alterations in oxygen transport and use are integral to the development of multiple organ failure; therefore, the ultimate goal of resuscitation is to restore effective tissue oxygenation and cellular metabolism. Hemodynamic monitoring is the cornerstone of management to promptly identify and appropriately manage (impending) organ dysfunction. Prospective randomized trials have confirmed outcome benefit when preemptive or early treatment is directed toward maintaining or restoring adequate tissue perfusion. However, treatment end points remain controversial, in large part because of current difficulties in determining what constitutes "optimal." Information gained from global whole-body monitoring may not detect regional organ perfusion abnormalities until they are well advanced. Conversely, the ideal "canary" organ that is readily accessible for monitoring, yet offers an early and sensitive indicator of tissue "unwellness," remains to be firmly identified. This review describes techniques available for real-time monitoring of tissue perfusion and metabolism and highlights novel developments that may complement or even supersede current tools.

  20. [Treatment and prevention of cancer treatment related oral mucositis].

    PubMed

    Ruiz-Esquide, Gonzalo; Nervi, Bruno; Vargas, Alex; Maíz, Alberto

    2011-03-01

    One of the most common and troublesome complications of modern intensive anticancer treatments is oral mucositis. The purpose of this review is to summarize current evidence and clinical guidelines regarding its prevention and therapy. The use of keratinocyte growth factor-1, supplementary glutamine and other recently developed treatment modalities are discussed. The injury of the oral mucosa caused by antineoplastic agents promotes the local expression of multiple pro-inflammatory and pro-apoptotic molecules and eventually leads to the development of ulcers. Such lesions predispose patients to several infectious and nutritional complications. Also, they lead to modification of treatment schedules, potentially affecting overall prognosis. Local cryotherapy with ice chips and phototherapy with low energy laser may be useful as preventive measures. Mouthwashes with allopurinol and phototherapy with low energy laser can be used as treatment. In radiotherapy, special radiation administration techniques should be used to minimize mucosal injury. Pain control should always be optimized, with the use of patient controlled analgesia and topical use of morphine. Supplemental glutamine should not be used outside of research protocols. Lastly, thorough attention should be paid to general care and hygiene measures.

  1. Gastric Mucosal Petechial Hemorrhages (Wischnewsky Lesions), Hypothermia, and Diabetic Ketoacidosis.

    PubMed

    Clark, Kenneth Howard; Stoppacher, Robert

    2016-09-01

    For more than 100 years since their initial description, gastric mucosal petechial hemorrhages have been discovered at autopsy in cases where environmental hypothermia was determined to be the cause of death. Although these lesions are frequently seen in deaths caused by environmental hypothermia, they can also be seen in cases where hypothermia is not implicated; however, this has been seldom described. We present a series of autopsy cases where hypothermia has been conclusively ruled out as a cause of death, in which Wischnewsky lesions are found. In all of these cases, diabetic ketoacidosis (DKA) was determined to be the proximate cause of death, as confirmed through clinical history, laboratory analysis, and absence of other anatomic or toxicological findings. We provide a mechanism of Wischnewsky lesion formation and how that mechanism relates to both hypothermia and ketoacidosis. Our data show that gastric mucosal petechial hemorrhages are not specific for hypothermia-related deaths, and are likely indicative of a state in which hypothermia and DKA have a common underlying pathophysiology, most likely a coagulopathy. Our data also illustrate that in autopsy cases where Wischnewsky lesions are found, DKA should be seriously considered as the underlying cause of death, particularly in the absence of indications of environmental hypothermia.

  2. The clinical characteristics of benign oral mucosal tumors

    PubMed Central

    Kaplan, Ilana; Gal, Gavriel; Chaushu, Gavriel; Allon, Dror M.

    2014-01-01

    Objectives: To investigate the clinical characteristics and pre-biopsy provisional diagnoses of benign oral mucosal tumors. Material and Methods: A 10- year retrospective analysis of all benign tumors of the oral mucosa, from a university- affiliated oral and maxillofacial surgery department. Results: 146 benign tumors were included. The mean age was 49.6 years, with an approximately equal gender distribution. The most prevalent tumor types were lipomatous tumors (27.4%), vascular (23.3%), and salivary gland tumors (16.5%). Tongue, labial and buccal mucosa were the most frequently involved sites. The vast majority (98.6%) presented as non-ulcerated masses. Only 2 (1.4%) presented as ulcerated masses. The clinical provisional diagnosis correctly classified lesions as non-malignant in 93.3%. In only 9 (6.7%) suspicion of malignancy was included in the provisional diagnosis. However, benign neoplasia was unsuspected in 42.1% of tumors. These cases were clinically classified as reactive. Conclusions: Benign tumors were most likely to be clinically correctly classified as non-malignant, but even in the setting of experienced oral surgeons, neoplasia was unsuspected in more than 40% of cases. This data strongly supports the need to biopsy every oral mucosal mass, since inaccurate clinical evaluation of the lesion’s biological nature was a frequent event. Key words:Malignant, benign, reactive, ulcerated mass, non-ulcerated mass, clinical diagnosis. PMID:24316705

  3. Altered Esophageal Mucosal Structure in Patients with Celiac Disease

    PubMed Central

    Pinto-Sánchez, María Inés; Nachman, Fabio D.; Fuxman, Claudia; Iantorno, Guido; Hwang, Hui Jer; Ditaranto, Andrés; Costa, Florencia; Longarini, Gabriela; Wang, Xuan Yu; Huang, Xianxi; Vázquez, Horacio; Moreno, María L.; Niveloni, Sonia; Bercik, Premysl; Smecuol, Edgardo; Mazure, Roberto; Bilder, Claudio; Mauriño, Eduardo C.; Verdu, Elena F.; Bai, Julio C.

    2016-01-01

    Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation. PMID:27446827

  4. Effects of spaceflight on the proliferation of jejunal mucosal cells

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  5. Cyclic GMP-AMP Displays Mucosal Adjuvant Activity in Mice

    PubMed Central

    Škrnjug, Ivana

    2014-01-01

    The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity – a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines. PMID:25295996

  6. A physical identity for the gastric mucosal barrier.

    PubMed

    Hills, B A

    1990-07-16

    An oligolamellar lining which is probably phospholipid has been demonstrated on the gastric mucosal surface of the rat by transmission electron microscopy using fixation procedures specially developed to avoid the destruction of hydrophobic surfaces. This structure is unlikely to be an artefact since the use of two hydrophobic probes in epifluorescence microscopy gave emissions characteristic o