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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. Luminal distension as a possible consequence of experimental intestinal perfusion

    PubMed Central

    Wingate, David; Hyams, Ashley; Phillips, Sidney

    1974-01-01

    In an experimental jejunal perfusion study, distress in healthy subjects occurred during eight out of 16 perfusions in which intestinal secretion was provoked. Calculation demonstrates the volumetric consequences of inadequate recovery of secretory perfusates, and analysis of the perfusion studies shows that distress was significantly associated with poor recovery of the perfusate. These observations are pertinent to increasing interest in the phenomenon of intestinal fluid secretion. PMID:4435588

  3. Evaluation of intestinal absorption and mucosal toxicity using two promoters. II. Rat instillation and perfusion studies.

    PubMed

    Maher, Sam; Wang, Xuexuan; Bzik, Victoria; McClean, Siobhan; Brayden, David J

    2009-11-01

    We compared the effectiveness of two absorption promoters, sodium caprate (C(10)) and melittin, in increasing the bioavailability (F) of poorly absorbed paracellular flux markers across the intestinal mucosae of rats in situ, together with examination of their effects on morphology. C(10) (100 mM) and melittin (50 microM) significantly increased absorption of FITC-dextran-4 kDa (FD4) following jejunal and colonic instillations. F of FD4 following jejunal instillations with C(10) was increased from 0.07% to 2.3%, while it was increased from 0.07% to 0.53% in the presence of melittin. F of FD4 following colonic instillations with C(10) was increased from 1% to 33% while melittin increased it from 1% to 7%. F of FD70 was unchanged in colonic instillations in the presence of either of the two agents, indicating size limitations of the permeability enhancement effects. In rat jejunal perfusions, C(10) (50 mM) and melittin (50 microM) significantly increased [(14)C]-mannitol permeability by 9- and 1.9-fold respectively. C(10) was more effective than melittin in increasing fluxes in all models. Histology of intestinal sections exposed to either promoter showed mild mucosal damage at those concentrations effective at promoting absorption. Electron microscopy revealed epithelial cell damage induced by both enhancers accompanied by truncation of microvilli, and sloughing. Overall, both melittin and C(10) improved bioavailability of polar sugars across the jejunum and colon of rats in situ, which was associated with some degree of mucosal damage. PMID:19664704

  4. Experimental glomerulonephritis in the isolated perfused rat kidney.

    PubMed Central

    Couser, W G; Steinmuller, D R; Stilmant, M M; Salant, D J; Lowenstein, L M

    1978-01-01

    The development of immune deposits on the subepithelial surface of the glomerular capillary wall was studied in isolated rat kidneys perfused at controlled perfusion pressure, pH, temperature, and flow rates with recirculating oxygenated perfusate containing bovine serum albumin (BSA) in buffer and sheep antibody to rat proximal tubular epithelial cell brush border antigen (Fx1A). Control kidney were perfused with equal concentrations of non-antibody immunoglobulin (Ig)G. Renal function was monitored by measuring inulin clearance, sodium reabsorption, and urine flow as well as BSA excretion and fractional clearance. Perfused kidneys were studied by light, immunofluorescence, and electron microscopy. All kidneys perfused with anti-Fx1A developed diffuse, finely granular deposits of IgG along the glomerular capillary wall by immunofluorescence. Electron microscopy revealed these deposits to be localized exclusively in the subepithelial space and slit pores. Similar deposits were produced in a nonrecirculating perfusion system, thereby excluding the formation of immune complexes in the perfusate caused by renal release of tubular antigen. Control kidneys perfused with nonantibody IgG did not develop glomerular immune deposits. Renal function and BSA excretion were the same in experimental and control kidneys. Glomerular deposits in antibody perfused kidneys were indistinguishable from deposits in rats injected with anti-Fx1A or immunized with Fx1A to produce autologous immune complex nephropathy. These studies demonstrate that subepithelial immune deposits can be produced in the isolated rat kidney by perfusion with specific antibody to Fx1A in the absence of circulating immune complexes. In this model deposits result from in situ complex formation rather than circulating immune complex deposition. Images PMID:372233

  5. Octreotide effectively decreases mucosal damage in experimental colitis.

    PubMed Central

    Eliakim, R; Karmeli, F; Okon, E; Rachmilewitz, D

    1993-01-01

    The effect of octreotide, a synthetic analogue of somatostatin, on the modulation of the acetic acid model of experimental colitis was examined. Colitis was induced by intracolonic administration of 2 ml of 5% acetic acid. The inflammatory response elicited by the acetic acid resulted in increased colonic synthesis of platelet activating factor, leukotriene B4 and decreased mucosal somatostatin levels. Subcutaneous administration of octreotide (10 micrograms/rat) 1 hour before or immediately after damage induction, as well as 1 and 23 hours after acetic acid application, resulted in a significant reduction in mucosal damage. The protective effect was accompanied by a significant reduction in platelet activating factor activity, leukotriene B4, and vasoactive intestinal peptide concentrations. There were no significant changes in mucosal leukotriene C4 and calcitonin gene related peptide levels. This study shows that acetic acid induced colitis is pharmacologically manipulated by octreotide. The mechanism of action of octreotide has not yet been fully determined. The potential use of octreotide in treating active inflammatory bowel disease remains to be evaluated. Images Figure 5 PMID:8381760

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

    PubMed

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

    2008-05-01

    Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial pCO2 gradient, DeltapCO2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial pCO2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63+/-2 [mean+/-SEM]; Acute Physiology and Chronic Health Evaluation II score, 20+/-1; Sequential Organ Failure Assessment score, 8+/-0). pHi, and the effects of bicarbonate and arterial and mucosal pCO2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27+/-0.01) due to low arterial bicarbonate and increased DeltapCO2. Low pHi (<7.32) at admission (n=58; mortality, 29% vs. 13% in those with pHi>or=7.32 at admission; P=0.061) was associated with an increased DeltapCO2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltapCO2; P=0.0003). An increased versus normal DeltapCO2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P<0.0001; n=39) and at 6 h (34% vs. 13%; P=0.016; n=45). A delayed normalization or persistently low pHi (n=47) or high DeltapCO2 (n=25) was associated with high mortality (low pHi [34%] vs. high DeltapCO2 [60%]; P=0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all Pperfusion and is associated with high mortality. Arterial bicarbonate contributes more to pHi than the DeltapCO2 but is not associated with mortality. Hyperventilation partly masks mucosal acidosis. Inadequate tissue perfusion may persist despite stable hemodynamics and contributes to poor outcome. PMID:18004228

  7. 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. PMID:26899317

  8. 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

  9. 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

  10. Implementing change in perfusion practice: quality improvement vs. experimentation?

    PubMed

    Newland, Richard F; Baker, Robert A

    2009-12-01

    The desire to optimize techniques and interventions that comprise clinical practice will inevitably involve the implementation of change in the process of care. To confirm the intended benefits of instituting clinical change, the process should be undertaken in a scientific manner. Although implementing changes in perfusion practice is limited by the availability of evidence based practice guidelines, we have the opportunity to audit our current practice according to institutional guidelines using quality improvement methods. Current electronic data collection technology is a useful tool available to facilitate the reporting of both clinical and process outcome improvements. The model of clinical effectiveness can be used as a systematic approach to introducing change in clinical practice, which involves reviewing the literature, acquiring appropriate skills and resources, auditing the change, and implementing continuous quality improvement to standardize the process. Finally, reporting the findings allows dissemination of the knowledge that can be generalized. Reporting change strengthens our efforts in clinical effectiveness, highlights the importance of perfusion practice, and increases the influence of the profession. PMID:20092082

  11. 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 5minutes, 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 30minutes. 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. PMID:26809237

  12. Importance of luminal and mucosal zinc in the mechanism of experimental gastric ulcer healing.

    PubMed

    Opoka, W; Adamek, D; Plonka, M; Reczynski, W; Bas, B; Drozdowicz, D; Jagielski, P; Sliwowski, Z; Adamski, P; Brzozowski, T

    2010-10-01

    Zinc has been reported to exert a gastroprotective action against various experimental gastric lesions suggesting that this trace element is involved in the integrity of the gastric mucosa. Compounds containing zinc, such as polaprezinc, were developed in Japan and used as an antiulcer drugs in the treatment of human peptic ulcer disease. However, the precise mechanism of Zn(2+) containing compounds and their effects on mucosal integrity, gastroprotection and ulcer healing remain unclear. We have determined the efficacy of zinc hydroaspartate, a compound containing Zn(2+), in the mechanism of gastric secretion and ulcer healing in rats with chronic gastric ulcers induced by acetic acid (initial ulcer area = 28 mm(2)). Rats with gastric ulcers were randomized into two groups: A) with gastric fistulas (GF) and B) without gastric fistulas and received a daily treatment with zinc hydroaspartate (32-130 mg/kg-d i.g.) for 3, 7 and 14 days. At the termination of each treatment, the area of gastric ulcers were examined by planimetry, the gastric blood flow (GBF) at ulcer margin was assessed by laser Doppler flowmetry and H(2)-gas clearance methods. The venous blood was withdrawn for a measurement of plasma gastrin levels by radioimmunoassay (RIA). The concentration of Zn(2+) in the gastric juice and mucosa at the ulcer margin were determined by differential pulse anodic stripping voltammetry (DPASV) and flame atomic absorption spectrometry (FAAS) methods and the gastric biopsy samples were taken for histopathological assessment of the quality of ulcer healing. The ulcers healed gradually, with the ulcer area in the vehicle control rats being diminished by 15%, 48% and 78% upon ulcer induction at 3, 7 and 14 days, respectively. Zinc hydroaspartate dose-dependently inhibited the area of gastric ulcer, the dose reducing this area by 50% (ID(50)) being about 60 mg/kg-d. The mucosal concentration of Zn(2+) significantly was unchanged from the baseline immediately after ulcer

  13. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

    PubMed Central

    Medeiros, Israel L.; Pêgo-Fernandes, Paulo M.; Mariani, Alessandro W.; Fernandes, Flávio G.; Unterpertinger, Fernando V.; Canzian, Mauro; Jatene, Fabio B.

    2012-01-01

    OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex® was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98). The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p = 0.035). The mean pulmonary compliance was 46.8 cm H2O in Group 1 and 49.3 ml/cm H2O in Group 2 (p = 0.816). The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p = 0.87). The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0), and the apoptotic cell counts were 118.75/mm2 and 137.50/mm2, respectively (p = 0.71). CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation. PMID:23018310

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

    PubMed Central

    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.

    2015-01-01

    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 [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]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 [14C]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 [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]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. PMID:26676251

  15. Extracorporeal machine perfusion of the pancreas: technical aspects and its clinical implications--a systematic review of experimental models.

    PubMed

    Kuan, Kean Guan; Wee, Mau Nam; Chung, Wen Yuan; Kumar, Rohan; Mees, Soeren Torge; Dennison, Ashley; Maddern, Guy; Trochsler, Markus

    2016-01-01

    Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is particularly susceptible to ischaemic-reperfusion injury, the criteria for pancreas and islet donation are especially strict. With a chronic shortage of donors, one critical challenge is to maximise organ availability and expand the donor pool. To achieve that, continuous improvement in organ preservation is required, with the aims of reducing ischaemia-reperfusion injury, prolong preservation time and improve graft function. Static cold storage, the only method used in clinical pancreas and islet cell transplant currently, has likely reached its plateau. Machine perfusion, hypothermic or normothermic, could hold the key to improving donor pancreas quality as well as quantity available for transplant. This article reviews the literature on experimental models of pancreas machine perfusion, examines the benefits of machine perfusion, the technical aspects and their clinical implications. PMID:26253243

  16. The Healing Effects of Autologous Mucosal Grafts in Experimentally Injured Rabbit Maxillary Sinuses

    PubMed Central

    Topdag, Murat; Kara, Ahmet; Konuk, Esma; Demir, Necdet; Ozturk, Murat; Calıskan, Sebla; Topdag, Deniz Ozlem; Ulubil, Arif; Keskin, Ibrahim Gurkan; Iseri, Mete

    2016-01-01

    Objectives Healing processes of the nose and paranasal sinuses are quite complex, and poorly understood. In this study, we aimed to compare the effect of mucosal autologous grafts on the degenerated rabbit maxillary sinus mucosa with spontaneous wound healing. It is hypothesized that mucosal grafts will enhance ciliogenesis and improve the morphology of regenerated cilia. Methods Ten female New Zealand rabbits were included in the study. They underwent external maxillary sinus surgery through a transcutaneous approach. A total of 20 maxillary sinuses were randomly divided into 2 groups: ‘spontaneous healing group’ and ‘autologous graft group.’ The animals were sacrificed at the 14th day after the surgery. Scanning electron microscope (SEM), and light microscope were used for the evaluation. Results Cellular composition of the graft group is better than the spontaneous healing group. The graft group had larger areas covered with ciliary epithelium than the spontaneous healing group, and the mean length of the cilias were also longer. Additionally, there were wider cilia with abnormal morphology areas in the spontaneous healing group. Conclusion In our opinion, covering of the denuded areas with a graft improves re-epithelization, and may prevent the early complications after sinus surgeries. PMID:26976026

  17. The role of gastric mucosal histamine in acid secretion and experimentally induced lesions in the rat.

    PubMed

    Andersson, K; Mattsson, H; Larsson, H

    1990-01-01

    The role played by histamine from enterochromaffin-like (ECL) cells and mast cells in gastric acid secretion and in the development of ethanol-induced gastric lesions was studied in the rat. This was done by examining the effects of inhibition of the histamine-producing enzyme histidine decarboxylase (HDC) with alpha-fluoromethylhistidine (alpha-FMH) and the effects of degranulation of the mucosal mast cells with dexamethasone. A single dose of alpha-FMH (50 mg/kg p.o.) inhibited the HDC activity by 94% but did not affect histamine levels in the gastric mucosa 2 h after dose. Repeated treatment resulted in an almost complete inhibition of HDC activity and in a reduction of histamine levels by 75%. Pentagastrin failed to stimulate acid secretion after 4 days treatment with alpha-FMH, whereas the acid response to histamine was unaffected in chronic gastric fistula rats. Ethanol failed to induce gastric lesions in rats pretreated for 4 days with dexamethasone whereas 4 days pretreatment with alpha-FMH did not influence ethanol-induced lesion formation. The present results show that histamine synthesis is required for pentagastrin-stimulated gastric acid secretion and that mucosal mast-cell histamine plays a role in the development of ethanol-induced gastric lesions. PMID:2210091

  18. 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

  19. Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in Experimental Ischemic Stroke

    PubMed Central

    Leoni, Renata F.; Paiva, Fernando F.; Kang, Byeong-Teck; Henning, Erica C.; Nascimento, George C.; Tannús, Alberto; De Araújo, Dráulio B.; Silva, Afonso C.

    2016-01-01

    Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23 ± 9%) than animals with left dominance (7 ± 5%, P < 0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation. PMID:24323754

  20. Insulin-Like Growth Factor-1 Contributes to Mucosal Repair by β-Arrestin2-Mediated Extracellular Signal-Related Kinase Signaling in Experimental Colitis.

    PubMed

    Chen, Tingting; Zheng, Fengping; Tao, Jin; Tan, Siwei; Zeng, Lixian; Peng, Xiaojie; Wu, Bin

    2015-09-01

    Insulin-like growth factor-1 (IGF-1) possesses the ability to attenuate intestinal damage and promote mucosal repair of colitis. β-Arrestins, as the scaffolding proteins of G protein-coupled receptors or non-G protein-coupled receptors signaling, can be involved in IGF-1-mediated signaling pathways. However, the interaction of IGF-1 and β-arrestin2 in the mucosal repair of experimental colitis remains unexplored. Ulcerative colitis was induced in β-arrestin2 wild-type mice and β-arrestin2 knockout littermates by using 3% dextran sulfate sodium for 5 days, followed by regular water consumption for 1, 2, 3, and 4 weeks to analyze the mucosal repair from experimental colitis. Disease activity index and histologic score analyses were performed. Apoptosis and proliferation were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Ki-67 staining, respectively. The expressions of β-arrestin2, phospho (p)-IGF-1R, and p-extracellular signal-regulated kinase (ERK)1/2 were examined. Furthermore, β-arrestin2 was overexpressed or altered in HCT116 cells by transfection before IGF-1 treatment in vitro. IGF-1 and β-arrestin2 expression was up-regulated in the repairing phase of experimental colitis. Targeted deletion of β-arrestin2 delayed the repair of colitis by inhibiting cell proliferation without affecting the levels of IGF-1 and p-IGF-1R. The β-arrestin2/ERK signaling pathway was involved in IGF-1-mediated mucosal repair through promoting epithelial cell and goblet cell regeneration from experimental colitis. These results indicate that IGF-1 contributes to the mucosal repair by β-arrestin2-mediated ERK signaling in experimental colitis. PMID:26362717

  1. 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. PMID:26410628

  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. Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat.

    PubMed Central

    Butzner, J D; Parmar, R; Bell, C J; Dalal, V

    1996-01-01

    BACKGROUND--The short chain fatty acid (SCFA) butyrate provides energy for colonocytes, stimulates colonic fluid and electrolyte absorption and is recognised as an effective treatment for multiple types of colitis. AIM--To examine the impact of butyrate enema therapy on the clinical course, severity of inflammation, and SCFA stimulated Na+ absorption in a chronic experimental colitis. METHODS--Distal colitis was induced in rats with a trinitrobenzenesulphonic acid (TNBS) enema. Five days after induction, rats were divided into groups to receive: no treatment, saline enemas, or 100 mM Na-butyrate enemas daily. On day 24, colonic damage score and tissue myeloperoxidase (MPO) activity were evaluated. Colon was mounted in Ussing chambers and Na+ transport and electrical activities were measured during a basal period and after stimulation with 25 mM butyrate. RESULTS--In the untreated and the saline enema treated TNBS groups, diarrhoea and extensive colonic damage were seen, associated with increased tissue MPO activities and absent butyrate stimulated Na+ absorption. In contrast, in the butyrate enema treated TNBS group, diarrhoea ceased, colonic damage score improved, and tissue MPO activity as well as butyrate stimulated Na+ absorption recovered to control values. CONCLUSION--Butyrate enema therapy stimulated colonic repair, as evidenced by clinical recovery, decreased inflammation, and restoration of SCFA stimulated electrolyte absorption. PMID:8707089

  5. 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

  6. Diffusion-perfusion relationships in skeletal muscle: models and experimental evidence from inert gas washout.

    PubMed

    Piiper, J; Meyer, M

    1984-01-01

    In order to study the dependence of blood-tissue gas exchange upon diffusion, the simultaneous washout of two inert gases of differing diffusivity was investigated in isolated-perfused dog gastrocnemius preparations. The muscles were equilibrated with CH4 and SF6 via arterial blood. The washout kinetics were determined from venous blood samples analyzed by gas chromatography. The results revealed the following features: The washout of the test gases was pronouncedly multi-exponential, and could be described by three exponential components when analyzed to 5% of the initial value. The non-exponential washout was attributed to unequal distribution of capillary blood flow to tissue volume. The mean ratio of washout rate constants CH4/SF6 was within 1.10-1.25 and was even smaller than the ratio expected for pure perfusion limitation (1.46). Therefore, no evidence for effective tissue-blood diffusion limitation was obtained. The observed washout rate constant ratio could be explained by a model with veno-arterial back diffusion which more strongly retards washout kinetics of the better diffusible gas (CH4) as compared to the less diffusible gas (SF6). PMID:6731103

  7. Mucosal immunoglobulins.

    PubMed

    Woof, Jenny M; Mestecky, Jiri

    2005-08-01

    Due to their vast surface area, the mucosal surfaces of the body represent a major site of potential attack by invading pathogens. The secretions that bathe mucosal surfaces contain significant levels of immunoglobulins (Igs), which play key roles in immune defense of these surfaces. IgA is the predominant antibody class in many external secretions and has many functional attributes, both direct and indirect, that serve to prevent infective agents such as bacteria and viruses from breaching the mucosal barrier. This review details current understanding of the structural and functional characteristics of IgA, including interaction with specific receptors (such as Fc(alpha)RI, Fc(alpha)/microR, and CD71) and presents examples of the means by which certain pathogens circumvent the protective properties of this important Ig. PMID:16048542

  8. A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.

    PubMed

    Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N

    2015-05-01

    The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation. PMID:25777770

  9. B7 interactions with CD28 and CTLA-4 control tolerance or induction of mucosal inflammation in chronic experimental colitis.

    PubMed

    Liu, Z; Geboes, K; Hellings, P; Maerten, P; Heremans, H; Vandenberghe, P; Boon, L; van Kooten, P; Rutgeerts, P; Ceuppens, J L

    2001-08-01

    CD28-B7 interaction plays a critical costimulatory role in inducing T cell activation, while CTLA-4-B7 interaction provides a negative signal that is essential in immune homeostasis. Transfer of CD45RB(high)CD4(+) T cells from syngeneic mice induces transmural colon inflammation in SCID recipients. This adoptive transfer model was used to investigate the contribution of B7-CD28/CTLA-4 interactions to the control of intestinal inflammation. CD45RB(high)CD4(+) cells from CD28(-/-) mice failed to induce mucosal inflammation in SCID recipients. Administration of anti-B7.1 (but not anti-B7.2) after transfer of wild-type CD45RB(high)CD4(+) cells also prevented wasting disease with colitis, abrogated leukocyte infiltration, and reduced production of proinflammatory cytokines IL-2 and IFN-gamma by lamina propria CD4(+) cells. In contrast, anti-CTLA-4 treatment led to deterioration of disease, to more severe inflammation, and to enhanced production of proinflammatory cytokines. Of note, CD25(+)CD4(+) cells from CD28(-/-) mice similar to those from the wild-type mice were efficient to prevent intestinal mucosal inflammation induced by the wild-type CD45RB(high) cells. The inhibitory functions of these regulatory T cells were effectively blocked by anti-CTLA-4. These data show that the B7-CD28 costimulatory pathway is required for induction of effector T cells and for intestinal mucosal inflammation, while the regulatory T cells function in a CD28-independent way. CTLA-4 signaling plays a key role in maintaining mucosal lymphocyte tolerance, most likely by activating the regulatory T cells. PMID:11466409

  10. Monitoring Cell Death in Regorafenib-Treated Experimental Colon Carcinomas Using Annexin-Based Optical Fluorescence Imaging Validated by Perfusion MRI

    PubMed Central

    Kazmierczak, Philipp M.; Burian, Egon; Eschbach, Ralf; Hirner-Eppeneder, Heidrun; Moser, Matthias; Havla, Lukas; Eisenblätter, Michel; Reiser, Maximilian F.; Nikolaou, Konstantin; Cyran, Clemens C.

    2015-01-01

    Objective To investigate annexin-based optical fluorescence imaging (OI) for monitoring regorafenib-induced early cell death in experimental colon carcinomas in rats, validated by perfusion MRI and multiparametric immunohistochemistry. Materials and Methods Subcutaneous human colon carcinomas (HT-29) in athymic rats (n = 16) were imaged before and after a one-week therapy with regorafenib (n = 8) or placebo (n = 8) using annexin-based OI and perfusion MRI at 3 Tesla. Optical signal-to-noise ratio (SNR) and MRI tumor perfusion parameters (plasma flow PF, mL/100mL/min; plasma volume PV, %) were assessed. On day 7, tumors underwent immunohistochemical analysis for tumor cell apoptosis (TUNEL), proliferation (Ki-67), and microvascular density (CD31). Results Apoptosis-targeted OI demonstrated a tumor-specific probe accumulation with a significant increase of tumor SNR under therapy (mean Δ +7.78±2.95, control: -0.80±2.48, p = 0.021). MRI detected a significant reduction of tumor perfusion in the therapy group (mean ΔPF -8.17±2.32 mL/100 mL/min, control -0.11±3.36 mL/100 mL/min, p = 0.036). Immunohistochemistry showed significantly more apoptosis (TUNEL; 11392±1486 vs. 2921±334, p = 0.001), significantly less proliferation (Ki-67; 1754±184 vs. 2883±323, p = 0.012), and significantly lower microvascular density (CD31; 107±10 vs. 182±22, p = 0.006) in the therapy group. Conclusions Annexin-based OI allowed for the non-invasive monitoring of regorafenib-induced early cell death in experimental colon carcinomas, validated by perfusion MRI and multiparametric immunohistochemistry. PMID:26393949

  11. 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.

  12. Correlation of Perfusion MRI and 18F-FDG PET Imaging Biomarkers for Monitoring Regorafenib Therapy in Experimental Colon Carcinomas with Immunohistochemical Validation

    PubMed Central

    Eschbach, Ralf S.; Fendler, Wolfgang P.; Kazmierczak, Philipp M.; Hacker, Marcus; Rominger, Axel; Carlsen, Janette; Hirner-Eppeneder, Heidrun; Schuster, Jessica; Moser, Matthias; Havla, Lukas; Schneider, Moritz J.; Ingrisch, Michael; Spaeth, Lukas; Reiser, Maximilian F.; Nikolaou, Konstantin; Cyran, Clemens C.

    2015-01-01

    Objectives To investigate a multimodal, multiparametric perfusion MRI / 18F-fluoro-deoxyglucose-(18F-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation. Materials and Methods Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 17 (n = 10 therapy group; n = 7 control group) female athymic nude rats (Hsd:RH-Foxn1rnu). Animals were imaged at baseline and after a one-week daily treatment protocol with regorafenib (10 mg/kg bodyweight) using a multimodal, multiparametric perfusion MRI/18F-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min), plasma volume (PV, %) and endothelial permeability-surface area product (PS, mL/100 mL/min) were calculated. In 18F-FDG-PET, tumor-to-background-ratio (TTB) was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor microvascular density (CD-31) and cell proliferation (Ki-67). Results Regorafenib significantly (p<0.01) suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min), PV (12.1±3.6 to 7.5±1.6%) and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min) as well as TTB (3.4±0.6 to 1.9±1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9) and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3) in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01) correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05). Conclusions A multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant

  13. 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 ...

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

    PubMed

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

    2014-08-21

    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. PMID:25069101

  15. 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.

  16. Mucosal dendritic cells shape mucosal immunity

    PubMed Central

    Chang, Sun-Young; Ko, Hyun-Jeong; Kweon, Mi-Na

    2014-01-01

    Dendritic cells (DCs) are key modulators that shape the immune system. In mucosal tissues, DCs act as surveillance systems to sense infection and also function as professional antigen-presenting cells that stimulate the differentiation of naive T and B cells. On the basis of their molecular expression, DCs can be divided into several subsets with unique functions. In this review, we focus on intestinal DC subsets and their function in bridging the innate signaling and adaptive immune systems to maintain the homeostasis of the intestinal immune environment. We also review the current strategies for manipulating mucosal DCs for the development of efficient mucosal vaccines to protect against infectious diseases. PMID:24626170

  17. 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.

  18. Experimental studies of the physiologic properties of technetium-99m agents: Myocardial transport of perfusion imaging agents

    SciTech Connect

    Meerdink, D.J.; Leppo, J.A. )

    1990-10-16

    The physiologic properties of new technetium-99m-labeled myocardial imaging agents (Tc-99m sestamibi, an isonitrile; and Tc-99m teboroxime, a boronic acid adduct of technetium dioxime) are discussed and compared to thallium-201 (Tl-201). Studies with isolated hearts, subcellular fractions and cell cultures indicate that Tc-99m sestamibi, Tc-99m teboroxime and Tl-201 do not share common transport or sequestration mechanisms. Although peak Tc-99m sestamibi myocardial extraction over time is about half that of Tl-201 at equivalent coronary blood flows, the amount of Tc-99m sestamibi that remains in the heart is similar to that of Tl-201 because of its higher retention efficiency. The high retention efficiency for Tc-99m sestamibi also results in minimal redistribution. In contrast, Tc-99m teboroxime myocardial extraction is higher than that of Tl-201, but its retention is less efficient, resulting in relatively rapid washout characteristics which may quickly result in tracer redistribution. During reperfusion after a no-flow period, Tc-99m sestamibi extraction and retention increase, but for Tc-99m teboroxime and Tl-201 these values tend to decrease. All tracers show adequate transport characteristics for perfusion imaging, and differences in transport and retention should lead to the development of new clinical protocols.27 references.

  19. 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...

  20. Mucosal immunity: its role in defense and allergy.

    PubMed

    Tlaskalová-Hogenová, Helena; Tucková, Ludmila; Lodinová-Zádniková, Rája; Stepánková, Renata; Cukrowska, Bozena; Funda, David P; Striz, Ilja; Kozáková, Hana; Trebichavský, Ilja; Sokol, Dan; Reháková, Zuzana; Sinkora, Jirí; Fundová, Petra; Horáková, Dana; Jelínková, Lenka; Sánchez, Daniel

    2002-06-01

    The interface between the organism and the outside world, which is the site of exchange of nutrients, export of products and waste components, must be selectively permeable and at the same time, it must constitute a barrier equipped with local defense mechanisms against environmental threats (e.g. invading pathogens). The boundaries with the environment (mucosal and skin surfaces) are therefore covered with special epithelial layers which support this barrier function. The immune system, associated with mucosal surfaces covering the largest area of the body (200-300 m(2)), evolved mechanisms discriminating between harmless antigens and commensal microorganisms and dangerous pathogens. The innate mucosal immune system, represented by epithelial and other mucosal cells and their products, is able to recognize the conserved pathogenic patterns on microbes by pattern recognition receptors such as Toll-like receptors, CD14 and others. As documented in experimental gnotobiotic models, highly protective colonization of mucosal surfaces by commensals has an important stimulatory effect on postnatal development of immune responses, metabolic processes (e.g. nutrition) and other host activities; these local and systemic immune responses are later replaced by inhibition, i.e. by induction of mucosal (oral) tolerance. Characteristic features of mucosal immunity distinguishing it from systemic immunity are: strongly developed mechanisms of innate defense, the existence of characteristic populations of unique types of lymphocytes, colonization of the mucosal and exocrine glands by cells originating from the mucosal organized tissues ('common mucosal system') and preferential induction of inhibition of the responses to nondangerous antigens (mucosal tolerance). Many chronic diseases, including allergy, may occur as a result of genetically based or environmentally induced changes in mechanisms regulating mucosal immunity and tolerance; this leads to impaired mucosal barrier

  1. 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

  2. Mucosal Immunology of Food Allergy

    PubMed Central

    Berin, M. Cecilia; Sampson, Hugh A.

    2013-01-01

    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 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 microbiome, are likely to shed light on factors responsible for the growing clinical problem of food allergy. PMID:23660362

  3. 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.

  4. Gasoline-induced mucositis

    SciTech Connect

    Hoffman, D.L.; Swanson, B.Z. Jr.; Lutins, N.D.

    1980-02-01

    Gasoline-induced mucositis may become more common because of fuel shortages or increased fuel cost. Dentists should, therefore, consider this oral irritant in the differential diagnosis of oral lesions.

  5. 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...

  6. Nasal mucosal biopsy

    MedlinePlus

    Biopsy - nasal mucosa; Nose biopsy ... to fast for a few hours before the biopsy. ... Nasal mucosal biopsy is usually done when abnormal tissue is seen during examination of the nose. It may also be done ...

  7. Mucosal delivery of vaccines.

    PubMed

    Del Giudice, G; Pizza, M; Rappuoli, R

    1999-09-01

    Oral delivery represents one of the most pursued approaches for large-scale human vaccination. Due to the different characteristics of mucosal immune response, as compared with systemic response, oral immunization requires particular methods of antigen preparation and selective strategies of adjuvanticity. In this paper, we describe the preparation and use of genetically detoxified bacterial toxins as mucosal adjuvants and envisage the possibility of their future exploitation for human oral vaccines. PMID:10525451

  8. 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

  9. Identification of epitopes recognised by mucosal CD4(+) T-cell populations from cattle experimentally colonised with Escherichia coli O157:H7.

    PubMed

    Corbishley, Alexander; Connelley, Timothy K; Wolfson, Eliza B; Ballingall, Keith; Beckett, Amy E; Gally, David L; McNeilly, Tom N

    2016-01-01

    Vaccines targeting enterohaemorrhagic Escherichia coli (EHEC) O157:H7 shedding in cattle are only partially protective. The correlates of protection of these vaccines are unknown, but it is probable that they reduce bacterial adherence at the mucosal surface via the induction of blocking antibodies. Recent studies have indicated a role for cellular immunity in cattle during colonisation, providing an impetus to understand the bacterial epitopes recognised during this response. This study mapped the epitopes of 16 EHEC O157:H7 proteins recognised by rectal lymph node CD4(+) T-cells from calves colonised with Shiga toxin producing EHEC O157:H7 strains. 20 CD4(+) T-cell epitopes specific to E. coli from 7 of the proteins were identified. The highly conserved N-terminal region of Intimin, including the signal peptide, was consistently recognised by mucosal CD4(+) T-cell populations from multiple animals of different major histocompatibility complex class II haplotypes. These T-cell epitopes are missing from many Intimin constructs used in published vaccine trials, but are relatively conserved across a range of EHEC serotypes, offering the potential to develop cross protective vaccines. Antibodies recognising H7 flagellin have been consistently identified in colonised calves; however CD4(+) T-cell epitopes from H7 flagellin were not identified in this study, suggesting that H7 flagellin may act as a T-cell independent antigen. This is the first time that the epitopes recognised by CD4(+) T-cells following colonisation with an attaching and effacing pathogen have been characterised in any species. The findings have implications for the design of antigens used in the next generation of EHEC O157:H7 vaccines. PMID:27590451

  10. Pulmonary ventilation/perfusion scan

    MedlinePlus

    V/Q scan; Ventilation/perfusion scan; Lung ventilation/perfusion scan ... A pulmonary ventilation/perfusion scan is actually two tests. They may be done separately or together. During the perfusion scan, a health ...

  11. Topical use of Rectogesic® and Emla® to improve cutaneous blood perfusion following thermal injury. A comparative experimental study.

    PubMed

    Tagkalakis, P; Dionyssopoulos, A; Karkavelas, G; Demiri, E

    2015-06-30

    Early post-burn ischemic necrosis of the skin is of particular interest in modern burn research. The purpose of this study was to test the hypothesis that blood perfusion could be improved by the topical application of vasoactive substances. A sample of 55 wistar rats was used to investigate the effect of 0,4% nitroglycerin ointment (Rectogesic(®)) comparatively to no application and placebo. The beneficiary action of 5% prilocaine/lidocaine cream (EMLA(®)) in burn blood perfusion was also tested comparatively to Rectogesic(®). Both preparations were tested respectively to non burned controls. Laser Doppler assessment of blood flow at 15, 30, 45, 60, 120 and 180 minutes after preparation application, demonstrated that the use of Rectogesic(®) improved perfusion at all measurements compared to placebo and to no preparation application (p&0,05). There was no statistical significant difference in the effect of the two preparations. PMID:27252612

  12. Topical use of Rectogesic® and Emla® to improve cutaneous blood perfusion following thermal injury. A comparative experimental study

    PubMed Central

    Tagkalakis, P.; Dionyssopoulos, A.; Karkavelas, G.; Demiri, E.

    2015-01-01

    Summary Early post-burn ischemic necrosis of the skin is of particular interest in modern burn research. The purpose of this study was to test the hypothesis that blood perfusion could be improved by the topical application of vasoactive substances. A sample of 55 wistar rats was used to investigate the effect of 0,4% nitroglycerin ointment (Rectogesic®) comparatively to no application and placebo. The beneficiary action of 5% prilocaine/lidocaine cream (EMLA®) in burn blood perfusion was also tested comparatively to Rectogesic®. Both preparations were tested respectively to non burned controls. Laser Doppler assessment of blood flow at 15, 30, 45, 60, 120 and 180 minutes after preparation application, demonstrated that the use of Rectogesic® improved perfusion at all measurements compared to placebo and to no preparation application (p&0,05). There was no statistical significant difference in the effect of the two preparations. PMID:27252612

  13. Hypothermia improves oral and gastric mucosal microvascular oxygenation during hemorrhagic shock in dogs.

    PubMed

    Vollmer, Christian; Schwartges, Ingo; Swertz, Meike; Beck, Christopher; Bauer, Inge; Picker, Olaf

    2013-01-01

    Hypothermia is known to improve tissue function in different organs during physiological and pathological conditions. The aim of this study was to evaluate the effects of hypothermia on oral and gastric mucosal microvascular oxygenation (μHbO2) and perfusion (μflow) under physiological and hemorrhagic conditions. Five dogs were repeatedly anesthetized. All animals underwent each experimental protocol (randomized cross-over design): hypothermia (34°C), hypothermia during hemorrhage, normothermia, and normothermia during hemorrhage. Microcirculatory and hemodynamic variables were recorded. Systemic (DO2) and oral mucosal (μDO2) oxygen delivery were calculated. Hypothermia increased oral μ HbO2 with no effect on gastric μHbO2. Hemorrhage reduced oral and gastric μHbO2 during normothermia (-36 ± 4% and -27 ± 7%); however, this effect was attenuated during additional hypothermia (-15 ± 5% and -11 ± 5%). The improved μ HbO2 might be based on an attenuated reduction in μ flow during hemorrhage and additional hypothermia (-51 ± 21 aU) compared to hemorrhage and normothermia (-106 ± 19 aU). μDO2 was accordingly attenuated under hypothermia during hemorrhage whereas DO2 did not change. Thus, in this study hypothermia alone improves oral μHbO2 and attenuates the effects of hemorrhage on oral and gastric μ HbO2. This effect seems to be mediated by an increased μDO2 on the basis of increased μ flow. PMID:24327826

  14. Mucosal injury and. gamma. -irradiation produce persistent gastric ulcers in the rabbit. Evaluation of antiulcer drug binding to experimental ulcer sites

    SciTech Connect

    Yokel, R.A.; Dickey, K.M. )

    1991-05-01

    A method producing persistent gastric ulcers in the rhesus monkey by combined mucosal injury and {gamma}-irradiation was modified and evaluated in the rabbit. {gamma}-Irradiation (800-1000 cGy) immediately after removal of 2-mm-diameter sections of antral mucosa resulted in ulcer craters 5-7 days later. Ulcer sites were characterized by loss of the mucosa, muscularis mucosa, and much of the submucosa. The exposed submucosa was coated with fibrin and necrotic debris infiltrated with heterophils, the rabbit equivalent of neutrophils. These ulcers strongly resemble human chronic gastric ulcers. Binding of Carafate (sucralfate; Marion Laboratories, Inc., Kansas City, MO) and Maalox (magnesia-alumina oral suspension; Wm. H. Rorer, Inc., Ft. Washington, PA) to ulcer and nearby nonulcer sites in the antrum was assessed 1 hour after drug dosing. Drug binding was determined by aluminum quantitation of stomach wall punch biopsies at necropsy. Both drugs significantly increased aluminum bound to the stomach wall compared with vehicle treatment. Significantly more antiulcer drug was bound to ulcer sites than to nearby nonulcer sites only after sucralfate administration. This model of persistent gastric ulcer should be useful to further study gastric ulcer pathogenesis and treatment.

  15. Developing a tissue perfusion sensor.

    PubMed

    Harvey, S L R; Parker, K H; O'Hare, D

    2007-01-01

    The development of a electrochemical tissue perfusion sensor is presented. The sensor is a platinum/platinum ring-disc microelectrode that relies on the principle of collector-generator to monitor mass transport within its vicinity. Tissue perfusion is a mass transport mechanism that describes the movement of respiratory gases, nutrients and metabolites in tissue. The sensor's capability of detecting perfusion at the cellular level in a continuous fashion is unique. This sensor will provide insight into the way nutrients and metabolites are transported in tissue especially in cases were perfusion is low such as in wounds or ischemic tissue. We present experimental work for the development and testing of the sensors in vitro. Experimental flow recordings in free steam solutions as well as the flow through tissue-like media are shown. Tests on post operative human tissue are also presented. The sensor's feature such as the continuous recoding capacities, spatial resolution and the measurement range from ml/min to microl/min are highlighted. PMID:18002549

  16. Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion.

    PubMed

    Bell, Robert M; Mocanu, Mihaela M; Yellon, Derek M

    2011-06-01

    In the late 19th century, a number of investigators were working on perfecting isolated heart model, but it was Oscar Langendorff who, in 1895, pioneered the isolated perfused mammalian heart. Since that time, the Langendorff preparation has evolved and provided a wealth of data underpinning our understanding of the fundamental physiology of the heart: its contractile function, coronary blood flow regulation and cardiac metabolism. In more recent times, the procedure has been used to probe pathophysiology of ischaemia/reperfusion and disease states, and with the dawn of molecular biology and genetic manipulation, the Langendorff perfused heart has remained a stalwart tool in the study of the impact upon the physiology of the heart by pharmacological inhibitors and targeted deletion or up-regulation of genes and their impact upon intracellular signalling and adaption to clinically relevant stressful stimuli. We present here the basic structure of the Langendorff system and the fundamental experimental rules which warrant a viable heart preparation. In addition, we discuss the use of the isolated retrograde perfused heart in the model of ischaemia-reperfusion injury ex-vivo, and its applicability to other areas of study. The Langendorff perfusion apparatus is highly adaptable and this is reflected not only in the procedure's longevity but also in the number of different applications to which it has been turned. PMID:21385587

  17. A Phantom Tissue System for the Calibration of Perfusion Measurements

    PubMed Central

    Mudaliar, Ashvinikumar V.; Ellis, Brent E.; Ricketts, Patricia L.; Lanz, Otto I.; Scott, Elaine P.; Diller, Thomas E.

    2008-01-01

    A convenient method for testing and calibrating surface perfusion sensors has been developed. A phantom tissue model is used to simulate the nondirectional blood flow of tissue perfusion. A computational fluid dynamics (CFD) model was constructed in Fluent® to design the phantom tissue and validate the experimental results. The phantom perfusion system was used with a perfusion sensor based on clearance of thermal energy. A heat flux gage measures the heat flux response of tissue when a thermal event (convective cooling) is applied. The blood perfusion and contact resistance are estimated by a parameter estimation code. From the experimental and analytical results, it was concluded that the probe displayed good measurement repeatability and sensitivity. The experimental perfusion measurements in the tissue were in good agreement with those of the CFD models and demonstrated the value of the phantom tissue system. PMID:19045509

  18. 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

  19. 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.

  20. 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.

  1. Experience with registered mucosal vaccines.

    PubMed

    Dietrich, Guido; Griot-Wenk, Monika; Metcalfe, Ian C; Lang, Alois B; Viret, Jean-François

    2003-01-30

    Most pathogens gain access to their host through mucosal surfaces. It is therefore desirable to develop vaccination strategies that lead to mucosal immune responses. Ideally, a vaccine should be administered mucosally in order to elicit mucosal protection. Several attenuated live viral and bacterial pathogens are registered as oral vaccines for human use, including the oral polio vaccine (Sabin) as well as attenuated strains of Salmonella typhi and Vibrio cholerae. These attenuated bacterial live vaccines-S. typhi Ty21a as well as V. cholerae CVD 103-HgR-are employed as vaccines against typhoid and cholera, respectively. In this manuscript, we review the immune responses that are induced by these vaccines, with a focus on mucosal immunity. PMID:12531339

  2. 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. PMID:21741878

  3. 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

  4. 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. PMID:26174763

  5. 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

  6. 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.

  7. Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats.

    PubMed

    Hernández-Muñoz, R; Montiel-Ruíz, C; Vázquez-Martínez, O

    2000-08-01

    The oxygen free radicals-induced lipid peroxidation (LP) has been implicated in the pathogenesis of acute ethanol-induced gastric mucosal lesions. However, the role of LP in the generation of chronic gastric mucosal injury is unknown. We have developed a model of chronic mucosal injury induced by continuous ethanol ingestion for 5 days and characterized by marked alterations in plasma membranes from gastric mucosa. Therefore, LP was evaluated in this experimental model. Indicators of peroxidative activity, mucosal glutathione content, thymidine kinase activity (an index of cell proliferation), and histamine H2-receptor (H2R) binding constants were quantified in animals undergoing gastric mucosal damage. The effect of famotidine, a H2R antagonist that readily ameliorates the chronic mucosal injury, was also tested. Increased free radicals and LP levels were detected during gastritis; however, a second, higher peak of LP was noted in mucosal plasma membranes after ethanol withdrawal (recovery period). This further increase of LP coincided with active cell proliferation, decreased mucosal glutathione levels, and diminished specific cimetidine binding by H2R. Administration of famotidine accelerated the mucosal proliferative process, inducing the second lipoperoxidative episode sooner, and preserved the content of glutathione. In addition, LP correlated directly with cell proliferation and inversely with mucosal membrane cimetidine binding. In conclusion, LP seems to be involved in chronic ethanol-induced gastric mucosal injury. However, a further enhancement of plasma membrane LP occurred, associated with increased DNA synthesis and diminished cimetidine binding by membrane H2R. Therefore, increased LP could also participate in the compensatory mucosal proliferation initiated after ethanol withdrawal. PMID:10950107

  8. Cheek mucosa territories perfused by perforators from the facial artery.

    PubMed

    Coronel-Banda, M E; Serra-Renom, J M; Lorente, M; Larrea-Terán, W P

    2015-01-01

    The cutaneous areas perfused by the cutaneous perforators of the facial artery have been well defined. However, the oral mucosal areas perfused by perforators of the facial artery have not been described. We studied 20 hemifaces from 10 cadavers. Perforators between the branching off sites of the labial arteries larger than 0.5 mm were selected and their diameters were measured; the distance between their exit point over the facial artery and the branching-off point from the superior labial artery was also measured. The selected perforators were injected with 1 ml of diluted ink. Both labial arteries were ligated to limit the study to the mucosal perforators from the facial artery. Seventy-four perforators from 20 hemifaces were studied; the mean diameter was 0.58 mm and the mean number per artery was 3.7. The total stained area, a triangle-shaped zone on the cheek, was determined. The more constant perforators larger than 0.5 mm were localized next to the branching-off site of the superior labial artery. With this information, flaps based on the mucosal perforators from the facial artery could be designed. PMID:25218801

  9. GPU-accelerated voxelwise hepatic perfusion quantification.

    PubMed

    Wang, H; Cao, Y

    2012-09-01

    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. PMID:22892645

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

    PubMed

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

    2016-07-01

    Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) (P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) (P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm(-2)·h(-1)) than in the proximal segment (368 nmol·cm(-2)·h(-1)) (P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability. PMID:27198192

  11. Perfusion in Britain: the early days.

    PubMed

    Braimbridge, Mark V

    2004-07-01

    Experimental perfusion was largely the province of Germany in the nineteenth century but in the mid-twentieth century the focus of perfusion switched to the USA with the explosive clinical advances of Lillehei, Kirklin and Cooley. British clinical perfusion started with Melrose in 1953 at the Postgraduate Medical School in London but, as in other centres at that time, stopped due to the high mortality. The arrival of hands-on experience of American expertise via returning research fellows and other visitors to the USA enabled the first successful on-going series to begin at the Hammersmith Hospital with Cleland in 1957 and then to spread around the country. The various problems of those early 1950s days are described in the units starting then. PMID:15376765

  12. 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. PMID:26700566

  13. Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node1

    PubMed Central

    Thompson, Joseph M.; Nicholson, Michael G.; Whitmore, Alan C.; Zamora, Melodie; West, Ande; Iwasaki, Akiko; Staats, Herman F.; Johnston, Robert E.

    2009-01-01

    The strongest mucosal immune responses are induced following mucosal Ag delivery and processing in the mucosal lymphoid tissues, and much is known regarding the immunological parameters which regulate immune induction via this pathway. Recently, experimental systems have been identified in which mucosal immune responses are induced following nonmucosal Ag delivery. One such system, footpad delivery of Venezuelan equine encephalitis virus replicon particles (VRP), led to the local production of IgA Abs directed against both expressed and codelivered Ags at multiple mucosal surfaces in mice. In contrast to the mucosal delivery pathway, little is known regarding the lymphoid structures and immunological components that are responsible for mucosal immune induction following nonmucosal delivery. In this study, we have used footpad delivery of VRP to probe the constituents of this alternative pathway for mucosal immune induction. Following nonmucosal VRP delivery, J chain-containing, polymeric IgA Abs were detected in the peripheral draining lymph node (DLN), at a time before IgA detection at mucosal surfaces. Further analysis of the VRP DLN revealed up-regulated α4β7 integrin expression on DLN B cells, expression of mucosal addressin cell adhesion molecule 1 on the DLN high endothelia venules, and production of IL-6 and CC chemokines, all characteristics of mucosal lymphoid tissues. Taken together, these results implicate the peripheral DLN as an integral component of an alternative pathway for mucosal immune induction. A further understanding of the critical immunological and viral components of this pathway may significantly improve both our knowledge of viral-induced immunity and the efficacy of viral-based vaccines. PMID:18566424

  14. Jejunal Perfusion of Simple and Conjugated Folates in Tropical Sprue

    PubMed Central

    Corcino, José J.; Reisenauer, Ann M.; Halsted, Charles H.

    1976-01-01

    Absorption of labeled simple 3′,5′,9′-3H pteroylmonoglutamate, ([3H]PG-1) and conjugated pteroyl-μ[14C]glutamyl-γ-hexaglutamate, ([14C]PG-7) folates was assessed in six patients with tropical sprue, before and after 6 mo of treatment, utilizing jejunal perfusion and urinary recovery techniques. Degradation products of [14C]PG-7 which were produced during perfusion were identified by DEAE-cellulose column chromatography. Jejunal mucosal activities of folate conjugase, lactase, sucrase, and maltase were measured in every patient. Malabsorption of both [3H]PG-1 and [14C]PG-7 was found in every untreated patient, with significant improvement after therapy. The urinary excretion of 3H and 14C paralleled the luminal disappearance of both isotopes. The chromatographic patterns of intraluminal degradation products of [14C]PG-7 obtained during perfusion did not differ from those previously found in normal subjects and were similar in studies performed before and after treatment. The activity of folate conjugase was increased in the mucosa of the untreated patients when compared to the post-treatment levels while the activities of mucosal lactase, sucrase, and maltase were originally low and increased significantly after therapy. These observations suggest that folate conjugase originates at a different mucosal locus than the brush border disaccharidases, and are consistent with previous evidence that folate conjugase is an intracellular enzyme. The present studies have demonstrated unequivocal malabsorption of both simple and conjugated folates in tropical sprue. In tropical sprue, folate malabsorption is the reflection of impaired folate transport and not of impaired hydrolysis. PMID:16695965

  15. The “Skull Flap” a new conceived device for decompressive craniectomy experimental study on dogs to evaluate the safety and efficacy in reducing intracranial pressure and subsequent impact on brain perfusion

    PubMed Central

    Salvatore, Chibbaro; Fabrice, Vallee; Marco, Marsella; Leonardo, Tigan; Thomas, Lilin; Benoit, Lecuelle; Bernard, George; Pierre, Kehrli; Eric, Vicaut; Paolo, Diemidio

    2013-01-01

    Background: Decompressive craniectomy (DC) is a procedure performed increasingly often in current neurosurgical practice. Significant perioperative morbidity may be associated to this procedure because of the large skull defect; also, later closure of the skull defect (cranioplasty) may be associated to post-operative morbidity as much as any other reconstructive operation. The authors present a newly conceived/developed device: The “Skull Flap” (SF). This system, placed at the time of the craniectomy, offers the possibility to provide cranial reconstruction sparing patients a second operation. In other words, DC and cranioplasty essentially take place at the same time and in addition, patients retain their own bone flap. The current study conducted on animal models, represents the logical continuation of a prior recent study, realized on cadaver specimens, to assess the efficacy and safety of this recently developed device. Materials and Methods: This is an experimental pilot study on dogs to assess both safety and efficacy of the SF device. Two groups of experimental raised intracranial pressure animal models underwent DC; in the first group of dogs, the bone flap was left in raised position above the skull defect using the SF device; on the second group the flap was discarded. All dogs underwent transcranial Doppler (TCD) to assess brain perfusion. Head computed tomography (CT) scan to determine flap position was also obtained in the group in which the SF device was placed. Results: SF has proved to be a strong fixation device that allows satisfactory brain decompression by keeping the bone flap elevated from the swollen brain; later on, the SF allows cranial reconstruction in a simple way without requiring a second staged operation. In addition, it is relevant to note that brain perfusion was measured and found to be better in the group receiving the SF (while the flap being in a raised as well as in its natural position) comparing to the other group

  16. Distribution of perfusion.

    PubMed

    Glenny, Robb; Robertson, H Thomas

    2011-01-01

    Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. PMID:23737171

  17. Importance of capillary perfusion.

    PubMed

    Hardaway, R M

    1979-11-01

    Perfusion is more critical than oxygen in the maintenance of cell viability. A high hematocrit or high fibrinogen level increases blood viscosity and predisposes to disseminated intravascular coagulation. It is recommended that a hematocrit of about 30 be maintained in periods of circulatory stress such as shock or extracorporeal circulation. PMID:495856

  18. Effects of chronic nitric oxide synthase inhibition in cold-restraint and ethanol-induced gastric mucosal damage in rats.

    PubMed

    Qiu, B S; Pfeiffer, C J; Cho, C H

    1996-01-01

    Gastric actions of Nw-nitro-1-arginine methyl ester (L-NAME) were investigated in rats, as this agent is a reliable nitric oxide synthase inhibitor L-NAME solutions were placed in subcutaneous osmotic minipumps which continuously released L-NAME at 0.1, 1.0, 10, or 40 mg/kg/day. L-NAME dose and time-dependently enhanced stress-induced gastric ulceration but did not affect mucosal mast cell population. Ulcerogenic actions of L-NAME were reversed by L-arginine but not by D-arginine. Ten L-NAME treatment also enhanced the ethanol-induced gastric mucosal damage, depressed gastric mucosal blood flow but did not alter gastric mucus, secretory volume, or acid output. It is concluded that in the present models, chronic nitric oxide synthase inhibition enhanced ulcerogenesis by decreasing mucosal resistance due to reduced mucosal blood perfusion. This implicates nitric oxide as a mucosal defense factor which acts in part by maintaining mucosal blood flow. PMID:8626050

  19. Intestinal mucosal tolerance and impact of gut microbiota to mucosal tolerance

    PubMed Central

    Chistiakov, Dimitry A.; Bobryshev, Yuri V.; Kozarov, Emil; Sobenin, Igor A.; Orekhov, Alexander N.

    2015-01-01

    The mucosal barriers are very sensitive to pathogenic infection, thereby assuming the capacity of the mucosal immune system to induce protective immunity to harmful antigens and tolerance against harmless substances. This review provides current information about mechanisms of induction of mucosal tolerance and about impact of gut microbiota to mucosal tolerance. PMID:25628617

  20. 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

  1. Research controversies in management of oral mucositis.

    PubMed

    Biron, P; Sebban, C; Gourmet, R; Chvetzoff, G; Philip, I; Blay, J Y

    2000-01-01

    The management of mucositis is the subject of many controversies, and the optimal treatment is still not known. Several evaluation scoring systems have been described, but no one of these is appropriate to all clinical situations: a simple scale such as that devised by the WHO can be used routinely, and more sophisticated ones can be implemented by trained experimenters working in research. We have considered the impact of each of the treatments currently available on each stage of mucositis. In attempts at prevention, self-care, in the sense of oral hygiene, must remain atraumatic. It is probably advisable to differentiate patients with good previous oral care, in whom tooth brushing is beneficial, from others, in whom the risk of hemorrhage and infection excludes any brushing. Before the dosage of chemotherapy is reduced, the curative or palliative intent of the strategy must be carefully evaluated. In the vascular phase protection of the proliferating cells is attempted by means of vasoconstriction (cryotherapy), cytoprotection (prostaglandin E2 and other antioxidants) or epithelial cell-inhibiting factors such as TGF-B3. Treatments applied in the epithelial phase are directed at increasing the cell proliferation to accelerate epithelial restoration by sucralfate and several growth factors: hematopoietic GF, which has demonstrated a direct effect on the mucosa (GM-CSF), or epithelial growth factors such as keratinocyte GF. In the ulcerative and bacteriological phase attempts are made to attenuate sepsis by means of antiseptics (chlorhexidine), amphotericin B and antiviral agents or antibiotic lozenges. In the healing phase application of the low-energy helium-neon laser has demonstrably been followed by a later time of onset, less pronounced peak severity and shorter duration of oral mucositis. After cancer treatment, oral hygiene, inhibition of oral flora, and pain relief are the main goals. Physiopathogen-specific treatment is the next step, with the emphasis

  2. Immunology of Gut Mucosal Vaccines

    PubMed Central

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

    2011-01-01

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

  3. Tissue distribution of exogenous amino acids during transport across the vascularly perfused anuran small intestine.

    PubMed Central

    Cheeseman, C I; King, I; Smith, M W

    1983-01-01

    Microdensitometric analysis of autoradiographs has been used to measure the distribution and intracellular concentration of L-leucine and L-lysine during transport across the vascularly perfused small intestine of Rana pipiens. L-leucine was not accumulated in the mucosal epithelium to a concentration higher than that in the lumen under steady-state conditions, whereas L-lysine was concentrated on average three- to four-fold. 2. At the end of 30 min loading, the majority of both amino acids were found in the mucosal epithelium and the villous core, although significant amounts were also present in the muscle. Lysine showed a gradient of accumulation within the mucosal epithelium along the length of the villous folds, the highest concentrations being achieved in the cells near the tip. Leucine showed no such gradient under steady-state conditions. 3. Superfusion of the mucosal surface of the tissue with leucine for only 3 min did reveal a gradient for uptake into the mucosal epithelium, although it was still not as steep as that seen for lysine. 4. The presence of leucine in the vascular bed while lysine was perfused through the lumen significantly lowered the concentration of lysine in the mucosal epithelium and villous core and eliminated the concentration gradient in the mucosal epithelium seen along the villous fold. 5. When leucine was perfused on its own through the vascular bed, the uptake into the muscle was greatly increased compared to when the amino acid was presented from the lumen. At the same time, the uptake into the mucosal epithelium was reduced by 45%. 6. Analysis of the tissue content of leucine after loading for 30 min from the lumen and then washing out the amino acid for 15 min showed that the mucosal epithelium, villous core and muscle had contributed 74%, 17% and 9% respectively to the total amino acid lost from the tissue. 7. These results are discussed with regard to the significance of the exit mechanisms for these amino acids and the

  4. 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.

  5. Effects of hydrochloric acid on duodenal and jejunal mucosal permeability in the rat

    SciTech Connect

    Nylander, O.; Kvietys, P.; Granger, D.N. )

    1989-10-01

    The effects of various concentrations of hydrochloric acid (1, 5, 10, and 100 mM) on mucosal permeability and acid disappearance (H+-dis) in duodenum and jejunum were studied in anesthetized rats. Mucosal permeability was assessed by measuring blood-to-lumen clearance of 51Cr-labeled EDTA (ED-Cl). Luminal alkalinization (LA) and H+-dis were determined by backtitration. ED-Cl was stable during saline perfusion and was not affected by changes in intestinal blood flow. Basal ED-Cl was four times higher in duodenum than in jejunum. Mucosal permeability of both duodenum and jejunum was not altered by 1 mM HCl. However, 5 mM HCl induced a 3.3-fold increase (P less than 0.001) in ED-Cl in jejunum but was without effect in duodenum. A 15-fold increase in ED-Cl was obtained in jejunum and a doubling (P less than 0.001) in ED-Cl was observed in duodenum when HCl concentration was increased to 10 mM HCl. One hundred millimolar HCl induced large increases of ED-Cl in both segments. The twofold increase of ED-Cl in response to 10 mM HCl in duodenum was completely reversible, whereas ED-Cl in jejunum was three to four times higher (P less than 0.05) than preacid levels 60 min after cessation of acid perfusion. The net increase in jejunal ED-Cl obtained after acid exposure was closely correlated (r = 0.99) with the net increase in LA, indicating leakage of interstitial fluid into the luminal solution. LA (saline perfusion) and H+-dis (HCl perfusion) were significantly higher in duodenum than in jejunum.

  6. 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

  7. 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

  8. Automated sonographic evaluation of testicular perfusion

    NASA Astrophysics Data System (ADS)

    Thierman, Jonathan S.; Clement, Gregory T.; Kalish, Leslie A.; O'Kane, Patrick L.; Frauscher, Ferdinand; Paltiel, Harriet J.

    2006-07-01

    Contrast-enhanced ultrasound (US) imaging is potentially applicable to the investigation of vascular disorders of the testis. We investigated the ability of two automated computer algorithms to analyse contrast-enhanced pulse inversion US data in a rabbit model of unilateral testicular ischaemia and to correctly determine relative testicular perfusion: nonlinear curve fitting of the US backscatter intensity as a function of time; and spectral analysis of the intensity time trace. We compared (i) five metrics based on the algorithmic data to testicular perfusion ratios obtained with radiolabelled microspheres, a reference standard; (ii) qualitative assessment of the US images by two independent readers blinded to the side of the experimental and control testes to the radiolabelled microsphere perfusion ratios; and (iii) results of the algorithmically-derived metrics to the qualitative assessments of the two readers. For the curve fit method, the algorithmically-derived metrics agreed with the reference standard in 54% to 68% of all cases. For the spectral method, the results agreed in 70% of all cases. The two readers agreed with the reference standard in 40% and 35% of all cases, respectively. These results suggest that automated methods of analysis may provide useful information in the assessment of testicular perfusion.

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

    PubMed

    Saadeh, Claire E

    2005-04-01

    Oral mucositis is a frequently encountered and potentially severe complication associated with administration of chemotherapy and radiotherapy. Although many pharmacologic interventions have been used for the prevention and treatment of oral mucositis, there is not one universally accepted strategy for its management. Most preventive and treatment strategies are based on limited, often anecdotal, clinical data. Basic oral hygiene and comprehensive patient education are important components of care for any patient with cancer at risk for development of oral mucositis. Nonpharmacologic approaches for the prevention of oral mucositis include oral cryotherapy for patients receiving chemotherapy with bolus 5-fluorouracil, and low-level laser therapy for patients undergoing hematopoietic stem cell transplantation. Chlorhexidine, amifostine, hematologic growth factors, pentoxifylline, glutamine, and several other agents have all been investigated for prevention of oral mucositis. Results have been conflicting, inconclusive, or of limited benefit. Treatment of established mucositis remains a challenge and focuses on a palliative management approach. Topical anesthetics, mixtures (also called cocktails), and mucosal coating agents have been used despite the lack of experimental evidence supporting their efficacy. Investigational agents are targeting the specific mechanisms of mucosal injury; among the most promising of these is recombinant human keratinocyte growth factor. PMID:15977916

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

    PubMed Central

    Kataoka, Kosuke; Fujihashi, Kohtaro

    2009-01-01

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

  11. Mucosal vaccination: lung versus nose.

    PubMed

    Vujanic, Ana; Sutton, Philip; Snibson, Kenneth J; Yen, Hung-Hsun; Scheerlinck, Jean-Pierre Y

    2012-07-15

    The induction of potent mucosal immune responses able to prevent the establishment of infection at the onset of mucosal pathogen colonisation represents a desirable but challenging goal for vaccine development. Here we compare nasal vaccine delivery with intra-pulmonary vaccination using a sheep lymphatic cannulation model. Our results demonstrate that nasal delivery of a non-infective ISCOMATRIX(®) influenza vaccine does not induce primary immune responses in the lymph draining the nasal lymph nodes, suggesting that local immune responses in the lymph nodes draining the nasal cavity are relatively weak. However, this mode of delivery can boost existing immunity in the nasal lymph. Using the same adjuvant we were able to induce very potent immune responses in both blood and bronchoalveolar lavage (BAL), following intra-pulmonary delivery of ISCOMATRIX(®) influenza vaccine, even when very small doses of antigen were employed. Lung delivery could also induce comparable immune responses against other recombinant antigens mixed with ISCOMATRIX(®) adjuvant and could therefore become a method of choice for the induction of immunity to mucosal pathogens infecting the lower respiratory tract. PMID:21492942

  12. Infectious salmon anaemia virus (ISAV) mucosal infection in Atlantic salmon.

    PubMed

    Aamelfot, Maria; McBeath, Alastair; Christiansen, Debes H; Matejusova, Iveta; Falk, Knut

    2015-01-01

    All viruses infecting fish must cross the surface mucosal barrier to successfully enter a host. Infectious salmon anaemia virus (ISAV), the causative agent of the economically important infectious salmon anaemia (ISA) in Atlantic salmon, Salmo salar L., has been shown to use the gills as its entry point. However, other entry ports have not been investigated despite the expression of virus receptors on the surface of epithelial cells in the skin, the gastrointestinal (GI) tract and the conjunctiva. Here we investigate the ISAV mucosal infection in Atlantic salmon after experimental immersion (bath) challenge and in farmed fish collected from a confirmed outbreak of ISA in Norway. We show for the first time evidence of early replication in several mucosal surfaces in addition to the gills, including the pectoral fin, skin and GI tract suggesting several potential entry points for the virus. Initially, the infection is localized and primarily infecting epithelial cells, however at later stages it becomes systemic, infecting the endothelial cells lining the circulatory system. Viruses of low and high virulence used in the challenge revealed possible variation in virus progression during infection at the mucosal surfaces. PMID:26490835

  13. Lung Ventilation/Perfusion Scan

    MedlinePlus

    ... from the NHLBI on Twitter. What Is a Lung Ventilation/Perfusion Scan? A lung ventilation/perfusion scan, or VQ scan, is a ... that measures air and blood flow in your lungs. A VQ scan most often is used to ...

  14. 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

  15. 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. PMID:9052297

  16. Topical and mucosal liposomes for vaccine delivery.

    PubMed

    Romero, Eder Lilia; Morilla, Maria Jose

    2011-01-01

    Mucosal (and in minor extent transcutanous) stimulation can induce local or distant mucosa secretory IgA. Liposomes and other vesicles as mucosal and transcutaneous adjuvants are attractive alternatives to parenteral vaccination. Liposomes can be massively produced under good manufacturing practices and stored for long periods, at high antigen/vesicle mass ratios. However, their uptake by antigen-presenting cells (APC) at the inductive sites remains as a major challenge. As neurotoxicity is a major concern in intranasal delivery, complexes between archaeosomes and calcium as well as cationic liposomes complexed with plasmids encoding for antigenic proteins could safely elicit secretory and systemic antigen-specific immune responses. Oral bilosomes generate intense immune responses that remain to be tested against challenge, but the admixing with toxins or derivatives is mandatory to reduce the amount of antigen. Most of the current experimental designs, however, underestimate the mucus blanket 100- to 1000-fold thicker than a 100-nm diameter liposome, which has first to be penetrated to access the underlying M cells. Overall, designing mucoadhesive chemoenzymatic resistant liposomes, or selectively targeted to M cells, has produced less relevant results than tailoring the liposomes to make them mucus penetrating. Opposing, the nearly 10 µm thickness stratum corneum interposed between liposomes and underlying APC can be surpassed by ultradeformable liposomes (UDL), with lipid matrices that penetrate up to the limit with the viable epidermis. UDL made of phospholipids and detergents, proved to be better transfection agents than conventional liposomes and niosomes, without the toxicity of ethosomes, in the absence of classical immunomodulators. PMID:21360692

  17. Eosinophils in mucosal immune responses

    PubMed Central

    Travers, J; Rothenberg, M E

    2015-01-01

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

  18. Ex vivo lung perfusion.

    PubMed

    Machuca, Tiago N; Cypel, Marcelo

    2014-08-01

    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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Dynamic chest image analysis: model-based pulmonary perfusion analysis with pyramid images

    NASA Astrophysics Data System (ADS)

    Liang, Jianming; Haapanen, Arto; Jaervi, Timo; Kiuru, Aaro J.; Kormano, Martti; Svedstrom, Erkki; Virkki, Raimo

    1998-07-01

    The aim of the study 'Dynamic Chest Image Analysis' is to develop computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected at different phases of the respiratory/cardiac cycles in a short period of time. We have proposed a framework for ventilation study with an explicit ventilation model based on pyramid images. In this paper, we extend the framework to pulmonary perfusion study. A perfusion model and the truncated pyramid are introduced. The perfusion model aims at extracting accurate, geographic perfusion parameters, and the truncated pyramid helps in understanding perfusion at multiple resolutions and speeding up the convergence process in optimization. Three cases are included to illustrate the experimental results.

  4. Respiratory mucosal permeability in asthma

    SciTech Connect

    Elwood, R.K.; Kennedy, S.; Belzberg, A.; Hogg, J.C.; Pare, P.D.

    1983-09-01

    The permeability of respiratory mucosa to technetium-labeled diethylenetriamine pentacetic acid (/sup 99m/Tc-DTPA) was measured in 10 clinically stable chronic asthmatics and the results were compared with those in 9 nonasthmatic control subjects. Nonspecific bronchial reactivity was measured using methacholine, and the PC20 was calculated. The intrapulmonary distribution and dose of the inhaled /sup 99m/Tc-DTPA was determined by a gamma camera and the half-life of the aerosolized label in the lung was calculated. The accumulation of radioactivity in the blood was monitored and a permeability index was calculated at 10, 25, and 60 min after aerosolization. Despite marked differences in airway reactivity, no differences in either parameter of permeability could be detected between the asthmatics and the control group. It is concluded that clinically stable asthmatics do not demonstrate increase mucosal permeability to small solutes when compared with normal subjects.

  5. 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

  6. Hydrostatic determinants of cerebral perfusion

    SciTech Connect

    Wagner, E.M.; Traystman, R.J.

    1986-05-01

    We examined the cerebral blood flow response to alterations in perfusion pressure mediated through decreases in mean arterial pressure, increases in cerebrospinal fluid (CSF) pressure, and increases in jugular venous (JV) pressure in 42 pentobarbital anesthetized dogs. Each of these three pressures was independently controlled. Cerebral perfusion pressure was defined as mean arterial pressure minus JV or CSF pressure, depending on which was greater. Mean hemispheric blood flow was measured with the radiolabeled microsphere technique. Despite 30-mm Hg reductions in mean arterial pressure or increases in CSF or JV pressure, CBF did not change as long as the perfusion pressure remained greater than approximately 60 mm Hg. However, whenever perfusion pressure was reduced to an average of 48 mm Hg, cerebral blood flow decreased 27% to 33%. These results demonstrate the capacity of the cerebral vascular bed to respond similarly to changes in the perfusion pressure gradient obtained by decreasing mean arterial pressure, increasing JV pressure or increasing CSF pressure, and thereby support the above definition of cerebral perfusion pressure.

  7. The mucosal immune system for vaccine development.

    PubMed

    Lamichhane, Aayam; Azegamia, Tatsuhiko; Kiyonoa, Hiroshi

    2014-11-20

    Mucosal surfaces are continuously exposed to the external environment and therefore represent the largest lymphoid organ of the body. In the mucosal immune system, gut-associated lymphoid tissues (GALTs), including Peyer's patches and isolated lymphoid follicles, play an important role in the induction of antigen-specific immune responses in the gut. GALTs have unique organogenesis characteristics and interact with the network of dendritic cells and T cells for the simultaneous induction and regulation of IgA responses and oral tolerance. In these lymphoid tissues, antigens are up taken by M cells in the epithelial layer, and antigen-specific immune responses are subsequently initiated by GALT cells. Nasopharynx- and tear-duct-associated lymphoid tissues (NALTs and TALTs) are key organized lymphoid structures in the respiratory tract and ocular cavities, respectively, and have been shown to interact with each other. Mucosal surfaces are also characterized by host-microbe interactions that affect the genesis and maturation of mucosa-associated lymphoid tissues and the induction and regulation of innate and acquired mucosal immune responses. Because most harmful pathogens enter the body through mucosal surfaces by ingestion, inhalation, or sexual contact, the mucosa is a candidate site for vaccination. Mucosal vaccination has some physiological and practical advantages, such as decreased costs and reduced risk of needle-stick injuries and transmission of bloodborne diseases, and it is painless. Recently, the application of modern bioengineering and biochemical engineering technologies, including gene transformation and manipulation systems, resulted in the development of systems to express vaccine antigens in transgenic plants and nanogels, which will usher in a new era of delivery systems for mucosal vaccine antigens. In this review, based on some of our research group's thirty seven years of progress and effort, we highlight the unique features of mucosal immune

  8. 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.

  9. Oral mucositis. A complication of radiotherapy

    SciTech Connect

    Rider, C.A. )

    1990-11-01

    Oral mucositis is a complication of head and neck radiotherapy. It is understood what causes the inflammation and what biological tissue changes occur, however, a definite cure for oral mucositis has not yet been found. Supportive treatments, analgesics, antimicrobials and anti-inflammatory agents have been prescribed, none of which has been a thorough measure of treatment. An effective cure for oral mucositis is still in the midst of scientific research. In the interim local palliative treatments will help to alleviate the patients', debilitating symptoms.

  10. Critical Roles of Intestinal Epithelial Vitamin D Receptor Signaling in Controlling Gut Mucosal Inflammation

    PubMed Central

    Li, Yan Chun; Chen, Yunzi; Du, Jie

    2015-01-01

    Although vitamin D receptor (VDR) is highly expressed in the intestine, the role of VDR signaling in the gut is not fully understood. Our recent studies unveil a regulatory circuit that centers gut epithelial VDR as a key molecule in the control of mucosal inflammation and colitis development. On the one hand, intestinal epithelial VDR signaling protects the integrity of the mucosal barrier by inhibiting inflammation-induced epithelial cell apoptosis. This barrier-protecting, anti-colitic activity is independent of the non-epithelial immune VDR actions. A healthy and intact mucosal barrier prevents bacterial invasion and thus reduces mucosal inflammation. On the other hand, inflammation in turn down-regulates epithelial VDR expression by inducing VDR-targeting microRNA-346, thus compromising mucosal barrier functions. Consistently, colonic epithelial VDR levels are markedly reduced in patients with inflammatory bowel diseases or in experimental colitis models, whereas vitamin D analog therapy that ameliorates colitis up-regulates epithelial VDR. Thus, gut epithelial VDR signaling appears to play an essential role in controlling mucosal inflammation and thus could be a useful therapeutic target in the management of inflammatory bowel diseases. PMID:25603468

  11. MR Perfusion Imaging in Acute Ischemic Stroke

    PubMed Central

    Copen, William A.; Schaefer, Pamela W.; Wu, Ona

    2011-01-01

    MR perfusion imaging offers the potential for measuring brain perfusion in acute stroke patients, at a time when treatment decisions based upon these measurements may affect outcomes dramatically. Rapid advancements in both acute stroke therapy and perfusion imaging techniques have resulted in continuing redefinition of the role that perfusion imaging should play in patient management. This review first discusses the basic pathophysiology of acute stroke, with specific attention to alterations in the various perfusion-related parameters that can be studied by MR perfusion imaging. Although these parameters are sometimes treated as somewhat interchangeable, they reveal greatly different information about brain perfusion. Therefore, subsequent discussion of the utility of different kinds of perfusion images focuses on the differences between them, as well as important artifacts that can complicate their interpretation. Finally, research on the continually evolving role of MR perfusion imaging in acute stroke care is summarized. PMID:21640299

  12. 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

  13. Exploiting Mucosal Immunity for Antiviral Vaccines.

    PubMed

    Iwasaki, Akiko

    2016-05-20

    Mucosal surfaces provide a remarkably effective barrier against potentially dangerous pathogens. Therefore, enhancing mucosal immunity through vaccines-strengthening that first line of defense-holds significant promise for reducing the burden of viral diseases. The large and varied class of viral pathogens, however, continues to present thorny challenges to vaccine development. Two primary difficulties exist: Viruses exhibit a stunning diversity of strategies for evading the host immune response, and even when we understand the nature of effective immune protection against a given virus, eliciting that protection is technically challenging. Only a few mucosal vaccines have surmounted these obstacles thus far. Recent developments, however, could greatly improve vaccine design. In this review, we first sketch out our understanding of mucosal immunity and then compare the herpes simplex virus, human immunodeficiency virus, and influenza virus to illustrate the distinct challenges of developing successful vaccines and to outline potential solutions. PMID:27168245

  14. Localized Pemphigus Vegetans without Mucosal Involvement

    PubMed Central

    Jain, VK; Jindal, N; Imchen, S

    2014-01-01

    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. PMID:24700958

  15. Tomographic digital subtraction angiography for lung perfusion estimation in rodents

    SciTech Connect

    Badea, Cristian T.; Hedlund, Laurence W.; De Lin, Ming; Boslego Mackel, Julie S.; Samei, Ehsan; Allan Johnson, G.

    2007-05-15

    In vivo measurements of perfusion present a challenge to existing small animal imaging techniques such as magnetic resonance microscopy, micro computed tomography, micro positron emission tomography, and microSPECT, due to combined requirements for high spatial and temporal resolution. We demonstrate the use of tomographic digital subtraction angiography (TDSA) for estimation of perfusion in small animals. TDSA augments conventional digital subtraction angiography (DSA) by providing three-dimensional spatial information using tomosynthesis algorithms. TDSA is based on the novel paradigm that the same time density curves can be reproduced in a number of consecutive injections of {mu}L volumes of contrast at a series of different angles of rotation. The capabilities of TDSA are established in studies on lung perfusion in rats. Using an imaging system developed in-house, we acquired data for four-dimensional (4D) imaging with temporal resolution of 140 ms, in-plane spatial resolution of 100 {mu}m, and slice thickness on the order of millimeters. Based on a structured experimental approach, we optimized TDSA imaging providing a good trade-off between slice thickness, the number of injections, contrast to noise, and immunity to artifacts. Both DSA and TDSA images were used to create parametric maps of perfusion. TDSA imaging has potential application in a number of areas where functional perfusion measurements in 4D can provide valuable insight into animal models of disease and response to therapeutics.

  16. Intestinal inflammation and mucosal barrier function.

    PubMed

    Sánchez de Medina, Fermín; Romero-Calvo, Isabel; Mascaraque, Cristina; Martínez-Augustin, Olga

    2014-12-01

    Intestinal mucosal barrier function is the capacity of the intestine to provide adequate containment of luminal microorganisms and molecules while preserving the ability to absorb nutrients. The central element is the epithelial layer, which physically separates the lumen and the internal milieu and is in charge of vectorial transport of ions, nutrients, and other substances. The secretion of mucus-forming mucins, sIgA, and antimicrobial peptides reinforces the mucosal barrier on the extraepithelial side, while a variety of immune cells contributes to mucosal defense in the inner side. Thus, the mucosal barrier is of physical, biochemical, and immune nature. In addition, the microbiota may be viewed as part of this system because of the mutual influence occurring between the host and the luminal microorganisms. Alteration of the mucosal barrier function with accompanying increased permeability and/or bacterial translocation has been linked with a variety of conditions, including inflammatory bowel disease. Genetic and environmental factors may converge to evoke a defective function of the barrier, which in turn may lead to overt inflammation of the intestine as a result of an exacerbated immune reaction toward the microbiota. According to this hypothesis, inflammatory bowel disease may be both precipitated and treated by either stimulation or downregulation of the different elements of the mucosal barrier, with the outcome depending on timing, the cell type affected, and other factors. In this review, we cover briefly the elements of the barrier and their involvement in functional defects and the resulting phenotype. PMID:25222662

  17. Role of bombesin on gut mucosal growth.

    PubMed Central

    Chu, K U; Evers, B M; Ishizuka, J; Townsend, C M; Thompson, J C

    1995-01-01

    OBJECTIVE: The authors examined the effects of exogenous bombesin (BBS) on gut mucosal growth in chow-fed rats and the mucosal regeneration after gut atrophy brought about by feeding an elemental diet and after intestinal injury produced by methotrexate (MTX). SUMMARY BACKGROUND DATA: Bombesin is one of many gastrointestinal peptides implicated in the regulation of gut mucosal growth. Although BBS is known to stimulate growth of normal pancreatic tissue, the trophic effect of BBS on gut mucosa is less clear and its exact role in gut mucosal regeneration and repair is not known. METHODS: Rats were fed a regular chow diet (control) or an elemental diet plus either saline or BBS (10 micrograms/kg). In another experiment, rats fed a chow diet and treated with saline or BBS were given MTX (20 micrograms/kg) or a single intraperitoneal injection. In all experiments, small and large bowel mucosa and pancreas were removed and analyzed for BBS-mediated proliferation. RESULTS: Bombesin produced significant mucosal proliferation of the small bowel at day 14, but not at day 7, in rats fed regular chow. In contrast, BBS treatment for 7 days produced significant proliferation in both the atrophic and injured gut mucosa of rats given elemental diet or MTX. CONCLUSIONS: Bombesin may be an important enterotrophic factor for normal mucosal proliferation and may be clinically beneficial as an agent to restore or maintain gut mucosa during periods of atrophy or injury. PMID:7618976

  18. Mucosal Immunology of HIV Infection

    PubMed Central

    Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

    2013-01-01

    Summary Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4+ T-cell responses, binding antibodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Further, immune therapies specifically directed towards boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. PMID:23772612

  19. Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model.

    PubMed

    Fijlstra, M; Rings, E H H M; Verkade, H J; van Dijk, T H; Kamps, W A; Tissing, W J E

    2011-02-01

    Patients with chemotherapy-induced gastrointestinal mucositis suffer from anorexia, diarrhea, and stomach pain, often causing weight loss and malnutrition. When the intestinal function during mucositis would be known, a rational feeding strategy might improve the nutritional state, accelerate recuperation, and increase survival of mucositis patients. We developed a methotrexate (MTX)-induced mucositis rat model to study nutrient digestion and absorption. To determine lactose digestion and absorption of its derivative glucose during mucositis, we injected Wistar rats intravenously with MTX (60 mg/kg) or 0.9% NaCl (controls). Four days later, we orally administered trace amounts of [1-(13)C]lactose and [U-(13)C]glucose and quantified the appearance of labeled glucose in the blood for 3 h. Finally, we determined plasma citrulline level and harvested the small intestine to assess histology, myeloperoxidase level, glycohydrolase activity, immunohistochemical protein, and mRNA expression. MTX-treated rats showed profound villus atrophy and epithelial damage. During the experimental period, the absorption of lactose-derived [1-(13)C]glucose was 4.2-fold decreased in MTX-treated rats compared with controls (P < 0.01). Lactose-derived [1-(13)C]glucose absorption correlated strongly with villus length (rho = 0.86, P < 0.001) and with plasma citrulline level (rho = 0.81, P < 0.001). MTX treatment decreased jejunal lactase activity (19.5-fold, P < 0.01) and immunohistochemical protein and mRNA expression (39.7-fold, P < 0.01) compared with controls. Interestingly, MTX treatment did not affect the absorption of [U-(13)C]glucose during the experimental period. We conclude that lactose digestion is severely decreased during mucositis while glucose absorption is still intact, when supplied in trace amounts. Plasma citrulline level might be a useful objective, noninvasive marker for lactose maldigestion during mucositis in clinic. PMID:21088238

  20. 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. PMID:26264867

  1. [Immunoglobulin for prevention of radiogenic mucositis].

    PubMed

    Mose, S; Adamietz, I A; Thilmann, C; Saran, F; Heyd, R; Knecht, R; Böttcher, H D

    1995-07-01

    Among various therapies administered during radiation-induced mucositis, treatment with immunoglobulin has proven clinically successful. In this study the efficacy of prophylactic applications of immunoglobulin was investigated from January 1992 through August 1993. Forty-two patients with histologically-proven head and neck cancer were given postoperative radiation treatment. In cases with macroscopic tumor residues or inoperability, combined radio-chemotherapy was given. This included 51.3 Gy at 1.9 Gy 5x/week, boosted to 10-26 Gy at 2 Gy 5x/week and carboplatin 60 mg/m2 at days 1-5 and 29-33. Panthenol (4x10 ml/day) and nystatin (4 x 1 ml/day) were given to 20 patients as prophylactic treatment for mucositis. Twenty-two subsequent patients also received intramuscular 800 mg (5 ml) human immunoglobulin (1x/week). According to the Seegenschmiedt/Sauer classification the extent of mucositis was determined 3x/week. Comparison of the distribution of maximal mucositis revealed a slightly more severe mucosal reaction in the control group (n.s.). Analysis of the mean degree of mucositis in both groups demonstrated statistically significant differences (p = 0.031) related to the whole collective and patients receiving concomitant chemotherapy while no effect of immunoglobulin was found in patients treated by radiation alone. In the immunoglobulin-treated-group, the time from the beginning of therapy to the first interruption was prolonged 5 days (37.5 +/- 13.1 vs. 42.7 +/- 13.3 days), but this difference was not significant. Although prophylactic application of immunoglobulin seemed to lower the degree of radiation-induced mucositis, this effect was less significant when compared to the immunoglobulin given in a therapeutic manner. PMID:7672999

  2. Pharmacokinetics of Antiretrovirals in Mucosal Tissue

    PubMed Central

    Cottrell, M.L.; Srinivas, N.; Kashuba, A.D.M.

    2015-01-01

    Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

  3. The effect of Aloe vera A. Berger (Liliaceae) on gastric acid secretion and acute gastric mucosal injury in rats.

    PubMed

    Yusuf, Sadiq; Agunu, Abdulkarim; Diana, Mshelia

    2004-07-01

    The effect of varying doses of ethanol extract of Aloe vera (Liliaceae) on acute gastric mucosal lesions induced by 0.6 M HCl and acid output was studied in the pylorus ligated and lumen perfuse rats, respectively. Acid secretion was determined by titration of the collected gastric juice to pH 7.0. Intraperitoneal injection of Aloe vera, dose dependently inhibited gastric acid secretion. The plant was more active as a gastroprotective agent at lower concentration against mucosal injury induced by 0.6 M HCl. In conclusion, Aloe vera is endowed with gastric acid anti-secretory activity and could protect the gastric mucosa at low concentrations against injurious agents. PMID:15182901

  4. [Direct and indirect mucosal wave imaging techniques].

    PubMed

    Krasnodębska, Paulina; Szkiełkowska, Agata

    2016-04-01

    The vocal folds play a key role in the process of phonation. Cyclical movements of the vocal folds model a space called glottis, what leads to voice formation. The space contains surface between the vocal folds and the inner surface of the arytenoid cartilages. The best indicator of the vocal folds vibratory function is the mucosal wave. The presence and size of the mucosal wave is widely recognized as an indicator of tension and plasticity of vocal folds. It is also essential in the process of creating a proper, resonant voice. In the article, current knowledge of mucosal wave imaging techniques is given. Imaging can be carried out directly and indirectly. Among the direct methods, the following are distinguished: laryngostroboscopy, laryngovideostroboscopy, videokymography and high-speed digital imaging. Indirect methods include: electroglottography, photoglottography and ultrasonography. PMID:27137829

  5. Novel vaccine development strategies for inducing mucosal immunity

    PubMed Central

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

    2012-01-01

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

  6. 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. PMID:25443679

  7. Oral mucositis in myelosuppressive cancer therapy.

    PubMed

    Epstein, J B; Schubert, M M

    1999-09-01

    Because the etiology of mucositis is multifactorial , approaches to prevention and management have also been multifactorial. Effective prevention and management of mucositis will reduce the pain and suffering experienced during cancer treatment. Oropharyngeal pain in cancer patients frequently requires systemic analgesics, adjunctive medications, physical therapy, and psychologic therapy in addition to oral care and topical treatments. Good oral hygiene reduces the severity of oral mucositis and does not increase the risk of bacteremia. Current approaches to management include frequent oral rinsing with saline or bicarbonate rinses, maintaining excellent oral hygiene, and using topical anesthetics and analgesics. Cryotherapy is a potential adjunctive approach in some cases. There are a number of approaches that appear to represent viable candidates for further study. Biologic response modifiers offer the potential for prevention and for acceleration of healing. Various cytokines will enter clinical trials in the near future; these offer the potential for reduction of epithelial cell sensitivity to the toxic effects of cancer therapy or for stimulation of repair of the damaged tissue. Other approaches include the use of medications to reduce exposure of the oral mucosa to chemotherapeutic drugs that are secreted in saliva. Antimicrobial approaches have met with conflicting results, little effect being seen with chlorhexidine and systemic antimicrobials in the prevention of mucositis in radiation patients. In patients with BMT and patients with leukemia, chlorhexidine may not be effective in preventing mucositis, although there may be reduction in oral colonization by Candida. Initial studies of topical antimicrobials that affect the gram-negative oral flora have shown reductions in ulcerative mucositis during radiation therapy but have not been assessed in leukemia/BMT. Among other approaches that require further study are low-energy lasers and anti

  8. Pentabody-mediated antigen delivery induces antigen-specific mucosal immune response.

    PubMed

    Li, Shenghua; Zheng, Wenju; Kuolee, Rhonda; Hirama, Tomoko; Henry, Matthew; Makvandi-Nejad, Shokouh; Fjällman, Ted; Chen, Wangxue; Zhang, Jianbing

    2009-05-01

    An efficient immunization system is essential for the development of mucosal vaccine. Cholera toxin (CT) and Escherichia coli heat labile toxin (LT) are among the strongest adjuvants tested in experimental animals but their use in humans has been hindered by their toxicity. On the other hand, the role of their non-toxic B-subunits, CTB or LTB, in enhancing mucosal immune response is not clear. We propose here a novel strategy for the induction of mucosal immune responses. Single domain antibodies (sdAbs) against a model antigen bovine serum albumin (BSA) were raised from the antibody repertoire of a llama immunized with BSA, pentamerized by fusing the sdAbs to CTB, generating the so-called pentabodies. These pentabodies were used to deliver the antigen by mixing the two components and administering the mixture to mice intranasally. One construct was equivalent to CT in helping induce mucosal immune response. It was also found that this ability was probably due to its high affinity to BSA, providing some insight into the controversial role of CTB in mucosal immunization: at least for BSA, the model antigen BSA employed in this study, CTB has to be tightly linked to the antigen to have adjuvant/immune-enhancing effect. PMID:19269688

  9. Use of a rotating wire cage for retention of animal cells in a perfusion fermentor.

    PubMed

    Varecka, R; Scheirer, W

    1987-01-01

    Separation of cells within a perfused suspension system is still a problem. We modified the rotating steel wire cage described by other researchers (2) for separation of single cells from suspension. The system was mounted to the stirrer shaft of a circular-loop fermenter. After optimization of fermenter design experimental data showed good separation of cells at useful perfusion rates. Data of a 5 l-prototype show with a mammalian tumor cell line a retention rate of better than 95% at a perfusion rate of D = 0.05. Scaling-up studies show a good scaling-up potential and a wide range of possible applications. PMID:3582756

  10. 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.

  11. Mucosal and systemic immunity in mice after intranasal immunization with recombinant Lactococcus lactis expressing ORF6 of PRRSV.

    PubMed

    Wang, Zhen-hua; Cao, Xiao-han; Du, Xiao-gang; Feng, Hai-bo; Di-Wang; He-Song; Zeng, Xian-yin

    2014-02-01

    The purpose of the study was to construct mucosal vaccine of a recombinant Lactococcus lactis expressing PRRSV ORF6 gene and evaluate mucosal and systemic immune response against PRRSV in mice after intranasal immunization. The result show that the vaccine can stimulate mice to produce specific IgG in serum and remarkable special s-IgA in lung lavage fluid, at the same time, the contents of cytokines IL-2 and IFN-γ of the experimental group were significant higher than those of the control group (P < 0.01), however, the contents of cytokines IL-4 was not different to the all groups. In summary, the constructed mucosal vaccine can significantly induce mucosal immune, humoral immunity and cellular immunity involved Th1 type cytokines, which will lay a theoretical foundation on immune mechanism and new efficient vaccines for PRRSV. PMID:24423464

  12. Plasma Cell Mucositis of Oro- and Hypopharynx: A Case Report

    PubMed Central

    Puvanendran, Mark; Lieder, Anja; Issing, Wolfgang

    2012-01-01

    Objective. To raise awareness of plasma cell mucositis as a rare differential diagnosis for oral mucosal ulceration and its macroscopic similarity to malignancy. Method. We report a patient who presented with oral features suggestive of malignancy. A biopsy revealed plasma cell mucositis. Results. The patient successfully had a full excision of one lesion and a spontaneous resolution of the other. Conclusion. With the increasing incidence of oral mucosal pathology, physicians should be aware of this differential diagnosis. PMID:22953106

  13. 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.

  14. Mechanisms of Neonatal Mucosal Antibody Protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Following an abrupt transition at birth from the sterile uterus to an environment with abundant commensal and pathogenic microbes, neonatal mammals are protected by maternal antibodies at mucosal surfaces. We show in mice that different antibody isotypes work in distinct ways to protect the neonatal...

  15. New frontiers in mucosal health in aquaculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The dramatic decline in sequencing costs brought about by a shift in the last 5-10 years to massively parallel sequencing platforms has far-reaching consequences for the study of mucosal health in aquaculture. Transcriptome sequencing and gene expression profiling (RNA-seq) offer a rapid approach t...

  16. CpG DNA as mucosal adjuvant.

    PubMed

    McCluskie, M J; Davis, H L

    1999-09-01

    We have previously found synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs to be a potent adjuvant to protein administered by intramuscular injection or intranasal inhalation to BALB/c mice. Herein we have further evaluated the potential of CpG ODN as a mucosal adjuvant to purified hepatitis B surface antigen (HBsAg) when administered alone or with cholera toxin (CT). CpG ODN and CT both augmented systemic (humoral and cellular) and mucosal immune responses against HBsAg, and these could be further enhanced with higher doses of adjuvant or boosting. Overall, antibody isotypes with CT alone were predominantly IgG1 (Th2-like) whereas they were predominantly IgG2a (Th1-like) with CpG ODN alone or in combination with CT. Results from this study indicate that stimulatory CpG ODN are promising new adjuvants for mucosal vaccination strategies, whether used alone or in combination with other mucosal adjuvants. PMID:10506647

  17. Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants.

    PubMed

    Pizza, M; Giuliani, M M; Fontana, M R; Monaci, E; Douce, G; Dougan, G; Mills, K H; Rappuoli, R; Del Giudice, G

    2001-03-21

    Most vaccines are still delivered by injection. Mucosal vaccination would increase compliance and decrease the risk of spread of infectious diseases due to contaminated syringes. However, most vaccines are unable to induce immune responses when administered mucosally, and require the use of strong adjuvant on effective delivery systems. Cholera toxin (CT) and Escherichia coli enterotoxin (LT) are powerful mucosal adjuvants when co-administered with soluble antigens. However, their use in humans is hampered by their extremely high toxicity. During the past few years, site-directed mutagenesis has permitted the generation of LT and CT mutants fully non toxic or with dramatically reduced toxicity, which still retain their strong adjuvanticity at the mucosal level. Among these mutants, are LTK63 (serine-to-lysine substitution at position 63 in the A subunit) and LTR72 (alanine-to-arginine substitution at position 72 in the A subunit). The first is fully non toxic, whereas the latter retains some residual enzymatic activity. Both of them are extremely active as mucosal adjuvants, being able to induce very high titers of antibodies specific for the antigen with which they are co-administered. Both mutants have now been tested as mucosal adjuvants in different animal species using a wide variety of antigens. Interestingly, mucosal delivery (nasal or oral) of antigens together with LTK63 or LTR72 mutants also conferred protection against challenge in appropriate animal models (e.g. tetanus, Helicobacter pylori, pertussis, pneumococci, influenza, etc). In conclusion, these LTK63 and LTR72 mutants are safe adjuvants to enhance the immunogenicity of vaccines at the mucosal level, and will be tested soon in humans. PMID:11257389

  18. Ex vivo lung graft perfusion.

    PubMed

    Briot, Raphaël; Gennai, Stéphane; Maignan, Maxime; Souilamas, Redha; Pison, Christophe

    2016-04-01

    This review proposes an update of the state of the art and the ongoing clinical trials of ex vivo lung perfusion for lung transplantation in patients. Ex vivo lung perfusion techniques (EVLP) can be used to evaluate a lung graft outside of the body. The goal of EVLP is to study the functional status of lung grafts that were first rejected for transplantation because they did not match all criteria for a conventional transplantation. After an EVLP evaluation, some of these lungs may be requalified for a possible transplantation in patients. This article proposes an overview of the developments of EVLP techniques. During EVLP, the perfusion and ventilation of the isolated lung preparation are very progressive in order to avoid oedema due to ischaemia-reperfusion injuries. Lung evaluation is mainly based on gasometric (PaO2/FiO2) and rheological criteria (low pulmonary arterial resistance). Several series of patients transplanted with EVLP evaluated lungs have been recently published with promising results. EVLP preparations also allow a better understanding of the physiopathology and treatments of ischaemia-reperfusion injuries. Organ procurements from "non-heart-beating" donors will probably require a wider application of these ex vivo techniques. The development of semi-automated systems might facilitate the clinical use of EVLP techniques. PMID:26746565

  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. 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. PMID:26384312

  1. 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

  2. Brief ex vivo perfusion with heparinized and/or citrated whole blood enhances tolerance of free muscle flaps to prolonged ischemia.

    PubMed

    Fowler, J D; Li, X; Cooley, B C

    1999-01-01

    This study investigated the use of heparinized and/or citrated whole blood as a perfusate for enhancing muscle tolerance to warm ischemia. Unilateral cutaneous trunci muscle flaps were harvested from Sprague-Dawley rats and stored for 10 hr at 22-24 degrees C prior to transplantation to the groin. One group served as a non-perfused control. In three experimental groups, the flaps were hand-perfused ex vivo with 1.0 ml of heparinized, citrated, or heparinized and citrated autogenous whole blood at physiological pressures. Perfusion was administered over a 10-min period 5 hr into the ischemic period. Flaps were revascularized on the femoral vessels and then harvested 48 hr following revascularization. Tissue injury was assessed by calculation of flap weight change (indicator of tissue edema), histochemical evaluation of muscle dehydrogenase activity (nitroblue tetrazolium assay), and light microscopy. All perfused groups had significantly higher muscle dehydrogenase activity compared with non-perfused controls (P < 0.005). Perfusion with combined heparin-citrated blood was significantly more protective than perfusion with either anticoagulant alone (P < 0.025). The only statistically significant reduction in percent flap edema was seen in the combined heparin-citrate perfusion of flaps compared with nonperfused controls (P < 0.05). Histologic evaluation confirmed a reduction in tissue edema in the perfused flaps. We conclude that mid-ischemic perfusion with heparinized and/or citrated blood limits the deleterious effects of extended warm ischemia. PMID:10231122

  3. Myocardial perfusion imaging using contrast echocardiography.

    PubMed

    Pathan, Faraz; Marwick, Thomas H

    2015-01-01

    Microbubbles are an excellent intravascular tracer, and both the rate of myocardial opacification (analogous to coronary microvascular perfusion) and contrast intensity (analogous to myocardial blood volume) provide unique insights into myocardial perfusion. A strong evidence base has been accumulated to show comparability with nuclear perfusion imaging and incremental diagnostic and prognostic value relative to wall motion analysis. This technique also provides the possibility to measure myocardial perfusion at the bedside. Despite all of these advantages, the technique is complicated, technically challenging, and has failed to scale legislative and financial hurdles. The development of targeted imaging and therapeutic interventions will hopefully rekindle interest in this interesting modality. PMID:25817740

  4. Estimating a regional ventilation-perfusion index

    PubMed Central

    Muller, P A; Li, T; Isaacson, D; Newell, J C; Saulnier, G J; Kao, Tzu-Jen; Ashe, Jeffrey

    2015-01-01

    This is a methods paper, where an approximation to the local ventilation-perfusion ratio is derived. This approximation, called the ventilation-perfusion index since it is not exactly the physiological ventilation-perfusion ratio, is calculated using conductivity reconstructions obtained using electrical impedance tomography. Since computation of the ventilation-perfusion index only requires knowledge of the internal conductivity, any conductivity reconstruction method may be used. The method is explained, and results are presented using conductivities obtained from two EIT systems, one using an iterative method and the other a linearization method. PMID:26006279

  5. 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. PMID:21635554

  6. 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. PMID:27133563

  7. Visualization of perfusion changes with laser speckle contrast imaging using the method of motion history image.

    PubMed

    Ansari, Mohammad Zaheer; Humeau-Heurtier, Anne; Offenhauser, Nikolas; Dreier, Jens P; Nirala, Anil Kumar

    2016-09-01

    Laser speckle contrast imaging (LSCI) is a real-time imaging modality reflecting microvascular perfusion. We report on the application of the motion history image (MHI) method on LSCI data obtained from the two hemispheres of a mouse. Through the generation of a single image, MHI stresses the microvascular perfusion changes. Our experimental results performed during a pinprick-triggered spreading depolarization demonstrate the effectiveness of MHI: MHI allows the visualization of perfusion changes without loss of resolution and definition. Moreover, MHI provides close results to the ones given by the generalized differences (GD) algorithm. However, MHI has the advantage of giving information on the temporal evolution of the perfusion variations, which GD does not. PMID:27321386

  8. Mucosal malignant melanoma of the maxillary sinus.

    PubMed

    Norhafizah, M; Mustafa, W M B W; Sabariah, A R; Shiran, M S; Pathmanathan, R

    2010-09-01

    Mucosal malignant melanoma (MMM) is an aggressive tumour occurring in the upper respiratory tract. It is rare compared to malignant melanoma of the skin. We report a case of a 53-year-old man with left paranasal swelling. A biopsy showed high-grade spindle cell tumour. Subsequently a subtotal maxillectomy was performed. Histopathological examination revealed a hypercellular tumour composed of mixed spindle and epitheloid cells with very occasional intracytoplasmic melanin pigment. The malignant cells were immunopositive for vimentin, S-100 protein and HMB-45. It was diagnosed as mucosal malignant melanoma (MMM). This article illustrates a rare case of MMM where the diagnosis may be missed or delayed without proper histopathological examination that include meticulous search for melanin pigment and appropriate immunohistochemical stains to confirm the diagnosis. Malignant melanoma can mimic many other types of high-grade malignancy and should be considered as a differential diagnosis in many of these instances. PMID:21939172

  9. 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. PMID:26826375

  10. Cough-induced Tracheobronchial Mucosal Bleeding.

    PubMed

    Hira, Harmanjit Singh

    2011-01-01

    A 56-year-old man presented with moderate hemoptysis. It was preceded by a severe bout of cough. Flexible bronchoscopy showed diffuse tracheobronchial mucosal petechiae and bleeding. The patient was not suffering with any coagulopathies. He did not receive antiplatelet drugs. Hemoptysis resolved with cough suppressant. Subsequent bronchoscopy revealed the complete resolution of petechiae. The mechanism of bleeding after the bout of coughing is discussed. PMID:23169019

  11. The microbiome and regulation of mucosal immunity.

    PubMed

    McDermott, Andrew J; Huffnagle, Gary B

    2014-05-01

    The gastrointestinal tract is a mucosal surface constantly exposed to foreign antigens and microbes, and is protected by a vast array of immunologically active structures and cells. Epithelial cells directly participate in immunological surveillance and direction of host responses in the gut and can express numerous pattern recognition receptors, including Toll-like receptor 5 (TLR5), TLR1, TLR2, TLR3, TLR9, and nucleotide oligomerization domain 2, as well as produce chemotactic factors for both myeloid and lymphoid cells following inflammatory stimulation. Within the epithelium and in the underlying lamina propria resides a population of innate lymphoid cells that, following stimulation, can become activated and produce effector cytokines and exert both protective and pathogenic roles during inflammation. Lamina propria dendritic cells play a large role in determining whether the response to a particular antigen will be inflammatory or anti-inflammatory. It is becoming clear that the composition and metabolic activity of the intestinal microbiome, as a whole community, exerts a profound influence on mucosal immune regulation. The microbiome produces short-chain fatty acids, polysaccharide A, α-galactosylceramide and tryptophan metabolites, which can induce interleukin-22, Reg3γ, IgA and interleukin-17 responses. However, much of what is known about microbiome-host immune interactions has come from the study of single bacterial members of the gastrointestinal microbiome and their impact on intestinal mucosal immunity. Additionally, evidence continues to accumulate that alterations of the intestinal microbiome can impact not only gastrointestinal immunity but also immune regulation at distal mucosal sites. PMID:24329495

  12. Topical cocaine for relief of mucosal pain.

    PubMed

    Newport, Kristina; Coyne, Patrick

    2010-06-01

    Painful mucosal lesions negatively affect quality of life. When located in the oral cavity, they can cause pain that interferes with speech and swallowing. Acute pain from intra-oral lesions is difficult to treat with conventional methods such as systemic opioids or viscous lidocaine. These cases exemplify a safe, fast and effective method for treating painful mouth lesions that are not responsive to standard treatments. Mr. D and Mr. G had from painful oral lesions caused by squamous cell carcinoma. Severe pain interfered with their ability to speak and swallow, resulting in poor nutrition and dehydration. 4% liquid cocaine, self-applied topically to the open mouth sores, resulted in relief within minutes in both cases. Repeated dosing every six hours allowed both patients to restart oral nutrition without any reported side effects. Topical cocaine has not been described for repeated dosing for oral or other mucosal pain. Potential side effects of mucosal administration include gingival recession and erythematous lesions. If the recommended topical doses are exceeded, liquid cocaine may be absorbed systemically causing a stimulant response or addiction. When used appropriately, however, this intervention can result in a dramatic improvement in quality of life and functional status. PMID:20504138

  13. Collaborative studies in mucosal immunology in Goroka.

    PubMed

    Clancy, Robert

    2010-01-01

    A collaborative program between the Papua New Guinea (PNG) Institute of Medical Research and the Hunter Mucosal Group has completed studies relevant to protection of the airways against bacterial infection. Specifically, these studies addressed the mucosal capacity to produce local immunoglobulins and the capacity of the airways to respond to an oral vaccine containing inactivated nontypeable Haemophilus influenzae (NTHi). The mucosal IgA response to NTHi antigens was blunted in both children and adults in PNG compared with that found in Australian children and adults, whose airways are colonized only intermittently. Despite this, when oral NTHi is given to Papua New Guinean adults with chronic airways disease, it is followed by a significant (50%) reduction in incidence of acute bronchitic episodes, and a 3-log reduction in density of colonization, which persisted about 10 months. The implications of these key findings are discussed with respect to both mechanism and wider control of pathology emanating from abnormal airways colonization in a PNG environment. PMID:23163182

  14. 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. PMID:26117595

  15. Chitosan-based mucosal adjuvants: Sunrise on the ocean.

    PubMed

    Xia, Yufei; Fan, Qingze; Hao, Dongxia; Wu, Jie; Ma, Guanghui; Su, Zhiguo

    2015-11-01

    Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials. In this review, the state of art of chitosan and its derivatives as mucosal adjuvants, including thermo-sensitive chitosan system as mucosal adjuvant that were newly developed by author's group, was described, as well as the clinical application perspective. After a brief introduction of mucosal adjuvants, chitosan and its derivatives as robust immune potentiator were discussed in detail and depth, in regard to the metabolism, safety profile, mode of actions and preclinical and clinical applications, which may shed light on the massive clinical application of chitosan as mucosal adjuvant. PMID:26271831

  16. 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

  17. 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.

  18. Gastric Mucosal Energy Metabolism and “Stress Ulceration,”

    PubMed Central

    Menguy, Rene; Masters, Y. F.

    1974-01-01

    Acute gastric erosions following hemorrhagic shock (stress ulceration) have been attributed to gastric hyperacidity, altered gastric secretion of mucus and an abnormal permeability of the gastric mucosa to H+. This report aims at presenting evidence supporting an alternate hypothesis: the event linking shock-induced gastric mucosal ischemia to mucosal necrosis is a deficit in gastric mucosal energy metabolism. Our experimental procedure consisted of harvesting the stomachs of rats and rabbits by “stop-freeze” (liquid N2) at different intervals after the induction of hemorrhagic shock. Levels of adenosine-phosphates and of glycolytic intermediates in gastric mucosa were measured. We studied the changes in the levels of these substrates produced by shock as well as by factors capable, when combined with shock, of rendering the gastric mucosa more vulnerable to stress ulceration. The influence of shock and of these modifying factors were evaluated by comparison with data from appropriately designed control experiments. In parallel experiments we examined the frequency of stress ulceration (gross and microscopic) under these same standard conditions. There have emerged from these studies a number of observations all based upon data with the highest statistical significance. The data are consonant with the hypothesis stated above: an energy deficit severe enough to cause cellular necrosis is the event linking shock-induced gastric mucosal ischemia and stress ulceration. ImagesFig. 1.Fig. 2. PMID:4278107

  19. 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. PMID:27031867

  20. 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

  1. 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.

  2. Roles of M cells in infection and mucosal vaccines

    PubMed Central

    Wang, Miao; Gao, Zeqian; Zhang, Zhongwang; Pan, Li; Zhang, Yongguang

    2014-01-01

    The mucosal immune system plays a crucial part in the control of infection. Exposure of humans and animals to potential pathogens generally occurs through mucosal surfaces, thus, strategies that target the mucosa seem rational and efficient vaccination measures. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity compared with parenteral vaccination. M cells are capable of transporting luminal antigens to the underlying lymphoid tissues and can be exploited by pathogens as an entry portal to invade the host. Therefore, targeting M-cell-specific molecules might enhance antigen entry, initiate the immune response, and induce protection against mucosal pathogens. Here, we outline our understanding of the distribution and function of M cells, and summarize the advances in mucosal vaccine strategies that target M cells. PMID:25483705

  3. Mucosal vaccines: novel advances in technology and delivery.

    PubMed

    Yuki, Yoshikazu; Kiyono, Hiroshi

    2009-08-01

    Mucosal vaccines are considered the most suitable type of vaccines to combat emerging and re-emerging infectious diseases because of their ability to induce both mucosal and systemic immunity. Considerable advances have been made toward the development of mucosal vaccines against influenza virus and rotavirus. Many additional mucosal vaccines are in development, including vaccines against cholera, typhoid, traveler's diarrhea and respiratory infections. In addition to oral and nasal vaccines, transcutaneous (or skin patch) and sublingual immunizations are now part of a new generation of mucosal vaccines. Furthermore, a rice-based oral vaccine (MucoRice) has been receiving global attention as a new form of cold chain-free vaccine, because it is stable at room temperature for a prolonged period. This review describes recent developments in mucosal vaccines with promising preclinical and clinical results. PMID:19627189

  4. Antibodies and Their Receptors: Different Potential Roles in Mucosal Defense

    PubMed Central

    Horton, Rachel E.; Vidarsson, Gestur

    2013-01-01

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

  5. Concurrent Mucosal Melanoma and Angiofibroma of the Nose

    PubMed Central

    Hwang, Jae Hyung; Ha, Jin Bu; Lee, Junguee; Lee, Joohyung

    2016-01-01

    Malignant melanoma rarely develops in the paranasal sinuses, and generally has a poor prognosis. However, mucosal melanoma can masquerade both clinically and histopathologically as a benign lesion, rendering accurate early diagnosis difficult. On the other hand, angiofibroma, a benign tumor, is more easily diagnosed than a mucosal melanoma, because the former exhibits specific histopathological features. No cases of concurrent angiofibroma and mucosal melanoma have been reported to date. We describe such a case below. PMID:27095516

  6. Microbiota and their role in the pathogenesis of oral mucositis.

    PubMed

    Vanhoecke, B; De Ryck, T; Stringer, A; Van de Wiele, T; Keefe, D

    2015-01-01

    Oral mucositis in patients undergoing cancer therapy is a significant problem. Its prevalence ranges between 20 and 100%, depending on treatment type and protocols and patient-based variables. Mucositis is self-limiting when uncomplicated by infection. Unfortunately, the incidence of developing a local or systemic infection during the course of the treatment is very high. At this stage, it is unclear which role oral microbiota play in the onset, duration, and severity of oral mucositis. Nevertheless, there is growing interest in this underexplored topic, and new studies are being undertaken to unravel their impact on the pathogenesis of mucositis. PMID:24456144

  7. TISSUE ENGINEERING PERFUSABLE CANCER MODELS

    PubMed Central

    Fong, E.L.; Santoro, M.; Farach-Carson, M.C.; Kasper, F.K.; Mikos, A.G.

    2014-01-01

    The effect of fluid flow on cancer progression is currently not well understood, highlighting the need for perfused tumor models to close this gap in knowledge. Enabling biological processes at the cellular level to be modeled with high spatiotemporal control, microfluidic tumor models have demonstrated applicability as platforms to study cell-cell interactions, effect of interstitial flow on tumor migration and the role of vascular barrier function. To account for the multi-scale nature of cancer growth and invasion, macroscale models are also necessary. The consideration of fluid dynamics within tumor models at both the micro- and macroscopic levels may greatly improve our ability to more fully mimic the tumor microenvironment. PMID:24634812

  8. 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.

  9. Topical protection of human esophageal mucosal integrity.

    PubMed

    Woodland, P; Batista-Lima, F; Lee, C; Preston, S L; Dettmar, P; Sifrim, D

    2015-06-15

    Patients with nonerosive reflux disease exhibit impaired esophageal mucosal integrity, which may underlie enhanced reflux perception. In vitro topical application of an alginate solution can protect mucosal biopsies against acid-induced changes in transepithelial electrical resistance (TER). We aimed to confirm this finding in a second model using 3D cell cultures and to assess prolonged protection in a biopsy model. We assessed the protective effect of a topically applied alginate solution 1 h after application. 3D cell cultures were grown by using an air-liquid interface and were studied in Ussing chambers. The apical surface was "protected" with 200 μl of either alginate or viscous control or was unprotected. The tissue was exposed to pH 3 + bile acid solution for 30 min and TER change was calculated. Distal esophageal mucosal biopsies were taken from 12 patients and studied in Ussing chambers. The biopsies were coated with either alginate or viscous control solution. The biopsies were then bathed in pH 7.4 solution for 1 h. The luminal chamber solution was replaced with pH 2 solution for 30 min. Percentage changes in TER were recorded. In five biopsies fluorescein-labeled alginate solution was used to allow immunohistological localization of the alginate after 1 h. In the cell culture model, alginate solution protected tissue against acid-induced change in TER. In biopsies, 60 min after protection with alginate solution, the acidic exposure caused a -8.3 ± 2.2% change in TER compared with -25.1 ± 4.5% change after protection with the viscous control (P < 0.05). Labeled alginate could be seen coating the luminal surface in all cases. In vitro, alginate solutions can adhere to the esophageal mucosa for up to 1 h and exert a topical protectant effect. Durable topical protectants can be further explored as first-line/add-on therapies for gastroesophageal reflux disease. PMID:25907692

  10. 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.

  11. 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

  12. Gastric Mucosal Protection by Aegle Marmelos Against Gastric Mucosal Damage: Role of Enterochromaffin Cell and Serotonin

    PubMed Central

    Singh, Purnima; Dutta, Shubha R.; Guha, Debjani

    2015-01-01

    Background/Aims: Serotonin (5-hydroxytryptamine; 5-HT) released from enterochromaffin (EC) cells in gastric mucosa inhibits gastric acidity by increasing the gastric mucus secretion. In the present study, we evaluated the effect of aqueous extract of Aegle marmelos (AM) ripe fruit pulp (250 mg/kg body weight) on mean ulcer index (MUI), EC cells, 5-HT content, and adherent mucosal thickness of ulcerated gastric tissue in adult albino rats. Material and Methods: Ulceration was induced by using aspirin (500 mg/kg, p.o.), cerebellar nodular lesion and applying cold-restraint stress. Results: In all cases increased MUI in gastric tissue along with decreased EC cell count was observed with concomitant decrease of 5-HT content and adherent mucosal thickness (P < 0.05). Pretreatment with AM for 14 days decreased MUI, increased EC cell count, and 5-HT content as well as adherent mucosal thickness in all ulcerated group (P < 0.05). Conclusion: AM produces gastric mucosal protection mediated by increased EC cell count and 5-HT levels. PMID:25672237

  13. Evaluation of a suspicious oral mucosal lesion.

    PubMed

    Williams, P Michele; Poh, Catherine F; Hovan, Allan J; Ng, Samson; Rosin, Miriam P

    2008-04-01

    Dentists who encounter a change in the oral mucosa of a patient must decide whether the abnormality requires further investigation. In this paper, we describe a systematic approach to the assessment of oral mucosal conditions that are thought likely to be premalignant or an early cancer. These steps, which include a comprehensive history, step-by-step clinical examination (including use of adjunctive visual tools), diagnostic testing and formulation of diagnosis, are routinely used in clinics affiliated with the British Columbia Oral Cancer Prevention Program (BC OCPP) and are recommended for consideration by dentists for use in daily practice. PMID:18387268

  14. 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

  15. Mucosal Lesions in an Allergy Practice.

    PubMed

    Kohorst, John J; Bruce, Alison J; Torgerson, Rochelle R

    2016-04-01

    The diagnosis and treatment of mucosal disease with an allergic pathogenesis are challenging. Oral allergy is often a hypersensitivity reaction with variable symptoms and physical exam findings. Clinical diagnosis requires a history of prior allergen exposure, a delay from exposure to clinical findings, and improvement following allergen removal. The past decades have seen great contributions to the field of oral allergy. The aim of this review is to provide an approach to the diagnosis and treatment of oral dermatologic disease with a focus on diseases with an investigated allergic pathogenesis. PMID:26922434

  16. Effect of Epicatechin against Radiation-Induced Oral Mucositis: In Vitro and In Vivo Study

    PubMed Central

    Kang, Sung Un; Kim, Jang Hee; Oh, Young-Taek; Park, Keun Hyung; Kim, Chul-Ho

    2013-01-01

    Purpose Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC), a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo. Experimental Design The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed. Results EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells. Conclusions This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis. PMID:23874895

  17. Comparative analysis of in situ versus ex situ perfusion on flow and microcirculation in kidney procurement: research on a porcine model

    PubMed Central

    2013-01-01

    Background The first crucial step in transplantation appears to be the effective rinsing of the graft during organ procurement. Even though there is strong suspicion that ex situ perfusion results in better rinsing of the graft, there is no proof for this hypothesis. The aim of this study was to analyse the differences of in situ and ex situ kidney perfusion in a porcine model. Methods Standardised multiorgan procurement was performed in 15 German landrace pigs. Perfusion was carried out using histidine–tryptophan–ketoglutarate solution (HTK) under the application of pressure. In one kidney, in situ perfusion via the aorta was carried out while the second kidney received ex situ perfusion via the renal artery (RA). Perfusate flow inside the aorta and the RA was recorded at different pressure steps. In order to visualise the effect on the microcirculation, different coloured microparticles (MPs; 10 μm) were administered via the aorta or RA. Subsequently, frozen sections of the explanted kidneys were analysed histologically and MPs were evaluated quantitatively. Results Ex situ kidney perfusion resulted in significantly improved flow rates (P<0.0001) compared with in situ perfusion. By applying ex situ perfusion it was even possible to attain physiological flow levels on the RA under the application of external pressure of 150 to 200 mmHg. The amount of MPs was able to highlight the positive impact of ex situ perfusion on microcirculation of the kidney graft (P<0.0001). Conclusions The use of MPs represents a valuable tool for quantitative investigation and illustration of kidney perfusion in experimental setups. Additional ex situ perfusion is able to improve the quality of kidney perfusion. PMID:23837545

  18. Mucosal Imprinting of Vaccine-Induced CD8+ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors

    PubMed Central

    Sandoval, Federico; Bureau, Michel-Francis; Freyburger, Ludovic; Clement, Olivier; Marcheteau, Elie; Gey, Alain; Fraisse, Guillaume; Bouguin, Cécilia; Merillon, Nathalie; Dransart, Estelle; Tran, Thi; Quintin-Colonna, Françoise; Autret, Gwennhael; Thiebaud, Marine; Suleman, Muhammad; Riffault, Sabine; Wu, Tzyy-Choou; Launay, Odile; Danel, Claire; Taieb, Julien; Richardson, Jennifer; Zitvogel, Laurence; Fridman, Wolf H.; Johannes, Ludger; Tartour, Eric

    2014-01-01

    Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route. This antitumor effect was dependent on CD8+ T cells. Indeed, only intranasal vaccination elicited mucosal-specific CD8+ T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8+ T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, dendritic cells from lung parenchyma, but not those from spleen, induced the expression of CD49a on cocultured specific CD8+ T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a, which supports the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8+ T cells that controlled their trafficking. Immunization route directly affected the efficacy of the cancer vaccine to control mucosal tumors. PMID:23408053

  19. 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.

  20. 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

  1. 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. PMID:23958351

  2. Gastrointestinal mucosal barrier function and diseases.

    PubMed

    Oshima, Tadayuki; Miwa, Hiroto

    2016-08-01

    The gastrointestinal mucosal barrier plays an essential role in the separation of the inside of the body from the outside environment. Tight junctions (TJs) are the most important component for construction of a constitutive barrier of epithelial cells, and they regulate the permeability of the barrier by tightly sealing the cell-cell junctions. TJ proteins are represented by claudins, occludin, junctional adhesion molecules, and scaffold protein zonula occludens. Among these TJ proteins, claudins are the major components of TJs and are responsible for the barrier and the polarity of the epithelial cells. Gastrointestinal diseases including reflux esophagitis, inflammatory bowel disease, functional gastrointestinal disorders, and cancers may be regulated by these molecules, and disruption of their functions leads to chronic inflammatory conditions and chronic or progressive disease. Therefore, regulation of the barrier function of epithelial cells by regulating the expression and localization of TJ proteins is a potential new target for the treatment of these diseases. Treatment strategies for these diseases might thus be largely altered if symptom generation and/or immune dysfunction could be regulated through improvement of mucosal barrier function. Since TJ proteins may also modify tumor infiltration and metastasis, other important goals include finding a good TJ biomarker of cancer progression and patient prognosis, and developing TJ protein-targeted therapies that can modify patient prognosis. This review summarizes current understanding of gastrointestinal barrier function, TJ protein expression, and the mechanisms underlying epithelial barrier dysregulation in gastrointestinal diseases. PMID:27048502

  3. Canine oral mucosal mast cell tumours.

    PubMed

    Elliott, J W; Cripps, P; Blackwood, L; Berlato, D; Murphy, S; Grant, I A

    2016-03-01

    Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco-regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present. PMID:24215587

  4. 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

  5. Mucosal Inducible NO Synthase-Producing IgA+ Plasma Cells in Helicobacter pylori-Infected Patients.

    PubMed

    Neumann, Laura; 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

    2016-09-01

    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

  6. The effect of lysolecithin on prostanoid and platelet-activating factor formation by human gall-bladder mucosal cells

    PubMed Central

    Nag, M. K.; Deshpande, Y. G.; Beck, D.; Li, A.

    1995-01-01

    It has been demonstrated that lysolecithin (lysophosphatidyl choline, LPC) produces experimental cholecystitis in cats mediated by arachidonic acid metabolites. LPC is a cytolytic agent that has been postulated as a contributing factor in the development of cholecystitis in humans. The purpose of this research was to evaluate the effect of LPC on human gall-bladder mucosal cell phospholipase A2 and cyclooxygenase activity. Gall-bladder mucosal cells were isolated from the gall-bladders of patients undergoing routine cholecystectomy. Fresh, isolated cells were maintained in tissue culture and stimulated with varying doses of LPC. Platelet-activating factor concentration was quantitated as an index of phospholipase A2 activity and prostanoids were measured as an index of cyclooxygenase activity. Also, the effect of LPC on cyclooxygenase 1 and 2 expression in microsomal protein was evaluated. LPC caused dose related increases in 6-keto-PGF1α and PAF produced by human gall-bladder mucosal cells. Exposure of human gall-bladder mucosal cells to LPC failed to elicit expression of constitutive cyclooxygenase-1, while the expression of inducible cyclooxygenase-2 was increased. The results of this study indicate that LPC induces the formation of prostanoids and PAF by human gall-bladder mucosal cells, suggesting that this substance may promote the development of gall-bladder inflammation. PMID:18475621

  7. 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

  8. Perfusion education and training in Europe.

    PubMed

    Merkle, Frank

    2006-01-01

    Perfusion education and training varies considerably throughout Europe. Unlike in the US, where a common curriculum for perfusion education has been established, each European country has its own education system. This fact is further complicated by a multitude of national languages and cultures. Thus, perfusion education programmes vary, not only in content, but also in their academic levels. This article aims to give a comprehensive overview of the situation in each of the 20 member states of the European Board of Cardiovascular Perfusion (EBCP). The EBCP delegates were polled for a description of the process of training and education of clinical perfusionists in their respective countries. Following the initial delegate poll in 2001, an update of the material was performed in spring 2005. In summary, training of clinical perfusionists in Europe varies considerably between countries. A professional body is necessary to oversee the training process and to guarantee a minimum level of clinical competency for cardiovascular perfusionists. PMID:16485693

  9. 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.

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

    PubMed

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

    2016-04-01

    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

  11. Effects of mucosal loading on vocal fold vibration

    NASA Astrophysics Data System (ADS)

    Tao, Chao; Jiang, Jack J.

    2009-06-01

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

  12. 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.

  13. Myocardial perfusion imaging with 201Tl.

    PubMed

    Pagnanelli, Robert A; Basso, Danny A

    2010-03-01

    The object of this review is to provide information about (201)Tl-thallous chloride in radionuclide myocardial perfusion imaging. This technique has experienced a recent resurgence because of the shortage of (99m)Tc. After reading this article, the technologist will be able to describe the properties and uptake mechanism of (201)Tl, the procedure for myocardial perfusion imaging with this agent, and the advantages and disadvantages of thallium, compared with the technetium agents. PMID:20159930

  14. 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.

  15. Mucosal Correlates of Protection in HIV-1-Exposed Seronegative Persons

    PubMed Central

    Shen, Ruizhong; Smith, Phillip D.

    2014-01-01

    Resistance to HIV-1 infection in HIV-1-exposed seronegative (HESN) persons offers a promising opportunity to identify mechanisms of “natural” protection. Unique features of the mucosa in particular may contribute to this protection. Here we highlight several key issues pertaining to the mucosal correlates of protection in HESN persons, including humoral immune responses, mechanisms of mucosal HIV-1-neutralization, immune cell activation, and role of the microbiota in mucosal responses. We also discuss mucosal model systems that can be used to investigate the mechanisms of resistance in HESN subjects. A clear understanding of the mucosal correlates of protection against HIV-1 in HESN persons will provide critical new insights for the development of effective vaccine and microbicide strategies for the prevention of HIV-1 transmission. PMID:24428610

  16. 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.

  17. Methodology for ventilation/perfusion SPECT.

    PubMed

    Bajc, Marika; Neilly, Brian; Miniati, Massimo; Mortensen, Jan; Jonson, Björn

    2010-11-01

    Ventilation/perfusion single-photon emission computed tomography (V/Q SPECT) is the scintigraphic technique of choice for the diagnosis of pulmonary embolism and many other disorders that affect lung function. Data from recent ventilation studies show that the theoretic advantages of Technegas over radiolabeled liquid aerosols are not restricted to the presence of obstructive lung disease. Radiolabeled macroaggregated human albumin is the imaging agent of choice for perfusion scintigraphy. An optimal combination of nuclide activities and acquisition times for ventilation and perfusion, collimators, and imaging matrix yields an adequate V/Q SPECT study in approximately 20 minutes of imaging time. The recommended protocol based on the patient remaining in an unchanged position during the initial ventilation study and the perfusion study allows presentation of matching ventilation and perfusion slices in all projections as well as in rotating volume images based upon maximum intensity projections. Probabilistic interpretation of V/Q SPECT should be replaced by a holistic interpretation strategy on the basis of all relevant information about the patient and all ventilation/perfusion patterns. PE is diagnosed when there is more than one subsegment showing a V/Q mismatch representing an anatomic lung unit. Apart from pulmonary embolism, other pathologies should be identified and reported, for example, obstructive disease, heart failure, and pneumonia. Pitfalls exist both with respect to imaging technique and scan interpretation. PMID:20920632

  18. IL-9 signaling as key driver of chronic inflammation in mucosal immunity.

    PubMed

    Neurath, Markus F; Finotto, Susetta

    2016-06-01

    Recent studies have highlighted a crucial regulatory role of the cytokine IL-9 in driving immune responses in chronic inflammatory and autoimmune diseases at mucosal surfaces. IL-9 activates various types of immune and non-immune cells carrying the membrane bound IL-9R. IL-9 signaling plays a pivotal role in controlling the differentiation and activation of these cells by inducing the Jak/STAT pathway. In particular, IL-9 induces activation of T helper cells and affects the function of various tissue resident cells such as mast cells and epithelial cells in the mucosa. Importantly, recent findings suggest that blockade of IL-9 signaling is effective in treating experimental models of autoimmune and chronic inflammatory diseases such as inflammatory bowel diseases, allergic disorders such as food allergy and asthma. Thus, blockade of IL-9 and IL-9R signaling emerges as potentially novel approach for therapy of inflammatory diseases in the mucosal immune system. PMID:26976761

  19. Changes in caecal microbiota and mucosal morphology of weaned pigs.

    PubMed

    Castillo, Marisol; Martín-Orúe, Susana M; Nofrarías, Miquel; Manzanilla, Edgar G; Gasa, Josep

    2007-10-01

    An experiment was designed to monitor the changes in caecal microbiota associated with early weaning. Twelve piglets (20+/-2 days) from six different litters were selected from a commercial source. For the two experimental groups, one animal from each litter was weaned onto a post-weaning diet (W) and the other remained with the sow (S). After 1 week, animals were sacrificed and caecal samples taken. Microbial counts for total bacteria, enterobacteria and lactobacilli populations were determined by quantitative PCR using SYBR Green dye. Microbial profiles were assessed by terminal restriction fragment length polymorphism (t-RFLP). Weaning promoted an increase in the enterobacteria:lactobacilli ratio (0.27 versus 1.67 log/log 16S rRNA gene copy number, P=0.05). Total bacteria and richness of the caecal microbial ecosystem (number of peaks) were similar in both experimental groups (49.3 for S and 53.4 for W, respectively, P=0.22), although the band patterns were clearly grouped in two different clusters by dendogram analysis. Weaning was also associated with a decrease in crypt density, an increase in mytotic index and a decrease in the number of goblet cells. A reduced immunological response was also observed and was manifested by an increase in intraepithelial lymphocytes and lymphocyte density in the lamina propria. Weaning appears to be critical in the establishment of the caecal microbiota in pigs with important changes, particularly in microbial groups and in caecal mucosal architecture. PMID:17532151

  20. Hypothermic machine perfusion of the liver and the critical balance between perfusion pressures and endothelial injury.

    PubMed

    't Hart, N A; van der Plaats, A; Leuvenink, H G D; van Goor, H; Wiersema-Buist, J; Verkerke, G J; Rakhorst, G; Ploeg, R J

    2005-01-01

    Hypothermic machine perfusion (HMP) provides better protection against cold ischemic injury than cold storage in marginal donor kidneys. Also, in liver transplantation a switch from static cold storage to HMP could be beneficial as it would allow longer preservation times and the use of marginal donors. A critical question concerning application of HMP in liver preservation is the crucial balance between perfusion pressure and occurrence of endothelial injury. Rat livers were cold-perfused for 24 hours to study perfusion pressures for both hepatic artery and portal vein. Cold storage served as control and was compared to HMP-preserved livers using a mean arterial perfusion pressure of 25 mm Hg and a portal perfusion pressure of 4 mm Hg (25% of normothermic liver circulation) and to HMP at 50 mm Hg and 8 mm Hg perfusion, respectively (50% of normothermic liver circulation). UW solution was enriched with 14.9 micromol/L propidium iodide (PI) to stain for dead cells and with an additional 13.5 micromol/L acridine orange to stain for viable hepatocytes. A low PI-positive cell count was found using HMP at 25% of normal circulation compared to cold storage. The PI count was high for the HMP group perfused at just 50% of normal circulation compared to HMP at 25% and compared to cold storage. In summary, for liver HMP, perfusion at 25% showed complete perfusion with minimal cellular injury. HMP using perfusion pressures of 25 mm Hg for the hepatic artery and 4 mm Hg for the portal vein is feasible without induction of endothelial injury. PMID:15808634

  1. 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

  2. [Pulmonary ventilation/perfusion ratio].

    PubMed

    Guenard, H

    1987-01-01

    The ratios of ventilatory (V) and perfusion (Q) flow rates in the lung are to a large extent responsible for the efficiency of gas exchange. In a simplified monocompartmental model of the lung, the arterial partial pressure of a given gas (Pa) is a function of several factors: the solubility of this gas in blood, its venous and inspired partial pressures and the V/Q ratio. In a multicompartemental model, the mean arterial partial pressure of the gas is a function of the individual values of Pa in each compartment as well as the distribution of V/Q ratios in the lung and the relationship between the concentration and the partial pressure of the gas. The heterogeneity of the distribution of V/Q results from those of both V and Q. Two factors are mainly responsible for this heterogeneity: the gravity and the morphometric characteristics of bronchi and vessels. V/Q ratios are partially controlled at least in low V/Q compartments since hypoxia in these compartments leads to pulmonary arteriolar vasoconstriction. However lungs V/Q ratios range from 0.1 to 10 with a mode around 1. Age, muscular exercise, posture, accelerations, anesthesia, O2 breathing, pulmonary pathology are factors which may alter the distribution of V/Q ratios. PMID:3332289

  3. Simultaneous detection of landmarks and key-frame in cardiac perfusion MRI using a joint spatial-temporal context model

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoguang; Xue, Hui; Jolly, Marie-Pierre; Guetter, Christoph; Kellman, Peter; Hsu, Li-Yueh; Arai, Andrew; Zuehlsdorff, Sven; Littmann, Arne; Georgescu, Bogdan; Guehring, Jens

    2011-03-01

    Cardiac perfusion magnetic resonance imaging (MRI) has proven clinical significance in diagnosis of heart diseases. However, analysis of perfusion data is time-consuming, where automatic detection of anatomic landmarks and key-frames from perfusion MR sequences is helpful for anchoring structures and functional analysis of the heart, leading toward fully automated perfusion analysis. Learning-based object detection methods have demonstrated their capabilities to handle large variations of the object by exploring a local region, i.e., context. Conventional 2D approaches take into account spatial context only. Temporal signals in perfusion data present a strong cue for anchoring. We propose a joint context model to encode both spatial and temporal evidence. In addition, our spatial context is constructed not only based on the landmark of interest, but also the landmarks that are correlated in the neighboring anatomies. A discriminative model is learned through a probabilistic boosting tree. A marginal space learning strategy is applied to efficiently learn and search in a high dimensional parameter space. A fully automatic system is developed to simultaneously detect anatomic landmarks and key frames in both RV and LV from perfusion sequences. The proposed approach was evaluated on a database of 373 cardiac perfusion MRI sequences from 77 patients. Experimental results of a 4-fold cross validation show superior landmark detection accuracies of the proposed joint spatial-temporal approach to the 2D approach that is based on spatial context only. The key-frame identification results are promising.

  4. 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

  5. Head and neck mucosal melanoma: a review.

    PubMed

    Lourenço, Silvia V; Fernandes, Juliana D; Hsieh, Ricardo; Coutinho-Camillo, Claudia M; Bologna, Sheyla; Sangueza, Martin; Nico, Marcello M S

    2014-07-01

    Head and neck mucosal melanoma (MM) is an aggressive and rare neoplasm of melanocytic origin. To date, few retrospective series and case reports have been reported on MM. This article reviews the current evidence on head and neck MM and the molecular pathways that mediate the pathogenesis of this disease. Head and neck MM accounts for 0.7%-3.8% of all melanomas and involve (in decreasing order of frequency) the sinonasal cavity, oral cavity, pharynx, larynx, and upper esophagus. Although many studies have examined MM of the head and neck and the underlying molecular pathways, individual genetic and molecular alterations were less investigated. Further studies are needed to complement existing data and to increase our understanding of melanocytes tumorigenesis. PMID:24423929

  6. Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion

    PubMed Central

    Ghisleni, Carmen; Bollmann, Steffen; Biason-Lauber, Anna; Poil, Simon-Shlomo; Brandeis, Daniel; Martin, Ernst; Michels, Lars; Hersberger, Martin; Suckling, John

    2015-01-01

    Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women. PMID:26356576

  7. Infection and mucosal injury in cancer treatment.

    PubMed

    Khan, S A; Wingard, J R

    2001-01-01

    The oral and gastrointestinal mucosa acts as an important mechanical barrier that prevents local or systemic invasion by microorganisms. Cytotoxic chemotherapy-induced mucosal injury (MI) of oral cavity and intestinal epithelium occurs in many patients treated for malignancy. Compromise of the mucosal barrier can contribute to local invasion by colonizing microorganisms and, subsequently, to systemic infection. Historically, gram-negative bacteremia has been the most problematic bacterial infection in neutropenic patients, but its incidence has reduced over time because of the use of prophylactic antibiotics. There has been a shift in the type of infecting organisms responsible for bacteremia in these patients, from predominantly gram-negative organisms to gram-positive cocci. The viridans group of streptococci is composed of the most frequent bacterial pathogens associated with MI. When speciated, oral colonizers such as Streptococcus mitis, Streptococcus oralis, and Streptococcus sangulis II are the most frequently identified pathogens. Other systemic infections caused by vancomycin-resistant enterococci, Stenotrophomonas maltophilia, and Candida species have also been associated with MI after cancer treatment. Infection can also exacerbate MI after cancer treatment. The best recognized example is herpes simplex virus type 1 (HSV-1). Latent virus is frequently reactivated in HSV-seropositive patients; this reactivation leads to stomatitis, which can be indistinguishable from MI caused by cytoreductive therapies. Antiviral prophylaxis or treatment can control the virus-induced MI and bring about overall amelioration of MI. Recognition of this infectious cause of MI is important in order for clinicians to anticipate and minimize oral toxicity and to facilitate optimal delivery of the antineoplastic regimen. PMID:11694563

  8. Optimization of isolated perfused/ventilated mouse lung to study hypoxic pulmonary vasoconstriction

    PubMed Central

    Yoo, Hae Young; Zeifman, Amy; Ko, Eun A.; Smith, Kimberly A.; Chen, Jiwang; Machado, Roberto F.; Zhao, You-Yang; Minshall, Richard D.; Yuan, Jason X.-J.

    2013-01-01

    Hypoxic pulmonary vasoconstriction (HPV) is a compensatory physiological mechanism in the lung that optimizes the matching of ventilation to perfusion and thereby maximizes gas exchange. Historically, HPV has been primarily studied in isolated perfused/ventilated lungs; however, the results of these studies have varied greatly due to different experimental conditions and species. Therefore, in the present study, we utilized the mouse isolated perfused/ventilated lung model for investigation of the role of extracellular Ca2+ and caveolin-1 and endothelial nitric oxide synthase expression on HPV. We also compared HPV using different perfusate solutions: Physiological salt solution (PSS) with albumin, Ficoll, rat blood, fetal bovine serum (FBS), or Dulbecco's Modified Eagle Medium (DMEM). After stabilization of the pulmonary arterial pressure (PAP), hypoxic (1% O2) and normoxic (21% O2) gases were applied via a ventilator in five-minute intervals to measure HPV. The addition of albumin or Ficoll with PSS did not induce persistent and strong HPV with or without a pretone agent. DMEM with the inclusion of FBS in the perfusate induced strong HPV in the first hypoxic challenge, but the HPV was neither persistent nor repetitive. PSS with rat blood only induced a small increase in HPV amplitude. Persistent and repetitive HPV occurred with PSS with 20% FBS as perfusate. HPV was significantly decreased by the removal of extracellular Ca2+ along with addition of 1 mM EGTA to chelate residual Ca2+ and voltage-dependent Ca2+ channel blocker (nifedipine 1 μM). PAP was also reactive to contractile stimulation by high K+ depolarization and U46619 (a stable analogue of thromboxane A2). In summary, optimal conditions for measuring HPV were established in the isolated perfused/ventilated mouse lung. Using this method, we further confirmed that HPV is dependent on Ca2+ influx. PMID:24015341

  9. True versus mild hyperthermia during isolated hepatic perfusion: effects on melphalan pharmacokinetics and liver function.

    PubMed

    Pilati, Pierluigi; Mocellin, Simone; Rossi, Carlo R; Ori, Carlo; Innocente, Federico; Scalerta, Romano; Ceccherini, Mauro; Da Pian, Pier Paolo; Nitti, Donato; Lise, Mario

    2004-08-01

    Hyperthermic antiblastic isolated hepatic perfusion (IHP) with melphalan has been recently proposed as an alternative therapeutic option for patients with unresectable liver tumors. Although melphalan-heat antiblastic synergism is at a maximum at temperatures higher than 41 degrees C, IHP has so far been performed in humans at lower temperatures. In this experimental work, we compared IHP under mild versus true hyperthermic conditions in terms of drug pharmacokinetics and liver function. Ten pigs were submitted to IHP with melphalan 1.5 mg/kg at a mean temperature of 40 degrees C (group A, n = 5) or 42 degrees C (group B, n = 5). After a 60-minute perfusion, a 15-minute washout was performed. Perfusate-to-plasma leakage was monitored using scintigraphy. Throughout perfusion, samples from the systemic blood, perfusate, and liver parenchyma were obtained to measure melphalan concentrations. Liver function was assessed using standard blood tests and the indocyanine green-based test. No deaths related to the IHP procedure were recorded. All animals had transient liver function impairment, with all liver function test results returning to normal within the observation period. At histologic examination, liver damage was similar under both hyperthermic conditions. Melphalan levels in the perfusate were not significantly different in the two study groups (the mean perfusate/plasma area under the curve from 0 to 60 minutes ratios were 463 and 501, respectively). These results correlated well with those obtained using the scintigraphic method. Liver drug concentrations remained unchanged after true hyperthermia IHP. Under true hyperthermic conditions, neither an increase in liver parenchyma toxicity nor changes in melphalan pharmacokinetics were observed. These findings support the use of true hyperthermia in the clinical setting to exploit fully the antitumor synergism between melphalan and heat. PMID:15457357

  10. Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue.

    PubMed

    Maidhof, Robert; Tandon, Nina; Lee, Eun Jung; Luo, Jianwen; Duan, Yi; Yeager, Keith; Konofagou, Elisa; Vunjak-Novakovic, Gordana

    2012-11-01

    Maintenance of normal myocardial function depends intimately on synchronous tissue contraction, driven by electrical activation and on adequate nutrient perfusion in support thereof. Bioreactors have been used to mimic aspects of these factors in vitro to engineer cardiac tissue but, due to design limitations, previous bioreactor systems have yet to simultaneously support nutrient perfusion, electrical stimulation and unconstrained (i.e. not isometric) tissue contraction. To the best of our knowledge, the bioreactor system described herein is the first to integrate these three key factors in concert. We present the design of our bioreactor and characterize its capability in integrated experimental and mathematical modelling studies. We then cultured cardiac cells obtained from neonatal rats in porous, channelled elastomer scaffolds with the simultaneous application of perfusion and electrical stimulation, with controls excluding either one or both of these two conditions. After 8 days of culture, constructs grown with simultaneous perfusion and electrical stimulation exhibited substantially improved functional properties, as evidenced by a significant increase in contraction amplitude (0.23 ± 0.10% vs 0.14 ± 0.05%, 0.13 ± 0.08% or 0.09 ± 0.02% in control constructs grown without stimulation, without perfusion, or either stimulation or perfusion, respectively). Consistently, these constructs had significantly improved DNA contents, cell distribution throughout the scaffold thickness, cardiac protein expression, cell morphology and overall tissue organization compared to control groups. Thus, the simultaneous application of medium perfusion and electrical conditioning enabled by the use of the novel bioreactor system may accelerate the generation of fully functional, clinically sized cardiac tissue constructs. PMID:22170772

  11. FATTY ACID CHAIN-ELONGATION IN PERFUSED RAT HEART: SYNTHESIS OF STEAROYLCARNITINE FROM PERFUSED PALMITATE

    PubMed Central

    Kerner, Janos; Minkler, Paul E.; Lesnefsky, Edward J.; Hoppel, Charles L.

    2009-01-01

    Rat hearts perfused for up to 60 min in the working mode with palmitate, but not with glucose, resulted in substantial formation of palmitoylcarnitine and stearoylcarnitine. To test whether lipolysis of endogenous lipids was responsible for the increased stearoylcarnitine content or whether some of the perfused palmitate underwent chain elongation, hearts were perfused with hexadecanoic-16,16,16-d3 acid (M+3). The pentafluorophenacyl ester of deuterium labeled stearoylcarnitine had an M+3 (639.4 m/z) compared to the unlabeled M+0 (636.3 m/z) consistent with a direct chain elongation of the perfused palmitate. Furthermore, the near equal isotope enrichment of palmitoyl- (90.2 ± 5.8 %) and stearoylcarnitine (78.0 ± 7.1 %) suggest that both palmitoyl- and stearoyl-CoA have ready access to mitochondrial carnitine palmitoyltransferase and that most of the stearoylcarnitine is derived from the perfused palmitate. PMID:17761175

  12. 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.

  13. Dental students' ability to detect and diagnose oral mucosal lesions.

    PubMed

    Ali, Mohammad A; Joseph, Bobby K; Sundaram, Devipriya B

    2015-02-01

    The aim of this study was to assess the ability of dental students in the screening clinic of the Kuwait University Dental Center to detect and diagnose oral mucosal lesions. Clinical examinations performed by dental students between January 2009 and February 2011 were included. All their findings regarding the oral mucosal lesions and dental carious lesions detected were recorded, after which the patients were re-examined by faculty examiners. The students rated their own ability to detect mucosal and carious lesions before each examination. Among the 341 patients screened, 375 oral mucosal lesions were found by the faculty examiners. Of those, the students detected 178 (47.5%). Out of the 375 lesions, including the ones they failed to detect, the students diagnosed 272 (72.5%) correctly. The students were more likely (p≤0.01) to correctly diagnose a mucosal lesion when they themselves had detected it (n=169/178) than when they failed to detect it and had it subsequently pointed out by the faculty examiners (n=103/197). The students were more competent in detecting carious lesions (p≤0.001) than in detecting mucosal lesions. A significantly higher proportion of students who felt confident in detecting mucosal lesions were actually more competent in detecting the lesions than those who were not confident (p≤0.001). Further educational strategies are needed to motivate Kuwait University dental students to develop the knowledge, skills, and judgment necessary to integrate a complete intraoral examination into their routine practice. PMID:25640618

  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. 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

  16. Modeling mucosal candidiasis in larval zebrafish by swimbladder injection.

    PubMed

    Gratacap, Remi L; Bergeron, Audrey C; Wheeler, Robert T

    2014-01-01

    Early defense against mucosal pathogens consists of both an epithelial barrier and innate immune cells. The immunocompetency of both, and their intercommunication, are paramount for the protection against infections. The interactions of epithelial and innate immune cells with a pathogen are best investigated in vivo, where complex behavior unfolds over time and space. However, existing models do not allow for easy spatio-temporal imaging of the battle with pathogens at the mucosal level. The model developed here creates a mucosal infection by direct injection of the fungal pathogen, Candida albicans, into the swimbladder of juvenile zebrafish. The resulting infection enables high-resolution imaging of epithelial and innate immune cell behavior throughout the development of mucosal disease. The versatility of this method allows for interrogation of the host to probe the detailed sequence of immune events leading to phagocyte recruitment and to examine the roles of particular cell types and molecular pathways in protection. In addition, the behavior of the pathogen as a function of immune attack can be imaged simultaneously by using fluorescent protein-expressing C. albicans. Increased spatial resolution of the host-pathogen interaction is also possible using the described rapid swimbladder dissection technique. The mucosal infection model described here is straightforward and highly reproducible, making it a valuable tool for the study of mucosal candidiasis. This system may also be broadly translatable to other mucosal pathogens such as mycobacterial, bacterial or viral microbes that normally infect through epithelial surfaces. PMID:25490695

  17. Modeling Mucosal Candidiasis in Larval Zebrafish by Swimbladder Injection

    PubMed Central

    Gratacap, Remi L.; Bergeron, Audrey C.; Wheeler, Robert T.

    2016-01-01

    Early defense against mucosal pathogens consists of both an epithelial barrier and innate immune cells. The immunocompetency of both, and their intercommunication, are paramount for the protection against infections. The interactions of epithelial and innate immune cells with a pathogen are best investigated in vivo, where complex behavior unfolds over time and space. However, existing models do not allow for easy spatio-temporal imaging of the battle with pathogens at the mucosal level. The model developed here creates a mucosal infection by direct injection of the fungal pathogen, Candida albicans, into the swimbladder of juvenile zebrafish. The resulting infection enables high-resolution imaging of epithelial and innate immune cell behavior throughout the development of mucosal disease. The versatility of this method allows for interrogation of the host to probe the detailed sequence of immune events leading to phagocyte recruitment and to examine the roles of particular cell types and molecular pathways in protection. In addition, the behavior of the pathogen as a function of immune attack can be imaged simultaneously by using fluorescent protein-expressing C. albicans. Increased spatial resolution of the host-pathogen interaction is also possible using the described rapid swimbladder dissection technique. The mucosal infection model described here is straightforward and highly reproducible, making it a valuable tool for the study of mucosal candidiasis. This system may also be broadly translatable to other mucosal pathogens such as mycobacterial, bacterial or viral microbes that normally infect through epithelial surfaces. PMID:25490695

  18. Mucosal healing in inflammatory bowel diseases: a systematic review.

    PubMed

    Neurath, Markus F; Travis, Simon P L

    2012-11-01

    Recent studies have identified mucosal healing on endoscopy as a key prognostic parameter in the management of inflammatory bowel diseases (IBD), thus highlighting the role of endoscopy for monitoring of disease activity in IBD. In fact, mucosal healing has emerged as a key treatment goal in IBD that predicts sustained clinical remission and resection-free survival of patients. The structural basis of mucosal healing is an intact barrier function of the gut epithelium that prevents translocation of commensal bacteria into the mucosa and submucosa with subsequent immune cell activation. Thus, mucosal healing should be considered as an initial event in the suppression of inflammation of deeper layers of the bowel wall, rather than as a sign of complete healing of gut inflammation. In this systematic review, the clinical studies on mucosal healing are summarised and the effects of anti-inflammatory or immunosuppressive drugs such as 5-aminosalicylates, corticosteroids, azathioprine, ciclosporin and anti-TNF antibodies (adalimumab, certolizumab pegol, infliximab) on mucosal healing are discussed. Finally, the implications of mucosal healing for subsequent clinical management in patients with IBD are highlighted. PMID:22842618

  19. [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. PMID:17086351

  20. 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. PMID:4168852

  1. Markedly Decreased Blood Perfusion of Pancreatic Islets Transplanted Intraportally Into the Liver

    PubMed Central

    Henriksnäs, Johanna; Lau, Joey; Zang, Guangxiang; Berggren, Per-Olof; Köhler, Martin; Carlsson, Per-Ola

    2012-01-01

    Experimental studies indicate low revascularization of intraportally transplanted islets. This study aimed to quantify, for the first time, the blood perfusion of intrahepatically transplanted islets and elucidate necessary factors for proper islet graft revascularization at this site. Yellow chameleon protein 3.0 islets expressing fluorescent protein in all cells were transplanted. Graft blood perfusion was determined by microspheres. The vascular density and relative contribution of donor blood vessels in revascularization was evaluated using islets expressing green fluorescent protein under the Tie-2 promoter. Blood perfusion of intrahepatic islets was as a mean only 5% of that of native islets at 1-month posttransplantation. However, there was a marked heterogeneity where blood perfusion was less decreased in islets transplanted without prior culture and in many cases restored in islets with disrupted integrity. Analysis of vascular density showed that distorted islets were well revascularized, whereas islets still intact at 1-month posttransplantation were almost avascular. Few donor endothelial cells were observed in the new islet vasculature. The very low blood perfusion of intraportally transplanted islets is likely to predispose for ischemia and hamper islet function. Since donor endothelial cells do not expand posttransplantation, disruption of islet integrity is necessary for revascularization to occur by recipient blood vessels. PMID:22315321

  2. Lumped-parameter tissue temperature-blood perfusion model of a cold-stressed fingertip.

    PubMed

    Shitzer, A; Stroschein, L A; Gonzalez, R R; Pandolf, K B

    1996-05-01

    A lumped-parameter model of a fingertip is presented. The semispherical model includes the effects of heat storage, heat exchange with the environment, and heat transport by blood perfusion. The thermal insulation on the surface of the fingertip is represented by the overall heat transfer coefficient that is calculated by common engineering formulas. The model is solved analytically for the simple case of constant blood perfusion rate. The general case of variable blood perfusion rates is solved by an Euler finite difference technique. At this stage, the model does not include active control mechanisms of blood perfusion. Thus the effects of cold-induced vasodilatation have to be superimposed and are modeled by symmetrical triangular waveforms because these were found to best depict the behavior of fingers exposed to cold environments. Results of this model were compared with experimental data obtained in two separate studies. One included 60-min infrared thermograms of the dorsal surface of bare hands of sedentary subjects horizontally suspended on a fish net in a 0 degree C environment. Another study, on gloved finger temperatures, involved 0 and -6.7 degrees C environments. Fingertip (nail bed) temperatures of both these studies were compared with model predictions. Blood perfusion rates were assumed and adjusted within physiologically reasonable limits. Comparison of measured and computed temperature records showed very good conformity in both cases studied. PMID:8727573

  3. 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.

  4. Spatial optimization in perfusion bioreactors improves bone tissue-engineered construct quality attributes.

    PubMed

    Papantoniou, Ioannis; Guyot, Yann; Sonnaert, Maarten; Kerckhofs, Greet; Luyten, Frank P; Geris, Liesbet; Schrooten, Jan

    2014-12-01

    Perfusion bioreactors have shown great promise for tissue engineering applications providing a homogeneous and consistent distribution of nutrients and flow-induced shear stresses throughout tissue-engineered constructs. However, non-uniform fluid-flow profiles found in the perfusion chamber entrance region have been shown to affect tissue-engineered construct quality characteristics during culture. In this study a whole perfusion and construct, three dimensional (3D) computational fluid dynamics approach was used in order to optimize a critical design parameter such as the location of the regular pore scaffolds within the perfusion bioreactor chamber. Computational studies were coupled to bioreactor experiments for a case-study flow rate. Two cases were compared in the first instance seeded scaffolds were positioned immediately after the perfusion chamber inlet while a second group was positioned at the computationally determined optimum distance were a steady state flow profile had been reached. Experimental data showed that scaffold location affected significantly cell content and neo-tissue distribution, as determined and quantified by contrast enhanced nanoCT, within the constructs both at 14 and 21 days of culture. However, gene expression level of osteopontin and osteocalcin was not affected by the scaffold location. This study demonstrates that the bioreactor chamber environment, incorporating a scaffold and its location within it, affects the flow patterns within the pores throughout the scaffold requiring therefore dedicated optimization that can lead to bone tissue engineered constructs with improved quality attributes. PMID:24902541

  5. Trophoblast viability in perfused term placental tissue and explant cultures limited to 7-24 hours.

    PubMed

    Di Santo, S; Malek, A; Sager, R; Andres, A-C; Schneider, H

    2003-01-01

    Human term-placental culture techniques such as villous explant or dual perfusion are commonly used to study trophoblast function under control and experimentally manipulated conditions. We have compared trophoblast viability during perfusion and in explants cultured under various conditions by monitoring glucose consumption, protein synthesis and secretion, expression of differentiation-specific genes, induction of stress proteins and apoptotic cell death. The tissue was obtained from term-placentae of uncomplicated pregnancies after elective Caesarean delivery. We observed a severe loss of trophoblast viability in explants irrespective of the culture conditions used. Over 7 h of culture the amount of the differentiation specific placental hormones hCG, hPL and leptin accumulated in the medium dropped significantly. Analysis of their expression by semi-quantitative and real-time RT-PCR revealed that the down-regulation of expression occurred at the transcriptional level. This transcriptional repression was accompanied by induction of the stress-proteins RTP and BiP/GRP78. Analysis of apoptotic cell death by TUNEL assay and immunohistochemical detection of the caspase-3-specific degradation product of cytokeratin 18 revealed prominent cell death after 7 h of culture. These results are in contrast to the findings obtained in perfused placental tissue where, after 7 h of culture, hormone secretion, expression of stress proteins and cell death were similar as in native tissue. This difference between villous explant incubation and dual perfusion is also reflected by a significantly higher consumption of glucose in perfused tissue. PMID:13129686

  6. Chitosan-based nanoparticles for mucosal delivery of RNAi therapeutics.

    PubMed

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

    2014-01-01

    RNA interference (RNAi) gene silencing by small interfering RNAs (siRNAs) offers a potent and highly specific therapeutic strategy; however, enabling technologies that overcome extracellular and intracellular barriers are required. Polycation-based nanoparticles (termed polyplexes) composed of the polysaccharide chitosan have been used to facilitate delivery of siRNA across mucosal surfaces following local administration. This chapter describes the mucosal barriers that need to be addressed in order to design an effective mucosal delivery strategy and the utilization of the mucoadhesive properties of chitosan. Focus is given to preparation methods and the preclinical application of chitosan nanoparticles for respiratory and oral delivery of siRNA. PMID:25409611

  7. Tolerance of gastric mucosal flap to postoperative irradiation

    SciTech Connect

    Devineni, V.R.; Hayden, R.; Fredrickson, J.; Sicard, G. )

    1991-05-01

    When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered.

  8. Mucosal disease of cattle: a late sequel to fetal infection.

    PubMed

    Roeder, P L; Drew, T W

    1984-03-31

    The introduction of a heifer which was persistently infected with bovine virus diarrhoea-mucosal disease virus into groups of pregnant cattle resulted in abortion, neonatal death, persistent infection and, subsequently, mucosal disease in the surviving progeny. Cattle affected with mucosal disease were invariably seronegative at the time of investigation and subsequent cases occurred only in calves previously identified as seronegative and persistently infected. The detection of virus antigen by immunofluorescent staining of cells obtained from the nasopharynx was shown to be an efficient and rapid method for identifying persistently infected cattle, correlating perfectly with virus isolation. PMID:6328725

  9. 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

  10. Acute toxicity and gastroprotective role of M. pruriens in ethanol-induced gastric mucosal injuries in rats.

    PubMed

    Golbabapour, Shahram; Hajrezaie, Maryam; 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

  11. Radionuclide cerebral perfusion imaging: Normal pattern

    SciTech Connect

    Goldsmith, S.J.; Stritzke, P.; Losonczy, M.; Vallabhajosula, S.; Holan, V.; DaCosta, M.; Muzinic, M.

    1991-12-31

    Regional cerebral perfusion imaging using a new class of {sup 99m}Tc and {sup 123}I labeled compounds which traverse the blood brain barrier and SPECT imaging technology provides an opportunity to assess this physiologic phenomenon during normal cerebral function and as a manifestation of disease in the central nervous system disease. These applications pose a challenge to the nuclear medicine physician for several reasons: (a) the complex and somewhat unfamiliar functional anatomy, (b) the marked regional differences in regional cerebral perfusion at rest, (c) the lack of understanding of the effect of variations in ambient conditions on regional cerebral perfusion. The difficulties in interpretation are augmented by the display itself. There is frequently no difficulty in differentiating between gray and white matter. However, the frequently used {open_quotes}hot body{close_quotes} color maps, introduce a good deal of contrast, producing displays with apparent interruption in regional cortical perfusion whereas black and white displays provide minimal contrast in the regional cortical activity. The authors sought to define how much variation in regional cerebral perfusion is {open_quotes}allowed{close_quotes} under controlled conditions, to establish a basis to interpret if changes in the environment, psychological interventions, or disease states are accompanied by a measurable change. 2 figs., 1 tab.

  12. Pulmonary perfusion during anesthesia and mechanical ventilation.

    PubMed

    Hedenstierna, G

    2005-06-01

    Cardiac output and the pulmonary perfusion can be affected by anesthesia and by mechanical ventilation. The changes contribute to impeded oxygenation of the blood. The major determinant of perfusion distribution in the lung is the relation between alveolar and pulmonary capillary pressures. Perfusion increases down the lung, due to hydrostatic forces. Since atelectasis is located in dependent lung regions, perfusion of non-ventilated lung parenchyma is common, producing shunt of around 8-10% of cardiac output. In addition, non-gravitational inhomogeneity of perfusion, that can be greater than the gravitational inhomogeneity, adds to impeded oxygenation of blood. Essentially all anaesthetics exert some, although mild, cardiodepressant action with one exception, ketamine. Ketamine may also increase pulmonary artery pressure, whereas other agents have little effect on pulmonary vascular tone. Mechanical ventilation impedes venous return and pushes blood flow downwards to dependent lung regions, and the effect may be striking with higher levels of PEEP. During one-lung anesthesia, there is shunt blood flow both in the non-ventilated and the ventilated lung, and shunt can be much larger in the ventilated lung than thought of. Recruitment manoeuvres shall be directed to the ventilated lung and other physical and pharmacological measures can be taken to manipulate blood flow in one lung anesthesia. PMID:15886595

  13. Perfusion harmonic imaging of the human brain

    NASA Astrophysics Data System (ADS)

    Metzler, Volker H.; Seidel, Guenter; Wiesmann, Martin; Meyer, Karsten; Aach, Til

    2003-05-01

    The fast visualisation of cerebral microcirculation supports diagnosis of acute cerebrovascular diseases. However, the commonly used CT/MRI-based methods are time consuming and, moreover, costly. Therefore we propose an alternative approach to brain perfusion imaging by means of ultrasonography. In spite of the low signal/noise-ratio of transcranial ultrasound and the high impedance of the skull, flow images of cerebral blood flow can be derived by capturing the kinetics of appropriate contrast agents by harmonic ultrasound image sequences. In this paper we propose three different methods for human brain perfusion imaging, each of which yielding flow images indicating the status of the patient's cerebral microcirculation by visualising local flow parameters. Bolus harmonic imaging (BHI) displays the flow kinetics of bolus injections, while replenishment (RHI) and diminution harmonic imaging (DHI) compute flow characteristics from contrast agent continuous infusions. RHI measures the contrast agents kinetics in the influx phase and DHI displays the diminution kinetics of the contrast agent acquired from the decay phase. In clinical studies, BHI- and RHI-parameter images were found to represent comprehensive and reproducible distributions of physiological cerebral blood flow. For DHI it is shown, that bubble destruction and hence perfusion phenomena principally can be displayed. Generally, perfusion harmonic imaging enables reliable and fast bedside imaging of human brain perfusion. Due to its cost efficiency it complements cerebrovascular diagnostics by established CT/MRI-based methods.

  14. Urokinase perfusion prevents intrahepatic ischemic-type biliary lesion in donor livers

    PubMed Central

    Lang, Ren; He, Qiang; Jin, Zhong-Kui; Han, Dong-Dong; Chen, Da-Zhi

    2009-01-01

    AIM: To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions (IITBLs). METHODS: A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions. The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year. The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year. In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver. The incidence of IITBLs was compared between the two groups. RESULTS: In the control group, the incidence of IITBLs was 5.9% (13/220 cases) after 3-11 mo of transplantation. In the experimental group, two recipients (1.4%) developed IITBLs at 3 and 6 mo after transplantation, respectively. The difference in the incidence between the two groups was statistically significant (P < 0.05). CONCLUSION: Double perfusion of cadaveric livers from non-heart-beating donors with urokinase may reduce the incidence of IITBLs. PMID:19630111

  15. Quantitative risk assessment for the induction of allergic contact dermatitis: uncertainty factors for mucosal exposures.

    PubMed

    Farage, Miranda A; Bjerke, Donald L; Mahony, Catherine; Blackburn, Karen L; Gerberick, G Frank

    2003-09-01

    The quantitative risk assessment (QRA) paradigm has been extended to evaluating the risk of induction of allergic contact dermatitis from consumer products. Sensitization QRA compares product-related, topical exposures to a safe benchmark, the sensitization reference dose. The latter is based on an experimentally or clinically determined 'no observable adverse effect level' (NOAEL) and further refined by incorporating 'sensitization uncertainty factors' (SUFs) that address variables not adequately reflected in the data from which the threshold NOAEL was derived. A critical area of uncertainty for the risk assessment of oral care or feminine hygiene products is the extrapolation from skin to mucosal exposures. Most sensitization data are derived from skin contact, but the permeability of vulvovaginal and oral mucosae is greater than that of keratinized skin. Consequently, the QRA for some personal products that are exposed to mucosal tissue may require the use of more conservative SUFs. This article reviews the scientific basis for SUFs applied to topical exposure to vulvovaginal and oral mucosae. We propose a 20-fold range in the default uncertainty factor used in the contact sensitization QRA when extrapolating from data derived from the skin to situations involving exposure to non-keratinized mucosal tissue. PMID:14678210

  16. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

    PubMed

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

    1995-05-01

    Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli. PMID:7541007

  17. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

    PubMed Central

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

    1995-01-01

    Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli. Images p665-a PMID:7541007

  18. Mucosal adherent bacterial dysbiosis in patients with colorectal adenomas.

    PubMed

    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

  19. 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

  20. 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

  1. Perfusion and ventilation of isolated canine lungs

    PubMed Central

    Otto, T. J.; Trenkner, M.; Stopczyk, A.; Gawdziński, M.; Chełstowska, B.

    1968-01-01

    In order to evaluate methods of preserving lungs for use in transplantation, experiments on 28 mongrel dogs were carried out. Two methods were tried—first, mechanical respiration of isolated lungs under deep hypothermia, with the vascular bed filled with blood; and, secondly, the perfusion of isolated lungs with the aid of a modified DeWall's apparatus. Allogenic transplantations of lungs preserved in both ways were carried out. Gasometric and histological examinations of preserved lungs, before and after transplantation, were performed. The best results were obtained with perfusion under hypothermic conditions; ventilation without perfusion resulted in failure. Lung transplantation was successful when, after being preserved, the lung remained unchanged. Major discrepancies between the macroscopic and microscopic findings in preserved lungs were observed. An original classification of the changes occurring in preserved lungs is proposed. PMID:4886091

  2. Mucosal Tolerance to Prevent Type 1 Diabetes: Can the Outcome Be Improved in Humans?

    PubMed Central

    Hanninen, Arno; Harrison, Leonard C.

    2004-01-01

    The results of trials in which autoantigens have been fed to individuals affected by autoimmune diseases - multiple sclerosis, rheumatoid arthritis and type 1 diabetes - have been disappointing in terms of clinical improvement. This is in striking contrast to the results in experimental rodent models of these diseases. The outcome of the recent DPT-1 trial testing oral insulin in individuals at risk of type 1 diabetes was also disappointing, in contrast to the effects of oral insulin in the non-obese diabetic (NOD) mouse model of type 1 diabetes. However, it is premature to conclude that mucosal tolerance works only in in-bred rodents and not in humans with autoimmune disease. Except for oral insulin in DPT-1, the human trials were performed in individuals with end-stage disease when this form of immune regulation might not be expected to be effective. Importantly, in no trial was an immune response to the autoantigen documented, to demonstrate that the dose was at least bioavailable. Furthermore, mucosal autoantigen administration is a 'double-edged sword' and in rodents can lead not only to regulatory and protective immunity but also to pathogenic, tissue-destructive immunity and exacerbation of autoimmune disease. When suppression of autoimmune disease is observed it may be because autoantigen was administered under conditions which minimize induction of pathogenic immunity. Thus, clinical protocols for mucosal autoantigen administration may need to be modified to favor induction of regulatory immunity. In this short review, we discuss recent studies in autoimmune diabetes-prone NOD mice indicating that with novel modifications mucosal autoantigen administration could be harnessed to prevent type 1 diabetes in humans. PMID:17491673

  3. Myocardial perfusion scintigraphy: the evidence.

    PubMed

    Underwood, S R; 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

    2004-02-01

    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

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

    PubMed

    Francis, Manjusha; Williams, Sheela

    2014-01-01

    Oral mucositis is a common, debilitating complication of cancer patients undergoing chemotherapy and radiotherapy, occurring in about 40 percent cases. Mucositis may limit the patient's ability to tolerate chemotherapy or radiation therapy, and nutrition status is compromised. The aim of the study was to assess the effect of Indian turmeric powder with honey as a complementary therapy on treatment induced oral mucositis. In the study, quasi experimental non-equivalent control group pre test post-test design was used and non-probability purposive sampling technique was adopted to select 60 cancer patients with treatment induced oral mucositis, 30 each in experimental and control group. The independent 't' value for post-test 2 and 3 (post-test 2: 2.86 for WHO OMAS and 4.58 for MPJ OMAS, post test 2: 5.42 for WHO OMAS and 7.2 for MPJ OMAS; p < 0.05) were significant between experimental and control group. It is inferred that the application of Indian turmeric and honey on treatment-induced oral mucositis is effective. PMID:26182820

  5. 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...

  6. Polymeric penetration enhancers promote humoral immune responses to mucosal vaccines.

    PubMed

    Klein, Katja; Mann, Jamie F S; Rogers, Paul; Shattock, Robin J

    2014-06-10

    Protective mucosal immune responses are thought best induced by trans-mucosal vaccination, providing greater potential to generate potent local immune responses than conventional parenteral vaccination. However, poor trans-mucosal permeability of large macromolecular antigens limits bioavailability to local inductive immune cells. This study explores the utility of polymeric penetration enhancers to promote trans-mucosal bioavailability of insulin, as a biomarker of mucosal absorption, and two vaccine candidates: recombinant HIV-1 envelope glycoprotein (CN54gp140) and tetanus toxoid (TT). Responses to vaccinating antigens were assessed by measurement of serum and the vaginal humoral responses. Polyethyleneimine (PEI), Dimethyl-β-cyclodextrin (DM-β-CD) and Chitosan enhanced the bioavailability of insulin following intranasal (IN), sublingual (SL), intravaginal (I.Vag) and intrarectal (IR) administration. The same penetration enhancers also increased antigen-specific IgG and IgA antibody responses to the model vaccine antigens in serum and vaginal secretions following IN and SL application. Co-delivery of both antigens with PEI or Chitosan showed the highest increase in systemic IgG and IgA responses following IN or SL administration. However the highest IgA titres in vaginal secretions were achieved after IN immunisations with PEI and Chitosan. None of the penetration enhancers were able to increase antibody responses to gp140 after I.Vag immunisations, while in contrast PEI and Chitosan were able to induce TT-specific systemic IgG levels following I.Vag administration. In summary, we present supporting data that suggest appropriate co-formulation of vaccine antigens with excipients known to influence mucosal barrier functions can increase the bioavailability of mucosally applied antigens promoting the induction of mucosal and systemic antibody responses. PMID:24657807

  7. Use of Transparent Film Dressing for Dermoscopy of Mucosal Lesions.

    PubMed

    Sorrell, Jennifer; Lauren, Christine T

    2016-01-01

    Genital and mucosal nevi are not uncommonly encountered in children. These type of nevi highlight challenges in performing a thorough dermoscopic examination. Contact dermoscopy can provide additional information about a nevus that non-contact dermoscopy cannot. We propose applying a sterile transparent film dressing over the dermatoscope to act as a waterproof barrier that is also impermeable to bacteria and viruses. This provides a sanitary way to evaluate nevi in genital skin as well as on other mucosal surfaces. PMID:26250593

  8. 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.

  9. 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.

  10. The "push-to-low" approach for optimization of high-density perfusion cultures of animal cells.

    PubMed

    Konstantinov, Konstantin; Goudar, Chetan; Ng, Maria; Meneses, Renato; Thrift, John; Chuppa, Sandy; Matanguihan, Cary; Michaels, Jim; Naveh, David

    2006-01-01

    High product titer is considered a strategic advantage of fed-batch over perfusion cultivation mode. The titer difference has been experimentally demonstrated and reported in the literature. However, the related theoretical aspects and strategies for optimization of perfusion processes with respect to their fed-batch counterparts have not been thoroughly explored. The present paper introduces a unified framework for comparison of fed-batch and perfusion cultures, and proposes directions for improvement of the latter. The comparison is based on the concept of "equivalent specific perfusion rate", a variable that conveniently bridges various cultivation modes. The analysis shows that development of economically competitive perfusion processes for production of stable proteins depends on our ability to dramatically reduce the dilution rate while keeping high cell density, i.e., operating at low specific perfusion rates. Under these conditions, titer increases significantly, approaching the range of fed-batch titers. However, as dilution rate is decreased, a limit is reached below which performance declines due to poor growth and viability, specific productivity, or product instability. To overcome these limitations, a strategy referred to as "push-to-low" optimization has been developed. This approach involves an iterative stepwise decrease of the specific perfusion rate, and is most suitable for production of stable proteins where increased residence time does not compromise apparent specific productivity or product quality. The push-to-low approach was successfully applied to the production of monoclonal antibody against tumor necrosis factor (TNF). The experimental results followed closely the theoretical prediction, providing a multifold increase in titer. Despite the medium improvement, reduction of the specific growth rate along with increased apoptosis was observed at low specific perfusion rates. This phenomenon could not be explained with limitation or

  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. Inside the brachycephalic nose: intranasal mucosal contact points.

    PubMed

    Schuenemann, Riccarda; Oechtering, Gerhard U

    2014-01-01

    The purpose of this study was to evaluate the prevalence of intranasal mucosal contact points in brachycephalic and normocephalic dogs. In total, 82 brachycephalic dogs (42 pugs and 40 French bulldogs) were evaluated by rhinoscopy for their intranasal mucosal contact and 25 normocephalic dogs were evaluated as a control group. Of those, 162 brachycephalic nasal cavities were evaluable and 140 had contact between intranasal structures (87%). Intraconchal and septoconchal mucosal contact points were the most commonly detected sites of contact. French bulldogs had a significantly higher prevalence of mucosal contact and had 3 mean contact points compared with 1.7 mean contact points per nasal cavity in pugs. Septal deviations were present in 62% of brachycephalic dogs. In the control group, mucosal contact points were present in only 7 of 50 nasal cavities (14%), and septal deviations occurred in 16% of those cases. Contact point average was 0.1 in large and 0.3 in small normocephalic dogs. Intranasal mucosal contact was identified as a common and previously unreported problem in brachycephalic dogs. Numerous contact points reduce the lumen of the intranasal passageways and indicate potential intranasal obstruction. Affected dogs might benefit from removal of obstructing conchae, potentially using laser-assisted turbinectomy. PMID:24659729

  13. Cancer therapy and oral mucositis. An appraisal of drug prophylaxis.

    PubMed

    Verdi, C J

    1993-09-01

    Oral mucositis as a consequence of cytotoxic therapy is a major cause of morbidity in cancer patients. Cancer therapy-induced tissue damage leading to mucositis can occur through either direct or indirect stomatotoxicity. Once mucositis has occurred, treatment consists of measures to palliate symptoms. The prevention of cancer therapy-induced oral mucositis is less standardised. Numerous drugs have been used as prophylactic agents to prevent chemo- and radiotherapy-induced mucositis. Controlled trials have shown some degree of prophylactic efficacy for sucralfate, chlorhexidine and benzydamine. Positive but non-placebo-controlled trials requiring more study have been conducted with dinoprostone (prostaglandin E2), silver nitrate, beta-carotene, pentoxifylline and lozenges containing polymixin B, tobramycin and amphotericin B. Current studies have shown a lack of efficacy with allopurinol and granulocyte colony-stimulating factor (G-CSF). Nonpharmacological methods such as oral cryotherapy and helium-neon laser treatments have shown some promise. At the present time no agent has been shown to be uniformly efficacious and can be accepted as standard therapy. Additional studies combining several agents or incorporating nonpharmacological manoeuvres for mucositis prevention are needed. PMID:8240724

  14. Mucosal immunoregulation: transcription factors as possible therapeutic targets.

    PubMed

    Doganci, Aysefa; Neurath, Markus F; Finotto, Susetta

    2005-10-01

    Much progress has been recently made with regard to our understanding of the mucosal immune system in health and disease. In particular, it has been shown that uncontrolled mucosal immune responses driven by lymphocytes or non-lymphoid cells may lead to immunological diseases such as allergy, hypersensitivity and inflammation. Thus, a more detailed understanding of mucosal immune regulation and decision making at mucosal surfaces is essential for a better understanding of mucosal immune responses in health and disease. Antigen presenting cells and T lymphocytes play a key role in controlling mucosal immune responses. To deal with this key task, T helper cells differentiate into functionally distinct subsets: TH1 (CD4+ T Helper cells), TH2, TH3, Tr1, and CD4+CD25+ T (Treg) cells. This review summarizes the role of antigen presenting cells, eosinophils, mast cells and T-cell subsets in the pathogenesis of allergic inflammation and intestinal inflammation. Furthermore, we discuss novel immunological treatment modalities for allergic inflammation (e.g. allergic asthma) and chronic intestinal inflammation (e.g. inflammatory bowel diseases (IBD)) such as the control of the expression of transcription factors to redirect pathological immune responses. PMID:16248825

  15. Successful endoscopic submucosal dissection for mucosal cancer of the duodenum.

    PubMed

    Shinoda, Masahiro; Makino, Atsushi; Wada, Masahiro; Kabeshima, Yasuo; Takahashi, Tsunehiro; Kawakubo, Hirofumi; Shito, Masaya; Sugiura, Hitoshi; Omori, Tai

    2010-01-01

    We report a case of mucosal duodenal cancer in a 62-year-old woman, which was successfully removed en bloc by endoscopic submucosal dissection (ESD). The patient underwent an upper gastrointestinal endoscopy at our hospital, which revealed an elevated flat mucosal lesion (type IIa) measuring 10 mm in diameter in the second portion of the duodenum. Histopathological examination of a biopsy specimen revealed features suggestive of a tubulovillous adenoma with severe atypia. As the findings suggested that the lesion had an adenocarcinoma component but was confined to the mucosal layer, we decided to carry out ESD and successfully removed the tumor in one piece. The resected tumor was 20 x 15 mm in size. Histopathological examination revealed that the lesion was a well-differentiated mucosal adenocarcinoma with no lymphovascular invasion. Mucosal duodenal cancer is extremely rare, and ESD of a lesion in the duodenum requires a high level of skill. To the best of our knowledge, this case is the first report of successful ESD carried out in a case of mucosal duodenal cancer. PMID:20078665

  16. Novel strategies using DNA for the induction of mucosal immunity.

    PubMed

    McCluskie, M J; Davis, H L

    1999-01-01

    The mucosal surfaces are the primary sites for transmission of most infectious diseases. However, most conventional vaccines are administered parenterally [e.g., by intramuscular (IM) or intradermal (ID) injection] and induce systemic but rarely mucosal immunity. Novel vaccination strategies capable of inducing both systemic and mucosal immune responses could greatly reduce infection and morbidity worldwide. One of the most exciting advances in vaccine technology in recent years has been the development of DNA vaccines, through which the antigen is synthesized in vivo after direct introduction of its encoding sequences. The vast majority of DNA vaccines have been delivered parenterally; however, in recent years a number of studies have reported successful mucosal immunization with DNA vaccines. The induction of strong immune responses following the introduction of DNA appears to be partly due to the potent adjuvant effect of unmethylated immunostimulatory CpG motifs present in the DNA backbone. Synthetic oligodeoxynucleotides (ODN) containing such immunostimulatory CpG motifs are potent adjuvants systemically and mucosally in mice, and have synergistic action with other adjuvants, such as alum and cholera toxin (CT). This article highlights the recent advances in vaccination strategies using DNA delivered to mucosal surfaces either as an antigen-encoding plasmid or as an adjuvant. PMID:10530431

  17. Clotrimazole nanoparticle gel for mucosal administration.

    PubMed

    Esposito, Elisabetta; Ravani, Laura; Contado, Catia; Costenaro, Andrea; Drechsler, Markus; Rossi, Damiano; Menegatti, Enea; Grandini, Alessandro; Cortesi, Rita

    2013-01-01

    In this study a formulation suitable to be applied on oral and/or vaginal mucosa has been developed for the treatment of fungal infections. The aim of the research is a comparison between clotrimazole (CLO) containing semisolid formulations based on monoolein aqueous dispersion (MAD) or nanostructured lipid carrier (NLC). MAD and NLC have been characterized in terms of morphology and dimensional distribution by cryogenic Transmission Electron Microscopy (cryo-TEM) and Photon Correlation Spectroscopy (PCS). CLO was encapsulated with high entrapment efficiency both in MAD and in NLC, according to Sedimentation Field Flow Fractionation (SdFFF) combined with HPLC. CLO recovery in MAD and NLC has been investigated by time. In order to obtain formulations with suitable viscosity for mucosal application, MAD was diluted with a carbomer gel, while NLC was directly viscosized by the addition of poloxamer 407 in the dispersion. The rheological properties of MAD and NLC after viscosizing have been investigated. Franz cell has been employed to study CLO diffusion from the different vehicles, evidencing diffusion rates from MAD and NLC superimposable to that obtained using Canesten(®). An anticandidal activity study demonstrated that both CLO-MAD and CLO-NLC were more active against Candida albicans with respect to the pure drug. PMID:25428089

  18. Mucosal effects of tenofovir 1% gel.

    PubMed

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

    2015-01-01

    Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored. PMID:25647729

  19. Mucosal effects of tenofovir 1% gel

    PubMed Central

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

    2015-01-01

    Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored. Clinical trial registration: NCT01232803. DOI: http://dx.doi.org/10.7554/eLife.04525.001 PMID:25647729

  20. Reflectance confocal microscopy for mucosal diseases.

    PubMed

    Cinotti, E; Labeille, B; Cambazard, F; Thuret, G; Gain, P; Perrot, J L

    2015-10-01

    Non-invasive, real-time microscopic imaging using in vivo reflectance confocal microscopy (RCM) has been demonstrated to be a useful tool for the evaluation of skin diseases and in particular for skin neoplasms. Recently, the RCM devices dedicated to the skin have also been applied to perform "virtual biopsies" of the oral, genital and ocular mucosa. In fact, mucosa is a sensitive area where non invasive imaging techniques are of high interest in order to spare biopsies and excisions. Mucosa is particularly suitable for RCM because of its thin or absent cornified layer and its thin epithelium that allows a deeper penetration of the laser with the consequent possibility of exploring deeper tissue levels. Besides, being useful for the diagnosis, RCM may be helpful to identify the area to be biopsied in case of large or multifocal lesions and may be regarded as a complementary technique for non invasive assessment of treatment efficacy. The RCM features of healthy mucosa are described and a revision of the literature of the mucosal diseases that can be diagnosed by RCM has been performed. PMID:26099354

  1. 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

  2. Mucosal Inflammatory Response to Salmonella typhimurium Infection

    PubMed Central

    Patel, Samir; McCormick, Beth A.

    2014-01-01

    The human intestinal epithelium consists of a single layer of epithelial cells that forms a barrier against food antigens and the resident microbiota within the lumen. This delicately balanced organ functions in a highly sophisticated manner to uphold the fidelity of the intestinal epithelium and to eliminate pathogenic microorganisms. On the luminal side, this barrier is fortified by a thick mucus layer, and on the serosal side exists the lamina propria containing a resident population of immune cells. Pathogens that are able to breach this barrier disrupt the healthy epithelial lining by interfering with the regulatory mechanisms that govern the normal balance of intestinal architecture and function. This disruption results in a coordinated innate immune response deployed to eliminate the intruder that includes the release of antimicrobial peptides, activation of pattern-recognition receptors, and recruitment of a variety of immune cells. In the case of Salmonella enterica serovar typhimurium (S. typhimurium) infection, induction of an inflammatory response has been linked to its virulence mechanism, the type III secretion system (T3SS). The T3SS secretes protein effectors that exploit the host’s cell biology to facilitate bacterial entry and intracellular survival, and to modulate the host immune response. As the role of the intestinal epithelium in initiating an immune response has been increasingly realized, this review will highlight recent research that details progress made in understanding mechanisms underlying the mucosal inflammatory response to Salmonella infection, and how such inflammatory responses impact pathogenic fitness of this organism. PMID:25071772

  3. Innate signals in mucosal immunoglobulin class switching.

    PubMed

    Puga, Irene; Cols, Montserrat; Cerutti, Andrea

    2010-11-01

    The intestinal mucosa contains large communities of commensal bacteria that process otherwise indigestible food components, synthesize essential vitamins, stimulate the maturation of the immune system, and form an ecologic niche that prevents the growth of pathogenic species. Conversely, the intestine provides the commensals with a stable habitat rich in energy derived from the ingested food. A delicate homeostatic balance maintains this mutualistic relationship without triggering a destructive inflammatory response. Commensals orchestrate intestinal homeostasis by entertaining an intimate dialogue with epithelial cells and immune cells lodged in the mucosa. Such a dialogue generates finely tuned signaling programs that ensure a state of hyporesponsiveness against noninvasive commensals and a state of active readiness against invasive pathogens. In this dialogue epithelial cells function as "interpreters" that continuously translate microbial messages to "instruct" immune cells as to the antigenic composition of the intestinal lumen. This education process initiates sophisticated defensive strategies that comprise massive production of IgA, a noninflammatory mucosal antibody class that generates immunity while preserving homeostasis. PMID:21050939

  4. Organ distribution of transgene expression following intranasal mucosal delivery of recombinant replication-defective adenovirus gene transfer vector

    PubMed Central

    Damjanovic, Daniela; Zhang, Xizhong; Mu, Jingyu; Fe Medina, Maria; Xing, Zhou

    2008-01-01

    It is believed that respiratory mucosal immunization triggers more effective immune protection than parenteral immunization against respiratory infection caused by viruses and intracellular bacteria. Such understanding has led to the successful implementation of intranasal immunization in humans with a live cold-adapted flu virus vaccine. Furthermore there has been an interest in developing effective mucosal-deliverable genetic vaccines against other infectious diseases. However, there is a concern that intranasally delivered recombinant viral-based vaccines may disseminate to the CNS via the olfactory tissue. Initial experimental evidence suggests that intranasally delivered recombinant adenoviral gene transfer vector may transport to the olfactory bulb. However, there is a lack of quantitative studies to compare the relative amounts of transgene products in the respiratory tract, lung, olfactory bulb and brain after intranasal mucosal delivery of viral gene transfer vector. To address this issue, we have used fluorescence macroscopic imaging, luciferase quantification and PCR approaches to compare the relative distribution of transgene products or adenoviral gene sequences in the respiratory tract, lung, draining lymph nodes, olfactory bulb, brain and spleen. Intranasal mucosal delivery of replication-defective recombinant adenoviral vector results in gene transfer predominantly in the respiratory system including the lung while it does lead to a moderate level of gene transfer in the olfactory bulb. However, intranasal inoculation of adenoviral vector leads to little or no viral dissemination to the major region of the CNS, the brain. These experimental findings support the efficaciousness of intranasal adenoviral-mediated gene transfer for the purpose of mucosal immunization and suggest that it may not be of significant safety concern. PMID:18261231

  5. JB-9322, a new selective histamine H2-receptor antagonist with potent gastric mucosal protective properties.

    PubMed Central

    Palacios, B.; Montero, M. J.; Sevilla, M. A.; Román, L. S.

    1995-01-01

    1. JB-9322 is a selective histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. 2. The affinity of JB-9322 for the guinea-pig atria histamine H2-receptor was approximately 2 times greater than that of ranitidine. 3. In vivo, the ID50 value for the inhibition of gastric acid secretion in pylorus-ligated rats was 5.28 mg kg-1 intraperitoneally. JB-9322 also dose-dependently inhibited gastric juice volume and pepsin secretion. In gastric lumen-perfused rats, intravenous injection of JB-9322 dose-dependently reduced histamine-, pentagastrin- and carbachol-stimulated gastric acid secretion. 4. JB-9322 showed antiulcer activity against aspirin and indomethacin-induced gastric lesions and was more potent than ranitidine. 5. JB-9322 effectively inhibited macroscopic gastric haemorrhagic lesions induced by ethanol. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ID50 value for these lesions was 1.33 mg kg-1. By contrast, ranitidine (50 mg kg-1) failed to reduce these lesions. In addition, the protective effect of JB-9322 was independent of prostaglandin synthesis. 6. These results indicate that JB-9322 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity. PMID:7647984

  6. The prognostic value of non-perfusion variables obtained during vasodilator stress myocardial perfusion imaging.

    PubMed

    Bajaj, Navkaranbir S; Singh, Siddharth; Farag, Ayman; El-Hajj, Stephanie; Heo, Jack; Iskandrian, Ami E; Hage, Fadi G

    2016-06-01

    Myocardial perfusion imaging (MPI) is an established diagnostic test that provides useful prognostic data in patients with known or suspected coronary artery disease. In more than half of the patients referred for stress testing, vasodilator stress is used in lieu of exercise. Unlike exercise, vasodilator stress does not provide information on exercise and functional capacity, heart rate recovery, and chronotropy, and ECG changes are less frequent. These non-perfusion data provide important prognostic and patient management information. Further, event rates in patients undergoing vasodilator MPI are higher than in those undergoing exercise MPI and even in those with normal images probably due to higher pretest risk. However, there are a number of non-perfusion variables that are obtained during vasodilator stress testing, which have prognostic relevance but their use has not been well emphasized. The purpose of this review is to summarize the prognostic values of these non-perfusion data obtained during vasodilator MPI. PMID:26940574

  7. Comparison of Systemic and Mucosal Immunization with Helper-Dependent Adenoviruses for Vaccination against Mucosal Challenge with SHIV

    PubMed Central

    Nehete, Bharti P.; Yang, Guojun; Buchl, Stephanie J.; Hanley, Patrick W.; Palmer, Donna; Montefiori, David C.; Ferrari, Guido; Ng, Philip; Sastry, K. Jagannadha; Barry, Michael A.

    2013-01-01

    Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test this, rhesus macaques were vaccinated by intramuscular (i.m.) or intravaginal (ivag.) routes with helper-dependent adenoviral (HD-Ad) vectors expressing HIV-1 envelope. Macaques were first immunized intranasally with species C Ad serotype 5 (Ad5) prior to serotype-switching with species C HD-Ad6, Ad1, Ad5, and Ad2 vectors expressing env followed by rectal challenge with CCR5-tropic SHIV-SF162P3. Vaccination by the systemic route generated stronger systemic CD8 T cell responses in PBMC, but weaker mucosal responses. Conversely, mucosal immunization generated stronger CD4 T cell central memory (Tcm) responses in the colon. Intramuscular immunization generated higher levels of env-binding antibodies, but neither produced neutralizing or cytotoxic antibodies. After mucosal SHIV challenge, both groups controlled SHIV better than control animals. However, more animals in the ivag. group had lower viral set points than in in the i.m. group. These data suggest mucosal vaccination may have improve protection against sexually-transmitted HIV. These data also demonstrate that helper-dependent Ad vaccines can mediate robust vaccine responses in the face of prior immunity to Ad5 and during four rounds of adenovirus vaccination. PMID:23844034

  8. Gradient-enhanced FAWSETS perfusion measurements

    NASA Astrophysics Data System (ADS)

    Marro, Kenneth I.; Lee, Donghoon; Hyyti, Outi M.

    2005-08-01

    This work describes the use of custom-built gradients to enhance skeletal muscle perfusion measurements acquired with a previously described arterial spin labeling technique known as FAWSETS (flow-driven arterial water stimulation with elimination of tissue signal). Custom-built gradients provide active control of the static magnetic field gradient on which FAWSETS relies for labeling. This allows selective, 180° modulations of the phase of the perfusion component of the signal. Phase cycling can then be implemented to eliminate all extraneous components leaving a signal that exclusively reflects capillary-level perfusion. Gradient-enhancement substantially reduces acquisition time and eliminates the need to acquire an ischemic signal to quantify perfusion. This removes critical obstacles to application of FAWSETS in organs other than skeletal muscle and makes the measurements more desirable for clinical environments. The basic physical principles of gradient-enhancement are demonstrated in flow phantom experiments and in vivo utility is demonstrated in rat hind limb during stimulated exercise.

  9. Urate synthesis in the perfused chick liver

    PubMed Central

    Barratt, Eileen; Buttery, Peter J.; Boorman, K. Neil

    1974-01-01

    Urate synthesis was studied in a perfused chicken liver preparation. The perfused liver had an ATP/ADP ratio of 0.29±0.05(6) compared with 0.34±0.07(10) in liver obtained from chicks under ether anaesthesia. Lactate/pyruvate ratios were 9.4±1.7(5) in the perfused liver and 14.8±1.8(5) in the rapidly sampled liver. Urate synthesis was only marginally stimulated by glycine, glutamine, aspartic acid or NH4Cl, but significant increases were observed with phosphoribosyl pyrophosphate, aminoimidazolecarboxylic acid riboside, inosine, inosinic acid and xanthine. Urate synthesis from glycine, glutamine, NH4Cl, asparagine, alanine, histidine and a mixture of 21 amino acids was obtained on inclusion of insulin in the perfusion medium. Evidence for the inclusion of the carbon of histidine into uric acid was obtained. Aspects of the energy consumption associated with the conversion of excess of amino acid into uric acid are considered. PMID:4462579

  10. 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

  11. Simplified prototyping of perfusable polystyrene microfluidics

    PubMed Central

    Tran, Reginald; Ahn, Byungwook; R. Myers, David; Qiu, Yongzhi; Sakurai, Yumiko; Moot, Robert; Mihevc, Emma; Trent Spencer, H.; Doering, Christopher; A. Lam, Wilbur

    2014-01-01

    Cell culture in microfluidic systems has primarily been conducted in devices comprised of polydimethylsiloxane (PDMS) or other elastomers. As polystyrene (PS) is the most characterized and commonly used substrate material for cell culture, microfluidic cell culture would ideally be conducted in PS-based microsystems that also enable tight control of perfusion and hydrodynamic conditions, which are especially important for culture of vascular cell types. Here, we report a simple method to prototype perfusable PS microfluidics for endothelial cell culture under flow that can be fabricated using standard lithography and wet laboratory equipment to enable stable perfusion at shear stresses up to 300 dyn/cm2 and pumping pressures up to 26 kPa for at least 100 h. This technique can also be extended to fabricate perfusable hybrid PS-PDMS microfluidics of which one application is for increased efficiency of viral transduction in non-adherent suspension cells by leveraging the high surface area to volume ratio of microfluidics and adhesion molecules that are optimized for PS substrates. These biologically compatible microfluidic devices can be made more accessible to biological-based laboratories through the outsourcing of lithography to various available microfluidic foundries. PMID:25379106

  12. 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.

  13. Galectin-4 Controls Intestinal Inflammation by Selective Regulation of Peripheral and Mucosal T Cell Apoptosis and Cell Cycle

    PubMed Central

    Paclik, Daniela; Danese, Silvio; Berndt, Uta; Wiedenmann, Bertram; Dignass, Axel; Sturm, Andreas

    2008-01-01

    Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease. PMID:18612433

  14. Cruciferous vegetables and glutathione: their effects on colon mucosal glutathione level and colon tumor development in rats induced by DMH.

    PubMed

    Chen, M F; Chen, L T; Boyce, H W

    1995-01-01

    The effect of a diet containing 10-40% lyophilized cabbage or broccoli as cruciferous vegetable or 10-40% lyophilized potato as noncruciferous vegetable fed for 14 days on the colon mucosal glutathione (GSH) level was studied in male rats. The GSH levels of the duodenum mucosa and the liver were also measured. Cabbage and broccoli enhanced the colon and duodenum mucosal GSH levels in a dose-related manner; potato had no effect. All three vegetables had no effect on the liver GSH level. The effect of GSH on colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH) was also examined in rats. Male Sprague-Dawley rats were injected with DMH (20 mg/kg body wt) weekly for 20 weeks. DMH lowered the colon mucosal GSH level. GSH (100 mg/day/rat) dissolved in the drinking water and given to rats during and after DMH injections had little or no effect on tumor incidence and total number of colon tumors. Tumors were larger in rats that received GSH than in those that received water. This study shows that the colon mucosal GSH level can be enhanced by feeding rats a diet high in cabbage or broccoli and that GSH added to the drinking water did not affect DMH-induced colon tumorigenesis under the experimental conditions used. PMID:7739917

  15. Liver Fat Content in Type 2 Diabetes: Relationship With Hepatic Perfusion and Substrate Metabolism

    PubMed Central

    Rijzewijk, Luuk J.; van der Meer, Rutger W.; Lubberink, Mark; Lamb, Hildo J.; Romijn, Johannes A.; de Roos, Albert; Twisk, Jos W.; Heine, Robert J.; Lammertsma, Adriaan A.; Smit, Johannes W.A.; Diamant, Michaela

    2010-01-01

    OBJECTIVE Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current study was to assess hepatic parenchymal perfusion, together with glucose and fatty acid metabolism, in relation to hepatic triglyceride content. RESEARCH DESIGN AND METHODS Fifty-nine men with well controlled type 2 diabetes and 18 age-matched healthy normoglycemic men were studied using positron emission tomography to assess hepatic tissue perfusion, insulin-stimulated glucose, and fasting fatty acid metabolism, respectively, in relation to hepatic triglyceride content, quantified by proton magnetic resonance spectroscopy. Patients were divided into two groups with hepatic triglyceride content below (type 2 diabetes-low) or above (type 2 diabetes-high) the median of 8.6%. RESULTS Type 2 diabetes-high patients had the highest BMI and A1C and lowest whole-body insulin sensitivity (ANOVA, all P < 0.001). Compared with control subjects and type 2 diabetes-low patients, type 2 diabetes-high patients had the lowest hepatic parenchymal perfusion (P = 0.004) and insulin-stimulated hepatic glucose uptake (P = 0.013). The observed decrease in hepatic fatty acid influx rate constant, however, only reached borderline significance (P = 0.088). In type 2 diabetic patients, hepatic parenchymal perfusion (r = −0.360, P = 0.007) and hepatic fatty acid influx rate constant (r = −0.407, P = 0.007) correlated inversely with hepatic triglyceride content. In a pooled analysis, hepatic fat correlated with hepatic glucose uptake (r = −0.329, P = 0.004). CONCLUSIONS In conclusion, type 2 diabetic patients with increased hepatic triglyceride content showed decreased hepatic parenchymal perfusion and hepatic insulin mediated glucose uptake, suggesting a potential modulating effect of hepatic fat

  16. Preliminary Study of Open Quotient in an Ex-Vivo Perfused Human Larynx Model

    PubMed Central

    Mendelsohn, Abie H.; Zhang, Zhaoyan; Luegmair, Georg; Orestes, Michael; Berke, Gerald S.

    2016-01-01

    Importance Scientific understanding human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. Due to its invasive nature, direct experimentation of human voice production has previously not been possible. The feasibility of an ex-vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation. Objective In this study, the relationship between adductor muscle group stimulation and the open quotient (OQ) of vocal fold vibration was investigated using an ex-vivo perfused human larynx. Design Human perfused tissue study. Setting Physiology Laboratory. Participants Human larynx is recovered from research-consented organ donors within two hours of cardiac death. Interventions, Main Outcomes and Measures Perfusion with donated human blood is re-established shortly after cardiac death. Human perfused phonation is achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles. The phonation resulting from the graded states of neuromuscular stimulations are evaluated through high-speed vibratory imaging. OQ is derived through digital kymography and glottal area waveform analysis. Results Under constant glottal flow, step-wise increase in adductor muscle group stimulation decreased OQ. Quantitatively, OQ values reached a lower limit of 0.42. Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit. Conclusions and Relevance For the first time in a neuromuscularly activated human larynx, a negative relationship between adductor muscle group stimulation and phonatory OQ was demonstrated. Further experience with the ex-vivo perfused human phonatory model will work to systematically define this causal relationship. PMID:26181642

  17. 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.

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

    PubMed

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

    2016-04-01

    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

  19. Comparing Normothermic Machine Perfusion Preservation With Different Perfusates on Porcine Livers From Donors After Circulatory Death.

    PubMed

    Liu, Q; Nassar, A; Farias, K; Buccini, L; Mangino, M J; Baldwin, W; Bennett, A; O'Rourke, C; Iuppa, G; Soliman, B G; Urcuyo-Llanes, D; Okamoto, T; Uso, T D; Fung, J; Abu-Elmagd, K; Miller, C; Quintini, C

    2016-03-01

    The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs. PMID:26663737

  20. 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

  1. Clinical Neuroimaging Using Arterial Spin-Labeled Perfusion MRI

    PubMed Central

    Wolf, Ronald L.; Detre, John A.

    2007-01-01

    SUMMARY The two most common methods for measuring perfusion with MRI are based on dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL). Although clinical experience to date is much more extensive with DSC perfusion MRI, ASL methods offer several advantages. The primary advantages are that completely noninvasive absolute cerebral blood flow (CBF) measurements are possible with relative insensitivity to permeability, and that multiple repeated measurements can be obtained to evaluate one or more interventions or to perform perfusion-based functional MRI. ASL perfusion and perfusion-based fMRI methods have been applied in many clinical settings, including acute and chronic cerebrovascular disease, CNS neoplasms, epilepsy, aging and development, neurodegenerative disorders, and neuropsychiatric diseases. Recent technical advances have improved the sensitivity of ASL perfusion MRI, and increasing use is expected in the coming years. This review focuses on ASL perfusion MRI and applications in clinical neuroimaging. PMID:17599701

  2. Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling

    PubMed Central

    Yazji, Ibrahim; Sodhi, Chhinder P.; Lee, Elizabeth K.; Good, Misty; Egan, Charlotte E.; Afrazi, Amin; Neal, Matthew D.; Jia, Hongpeng; Lin, Joyce; Branca, Maria F.; Prindle, Thomas; Richardson, Ward M.; Ozolek, John; Billiar, Timothy R.; Binion, David G.; Gladwin, Mark T.; Hackam, David J.

    2013-01-01

    Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by severe intestinal necrosis and for which breast milk represents the most effective protective strategy. Previous studies have revealed a critical role for the lipopolysaccharide receptor toll-like receptor 4 (TLR4) in NEC development through its induction of mucosal injury, yet the reasons for which intestinal ischemia in NEC occurs in the first place remain unknown. We hypothesize that TLR4 signaling within the endothelium plays an essential role in NEC development by regulating perfusion to the small intestine via the vasodilatory molecule endothelial nitric oxide synthase (eNOS). Using a unique mouse system in which we selectively deleted TLR4 from the endothelium, we now show that endothelial TLR4 activation is required for NEC development and that endothelial TLR4 activation impairs intestinal perfusion without effects on other organs and reduces eNOS expression via activation of myeloid differentiation primary response gene 88. NEC severity was significantly increased in eNOS−/− mice and decreased upon administration of the phosphodiesterase inhibitor sildenafil, which augments eNOS function. Strikingly, compared with formula, human and mouse breast milk were enriched in sodium nitrate—a precursor for enteral generation of nitrite and nitric oxide—and repletion of formula with sodium nitrate/nitrite restored intestinal perfusion, reversed the deleterious effects of endothelial TLR4 signaling, and reduced NEC severity. These data identify that endothelial TLR4 critically regulates intestinal perfusion leading to NEC and reveal that the protective properties of breast milk involve enhanced intestinal microcirculatory integrity via augmentation of nitrate–nitrite–NO signaling. PMID:23650378

  3. Multi-modality imaging for the assessment of myocardial perfusion with emphasis on stress perfusion CT and MR imaging.

    PubMed

    Ko, Sung Min; Hwang, Hweung Kon; Kim, Sung Mok; Cho, Ihn Ho

    2015-06-01

    High-quality and non-invasive diagnostic tools for assessing myocardial ischemia are necessary for therapeutic decisions regarding coronary artery disease. Myocardial perfusion has been studied using myocardial contrast echo perfusion, single-photon emission computed tomography, positron emission tomography, cardiovascular magnetic resonance, and, more recently, computed tomography. The addition of coronary computed tomography angiography to myocardial perfusion imaging improves the specificity and overall diagnostic accuracy of detecting the hemodynamic significance of coronary artery stenosis. This study reviews the benefits, limitations, and imaging findings of various imaging modalities for assessing myocardial perfusion, with particular emphasis on stress perfusion computed tomography and cardiovascular magnetic resonance imaging. PMID:25809387

  4. Role of Capsule and Suilysin in Mucosal Infection of Complement-Deficient Mice with Streptococcus suis

    PubMed Central

    Seitz, Maren; Beineke, Andreas; Singpiel, Alena; Willenborg, Jörg; Dutow, Pavel; Goethe, Ralph; Valentin-Weigand, Peter; Klos, Andreas

    2014-01-01

    Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3−/− mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal S. suis infection. S. suis WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3−/− mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3−/− mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT and C3−/− blood depended on capsule but not suilysin expression. Interestingly, S. suis invasion of inner organs was also detectable in C5aR−/− mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal S. suis infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal S. suis serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity. PMID:24686060

  5. 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

  6. 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

  7. 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

  8. 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

  9. Chemotherapy-induced oral mucositis. Prevention and management.

    PubMed

    Knox, J J; Puodziunas, A L; Feld, R

    2000-10-01

    Oral mucositis is a frequent and potentially severe complication of chemotherapy which has a considerable impact on patient quality of life. While the management of other chemotherapy-related toxicities has improved, the incidence of mucositis is increasing. A critical review of the literature published between 1985 and 1999 reveals very few strategies or agents with proven efficacy, leaving few recommendations for the standard care in the prevention and treatment of mucositis at this time. Recommendations that can be made include: reducing patient risk factors, implementing proven preventative interventions such as utilising oral ice chips with fluorouracil chemotherapy, and optimising supportive care practices individualised to the patients' needs and symptoms. Progress in understanding the pathophysiology of mucositis at the molecular level has led to the evaluation of a number of new investigational agents, specifically those directed to the epithelial mucosa, such as mitogens and epithelial growth factors. These appear to be very promising in preclinical studies. Randomised clinical trials with these agents may finally demonstrate an impact on the clinical practice of mucositis management in the coming years. PMID:11087004

  10. Induction of apoptosis of lymphocytes in rat mucosal immune system

    PubMed Central

    Chen, Xue-Qing; Zhang, Wan-Dai; Song, Yu-Gang; Zhou, Dian-Yuan

    1998-01-01

    AIM: To undergo apoptosis during negative and positive selection processes in rat mucosal immune system which are implicated in the pathogenesis of various mucosal diseases. METHODS: Female Sprague-Dawley rats were given protein synthesis inhibitor, cycloheximide, intravenously or intraperitoneally, an apoptosis was recognized by morphological hallmark under light and electronmicroscopy, and the expression of proliferating cell nuclear antigen was visualized immunohistochemically. RESULTS: The apoptosis of mucosal lymphocytes in the digestive tract, as well as in trachea, uterus and lacrimal gland was induced by cycloheximide ( > 1.0 mg·kg-1 body weight), which were located mainly in lamina propria and germinal centers of lymphoid nodules. At the same time, a portion of crypt epithelial cells of proliferating zone in small and large intestine, and the epithelial cells in genital tract were also found to undergo apoptosis. Immunostainings showed that apoptotic cells expressed proliferating cell nuclear antigen. CONCLUSION: Apoptosis of lymphocytes in mucosal immune system can be induced by cycloheximide. This model will facilitate the understanding of normal mucosal immune system and its role in the pathogenesis of related diseases such as inflammatory bowel diseases. PMID:11819221

  11. Mucosal Immune Development in Early Life: Setting the Stage.

    PubMed

    Brugman, Sylvia; Perdijk, Olaf; van Neerven, R J Joost; Savelkoul, Huub F J

    2015-08-01

    Our environment poses a constant threat to our health. To survive, all organisms must be able to discriminate between good (food ingredients and microbes that help digest our food) and bad (pathogenic microbes, viruses and toxins). In vertebrates, discrimination between beneficial and harmful antigens mainly occurs at the mucosal surfaces of the respiratory, digestive, urinary and genital tract. Here, an extensive network of cells and organs form the basis of what we have come to know as the mucosal immune system. The mucosal immune system is composed of a single epithelial cell layer protected by a mucus layer. Different immune cells monitor the baso-lateral side of the epithelial cells and dispersed secondary lymphoid organs, such as Peyer's patches and isolated lymphoid follicles are equipped with immune cells able to mount appropriate and specific responses. This review will focus on the current knowledge on host, dietary and bacterial-derived factors that shape the mucosal immune system before and after birth. We will discuss current knowledge on fetal immunity (both responsiveness and lymphoid organ development) as well as the impact of diet and microbial colonization on neonatal immunity and disease susceptibility. Lastly, inflammatory bowel disease will be discussed as an example of how the composition of the microbiota might predispose to disease later in life. A fundamental understanding of the mechanisms involved in mucosal immune development and tolerance will aid nutritional intervention strategies to improve health in neonatal and adult life. PMID:25666708

  12. Luminal perfusion of isolated gastric glands.

    PubMed

    Waisbren, S J; Geibel, J; Boron, W F; Modlin, I M

    1994-04-01

    We have extended to rabbit gastric glands the technique for perfusing single isolated renal tubules. We isolated glands by hand dissection and used concentric glass pipettes to hold them and perfuse their lumina. Parietal cells (PCs), which tended to be located toward the gland opening, were identified by their pyramidal shape, large size, and autofluorescence. Chief cells (CCs) were identified by their round shape and smaller size. In some experiments, we perfused the lumen with hydroxypyrenetrisulfonate, a pH-sensitive fluorophore, at pH 7.4 and used digital image processing to monitor luminal pH (pH1). Solutions were buffered with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid to pH 7.4 at 37 degrees C. With fast perfusion, we found no evidence of decreased pH1, even with stimulation by 10 microM carbachol. With slow perfusion, pH1 often fell below the dye's sensitive range (pH < 5), especially at low perfusate buffering power. In other experiments, we loaded cells with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein and monitored intracellular pH (pHi) in multiple individual PCs and CCs in a single gland. Mean pHi was 7.21 +/- 0.02 (n = 136 cells) for PCs and 7.27 +/- 0.03 (n = 103) for CCs. To examine the response to decreased pH1 and basolateral pH (pHb), we lowered pHb to 6.4 or lowered pH1 to 3.4 or 1.4. Lowering pHb to 6.4 for approximately 1 min caused pHi to fall reversibly by 0.39 +/- 0.05 (n = 53) in PCs and 0.58 +/- 0.03 (n = 50) in CCs. Lowering pH1 to 3.4 or 1.4 caused no significant pHi changes in PCs (n = 38 and 82) or in CCs (n = 44 and 77). Carbachol did not affect the response to changes in pH1 or pHb. We conclude that the apical surfaces of PCs and CCs are unusually resistant to extreme pH gradients. PMID:8178950

  13. 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

  14. Comparison of Indocyanine Green Angiography and Laser Speckle Contrast Imaging for the Assessment of Vasculature Perfusion

    PubMed Central

    Towle, Erica L.; Richards, Lisa M.; Kazmi, S. M. Shams; Fox, Douglas J.; Dunn, Andrew K.

    2013-01-01

    BACKGROUND Assessment of the vasculature is critical for overall success in cranial vascular neurological surgery procedures. Although several methods of monitoring cortical perfusion intraoperatively are available, not all are appropriate or convenient in a surgical environment. Recently, 2 optical methods of care have emerged that are able to obtain high spatial resolution images with easily implemented instrumentation: indocyanine green (ICG) angiography and laser speckle contrast imaging (LSCI). OBJECTIVE To evaluate the usefulness of ICG and LSCI in measuring vessel perfusion. METHODS An experimental setup was developed that simultaneously collects measurements of ICG fluorescence and LSCI in a rodent model. A 785-nm laser diode was used for both excitation of the ICG dye and the LSCI illumination. A photothrombotic clot model was used to occlude specific vessels within the field of view to enable comparison of the 2 methods for monitoring vessel perfusion. RESULTS The induced blood flow change demonstrated that ICG is an excellent method for visualizing the volume and type of vessel at a single point in time; however, it is not always an accurate representation of blood flow. In contrast, LSCI provides a continuous and accurate measurement of blood flow changes without the need of an external contrast agent. CONCLUSION These 2 methods should be used together to obtain a complete understanding of tissue perfusion. PMID:22843129

  15. 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

  16. Pathogenesis of mucosal biofilm infections: challenges and progress

    PubMed Central

    Dongari-Bagtzoglou, Anna

    2009-01-01

    Living-tissue biofilms remained unrecognized until very recently, mainly as a result of traditional microbial sampling techniques or histologic processing, which disrupt the spatial organization of the tissue microorganisms. Thus, the biofilm nature of certain mucosal infections was frequently unintentionally missed or disregarded. To a large extent, the study of human tissue biofilms is still in its infancy. However, with the advent of newer methodologies, such as fluorescent in situ hybridization and endoscopic confocal laser scanning microscopy, which combine the identification of microbes with in situ, direct visualization of their relationships with each other and with their substratum, mucosal tissue biofilms are becoming easier to study and, thus, their role in human infections is becoming more apparent. This review summarizes the challenges in the study of tissue biofilms, proposes two inflammation-centered – albeit opposite – pathogenetic models of mucosal tissue biofilm infections and suggests directions for future research and novel therapeutic approaches. PMID:18380602

  17. Perfusion techniques for minimally invasive valve procedures.

    PubMed

    de Jong, A; Popa, B A; Stelian, E; Karazanishvili, L; Lanzillo, G; Simonini, S; Renzi, L; Diena, M; Tesler, U F

    2015-05-01

    In this paper, we present, in detail, the simplified perfusion technique that we have adopted since January 2009 and that we have utilized in 200 cases for cardiac minimally invasive valvular procedures that were performed through a right lateral mini-thoracotomy in the 3(rd)-4(th) intercostal space. Cardiopulmonary bypass was achieved by means of the direct cannulation of the ascending aorta and the insertion of a percutaneous venous cannula in the femoral vein. A flexible aortic cross-clamp was applied through the skin incision and cardioplegic arrest was obtained with the antegrade delivery of a crystalloid solution. Gravity drainage was enhanced by vacuum-assisted aspiration. There were no technical complications related to this perfusion technique that we have adopted in minimally invasive surgical procedures. PMID:25280878

  18. Assessment of cerebral perfusion in childhood strokes

    SciTech Connect

    Gates, G.F.; Fishman, L.S.; Segall, H.D.

    1982-11-01

    Thirty-three children who had strokes were studied by dynamic and static scintigraphy, 29 by CT scanning, and 10 by cerebral angiography. The accuracy of dynamic scintigraphy in stroke detection during the first week of clinical symptoms was 94% while CT scanning was 60% accurate and static scintigraphy 11% accurate. During the second week the accuracy of CT scanning increased to 100%, but static scintigraphy improved to only 50%. Fifty percent of scintiangiograms performed during the first week showed either luxuriant perfusion or flip-flop patterns. In some patients these two flow patterns changed to that of cerebral hemispheric ischemia after going through a phase during which perfusion appeared to be equal in the two hemispheres. Dynamic scintigraphy is believed to be the test of choice for stroke detection in children during the first week.

  19. Visual analysis of longitudinal brain tumor perfusion

    NASA Astrophysics Data System (ADS)

    Glaßer, Sylvia; Oeltze, Steffen; Preim, Uta; Bjørnerud, Atle; Hauser, Helwig; Preim, Bernhard

    2013-02-01

    In clinical research on diagnosis and evaluation of brain tumors, longitudinal perfusion MRI studies are acquired for tumor grading as well as to monitor and assess treatment response and patient prognosis. Within this work, we demonstrate how visual analysis techniques can be adapted to multidimensional datasets from such studies within a framework to support the computer-aided diagnosis of brain tumors. Our solution builds on two innovations: First, we introduce a pipeline yielding comparative, co-registered quantitative perfusion parameter maps over all time steps of the longitudinal study. Second, based on these time-dependent parameter maps, visual analysis methods were developed and adapted to reveal valuable insight into tumor progression, especially regarding the clinical research area of low grade glioma transformation into high grade gliomas. Our examination of four longitudinal brain studies demonstrates the suitability of the presented visual analysis methods and comprises new possibilities for the clinical researcher to characterize the development of low grade gliomas.

  20. Animal models of ex vivo lung perfusion as a platform for transplantation research

    PubMed Central

    Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir; Jr, Don Hayes; Black, Sylvester M; Whitson, Bryan A

    2014-01-01

    Ex vivo lung perfusion (EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time, EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result, this technique provides unique advantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript, we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine. PMID:24977117

  1. Animal models of ex vivo lung perfusion as a platform for transplantation research.

    PubMed

    Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir; Hayes, Don; Black, Sylvester M; Whitson, Bryan A

    2014-05-20

    Ex vivo lung perfusion (EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time, EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result, this technique provides unique advantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript, we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine. PMID:24977117

  2. Gluconeogenesis in the perfused rat liver.

    PubMed

    Hems, R; Ross, B D; Berry, M N; Krebs, H A

    1966-11-01

    1. A modification of the methods of Miller and of Schimassek for the perfusion of the isolated rat liver, suitable for the study of gluconeogenesis, is described. 2. The main modifications concern the operative technique (reducing the period of anoxia during the operation to 3min.) and the use of aged (non-glycolysing) red cells in the semi-synthetic perfusion medium. 3. The performance of the perfused liver was tested by measuring the rate of gluconeogenesis, of urea synthesis and the stability of adenine nucleotides. Higher rates of gluconeogenesis (1mumole/min./g.) from excess of lactate and of urea synthesis from excess of ammonia (4mumoles/min./g. in the presence of ornithine) were observed than are likely to occur in vivo where rates are limited by the rate of supply of precursor. The concentrations of the three adenine nucleotides in the liver tissue were maintained within 15% over a perfusion period of 135min. 4. Ca(2+), Na(+), K(+), Mg(2+) and phosphate were found to be required at physiological concentrations for optimum gluconeogenesis but bicarbonate and carbon dioxide could be largely replaced by phosphate buffer without affecting the rate of gluconeogenesis. 5. Maximal gluconeogenesis did not decrease maximal urea synthesis in the presence of ornithine and ammonia and vice versa. This indicates that the energy requirements were not limiting the rates of gluconeogenesis or of urea synthesis. 6. Addition of lactate, and especially ammonium salts, increased the uptake of oxygen more than expected on the basis of the ATP requirements of the gluconeogenesis and urea synthesis. PMID:5966267

  3. 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. PMID:26156231

  4. STARVATION INDUCED PROXIMAL GUT MUCOSAL ATROPHY DIMINISHED WITH AGING

    PubMed Central

    Song, Juquan; Wolf, Steven E.; Wu, Xiao-Wu; Finnerty, Celeste C.; Gauglitz, Gerd G.; Herndon, David N.; Jeschke, Marc G.

    2013-01-01

    Background Starvation induces small bowel atrophy with increased intestinal epithelial apoptosis and decreased proliferation. Here, we examined these parameters after starvation in aged animals. Methods Sixty-four 6 week-old and 26 month-old C57BL/6 mice were randomly assigned to either an ad libitum fed or fasted group. The small bowel was harvested at 12, 48, and 72 hours following starvation. Proximal gut mucosal height was measured and epithelial cells counted. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Proliferation was determined by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). Comparison of fed vs. fasted and adult vs. old groups was done by one-way ANOVA with Tukey’s test and unpaired t-test. Significance was accepted at p<0.05. Results Aged mice had higher proximal gut weights, mucosal heights and cell numbers at baseline compared with the adult group (p<0.05). The rate of apoptosis was lower in the aged (p<0.05) while proliferation was not different between groups before starvation. After starvation, proximal gut wet weight decreased only in adult mice (p<0.05); Gut mucosal height and mucosal cell number decreased greater in adult than in aged mice (p<0.05). This was related to decreased proliferation only in the adult group (p<0.05). The fold of epithelial apoptosis increased was higher in the aged group than in the adult after starvation (p<0.05). Conclusions Gut mucosal kinetics change with age had lower rates of apoptosis and greater mucosal mass; the character of starvation-induced atrophy is diminished with aging. PMID:19126762

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. Perfusion computed tomography in renal cell carcinoma.

    PubMed

    Das, Chandan J; Thingujam, Usha; Panda, Ananya; Sharma, Sanjay; Gupta, Arun Kumar

    2015-07-28

    Various imaging modalities are available for the diagnosis, staging and response evaluation of patients with renal cell carcinoma (RCC). While contrast enhanced computed tomography (CT) is used as the standard of imaging for size, morphological evaluation and response assessment in RCC, a new functional imaging technique like perfusion CT (pCT), goes down to the molecular level and provides new perspectives in imaging of RCC. pCT depicts regional tumor perfusion and vascular permeability which are indirect parameters of tumor angiogenesis and thereby provides vital information regarding tumor microenvironment. Also response evaluation using pCT may predate the size criteria used in Response Evaluation Criteria in Solid Tumors, as changes in the perfusion occurs earlier following tissue kinase inhibitors before any actual change in size. This may potentially help in predicting prognosis, better selection of therapy and more accurate and better response evaluation in patients with RCC. This article describes the techniques and role of pCT in staging and response assessment in patients with RCCs. PMID:26217456

  10. Parallel perfusion imaging processing using GPGPU

    PubMed Central

    Zhu, Fan; Gonzalez, David Rodriguez; Carpenter, Trevor; Atkinson, Malcolm; Wardlaw, Joanna

    2012-01-01

    Background and purpose The objective of brain perfusion quantification is to generate parametric maps of relevant hemodynamic quantities such as cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) that can be used in diagnosis of acute stroke. These calculations involve deconvolution operations that can be very computationally expensive when using local Arterial Input Functions (AIF). As time is vitally important in the case of acute stroke, reducing the analysis time will reduce the number of brain cells damaged and increase the potential for recovery. Methods GPUs originated as graphics generation dedicated co-processors, but modern GPUs have evolved to become a more general processor capable of executing scientific computations. It provides a highly parallel computing environment due to its large number of computing cores and constitutes an affordable high performance computing method. In this paper, we will present the implementation of a deconvolution algorithm for brain perfusion quantification on GPGPU (General Purpose Graphics Processor Units) using the CUDA programming model. We present the serial and parallel implementations of such algorithms and the evaluation of the performance gains using GPUs. Results Our method has gained a 5.56 and 3.75 speedup for CT and MR images respectively. Conclusions It seems that using GPGPU is a desirable approach in perfusion imaging analysis, which does not harm the quality of cerebral hemodynamic maps but delivers results faster than the traditional computation. PMID:22824549

  11. Whole Animal Perfusion Fixation for Rodents

    PubMed Central

    Gage, Gregory J.; Kipke, Daryl R.; Shain, William

    2012-01-01

    The goal of fixation is to rapidly and uniformly preserve tissue in a life-like state. While placing tissue directly in fixative works well for small pieces of tissue, larger specimens like the intact brain pose a problem for immersion fixation because the fixative does not reach all regions of the tissue at the same rate 5,7. Often, changes in response to hypoxia begin before the tissue can be preserved 12. The advantage of directly perfusing fixative through the circulatory system is that the chemical can quickly reach every corner of the organism using the natural vascular network. In order to utilize the circulatory system most effectively, care must be taken to match physiological pressures 3. It is important to note that physiological pressures are dependent on the species used. Techniques for perfusion fixation vary depending on the tissue to be fixed and how the tissue will be processed following fixation. In this video, we describe a low-cost, rapid, controlled and uniform fixation procedure using 4% paraformaldehyde perfused via the vascular system: through the heart of the rat to obtain the best possible preservation of the brain for immunohistochemistry. The main advantage of this technique (vs. gravity-fed systems) is that the circulatory system is utilized most effectively. PMID:22871843

  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. Towards robust deconvolution of low-dose perfusion CT: sparse perfusion deconvolution using online dictionary learning.

    PubMed

    Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C

    2013-05-01

    Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

  14. Towards robust deconvolution of low-dose perfusion CT: Sparse perfusion deconvolution using online dictionary learning

    PubMed Central

    Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.

    2014-01-01

    Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

  15. CT Perfusion Dynamics of Intracranial Tuberculomas

    PubMed Central

    N., Jayakumar Peruvumba; Shivashankar, Ravishankar

    2015-01-01

    Aims To study perfusion characteristics of intracranial tuberculomas and analyze changes with anti tubercular treatment. Materials and Methods Nineteen patients of histologically proven intracranial tuberculomas were included in the study of which 9 were not on antitubercular treatment and ten were on antitubercular treatment (6 patients on treatment for less than 2 months and 4 were more than 6 months). All patients underwent CT perfusion (CTP) and CTP parameters like rCBV and rCBF were obtained from entire lesion, center and capsule of lesions and compared. Results CTP parameters like rCBF and rCBV were significantly low in all the three ROIs in the group not on treatment compared to that of on treatment ; rCBF and rCBV of entire lesion (p=0.018 and p=0.005 respectively), capsule (p=0.045 and p=0.010 respectively) and center of the lesion (p=0.020 and p=0.009) respectively). Tuberculomas on antitubercular treatment of more than six months showed reduced rCBF and rCBV in entire lesion (p=0.01 & p=0.01 respectively), capsule (p=0.04 & p=0.03 respectively) and center (p=0.08 & p=0.05 respectively) compared to those on treatment for less than two months. Similarly tuberculomas on treatment for six months did not show significant difference in rCBF and rCBV compared to tuberculomas who were not on treatment. Tuberculomas on treatment for less than two months showed statistically increased rCBF and rCBV in entire lesion (p=0.01 & p=0.04 respectively), capsule (p=0.03 & p=0.01 respectively) and center (p= 0.03 &=0.01) compared to those not on treatment. Conclusion Intracranial tuberculomas not on treatment and those on treatment for around six months show low perfusion and tuberculomas on treatment for less than two months show high perfusion. These findings suggest that serial perfusion profiles of tuberculomas on treatment could possibly be seen as surrogate markers of response to treatment. PMID:26155528

  16. Developing a Benchmarking Process in Perfusion: A Report of the Perfusion Downunder Collaboration

    PubMed Central

    Baker, Robert A.; Newland, Richard F.; Fenton, Carmel; McDonald, Michael; Willcox, Timothy W.; Merry, Alan F.

    2012-01-01

    Abstract: Improving and understanding clinical practice is an appropriate goal for the perfusion community. The Perfusion Downunder Collaboration has established a multi-center perfusion focused database aimed at achieving these goals through the development of quantitative quality indicators for clinical improvement through benchmarking. Data were collected using the Perfusion Downunder Collaboration database from procedures performed in eight Australian and New Zealand cardiac centers between March 2007 and February 2011. At the Perfusion Downunder Meeting in 2010, it was agreed by consensus, to report quality indicators (QI) for glucose level, arterial outlet temperature, and pCO2 management during cardiopulmonary bypass. The values chosen for each QI were: blood glucose ≥4 mmol/L and ≤10 mmol/L; arterial outlet temperature ≤37°C; and arterial blood gas pCO2 ≥ 35 and ≤45 mmHg. The QI data were used to derive benchmarks using the Achievable Benchmark of Care (ABC™) methodology to identify the incidence of QIs at the best performing centers. Five thousand four hundred and sixty-five procedures were evaluated to derive QI and benchmark data. The incidence of the blood glucose QI ranged from 37–96% of procedures, with a benchmark value of 90%. The arterial outlet temperature QI occurred in 16–98% of procedures with the benchmark of 94%; while the arterial pCO2 QI occurred in 21–91%, with the benchmark value of 80%. We have derived QIs and benchmark calculations for the management of several key aspects of cardiopulmonary bypass to provide a platform for improving the quality of perfusion practice. PMID:22730861

  17. 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

  18. The association between cytokines and intestinal mucosal immunity among broilers fed on diets supplemented with fluorine.

    PubMed

    Luo, Qin; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Liu, Juan; Wu, Bangyuan; Deng, Yubing

    2013-05-01

    Fluorine (F) bioaccumulation has been reported in the organs and tissues of organisms, including intestine. The intestinal mucosa is very important to the immune development. Meanwhile, cytokines are present in the normal intestinal mucosal and play an important role in the immune function. Thus, changes of the cytokine contents are related to the state of intestinal mucosal immunity. In this study, we investigated the changes in contents of cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interferon gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) induced by dietary high F in the mucosa of different parts of intestines (duodenum, jejunum, and ileum) by enzyme-linked immunosorbent assay. A total of 280 one-day-old healthy avian broilers were randomly divided into four groups and fed on a corn-soybean basal diet as control diet (F 22.6 mg/kg) or the same basal diet supplemented with 400, 800, and 1,200 mg F/kg (high F groups I, II, and III) in the form of sodium fluoride for 42 days. The experimental data showed that the contents of IL-2, IL-4, IL-6, IFN-γ, and TNF-α in the intestinal mucosa were significantly decreased in the high F groups II and III when compared with those of the control group from 14 to 42 days of age. It was concluded that dietary F in the range of 800-1,200 mg/kg significantly reduced the contents of aforementioned cytokines in the intestinal mucosa of broilers, which could impact the function of intestinal mucosal immunity through the pathways that decreased the lymphocyte population and/or lymphocyte activation. PMID:23354543

  19. Biochanin A Gastroprotective Effects in Ethanol-Induced Gastric Mucosal Ulceration in Rats

    PubMed Central

    Hajrezaie, Maryam; Salehen, NurAin; Karimian, Hamed; Zahedifard, Maryam; Shams, Keivan; Batran, Rami Al; Majid, Nazia Abdul; Khalifa, Shaden A. M.; Ali, Hapipah Mohd; El-Seedi, Hesham; Abdulla, Mahmood Ameen

    2015-01-01

    Background Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats` stomachs. Methodology The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA. Conclusions This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp

  20. 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.

  1. 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.

  2. A method of thymic perfusion and its evaluation

    PubMed Central

    Ekwueme, O.

    1973-01-01

    The development and evaluation of a method of isolated ex vivo perfusion of the rabbit thymus using diluted autologous blood is described. The data indicate that the viability of the preparation is maintained at a satisfactory level during the period of perfusion. These results suggest that the isolated perfused thymus would be a useful new approach to studies of thymus function. ImagesFig. 2Fig. 8Fig. 9Fig. 10Fig. 11 PMID:4747584

  3. 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

  4. Radiation induced oral mucositis: a review of current literature on prevention and management.

    PubMed

    Mallick, Supriya; Benson, Rony; Rath, G K

    2016-09-01

    Oral mucositis (OM) is a major limiting acute side effect of radiotherapy for head and neck cancer. The spectrum of problems associated with mucositis includes oral pain, odynophagia, reduced oral intake, and secondary infections. Incidence of mucositis is increased with addition of concurrent chemotherapy as well as altered fractionation schedules. This leads to treatment interruption and suboptimal disease control. Hence, prevention as well as timely management of OM is necessary for optimum tumor control. We reviewed the English literature with key words "Radiation induced mucositis, Mucositis, Oral Mucositis" to find relevant articles describing incidence, pathophysiology, prophylaxis, and treatment of oral mucositis. Prevention and treatment of OM is an active area of research. Maintenance of oral hygiene is an important part in prevention of OM. A battery of agents including normal saline and alkali (soda bicarbonate) mouth washes, low level laser therapy, and benzydamine (non-steroidal analgesic and anti-inflammatory) have effectiveness in the prevention and treatment of radiation induced oral mucositis. Chlorhexidine mouth gargles are recommended for prevention of chemotherapy induced oral mucositis but is not recommended for radiotherapy associated mucositis. Treatment of co-existing infection is also important and both topical (povidone iodine) and systemic anti fungals should be used judiciously. Radiation induced oral mucositis is a common problem limiting the efficacy of radiation by increasing treatment breaks. Adequate prophylaxis and treatment may limit the severity of radiation mucositis and improve compliance to radiation which may translate in better disease control and survival. PMID:26116012

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

    PubMed Central

    Präbst, K.; Beier, J. P.; Meyer, A.; Horch, R. E.

    2016-01-01

    Summary: 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. PMID:27200244

  6. 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.

  7. Perfusion CT imaging of the liver: review of clinical applications

    PubMed Central

    Oğul, Hayri; Kantarcı, Mecit; Genç, Berhan; Pirimoğlu, Berhan; Çullu, Neşat; Kızrak, Yeşim; Yılmaz, Ömer; Karabulut, Nevzat

    2014-01-01

    Perfusion computed tomography (CT) has a great potential for determining hepatic and portal blood flow; it offers the advantages of quantitative determination of lesion hemodynamics, distinguishing malignant and benign processes, as well as providing morphological data. Many studies have reported the use of this method in the assessment of hepatic tumors, hepatic fibrosis associated with chronic liver disease, treatment response following radiotherapy and chemotherapy, and hepatic perfusion changes after radiological or surgical interventions. The main goal of liver perfusion imaging is to improve the accuracy in the characterization of liver disorders. In this study, we reviewed the clinical application of perfusion CT in various hepatic diseases. PMID:24834487

  8. Radionuclide Tracers for Myocardial Perfusion Imaging and Blood Flow Quantification.

    PubMed

    deKemp, Robert A; Renaud, Jennifer M; Klein, Ran; Beanlands, Rob S B

    2016-02-01

    Myocardial perfusion imaging is performed most commonly using Tc-99m-sestamibi or tetrofosmin SPECT as well as Rb-82-rubidium or N-13-ammonia PET. Diseased-to-normal tissue contrast is determined by the tracer retention fraction, which decreases nonlinearly with flow. Reduced tissue perfusion results in reduced tracer retention, but the severity of perfusion defects is typically underestimated by 20% to 40%. Compared to SPECT, retention of the PET tracers is more linearly related to flow, and therefore, the perfusion defects are measured more accurately using N-13-ammonia or Rb-82. PMID:26590778

  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. PMID:27196368

  10. 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

  11. 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). PMID:27004972

  12. 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

    2015-12-01

    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/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. PMID:26720873

  13. Gut Check: IFNγ Delays Mucosal Recovery during Antibiotic Therapy.

    PubMed

    Chung, Lawton K; Bliska, James B

    2016-08-10

    Antibiotic therapy has been largely ineffective in improving clinical outcomes following Salmonellosis, yet the reasons why remain obscure. In this issue of Cell Host & Microbe, Dolowschiak et al. (2016) report that IFNγ produced by NK and T cells following antibiotic treatment of acute Salmonella infection limits mucosal remission. PMID:27512899

  14. 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.

  15. 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.

  16. 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.

  17. 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 ...

  18. Palifermin: new drug. Prevention of oral mucositis: inappropriate evaluation.

    PubMed

    2007-08-01

    (1) Patients treated with high-dose chemotherapy combined with total body irradiation (myeloablative therapy) often develop oral mucositis. Prevention is based mainly on sucking ice during chemotherapy. (2) Palifermin is a growth factor marketed for the prevention of severe oral mucositis in adults with malignant haemopathies who are receiving myeloablative therapy followed by peripheral stem cell autografting. (3) Palifermin has not been compared with sucking ice, despite the efficacy of this simple treatment. (4) In a randomised placebo-controlled double-blind trial involving 212 adult patients treated with high-dose chemotherapy and total body irradiation, palifermin reduced the incidence of severe oral mucositis (63% versus 98%) and its duration (about 3 days versus 9 days). The myeloablative regimen used in this trial is not that commonly used in Europe. The efficacy of palifermin during less aggressive regimens, which cause less severe oral mucositis, is not known. (5) The main adverse events noted in clinical trials were erythema and cutaneous oedema. It is not known whether palifermin increases the long-term risk of cancer. (6) Treatment with palifermin is expensive, 4800.00 euros in France); the optimal dosing schedule is not known and the unit dose chosen by the manufacturer is wastefully large. (7) In practice, it remains to be demonstrated that palifermin is more effective than simply sucking ice. PMID:17724832

  19. 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.

  20. Oral and intestinal mucositis - causes and possible treatments.

    PubMed

    Duncan, M; Grant, G

    2003-11-01

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

  1. Age and Helicobacter pylori decrease gastric mucosal surface hydrophobicity independently

    PubMed Central

    Hackelsberger, A; Platzer, U; Nilius, M; Schultze, V; Gunther, T; Dominguez-Munoz, J; Malfertheiner, P

    1998-01-01

    Background—Gastric mucosal surface hydrophobicity (GMSH) is an essential component of the mucosal defence system that is decreased by Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs). Gastric ulcers occur predominantly in elderly subjects, and may thus reflect diminished mucosal resistance. 
Aims—To investigate whether aging decreases GMSH. 
Patients—One hundred and twenty patients without peptic ulcer disease were divided into three age groups: I (41 years or below); II (41-64 years); and III (65 years or above). 
Methods—Biopsy specimens were taken from the antrum, corpus, and cardia for histology (Sydney system), urease testing for H pylori, and for contact angle measurement of GMSH with a goniometer. The presence of specific H pylori antibodies was checked by immunoblotting. 
Results—Fifty two patients (43%) were infected, and 68 were uninfected with H pylori. GMSH at all biopsy sites was lower in H pylori infected subjects (p=0.0001), but also decreased with age independently of infection status (p=0.0001). The most notable decrease in GMSH occurred between age groups I and II in those with, and between age groups II and III in those without, H pylori infection. GMSH was greater in antral than in corpus mucosa in both infected (p=0.0001) and uninfected patients (p=0.0003). 
Conclusions—A physiological decrease in GMSH with aging may contribute to the risk of ulcer development in the elderly, and may act synergistically with H pylori and/or NSAIDs on gastric mucosal defence. 

 Keywords: gastric mucosal defence; surface hydrophobicity; aging; Helicobacter pylori PMID:9824570

  2. Mucosal immunologic responses in cholera patients in Bangladesh.

    PubMed

    Uddin, Taher; Harris, Jason B; Bhuiyan, Taufiqur Rahman; Shirin, Tahmina; Uddin, Muhammad Ikhtear; Khan, Ashraful Islam; Chowdhury, Fahima; LaRocque, Regina C; Alam, Nur Haque; Ryan, Edward T; Calderwood, Stephen B; Qadri, Firdausi

    2011-03-01

    Vibrio cholerae O1 causes dehydrating diarrhea with a high mortality rate if untreated. The infection also elicits long-term protective immunity. Since V. cholerae is noninvasive, mucosal immunity is likely important for protection. In this study, we compared humoral immune responses in the duodenal mucosa and blood of cholera patients at different time points after the onset of disease and compared them with those of healthy controls (HCs). Immune responses to lipopolysaccharide (LPS) and the recombinant cholera toxin B subunit (rCTB) were assessed by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. Significant increases in V. cholerae LPS-specific IgA and IgG antibody levels were seen in duodenal extracts on day 30, but the levels decreased to baseline by day 180; plasma V. cholerae LPS-specific IgA levels remained elevated longer. Levels of mucosal CTB antibodies also peaked on day 30, but the increase reached statistical significance only for IgG. A significant correlation was found between the CTB antibody-secreting cell (ASC) response in the circulatory system on day 7 and subsequent CTB-specific IgA levels in duodenal extracts on day 30 and the numbers of CTB-specific IgA ASCs in duodenal tissues on day 180. The proportion (0.07%) of mucosal V. cholerae LPS IgA ASCs peaked on day 30 and remained elevated through day 180 compared to that of HCs (P = 0.03). These results suggest that protective immunity against V. cholerae is not likely mediated by the constitutive secretion of antibodies at the mucosal surface; our results are consistent with those of other studies that suggest instead that anamnestic immune responses of mucosal lymphocytes may play a major role in protection against cholera. PMID:21248157

  3. 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.

  4. Diagnostic Accuracy of Mucosal Biopsy versus Endoscopic Mucosal Resection in Barrett's Esophagus and Related Superficial Lesions.

    PubMed

    Elsadek, Hany M; Radwan, Mamdouh M

    2015-01-01

    Background. Endoscopic surveillance for early detection of dysplastic or neoplastic changes in patients with Barrett's esophagus (BE) depends usually on biopsy. The diagnostic and therapeutic role of endoscopic mucosal resection (EMR) in BE is rapidly growing. Objective. The aim of this study was to check the accuracy of biopsy for precise histopathologic diagnosis of dysplasia and neoplasia, compared to EMR in patients having BE and related superficial esophageal lesions. Methods. A total of 48 patients with previously diagnosed BE (36 men, 12 women, mean age 49.75 ± 13.3 years) underwent routine surveillance endoscopic examination. Biopsies were taken from superficial lesions, if present, and otherwise from BE segments. Then, EMR was performed within three weeks. Results. Biopsy based histopathologic diagnoses were nondysplastic BE (NDBE), 22 cases; low-grade dysplasia (LGD), 14 cases; high-grade dysplasia (HGD), 8 cases; intramucosal carcinoma (IMC), two cases; and invasive adenocarcinoma (IAC), two cases. EMR based diagnosis differed from biopsy based diagnosis (either upgrading or downgrading) in 20 cases (41.67%), (Kappa = 0.43, 95% CI: 0.170-0.69). Conclusions. Biopsy is not a satisfactory method for accurate diagnosis of dysplastic or neoplastic changes in BE patients with or without suspicious superficial lesions. EMR should therefore be the preferred diagnostic method in such patients. PMID:27347544

  5. The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft.

    PubMed

    Wu, Z Y; Smithers, B M; Parsons, P G; Roberts, M S

    1997-01-01

    An isolated rat hindlimb perfusion model carrying xenografts of the human melanoma cell line MM96 was used to study the effects of perfusion conditions on melphalan distribution. Krebs-Henseleit buffer and Hartmann's solution containing 4.7% bovine serum albumin (BSA) or 2.8% dextran 40 were used as perfusates. Melphalan concentrations in perfusate, tumour nodules and normal tissues were measured using high-performance liquid chromatography (HPLC). Increasing the perfusion flow rates (from 4 to 8 ml min(-1)) resulted in higher tissue blood flow (determined with 51Cr-labelled microspheres) and melphalan uptake by tumour and normal tissues. The distribution of melphalan within tumour nodules and normal tissues was similar for both Krebs-Henseleit buffer and Hartmann's solution; however, tissue concentrations of melphalan were significantly higher for a perfusate containing 2.8% dextran 40 than for one containing 4.7% BSA. The melphalan concentration in the tumour was one-third of that found in the skin if the perfusate contained 4.7% BSA. In conclusion, this study has shown that a high perfusion flow enhances the delivery of melphalan into implanted tumour nodules and normal tissues, and a perfusate with low melphalan binding (no albumin) is preferred for maximum uptake of drug by the tumour. PMID:9099965

  6. 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

  7. 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

  8. Chronic parenterally administered nicotine and stress- or ethanol-induced gastric mucosal damage in rats.

    PubMed

    Wong, D; Ogle, C W

    1995-01-13

    Mini-osmotic pumps containing solutions of either 0.9% NaCl (infused at the rate of 0.5 microliter/h) or nicotine (infused in doses of 0.224, 1.03 or 1.88 mg/kg per day) were implanted s.c. into rats 12 days before experimentation. The alkaloid increased solid food consumption, but fluid intake and average weight gain were similar among the animals given saline or nicotine. Chronic nicotine treatment dose dependently intensified cold (4 degrees C)-restraint stress-induced ulceration and increased mast cell degranulation. Oral administration of 40% ethanol to nicotine-treated animals also produced greater mucosal damage; mast cell degranulation by ethanol was significantly worsened after alkaloid treatment. These findings show that the stress ulcer-intensifying action of the alkaloid is mainly through a systemic mechanism. In the case of ethanol-evoked mucosal damage, in addition to a topical effect, stimulation of the stomach wall ganglia is likely to participate in the exaggerated post-vagal ulcerogenic responses as seen in stress. PMID:7720788

  9. Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility

    SciTech Connect

    Aw, Tak Yee . E-mail: taw@lsuhsc.edu

    2005-05-01

    The intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation of oxidants like peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as inflammation and cancer. Despite this recognition, we know little of the pathways of intestinal transport, metabolism, and luminal disposition of dietary peroxides in vivo or of the underlying mechanisms of lipid peroxide-induced genesis of intestinal disease processes. This chapter summarizes our current understanding of the determinants of intestinal absorption and metabolism of peroxidized lipids. I will review experimental evidence from our laboratory and others (Table 1) supporting the pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and how reductant availability can be compromised under chronic stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and redox contribution to genesis of gut disorders. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of luminal GSH in preserving the integrity of the intestinal epithelium.

  10. 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. PMID:26202372

  11. Repeatability, Reproducibility and Standardisation of a Laser Doppler Imaging Technique for the Evaluation of Normal Mouse Hindlimb Perfusion

    PubMed Central

    Greco, Adelaide; Ragucci, Monica; Liuzzi, Raffaele; Gargiulo, Sara; Gramanzini, Matteo; Coda, Anna Rita Daniela; Albanese, Sandra; Mancini, Marcello; Salvatore, Marco; Brunetti, Arturo

    2013-01-01

    Background Preclinical perfusion studies are useful for the improvement of diagnosis and therapy in dermatologic, cardiovascular and rheumatic human diseases. The Laser Doppler Perfusion Imaging (LDPI) technique has been used to evaluate superficial alterations of the skin microcirculation in surgically induced murine hindlimb ischemia. We assessed the reproducibility and the accuracy of LDPI acquisitions and identified several critical factors that could affect LDPI measurements in mice. Methods Twenty mice were analysed. Statistical standardisation and a repeatability and reproducibility analysis were performed on mouse perfusion signals with respect to differences in body temperature, the presence or absence of hair, the type of anaesthesia used for LDPI measurements and the position of the mouse body. Results We found excellent correlations among measurements made by the same operator (i.e., repeatability) under the same experimental conditions and by two different operators (i.e., reproducibility). A Bland-Altman analysis showed the absence of bias in repeatability (p = 0.29) or reproducibility (p = 0.89). The limits of agreement for repeatability were –0.357 and –0.033, and for reproducibility, they were –0.270 and 0.238. Significant differences in perfusion values were observed in different experimental groups. Conclusions Different experimental conditions must be considered as a starting point for the evaluation of new drugs and strategic therapies. PMID:23275085

  12. Mucosal immunity and protection against HIV/SIV infection: strategies and challenges for vaccine design

    PubMed Central

    Demberg, Thorsten; Robert-Guroff, Marjorie

    2012-01-01

    To date most HIV vaccine strategies have focused on parenteral immunization and systemic immunity. These approaches have not yielded the efficacious HIV vaccine urgently needed to control the AIDS pandemic. As HIV is primarily mucosally transmitted, efforts are being refocused on mucosal vaccine strategies, in spite of complexities of immune response induction and evaluation. Here we outline issues in mucosal vaccine design and illustrate strategies with examples from the recent literature. Development of a successful HIV vaccine will require in depth understanding of the mucosal immune system, knowledge that ultimately will benefit vaccine design for all mucosally transmitted infectious agents. PMID:19241252

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

    PubMed

    Aghamohamamdi, Azar; Hosseinimehr, Seyed Jalal

    2016-03-01

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

  14. Nitrogen metabolism in the isolated perfused rat liver. Nitrogen balance, redox state and rates of proteolysis.

    PubMed

    Parrilla, R; Goodman, M N

    1974-03-01

    Nitrogen balances were measured in isolated perfused rat livers in the presence and absence of nitrogen donors. In all instances the balance apparently was incomplete. The expression [alanine][alpha-oxoglutarate]/[pyruvate][glutamate] remained fairly constant under the metabolic conditions studied, indicating that it may be at near-equilibrium. The source of the extra nitrogen seems to be derived from increased hepatic proteolysis. The addition of a nitrogen donor to the perfusate arrested proteolysis, as did the addition of pyruvate. The free mitochondrial [NAD(+)]/[NADH] ratio, calculated from the glutamate dehydrogenase and beta-hydroxybutyrate dehydrogenase reactants, showed similar values and exhibited parallel changes under most metabolic situations studied. These results suggest that, under the reported experimental conditions, both dehydrogenases share a common mitochondrial NAD pool. Glutamate dehydrogenase plays an important role in hepatic nitrogen metabolism in vivo. PMID:4372991

  15. Oral mucosal injury caused by cancer therapies: current management and new frontiers in research.

    PubMed

    Jensen, Siri B; Peterson, Douglas E

    2014-02-01

    This invited update is designed to provide a summary of the state-of-the-science regarding oral mucosal injury (oral mucositis) caused by conventional and emerging cancer therapies. Current modeling of oral mucositis pathobiology as well as evidence-based clinical practice guidelines for prevention and treatment of oral mucositis are presented. In addition, studies addressing oral mucositis as published in the Journal of Oral Pathology and Medicine 2008-2013 are specifically highlighted in this context. Key research directions in basic and translational science associated with mucosal toxicity caused by cancer therapies are also delineated as a basis for identifying pathobiologic and pharmacogenomic targets for interventions. This collective portfolio of research and its ongoing incorporation into clinical practice is setting the stage for the clinician in the future to predict mucosal toxicity risk and tailor therapeutic interventions to the individual oncology patient accordingly. PMID:24261541

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

    SciTech Connect

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

    1994-02-01

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

  17. 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…

  18. 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. PMID:26834289

  19. Sustained ventilation: perfusion imbalance during hemodialysis.

    PubMed

    Milner, L S; Rothberg, A D; Thomson, P D; Stothart, M

    1983-06-01

    Five children between the ages of 6 and 15 years, who required chronic hemodialysis (HD) for renal failure, were studied to evaluate the central and pulmonary effects of HD on gas exchange. Acetate dialysate was used, and dialysate pO2 and pCO2, arterial pO2 and pCO2, endtidal CO2 and minute ventilation were measured pre-HD and 15, 30, 60, 120 and 240 minutes after commencement of HD. Arterial-alveolar CO2 gradient (aADCO2) was calculated to determine the ventilation: perfusion (V/Q) status. Minute ventilation did not change significantly from the pre-HD value of 8.9 +/- 1.1 l/min (mean +/- SD). The aADCO2 increased significantly from 3.2 +/- 3.7 mmHg to 8.4 +/- 2.4 mmHg at 15 mins (p less than .01) and was still elevated at 120 mins. (9.1 +/- 3.4 mmHg, p less than .02). There was a weak but significant inverse relationship between aADCO2 and arterial pO2 (r -0.42, p less than 0.05). The results suggest that, in these children, dialysed at altitude, dialysis-related hypoxemia appears to be the result of a sustained V/Q mismatch, possibly related to a decrease in pulmonary perfusion. PMID:6413444

  20. Diagnosing acute lacunar infarction using CT perfusion.

    PubMed

    Cao, Wenjie; Yassi, Nawaf; Sharma, Gagan; Yan, Bernard; Desmond, Patricia M; Davis, Stephen M; Campbell, Bruce C V

    2016-07-01

    The value of CT perfusion (CTP) in detecting acute lacunar infarcts (LACI) has not been well established. We tested the sensitivity of CTP for LACI. CTP maps of consecutive stroke patients from 2009-2013 were examined. MRI diffusion imaging was used to identify those with LACI. Two stroke neurologists independently evaluated the CTP maps for evidence of a perfusion lesion in a deep perforating artery territory. Cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to maximum (Tmax) maps were first examined in isolation and then in combination. Inter-observer agreement was measured using Cohen's κ. The lesions identified were later confirmed against the diffusion MRI reference and the sensitivity and specificity of CTP maps calculated. A total of 63 patient scans were analysed. There were 32 patients with MRI-confirmed LACI within the coverage of CTP; 18 in the striatum, 10 thalamic, and four in the corona radiata. Another 31 patients had normal MRI. Inter-rater agreement was good (κ=0.83). Sensitivity (blinded consensus) was highest for MTT (56.2%) compared to Tmax (25%, p<0.001), CBV (9.3%, p=0.021) and CBF (43.7%, p<0.001). MTT maps enable detection of a significant proportion of LACI using CTP. PMID:26899357

  1. 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

  2. Spatio-temporal simulation of first pass drug perfusion in the liver.

    PubMed

    Schwen, Lars Ole; Krauss, Markus; Niederalt, Christoph; Gremse, Felix; Kiessling, Fabian; Schenk, Andrea; Preusser, Tobias; Kuepfer, Lars

    2014-03-01

    The liver is the central organ for detoxification of xenobiotics in the body. In pharmacokinetic modeling, hepatic metabolization capacity is typically quantified as hepatic clearance computed as degradation in well-stirred compartments. This is an accurate mechanistic description once a quasi-equilibrium between blood and surrounding tissue is established. However, this model structure cannot be used to simulate spatio-temporal distribution during the first instants after drug injection. In this paper, we introduce a new spatially resolved model to simulate first pass perfusion of compounds within the naive liver. The model is based on vascular structures obtained from computed tomography as well as physiologically based mass transfer descriptions obtained from pharmacokinetic modeling. The physiological architecture of hepatic tissue in our model is governed by both vascular geometry and the composition of the connecting hepatic tissue. In particular, we here consider locally distributed mass flow in liver tissue instead of considering well-stirred compartments. Experimentally, the model structure corresponds to an isolated perfused liver and provides an ideal platform to address first pass effects and questions of hepatic heterogeneity. The model was evaluated for three exemplary compounds covering key aspects of perfusion, distribution and metabolization within the liver. As pathophysiological states we considered the influence of steatosis and carbon tetrachloride-induced liver necrosis on total hepatic distribution and metabolic capacity. Notably, we found that our computational predictions are in qualitative agreement with previously published experimental data. The simulation results provide an unprecedented level of detail in compound concentration profiles during first pass perfusion, both spatio-temporally in liver tissue itself and temporally in the outflowing blood. We expect our model to be the foundation of further spatially resolved models of the

  3. Spatio-Temporal Simulation of First Pass Drug Perfusion in the Liver

    PubMed Central

    Schwen, Lars Ole; Krauss, Markus; Niederalt, Christoph; Gremse, Felix; Kiessling, Fabian; Schenk, Andrea; Preusser, Tobias; Kuepfer, Lars

    2014-01-01

    The liver is the central organ for detoxification of xenobiotics in the body. In pharmacokinetic modeling, hepatic metabolization capacity is typically quantified as hepatic clearance computed as degradation in well-stirred compartments. This is an accurate mechanistic description once a quasi-equilibrium between blood and surrounding tissue is established. However, this model structure cannot be used to simulate spatio-temporal distribution during the first instants after drug injection. In this paper, we introduce a new spatially resolved model to simulate first pass perfusion of compounds within the naive liver. The model is based on vascular structures obtained from computed tomography as well as physiologically based mass transfer descriptions obtained from pharmacokinetic modeling. The physiological architecture of hepatic tissue in our model is governed by both vascular geometry and the composition of the connecting hepatic tissue. In particular, we here consider locally distributed mass flow in liver tissue instead of considering well-stirred compartments. Experimentally, the model structure corresponds to an isolated perfused liver and provides an ideal platform to address first pass effects and questions of hepatic heterogeneity. The model was evaluated for three exemplary compounds covering key aspects of perfusion, distribution and metabolization within the liver. As pathophysiological states we considered the influence of steatosis and carbon tetrachloride-induced liver necrosis on total hepatic distribution and metabolic capacity. Notably, we found that our computational predictions are in qualitative agreement with previously published experimental data. The simulation results provide an unprecedented level of detail in compound concentration profiles during first pass perfusion, both spatio-temporally in liver tissue itself and temporally in the outflowing blood. We expect our model to be the foundation of further spatially resolved models of the

  4. 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.

  5. [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. PMID:25700252

  6. The mucosal humoral immune response of the horse to infective challenge and vaccination with equine herpesvirus-1 antigens.

    PubMed

    Breathnach, C C; Yeargan, M R; Sheoran, A S; Allen, G P

    2001-11-01

    Equine herpesvirus-1 (EHV-1) remains a frequent cause of upper respiratory tract infection and abortion in horses worldwide. However, little is known about the local antibody response elicited in the upper airways of horses following exposure to EHV-1. This study analysed the mucosal humoral immune response of weanling foals following experimental infection with virulent EHV-1, or vaccination with either of 2 commercial vaccines. Twenty weanlings were assigned to 5 groups and were inoculated with, or vaccinated against, EHV-1 following different regimens. Finally, all weanlings were simultaneously challenged intranasally with virulent EHV-1 Army 183 (A183). Nasal wash and serum samples were collected at regular intervals until 13 weeks after final challenge. Nasal washes were assayed for EHV-1-specific equine IgGa, IgGb, IgG(T), IgA, IgM and total virus-specific antibody using an indirect, quantitative ELISA. Total serum antibody responses were also monitored, and clinical signs of EHV-disease were recorded for each individual. Virus-specific IgA dominated the mucosal antibody response elicited in weanlings inoculated with A183, being detectable at up to 3.1 microg/mg total IgA 13 weeks after challenge. Neither inactivated EHV-1 administered i.m., nor attenuated EHV-1 administered intranasally induced detectable mucosal antibodies. EHV-1-specific mucosal antibodies impeded EHV-1 plaque formation in vitro. Such virus-neutralising antibody probably contributes to a reduction of shedding of EHV-1 from the respiratory tract of virus-infected horses. PMID:11770985

  7. Protective effects of Ankaferd blood stopper on aspirin-induced oxidative mucosal damage in a rat model of gastric injury.

    PubMed

    Hasgul, Rukiye; Uysal, Sema; Haltas, Hacer; Akyol, Sumeyye; Yuksel, Yasemin; Gurel, Ayse; Armutcu, Ferah

    2014-11-01

    The exposure of gastric mucosa to damaging factors, such as ethanol and some therapeutic drugs, produces pathological changes: inflammatory process, hemorrhagic erosions and even acute ulcers. Ankaferd blood stopper (ABS) comprises a standardized mixture of five different plant extracts. The purpose of our present investigations is to explain the participation of reactive oxygen species in acute gastric mucosal damage by acetylsalicylic acid (ASA) and the effects of new hemostatic agent ABS. Experiments were carried out on 23 male Wistar rats. To assess gastric mucosal damage, biochemical and histopathological data were used. The colorimetric assays were used to determine the malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The level of myeloperoxidase (MPO) activity, the level of nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay technique. We demonstrated that the biological effects of ROS were estimated by measuring the tissue and plasma levels of MDA, the products of lipid peroxidation, as well as the activity of SOD and the scavenger of ROS produced by ASA in the experiment group. Moreover, it was found that MPO activity as well as NO and TNF-α levels also demonstrated significant improvement by ABS treatment. The pathogenesis of experimental ASA-induced mucosal damage in rat stomach includes the generation of ROS that seems to play an important role, due to the generation of lipid peroxides, accompanied by the impairment of antioxidative enzyme activity of cells. ABS appeared to attenuate the oxidative and inflammatory changes caused by ASA-induced gastric mucosal damage in rats. PMID:23114375

  8. 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.

  9. 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

  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. 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.

  12. Immunotherapies Targeting Fish Mucosal Immunity - Current Knowledge and Future Perspectives.

    PubMed

    Koshio, Shunsuke

    2015-01-01

    In recent years, studies on the mucosal immunity in fish species have shown much progress. Although there are some organs such as skin, gills, and gut are directly associated with the mucosal immunity of fish species, this mini review emphasizes the general knowledge on the role and production figures of skin mucus and factors affecting the secretion of skin mucus of fish species. As the skin mucus of fish species is the first defense line for protection against invading microorganisms such as pathogens (bacteria, virus), parasites, etc., the information for understanding the roles of the skin mucus is very important. Furthermore, the information in the review will shed light on the development of high quality aquafeeds for the sustainable aquaculture field as well. PMID:26779184

  13. 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. PMID:27085913

  14. Microbiota-Host Interactions in Mucosal Homeostasis and Systemic Autoimmunity

    PubMed Central

    Longman, Randy S.; Yang, Yi; Diehl, Gretchen E.; Kim, Sangwon V.; Littman, Dan R.

    2015-01-01

    The vertebrate intestinal tract is colonized by hundreds of species of bacteria that must be compartmentalized and tolerated to prevent invasive growth and harmful inflammatory responses. Signaling initiated by commensal bacteria shapes antigen-specific mucosal and systemic adaptive immunity. A distinct type of effector CD4+ T cells, Th17 cells, play a key role in coordinating the inflammatory immune responses that afford protection to pathogens at the mucosal interface. Balancing this powerful inflammatory response, regulatory T cells limit collateral damage and provide antigen-specific tolerance to both food and microbial antigens. Here, we discuss the implications for how the microbiota as a whole contribute to compartmentalization from the host and how individual constituents of the microbiota influence the functions and repertoire of effector T cells and organ-specific autoimmune disease. PMID:24913313

  15. Prevalence of Oral Mucosal Lesions in Male Smokers and Nonsmokers

    PubMed Central

    Ahmadi-Motamayel, Fatemeh; Falsafi, Parisa; Hayati, Zahra; Rezaei, Farzad

    2013-01-01

    Tobacco smoking is one of the most important risk factors for the development of oral mucosal lesions such as leukoplakia and hairy tongue. Controversy exists in the literature, however, about the prevalence of oral lesions in smokers. The aim of this study was to evaluate oral lesions in male smokers compared with nonsmokers in Hamadan. A total of 516 male participants were assessed, 258 of whom were smokers and 258 of whom were healthy nonsmokers. The prevalence of lesions was evaluated by clinical observation and biopsy. We found that the most prevalent lesions among smokers were gingival problems and coated tongue; smokers had significantly more lesions than did nonsmokers. Malignant and premalignant lesions were found in a higher age range. Among all participants in our study, we found a large number of oral mucosal lesions in smokers that had a strong correlation with smoking. Dental services need to implement care and health education for smokers to promote health. PMID:24010068

  16. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions.

    PubMed

    Zhu, Li; Yang, Zhong-Cheng; Li, Ao; Cheng, De-Chang

    2000-02-01

    AIM:To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS:A rat model with 30% TBSA full thickness burn injury was employed and the gastric acid production,together with gastric mucosal blood flow (GMBF) and energy charge (EC) were measured serially within 48h postburn.RESULTS:The gastric acid production in the acute shock period was markedly inhibited after severe burn injury.At the 3rd h postburn,the gastric juice volume, total acidity and acid output were already significantly decreased (P < 0.01 =, and reached the lowest point, 0.63mL/L ± 0.20mL/L, 10.81mmol/L ± 2.58mmol/L and 2.23mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, consistent with the trend of gastric acid production changes.CONCLUSION:Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of anti-acid drugs during burn shock period was unreasonable in some respects. Therefore, taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment. PMID:11819529

  17. Metabolic alterations to the mucosal microbiota in inflammatory bowel disease

    PubMed Central

    Davenport, Michael; Poles, Jordan; Leung, Jacqueline M.; Wolff, Martin J.; Abidi, Wasif M.; Ullman, Thomas; Mayer, Lloyd; Cho, Ilseung; Loke, P'ng

    2014-01-01

    Background Inflammation during inflammatory bowel disease (IBD) may alter nutrient availability to adherent mucosal bacteria and impact their metabolic function. Microbial metabolites may regulate intestinal CD4+ T cell homeostasis. We investigated the relationship between inflammation and microbial function by inferred metagenomics of the mucosal microbiota from colonic pinch biopsies of IBD patients. Methods Paired pinch biopsy samples of known inflammation states were analyzed from UC (23), CD (21) and controls (24) by 16S ribosomal sequencing, histopathology and flow cytometry. PICRUSt was used to generate metagenomic data, and derive relative Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway abundance information. Leukocytes were isolated from paired biopsy samples and analyzed by multi-color flow cytometry. Active inflammation was defined by neutrophil infiltration into the epithelium Results Carriage of metabolic pathways in the mucosal microbiota was relatively stable among IBD patients despite large variations in individual bacterial community structures. However, microbial function was significantly altered in inflamed tissue of UC patients, with a reduction in carbohydrate and nucleotide metabolism in favor of increased lipid and amino acid metabolism. These differences were not observed in samples from CD patients. In CD, microbial lipid, carbohydrate, and amino acid metabolism was tightly correlated with frequency of CD4+Foxp3+ Tregs, whereas in UC these pathways were correlated with frequency of CD4+IL-22+ (TH22) cells. Conclusions Metabolic pathways of the mucosal microbiota in CD do not vary as much as UC with inflammation state, indicating a more systemic perturbation of host-bacteria interactions in CD compared to more localized dysfunction in UC. PMID:24583479

  18. Compartmentalization of the mucosal immune responses to commensal intestinal bacteria.

    PubMed

    Macpherson, Andrew J; Uhr, Therese

    2004-12-01

    Mammals coexist with a luxuriant load of bacteria in the lower intestine (up to 10(12) organisms/g of intestinal contents). Although these bacteria do not cause disease if they remain within the intestinal lumen, they contain abundant immunostimulatory molecules that trigger immunopathology if the bacteria penetrate the body in large numbers. The physical barrier consists only of a single epithelial cell layer with overlying mucus, but comparisons between animals kept in germ-free conditions and those colonized with bacteria show that bacteria induce both mucosal B cells and some T cell subsets; these adaptations are assumed to function as an immune barrier against bacterial penetration, but the mechanisms are poorly understood. In mice with normal intestinal flora, but no pathogens, there is a secretory IgA response against bacterial membrane proteins and other cell wall components. Whereas induction of IgA against cholera toxin is highly T help dependent, secretory IgA against commensal bacteria is induced by both T independent and T dependent pathways. When animals are kept in clean conditions and free of pathogens, there is still a profound intestinal secretory IgA response against the commensal intestinal flora. However, T dependent serum IgG responses against commensal bacteria do not occur in immunocompetent animals unless they are deliberately injected intravenously with 10(4) to 10(6) organisms. In other words, unmanipulated pathogen-free mice are systemically ignorant but not tolerant of their commensal flora despite the mucosal immune response to these organisms. In mice that are challenged with intestinal doses of commensal bacteria, small numbers of commensals penetrate the epithelial cell layer and survive within dendritic cells (DC). These commensal-loaded DC induce IgA, but because they are confined within the mucosal immune system by the mesenteric lymph nodes, they do not induce systemic immune responses. In this way the mucosal immune responses

  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. Analytical estimation of ultrasound properties, thermal diffusivity, and perfusion using magnetic resonance-guided focused ultrasound temperature data.

    PubMed

    Dillon, C R; Borasi, G; Payne, A

    2016-01-21

    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

  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. Myofibroblasts in the mucosal layer of the uterine tube.

    PubMed

    Walter, I

    1998-01-01

    Uterine tubes from cow, sheep, horse, pig, dog, cat, rabbit, and guinea pig were examined immunohistochemically for presence and distribution of contractile cells in the mucosal lamina propria. We tested for the presence of alpha-smooth muscle actin, tropomyosin, desmin, smooth muscle myosin (heavy chain) and cytoskeletal proteins vimentin and cytokeratin. Immunostaining for alpha-smooth muscle actin showed two distribution patterns: either positive cells were freely dispersed in the mucosal lamina propria or a distinct subepithelial layer of positive cells was seen. The first distribution pattern was found in the isthmic uterine tube segments of all animals examined. Alpha-smooth muscle actin was colocalized with tropomyosin (all species), desmin (horse, sheep), and smooth muscle myosin (sheep, cow). All these cells were found reactive with anti-vimentin but not with anticytokeratin and therefore were classified as myofibroblasts. A distinct subepithelial layer of alpha-actin and tropomyosin positive cells was seen in horse fimbriae. In other examined species alpha-smooth muscle actin immunoreactivity in the subepithelial region was very weak. Contractile cells in the uterine tube mucosa were supposed to influence mucosal condition and motility, and therefore to play a role in gamete transport. PMID:11315956

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

    PubMed Central

    Symonds, R. P.

    1998-01-01

    Mucositis may be a painful, debilitating, dose-limiting side-effect of both chemotherapy and radiotherapy for which there is no widely accepted prophylaxis or effective treatment. The basis of management is pain relief, prevention of dehydration and adequate nutrition. When tested vigorously, most antiseptic mouthwashes and anti-ulcer agents are ineffective. Simple mechanical cleansing by saline is the most effective traditional measure. A variety of new agents are effective. Granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) act outwith the haemopoeitic system and can reduce mucositis, but the best schedule, dosage and method of administration is not known or which is the best growth factor to prevent this side-effect. A placebo-controlled randomized trial of antibiotic pastilles has shown a significant reduction in mucositis and weight loss during radiotherapy for head and neck cancer. Another method to reduce radiation effects in normal tissue is to stimulate cells to divide before radiotherapy by silver nitrate or interleukin 1. These methods may be particularly effective when given along with hyperfractionated radiation treatment such as CHART. PMID:9635851

  4. 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

  5. Epidemiology of mucosal human papillomavirus infection and associated diseases.

    PubMed

    Trottier, Helen; Burchell, Ann N

    2009-01-01

    This article describes the epidemiology of mucosal human papillomavirs (HPV) in adults and children, its mode of transmission and its associated diseases. Over 40 genotypes of HPV infect the epithelial lining of the anogenital tract and other mucosal areas of the body. HPV is the most common sexually transmitted infection globally, with high prevalences found in both females and males. The predominant route of transmission is via sexual contact, although mother-to-child transmission is also possible. HPV infection may exist asymptomatically or may induce the formation of benign or malignant tumours in the genital, oral or conjunctival mucosa. Although most infections clear spontaneously, those that persist result in substantial morbidity and invoke high costs associated with the treatment of clinically relevant lesions. Some 13-18 mucosal HPV types are considered to have high oncogenic potential. HPV is recognized unequivocally as the main causal factor for cervical cancer, and is further responsible for a substantial proportion of many other anogenital neoplasms and head and neck cancers. Infections with HPV types that have low oncogenic risk, such as HPV-6 and 11, are associated with benign lesions of the anogenital areas known as condylomata acuminata (genital warts), oral papillomas, conjunctival papillomas, as well as low-grade squamous intra-epithelial lesions of the cervix. Perinatally acquired HPV can also cause recurrent respiratory papillomatosis in infants and young children. The implementation of HPV vaccination therefore has the potential to prevent a substantial proportion of HPV-related disease in the future. PMID:19684442

  6. The Effect of Peritoneal Air Exposure on Intestinal Mucosal Barrier

    PubMed Central

    Bao, Jun; Tan, Shanjun; Yu, Wenkui; Lin, Zhiliang; Dong, Yi; Chen, Qiyi; Shi, Jialiang; Duan, Kaipeng; Bai, Xiaowu; Xu, Lin; Li, Jieshou

    2014-01-01

    Background. Damage of the intestinal mucosa barrier may result in intestinal bacterial and endotoxin translocation, leading to local and systemic inflammation. The present study was designed to investigate whether peritoneal air exposure induces damage of intestinal mucosal barrier. Methods. Sprague-Dawley rats (weighing 210 to 230 g) were randomized into five groups (6/group): a control group, a sham group, and three exposure groups with peritoneal air exposure for 1, 2, and 3 h, respectively. At 24 h after surgery, blood and terminal ileum were sampled. The serum D-lactate levels were determined using an ELISA kit. The intestinal permeability was determined by measuring the intestinal clearance of FITC-dextran (FD4). The histopathological changes in terminal ileum were also assessed. Results. Compared with the controls, peritoneal air exposure caused an increase in both serum D-lactate level and intestinal FD4 clearance, which were proportional to the length of peritoneal air exposure and correlated to Chiu's scores, indices for intestinal mucosal injury. Edema and inflammatory cells were also observed in mucosa and submucosa of ileum in three exposure groups. Conclusions. Peritoneal air exposure could induce damage to the intestinal mucosal barrier, which is proportional to the time length of peritoneal air exposure. PMID:25210511

  7. 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. PMID:25414413

  8. Mucosal transmission and pathogenesis of chronic wasting disease in ferrets.

    PubMed

    Perrott, Matthew R; Sigurdson, Christina J; Mason, Gary L; Hoover, Edward A

    2013-02-01

    Chronic wasting disease (CWD) of cervids is almost certainly transmitted by mucosal contact with the causative prion, whether by direct (animal-to-animal) or indirect (environmental) means. Yet the sites and mechanisms of prion entry remain to be further understood. This study sought to extend this understanding by demonstrating that ferrets exposed to CWD via several mucosal routes developed infection, CWD prion protein (PrP(CWD)) amplification in lymphoid tissues, neural invasion and florid transmissible spongiform encephalopathy lesions resembling those in native cervid hosts. The ferrets developed extensive PrP(CWD) accumulation in the nervous system, retina and olfactory epithelium, with lesser deposition in tongue, muscle, salivary gland and the vomeronasal organ. PrP(CWD) accumulation in mucosal sites, including upper respiratory tract epithelium, olfactory epithelium and intestinal Peyer's patches, make the shedding of prions by infected ferrets plausible. It was also observed that regionally targeted exposure of the nasopharyngeal mucosa resulted in an increased attack rate when compared with oral exposure. The latter finding suggests that nasal exposure enhances permissiveness to CWD infection. The ferret model has further potential for investigation of portals for initiation of CWD infection. PMID:23100363

  9. Regional Myocardial Perfusion Rates in Patients with Coronary Artery Disease

    PubMed Central

    Cannon, Paul J.; Dell, Ralph B.; Dwyer, Edward M.

    1972-01-01

    Regional myocardial perfusion rates were estimated from the myocardial washout of 133Xenon in 24 patients with heart disease whose coronary arteriograms were abnormal and 17 similar subjects whose coronary arteriograms were judged to be normal. Disappearance rates of 133Xe from multiple areas of the heart were monitored externally with a multiple-crystal scintillation camera after the isotope had been injected into a coronary artery and local myocardial perfusion rates were calculated by the Kety formula. The mean myocardial perfusion rates in the left ventricle exceeded those in the right ventricle or atrial regions in subjects without demonstrable coronary artery disease. In this group there was a significant lack of homogeneity of local perfusion rates in left ventricular myocardium; the mean coefficient of variation of left ventricular local perfusion rates was 15.8%. In the patients with radiographically demonstrable coronary artery disease, a variety of myocardial perfusion patterns were observed. Local capillary blood flow rates were depressed throughout the myocardium of patients with diffuse coronary disease but were subnormal only in discrete myocardial regions of others with localized occlusive disease. Local myocardial perfusion rates were similar to those found in the group with normal coronary arteriograms in patients with slight degrees of coronary disease and in those areas of myocardium distal to marked coronary constrictions or occlusions which were well supplied by collateral vessels. In subjects with right coronary disease, the mean right ventricular perfusion rates were significantly subnormal; in seven subjects of this group perfusion of the inferior left ventricle by a dominant right coronary artery was absent or depressed. The average mean left ventricular perfusion rate of 12 subjects with significant disease of two or more branches of the left coronary artery was significantly lower than that of the group with normal left coronary

  10. 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

  11. Investigation of Gastroduodenal Mucosal Injury in Japanese Asymptomatic Antiplatelet Drug Users.

    PubMed

    Sogabe, Masahiro; Okahisa, Toshiya; Nakasono, Masahiko; Fujino, Yasuteru; Mitsui, Yasuhiro; Takaoka, Yoshihumi; Kimura, Tetsuo; Okamoto, Koichi; Muguruma, Naoki; Takayama, Tetsuji

    2015-07-01

    Antiplatelet drugs are widely used for the prevention of cardiovascular disease and cerebral vascular disorders. Although there have been several studies on gastroduodenal mucosal injury with gastrointestinal (GI) symptoms such as GI bleeding, in antiplatelet drug users (including low-dose aspirin (LDA)), there have been few reports on the association between antiplatelet drug use and gastroduodenal mucosal injury in asymptomatic antiplatelet drug users. This study was a cross-sectional study elucidating the association between antiplatelet drug use and gastroduodenal mucosal injury in asymptomatic antiplatelet drug users.Subjects were 186 asymptomatic Japanese antiplatelet drug users who underwent a regular health checkup. Subjects were divided into those with and without gastroduodenal mucosal injury endoscopically, and the association between gastroduodenal mucosal injury and other data in asymptomatic antiplatelet drug users was investigated.The prevalence of males and drinkers were significantly higher in subjects with gastroduodenal mucosal injury than in those without. In addition, the prevalence of proton pump inhibitor (PPI) users was significantly lower in subjects with gastroduodenal mucosal injury than in subjects without gastroduodenal mucosal injury. Logistic regression analysis showed PPI (odds ratios: 0.116; 95% confidence intervals: 0.021-0.638; P < 0.05) was a significant predictor of a decreased prevalence of gastroduodenal mucosal injury and closed-type (C-type) atrophy (3.172; 1.322-7.609; P < 0.01) was a significant predictor of an increased prevalence of severe gastroduodenal mucosal injury in asymptomatic antiplatelet drug users.Gender and lifestyle, such as drinking, may have an impact on risk of gastroduodenal mucosal injury in asymptomatic subjects taking antiplatelet drugs. Although PPI is a significant predictor of a decreased prevalence of gastroduodenal mucosal injury, including in asymptomatic antiplatelet drug users, status of

  12. Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture

    PubMed Central

    Huang, Song-Bin; Chou, Dean; Chang, Yu-Han; Li, Ke-Cing; Chiu, Tzu-Keng; Ventikos, Yiannis; Wu, Min-Hsien

    2015-01-01

    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. PMID:26669749

  13. 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.

  14. 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

    2015-01-01

    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. PMID:26669749

  15. 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

  16. IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity.

    PubMed

    Yoshida, Masaru; Masuda, Atsuhiro; Kuo, Timothy T; Kobayashi, Kanna; Claypool, Steven M; Takagawa, Tetsuya; Kutsumi, Hiromu; Azuma, Takeshi; Lencer, Wayne I; Blumberg, Richard S

    2006-12-01

    Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. FcRn, through its ability to secrete and absorb IgG, thus integrates luminal antigen encounters with systemic immune compartments and, as such, provides essential host defense and immunoregulatory functions at the mucosal surfaces. PMID:17051393

  17. 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.

  18. 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.

  19. 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

  20. The effect of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart.

    PubMed

    Khedun, S M; Maharaj, B; Leary, W P; Lockett, C J

    1992-01-01

    This investigation was conducted to determine the influence of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart and myocardial electrolyte levels. Ventricular fibrillation threshold was measured using the Langendorff perfusion apparatus. Heart rate was measured by a universal digital counter and the cardiac flow by collecting the outflow of the heating chamber below the heart into a graduated measuring cylinder. Magnesium and zinc were measured by atomic absorption spectrophotometry and potassium by flame photometry. Two groups of rats were studied; those in the experimental group were given 0.2 ml of hexane and the control group 0.2 ml olive oil subcutaneously for 90 days. Their hearts were removed under anaesthesia. Half of the experimental and control hearts were mounted on the Langendorff perfusion apparatus and the heart rate, coronary flow and ventricular fibrillation threshold were measured. The hearts of the other half were used to measure myocardial electrolyte levels. In the experimental group the ventricular fibrillation threshold decreased (4.72 (S.D. +/- 1.87) vs 9.48 (S.D. +/- 2.98); P less than 0.001). There was no change in the coronary flow and heart rate in between the groups. The mean myocardial potassium levels (2586 (S.D. +/- 162) vs 2968 (S.D. +/- 218) micrograms/g; P less than 0.001), magnesium levels (164 (S.D. +/- 28) vs 208 (S.D. +/- 18) micrograms/g; P less than 0.001) and zinc levels (19.6 (S.D. +/- 4) vs 33.8 (S.D. +/- 6.8) micrograms/g; P less than 0.001) were significantly lower in the hexane-treated group compared to controls. Hexane, a constituent of glue and benzine, is cardiotoxic; marked derangement in myocardial electrolytes and a reduced ventricular fibrillation threshold, indicating an increased myocardial vulnerability to arrhythmias, was noted in the experimental animals. PMID:1729763

  1. Perfusion of isolated organs and the first heart-lung machine.

    PubMed

    Zimmer, H G

    2001-09-01

    In 1885, Max von Frey (1852-1932), while working in Carl Ludwig's Physiological Institute in Leipzig, Germany, designed an apparatus that had criteria characteristic of a heart-lung machine. With this device, he perfused the entire lower extremity of dogs, and took measurements of oxygen consumption, and carbon dioxide and lactate production. In 1935, another type of perfusion apparatus was constructed by Charles A Lindbergh (1902-1973). This device was the result of cooperation with Alexis Carrel (1873-1944) who was a pioneer of experimental organ transplantation. Using Lindbergh's pulsating device, organs such as thyroid, ovary, suprarenal gland, spleen, heart and kidney from fowls and cats were perfused with an oxygenated medium, and were maintained under sterile conditions. Beginning in 1934, John H Gibbon (1903-1973) developed and tested a heart-lung machine to institute cardiopulmonary bypass in cats during experimental occlusion of the pulmonary artery. In 1953, he performed the first successful open-heart operation in a patient using a heart-lung machine. This included elements that were similar to those used by von Frey - ie, the oxygenator and the pumps for continuous circulation of blood. A comparison of the three experimental devices revealed the following: the application for experimental purposes preceded clinical use; the development shifted from Europe to the United States, and was achieved by people who were not specialists; and the intention to build such a device was first purely scientific interest, but later shifted to the care for and treatment of patients with heart and circulatory defects by open-heart surgery. PMID:11586387

  2. 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.

  3. Contact-free monitoring of circulation and perfusion dynamics based on the analysis of thermal imagery

    PubMed Central

    Pereira, Carina Barbosa; Czaplik, Michael; Blanik, Nikolai; Rossaint, Rolf; Blazek, Vladimir; Leonhardt, Steffen

    2014-01-01

    Acute circulatory disorders are commonly associated with systemic inflammatory response (SIRS) and sepsis. During sepsis, microcirculatory perfusion is compromised leading to tissue hypoperfusion and potentially to multiple organ dysfunction. In the present study, acute lung injury (ALI), one of the major causes leading to SIRS and sepsis, was experimentally induced in six female pigs. To investigate the progress of body temperature distribution, measurements with a long-wave infrared camera were carried out. Temperature centralization was evidenced during ALI owing to impairments of peripheral perfusion. In addition, statistical analysis demonstrated strong correlations between (a) standard deviation of the skin temperature distribution (SD) and shock index (SI) (p<0.0005), (b) SD and mean arterial pressure (MAP) (p<0.0005), (c) ΔT/Δx and SI (p<0.0005), as well as between (d) ΔT/Δx and MAP (p<0.0005). For clarification purposes, ΔT/Δx is a parameter implemented to quantify the spatial temperature gradient. This pioneering study created promising results. It demonstrated the capacity of infrared thermography as well as of the indexes, SD and ΔT/Δx, to detect impairments in both circulation and tissue perfusion. PMID:24761290

  4. 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.

  5. 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

  6. Electromechanical activities of human uteri during extra-corporeal perfusion with ovarian steroids.

    PubMed

    Bulletti, C; Prefetto, R A; Bazzocchi, G; Romero, R; Mimmi, P; Polli, V; Lanfranchi, G A; Labate, A M; Flamigni, C

    1993-10-01

    A new experimental system was designed to study human uterine activities based on the extra-corporeal perfusion of isolated human uteri. Electromechanical activities in the uterine wall were recorded using bipolar silver-silver electrodes, endoluminal pressure catheters and a dedicated acquisition, storage and analytical system. The electrical signals recorded were isolated spikes and rhythmic activities; the last being primarily associated with organized mechanical events. Perfusion media containing 17 beta-oestradiol alone or with progesterone were used for those uteri obtained during proliferative (n = 5) or secretory (n = 5) phases of the menstrual cycle, respectively. Progesterone caused a reduction of frequency (P < 0.001) and duration (P < 0.001) of the rhythmic electrical activity, and decreased the endoluminal pressure at both detection sites (P < 0.01). 17 beta-Oestradiol increased both frequency (P < 0.001) and duration (P < 0.001) of the rhythmic electrical activity as well as the endoluminal pressure at two different detection sites (3 and 5 cm from the fundus) (P < 0.05). Significant differences between the fundus and cervix sites in the uterine wall were detected. In conclusion, uterine perfusion would be useful to examine the effects of uterotonic and tocolytic drugs before administration to humans, at no risk to the patients. Oestrogens increase and progesterone decreases both electrical and mechanical uterine activities. PMID:8300807

  7. Ex vivo lung perfusion in Brazil

    PubMed Central

    Abdalla, Luis Gustavo; Braga, Karina Andrighetti de Oliveira; Nepomuceno, Natalia Aparecida; Fernandes, Lucas Matos; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2016-01-01

    Objective: To evaluate the use of ex vivo lung perfusion (EVLP) clinically to prepare donor lungs for transplantation. Methods: A prospective study involving EVLP for the reconditioning of extended-criteria donor lungs, the criteria for which include aspects such as a PaO2/FiO2 ratio < 300 mmHg. Between February of 2013 and February of 2014, the lungs of five donors were submitted to EVLP for up to 4 h each. During EVLP, respiratory mechanics were continuously evaluated. Once every hour during the procedure, samples of the perfusate were collected and the function of the lungs was evaluated. Results: The mean PaO2 of the recovered lungs was 262.9 ± 119.7 mmHg at baseline, compared with 357.0 ± 108.5 mmHg after 3 h of EVLP. The mean oxygenation capacity of the lungs improved slightly over the first 3 h of EVLP-246.1 ± 35.1, 257.9 ± 48.9, and 288.8 ± 120.5 mmHg after 1, 2, and 3 h, respectively-without significant differences among the time points (p = 0.508). The mean static compliance was 63.0 ± 18.7 mmHg, 75.6 ± 25.4 mmHg, and 70.4 ± 28.0 mmHg after 1, 2, and 3 h, respectively, with a significant improvement from hour 1 to hour 2 (p = 0.029) but not from hour 2 to hour 3 (p = 0.059). Pulmonary vascular resistance remained stable during EVLP, with no differences among time points (p = 0.284). Conclusions: Although the lungs evaluated remained under physiological conditions, the EVLP protocol did not effectively improve lung function, thus precluding transplantation. PMID:27167429

  8. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia.

    PubMed

    Dillon, S M; Lee, E J; Kotter, C V; Austin, G L; Dong, Z; Hecht, D K; Gianella, S; Siewe, B; Smith, D M; Landay, A L; Robertson, C E; Frank, D N; Wilson, C C

    2014-07-01

    Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection. PMID:24399150

  9. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia

    PubMed Central

    Dillon, SM; Lee, EJ; Kotter, CV; Austin, GL; Dong, Z; Hecht, DK; Gianella, S; Siewe, B; Smith, DM; Landay, AL; Robertson, CE; Frank, DN; Wilson, CC

    2014-01-01

    HIV-1 infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T cell activation, inflammation and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1 infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared to uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1 infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation and blood T cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection. PMID:24399150

  10. CT Perfusion of the Liver: Principles and Applications in Oncology

    PubMed Central

    Kim, Se Hyung; Kamaya, Aya

    2014-01-01

    With the introduction of molecularly targeted chemotherapeutics, there is an increasing need for defining new response criteria for therapeutic success because use of morphologic imaging alone may not fully assess tumor response. Computed tomographic (CT) perfusion imaging of the liver provides functional information about the microcirculation of normal parenchyma and focal liver lesions and is a promising technique for assessing the efficacy of various anticancer treatments. CT perfusion also shows promising results for diagnosing primary or metastatic tumors, for predicting early response to anticancer treatments, and for monitoring tumor recurrence after therapy. Many of the limitations of early CT perfusion studies performed in the liver, such as limited coverage, motion artifacts, and high radiation dose of CT, are being addressed by recent technical advances. These include a wide area detector with or without volumetric spiral or shuttle modes, motion correction algorithms, and new CT reconstruction technologies such as iterative algorithms. Although several issues related to perfusion imaging—such as paucity of large multicenter trials, limited accessibility of perfusion software, and lack of standardization in methods—remain unsolved, CT perfusion has now reached technical maturity, allowing for its use in assessing tumor vascularity in larger-scale prospective clinical trials. In this review, basic principles, current acquisition protocols, and pharmacokinetic models used for CT perfusion imaging of the liver are described. Various oncologic applications of CT perfusion of the liver are discussed and current challenges, as well as possible solutions, for CT perfusion are presented. © RSNA, 2014 Online supplemental material is available for this article. PMID:25058132

  11. Oral Pseudoephedrine Decreases the Rate of Trans-mucosal Nitrous Oxide Exchange for the Middle Ear

    PubMed Central

    Teixeira, Miriam S.; Alper, Cuneyt M.; Martin, Brian S; Cullen Doyle, Brendan M.; Doyle, William J.

    2015-01-01

    Objective Determine if oral pretreatment with a vasoconstrictor decreases the blood to middle-ear exchange-rate of the perfusion-limited gas, Nitrous Oxide (N2O). Study Design Randomized, double-blind, crossover study. Methods Ten adult subjects with and 10 without past middle-ear disease completed paired experimental sessions, identical but for oral pretreatment with either pseudoephedrine HCL or lactose placebo. At each session, subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes (acclimation period), 50% N2O:50% O2 for 20 minutes (experimental period) and 100% O2 for 10 minutes (recovery period). Throughout, heart-rate, blood-pressure and O2 saturation were monitored and bilateral middle-ear pressures were recorded by tympanometry every minute. The primary outcome was the slope of the middle-ear pressure-time function for the experimental period which estimates the volume N2O exchange-rate. Using repeated measures ANOVA, the effects of Group (disease history), Treatment (active vs. placebo) and Period (1 vs. 2) on the recorded vital signs, and of Group, Treatment and Ear (left/right) on the middle-ear pressure-time slope were evaluated for statistical significance. Results Statistically significant effects of Period on O2 saturation (Period 2>Period 1) and of Treatment on heart-rate (Active>Placebo) were documented. Only Treatment was statistically significant for the middle-ear pressure-time slope with a shallower slope characterizing the active treatment session. Conclusion The volume exchange-rate across the middle-ear mucosa of perfusion-limited gases can be modulated pharmacologically. Theoretically, similar drugs can be used to reduce the requisite Eustachian tube opening efficiency for adequate middle-ear pressure regulation. PMID:26152838

  12. Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

    PubMed Central

    de Meis, Juliana; Barreto de Albuquerque, Juliana; Silva dos Santos, Danielle; Farias-de-Oliveira, Désio Aurélio; Berbert, Luiz Ricardo; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2013-01-01

    Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. PMID:23898334

  13. Ghrelin protects musculocutaneous tissue from ischemic necrosis by improving microvascular perfusion.

    PubMed

    Rezaeian, F; Wettstein, R; Scheuer, C; Bäumker, K; Bächle, A; Vollmar, B; Menger, M D; Harder, Y

    2012-02-01

    Persistent ischemia in musculocutaneous tissue may lead to wound breakdown and necrosis. The objective of this experimental study was to analyze, whether the gastric peptide ghrelin prevents musculocutaneous tissue from necrosis and to elucidate underlying mechanisms. Thirty-two C57BL/6 mice equipped with a dorsal skinfold chamber containing ischemic musculocutaneous tissue were allocated to four groups: 1) ghrelin; 2) N(ω)-nitro-l-arginine methyl ester (l-NAME); 3) ghrelin and l-NAME; and 4) control. Microcirculation, inflammation, angiogenesis, and tissue survival were assessed by fluorescence microscopy. Inducible and endothelial nitric oxide synthase (iNOS I and eNOS), vascular endothelial growth factor (VEGF), as well as nuclear factor κB (NF-κB) were assessed by Western blot analysis. Ghrelin-treated animals showed an increased expression of iNOS and eNOS in critically perfused tissue compared with controls. This was associated with arteriolar dilation, increased arteriolar perfusion, and a sustained functional capillary density. Ghrelin further upregulated NF-κB and VEGF and induced angiogenesis. Finally, ghrelin reduced microvascular leukocyte-endothelial cell interactions, apoptosis, and overall tissue necrosis (P < 0.05 vs. control). Inhibition of nitric oxide by l-NAME did not affect the anti-inflammatory and angiogenic action of ghrelin but completely blunted the ghrelin-induced tissue protection by abrogating the arteriolar dilation, the improved capillary perfusion, and the increased tissue survival. Ghrelin prevents critically perfused tissue from ischemic necrosis. Tissue protection is the result of a nitric oxide synthase-mediated improvement of the microcirculation but not due to induction of angiogenesis or attenuation of inflammation. This might represent a promising, noninvasive, and clinically applicable approach to protect musculocutaneous tissue from ischemia. PMID:22159999

  14. 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) PMID:6661747

  15. 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. PMID:12952126

  16. Perfusion CT imaging of treatment response in oncology.

    PubMed

    Prezzi, Davide; Khan, Aisha; Goh, Vicky

    2015-12-01

    Perfusion CT was first described in the 1970s but has become accepted as a clinical technique in recent years. In oncological practice Perfusion CT allows the downstream effects of therapies on the tumour vasculature to be monitored. From the dynamic changes in tumour and vascular enhancement following intravenous iodinated contrast agent administration, qualitative and quantitative parameters may be derived that reflect tumour perfusion, blood volume, and microcirculatory changes with treatment. This review outlines the mechanisms of action of available therapies and state-of-the-art imaging practice. PMID:25864440

  17. Deep Vein Thrombosis Presenting on Pulmonary Ventilation and Perfusion Scintigraphy.

    PubMed

    Itani, Malak; Fair, Joanna; Hillman, Zachary; Behnia, Fatemeh; Elojeimy, Saeed

    2016-10-01

    A 52-year-old woman presenting with dyspnea was referred for a ventilation and perfusion scan (VQ). VQ images (with Tc-DTPA [diethylene triamine pentaacetic acid aerosol] and Tc-MAA [macroaggregated albumin]) initially appeared normal; however, count rates on perfusion images were similar to ventilation images, implying little Tc-MAA had reached the lungs. Spot images of the injected extremity demonstrated focal Tc-MAA accumulation worrisome for a venous thrombus, subsequently confirmed by Doppler ultrasound. Careful attention to relative radiotracer count rates on VQ scans is crucial to ensure diagnostic utility. In addition, abnormal low perfusion radiotracer counts may unveil other pathology with important clinical implications. PMID:27556796

  18. Prognostic value of normal regadenoson stress perfusion cardiovascular magnetic resonance

    PubMed Central

    2013-01-01

    Background Regadenoson is a vasodilator stress agent that selectively activates the A2A receptor. Compared to adenosine, regadenoson is easier to administer and results in fewer side effects. Although extensively studied in patients undergoing nuclear perfusion imaging (MPI), its use for perfusion cardiovascular magnetic resonance (CMR) is not well described. The aim of this study was to determine the prognostic value of a normal regadenoson perfusion CMR in patients with known or suspected coronary artery disease. Methods Patients with known or suspected coronary artery disease were prospectively enrolled to receive perfusion CMR (Philips 1.5 T) with regadenoson. Three short-axis slices of the left ventricle (LV) were obtained during first pass of contrast using a hybrid GRE-EPI pulse sequence (0.075 mmol/kg Gadolinium-DTPA-BMA at 4 ml/sec). Imaging was performed 1 minute after injection of regadenoson (0.4 mg) and repeated 15 minutes after reversal of hyperemia with aminophylline (125 mg). Perfusion defects were documented if they persisted for ≥2 frames after peak enhancement of the LV cavity. CMR was considered abnormal if there was a resting wall motion abnormality, decreased LVEF (<40%), presence of LGE, or the presence of a perfusion defect during hyperemia. All patients were followed for a minimum of 1 year for major adverse cardiovascular event (MACE) defined as coronary revascularization, non-fatal myocardial infarction, and cardiovascular death. Results 149 patients were included in the final analysis. Perfusion defects were noted in 43/149 (29%) patients; 59/149 (40%) had any abnormality on CMR. During the mean follow-up period of 24 ± 9 months, 17/149 (11.4%) patients experienced MACE. The separation in the survival distributions for those with perfusion defects and those without perfusion defects was highly significant (log-rank p = 0.0001). When the absence of perfusion defects was added to the absence of other resting CMR

  19. Myocardial Perfusion: Characteristics of Distal Intramyocardial Arteriolar Trees.

    PubMed

    Zamir, Mair; Vercnocke, Andrew J; Edwards, Phillip K; Anderson, Jill L; Jorgensen, Steven M; Ritman, Erik L

    2015-11-01

    A combination of experimental, theoretical, and imaging methodologies is used to examine the hierarchical structure and function of intramyocardial arteriolar trees in porcine hearts to provide a window onto a region of myocardial microvasculature which has been difficult to fully explore so far. A total of 66 microvascular trees from 6 isolated myocardial specimens were analyzed, with a cumulative number of 2438 arteriolar branches greater than or equal to 40 μm lumen diameter. The distribution of flow rates within each tree was derived from an assumed power law relationship for that tree between the diameter of vessel segments and flow rates that are consistent with that power law and subject to conservation of mass along hierarchical structure of the tree. The results indicate that the power law index increases at levels of arteriolar vasculature closer to the capillary level, consistent with a concomitant decrease in shear stress acting on endothelial tissue. These results resolve a long standing predicament which could not be resolved previously because of lack of data about the 3D, interconnected, arterioles. In the context of myocardial perfusion, the results indicate that the coefficient of variation of flow rate in pre-capillary distal arterioles is high, suggesting that heterogeneity of flow rate in these arterioles is not entirely random but may be due at least in part to active control. PMID:25952363

  20. Prevention and treatment of oropharyngeal mucositis following cancer therapy: are there new approaches?

    PubMed

    Kwong, Karis K F

    2004-01-01

    Oropharyngeal mucositis is an acute and distressing toxic effect of chemotherapy and head and neck irradiation. This oral sequela significantly impairs the daily functioning and quality of life of patients. The biological basis of mucositis is quite complex, involving sequential interaction of chemotherapeutic drugs or irradiation on mitosis of proliferating epithelium, a number of cytokines, and elements of oral microbial environment. Various interventions based on biological attenuation have been tested for mucositis. Such interventions have been reviewed elsewhere; however, most reviews focus on biomedical outcomes. Little attention has been paid to mucositis outcomes with oral morbidity or psychosocial aspects. The purpose of this article is to review the current research studies on the prevention and treatment of oropharyngeal mucositis following chemotherapy, radiotherapy, and bone marrow transplantation with an emphasis on biomedical, oral symptomatic, and functional impairment outcomes. In addition, further avenues of mucositis management, including psychotherapeutic intervention and integrated and stage-based treatment approaches are discussed. PMID:15238805

  1. EFFECT ON PERFUSION VALUES OF SAMPLING INTERVAL OF CT PERFUSION ACQUISITIONS IN NEUROENDOCRINE LIVER METASTASES AND NORMAL LIVER

    PubMed Central

    Ng, Chaan S.; Hobbs, Brian P.; Wei, Wei; Anderson, Ella F.; Herron, Delise H.; Yao, James C.; Chandler, Adam G.

    2014-01-01

    Objective To assess the effects of sampling interval (SI) of CT perfusion acquisitions on CT perfusion values in normal liver and liver metastases from neuroendocrine tumors. Methods CT perfusion in 16 patients with neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow, blood volume, mean transit time, permeability, and hepatic arterial fraction, for tumor and normal liver. CT perfusion values for the reference sampling interval of 0.5s (SI0.5) were compared with those of SI datasets of 1s, 2s, 3s and 4s, using mixed-effects model analyses. Results Increases in SI beyond 1s were associated with significant and increasing departures of CT perfusion parameters from reference values at SI0.5 (p≤0.0009). CT perfusion values deviated from reference with increasing uncertainty with increasing SIs. Findings for normal liver were concordant. Conclusion Increasing SIs beyond 1s yield significantly different CT perfusion parameter values compared to reference values at SI0.5. PMID:25626401

  2. Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats

    PubMed Central

    Ismail, Iza Farhana; Abdul Majid, Nazia; Kadir, Farkaad A.; Al-Bayaty, Fouad; Awang, Khalijah

    2012-01-01

    Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer. PMID:23365597

  3. 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.

  4. Gastric mucosal injury in systemic lupus erythematosus patients receiving pulse methylprednisolone therapy

    PubMed Central

    Luo, Jiing-Chyuan; Chang, Full-Young; Chen, Tseng-Shing; Ng, Yee-Yung; Lin, Han-Chieh; Lu, Ching-Liang; Chen, Chih-Yen; Lin, Hsiao-Yi; Lee, Shou-Dong

    2009-01-01

    AIMS Whether glucocorticoids induce gastric mucosal injury remains uncertain. We investigated whether very high-dose steroids caused gastric mucosal injury in systemic lupus erythematous (SLE) patients and evaluated the possible risk factors for mucosal injury. METHODS In this prospective paired study, 67 SLE patients who had received pulse methylprednisolone therapy were enrolled. Each patient underwent endoscopic examination and tissue and blood sampling before and after pulse steroid therapy. Mucosal injury was diagnosed if the follow-up injury scale was higher than the initial scale. Examined parameters included Helicobacter pylori infection, cyclooxygenase (COX)-1 and COX-2 activity, and current nonsteroidal anti-inflammatory drug (NSAID) usage including aspirin. RESULTS Eleven (16.4%) of 67 cases who developed gastric mucosal injury after pulse therapy had significantly higher rates of peptic ulcer history, NSAID/aspirin use, lower gastric thromboxane B2 and prostaglandin E2 levels when compared with cases without gastric mucosal injury (P < 0.05). Infection by H. pylori was not a risk factor for gastric mucosal injury. Multivariate logistic regression analysis showed that NSAID/aspirin use was the only risk factor for gastric mucosal injury in these patients (odds ratio 26.99, 95% confidence interval 4.91, 148.57, P < 0.0001). Pulse steroid therapy alone did not induce gastric mucosal injury in fifty SLE patients without taking any NSAID/aspirin. CONCLUSIONS Use of NSAIDs/aspirin, but not H. pylori infection, increases gastric mucosal injury in SLE patients receiving pulse methylprednisolone therapy. Very high-dose steroids de novo seem not to induce gastric mucosal injury in these patients. A larger case-controlled study enrolling a heterogeneous population is needed to clarify the role of glucocorticoids in gastric mucosal injury. PMID:19694746

  5. Mucosal and systemic cellular immune responses induced by Toxoplasma gondii antigens in cyst orally infected mice.

    PubMed Central

    Chardès, T; Velge-Roussel, F; Mevelec, P; Mevelec, M N; Buzoni-Gatel, D; Bout, D

    1993-01-01

    This study was performed to determine the T-cellular immune responses following Toxoplasma gondii oral infection and to assess further toxoplasma antigens on their ability to stimulate in vitro mucosal and systemic T-cell immunity. Parasite-specific cellular immune responses in Peyer's patches (PP), in mesenteric lymph nodes (MLN) and in spleen (SPL) were investigated using a lymphoblastic transformation test following oral infection of mice with strain 76K cysts of T. gondii. An early toxoplasma sonicate-induced mucosal T-cell proliferation occurred in MLN and PP with a peak responsiveness on day 6 post-infection (PI) and rapidly reached background levels on day 7 PI in PP and on day 8 PI in mesenteric lymph nodes. A later splenic cellular blastogenesis was observed from day 28 PI and persisted throughout the experiment (day 91). At the time of T-cell proliferation, FACS analyses revealed a decrease in the relative percentages of CD4+ and CD8+ T cells with a predominance of CD8+ lymphocytes which leads to an inversion of the CD4/CD8 ratios. We found that CBA/J is a high responder mouse strain in the induction of mesenteric and splenic T-lymphocyte blastogenesis compared to the intermediate responder BALB/c and low responder C57BL/6. Toxoplasma gondii antigens SAG1 (30,000 MW) and GRA4 (40,000-41,000 MW), which are known to induce locally IgA antibodies, are shown to stimulate primed mucosal T lymphocytes from CBA/J and BALB/c mice whereas no proliferation was demonstrated with C57BL/6 T cells. 229-242 peptide, derived from the deduced amino acid sequence of GRA4, only induces detectable proliferation of primed-CBA/J T lymphocytes. Following oral experimental infection, the in vitro mesenteric response to a toxoplasma sonicate is dominated by a Th2-type cytokine pattern whereas a predominant Th1 cytokine response is observed in the spleen. Finally, in vitro stimulation of mesenteric T cells with the three defined toxoplasma antigens resulted in secretion of

  6. Factors associated with mucosal pain in patients with partial removable dental prostheses.

    PubMed

    Kumagai, H; Fueki, K; Yoshida-Kohno, E; Wakabayashi, N

    2016-09-01

    The aim of this study was to investigate factors associated with mucosal pain in patients with partial removable dental prostheses (PRDPs). In this hospital-based cross-sectional study, 333 patients wearing 500 PRDPs (mean age 71·4 years, men 33·3%) were consecutively recruited from prosthetic clinic of a dental hospital in Japan. Subjects rated pain intensity and frequency of denture-bearing mucosa. An examiner recorded age, gender and systemic diseases as well as dental, mucosa, denture, sensory, behavioural- and psychological-related characteristics that were possibly associated with the mucosal pain. Multivariate analyses were performed to analyse factors related to mucosal pain. Pain intensity was rated as more than score 0 (presence) in 34·2% (171/500) PRDPs, and pain was experienced after denture delivery in 42·8% (214/500) PRDPs. Logistic regression analyses showed that younger age, mucosal damage, poor mucosal condition, bone prominence, poor residual ridge, higher pain sensitivity, presence of awake bruxism, perception of oral dryness, interim denture wear and high number of missing teeth were significant independent predictors for the presence of the mucosal pain intensity and/or frequency (P < 0·05). Multiple factors are associated with mucosal pain in patients with PRDPs. Oral mucosal characteristics, age, pain sensitivity and behavioural factors seem to be more critical for mucosal pain than distribution of missing teeth and number of abutment teeth. PMID:27289212

  7. Mucositis in head and neck cancer: economic and quality-of-life outcomes.

    PubMed

    Peterman, A; Cella, D; Glandon, G; Dobrez, D; Yount, S

    2001-01-01

    Outcomes research typically assesses three major health care outcomes, including quantity of life, quality of life (QOL), and health care cost. This article highlights the impact of treatment-associated mucositis on health care costs and QOL. After a background description of the economic analyses of overall cancer treatment costs and of the incremental costs associated with other treatment side effects, data from a retrospective study of mucositis-specific costs are presented. The second half of this article reviews current knowledge about the effect that mucositis has on QOL. Because the empirical work that specifically evaluates mucositis and QOL is quite limited, studies examining proxies for mucositis grading are described. These include studies comparing the QOL of patients currently undergoing treatment, in which symptoms likely to be associated with mucositis are worse, with that of patients who have completed treatment. Also discussed are investigations examining both the relationship between specific mucositis-associated symptoms, such as pain and difficulty swallowing, and QOL and the weighting of different domains of mucositis-associated problems. Finally, several future research directions are suggested, with the intent of expanding knowledge about the economic and QOL impact of mucositis in patients treated for head and neck cancer. PMID:11694566

  8. Augmentation of the gastric mucosal defense mechanism induced by KW-5805, a novel antiulcer agent.

    PubMed

    Tanaka, H; Kosaka, N; Tomaru, A; Shuto, K; Ogihara, T; Sato, N

    1989-01-01

    KW-5805 (a new antiulcer agent), given p. o. at 30 mg/kg to rats, significantly increased the amount of gastric adherent mucus and mucosal glycoproteins. Gastric mucosal glucosamine synthetase activity was significantly enhanced by KW-5805 (30 mg/kg, p. o.). KW-5805 (10, 30 mg/kg, p. o.) significantly suppressed the decrease of gastric mucosal blood volume and oxygen sufficiency induced by hemorrhagic shock. The agent also significantly inhibited the extravasation of Evans blue into the gastric mucosa after ischemia-reinfusion. In conclusion, KW-5805 increased biosynthesis, storage and secretion of gastric mucus and improved the gastric mucosal hemodynamics. PMID:2595291

  9. Evaluation of topical external medicine for 5-fluorouracil-induced oral mucositis in hamsters.

    PubMed

    Mitsuhashi, Hiromi; Suemaru, Katsuya; Li, Bingjin; Cui, Ranji; Araki, Hiroaki

    2006-12-01

    Oral ulcerative mucositis is a common and painful toxicity associated with chemotherapy for cancer. Current treatment for chemotherapy-induced oral mucositis is largely palliative, and no adequate treatment with conclusive evidence exists. The purpose of this study was to evaluate the potential effectiveness of the topical external medicines used in clinical settings, and the authors investigated the effects of 1% azulene ointment, 0.12% dexamethasone ointment, and polaprezinc-sodium alginate suspension on an animal model for oral mucositis induced by chemotherapy. Oral mucositis was induced in hamsters through a combination treatment of 5-fluorouracil and mild abrasion of the cheek pouch. Each drug was administered topically to the oral mucosa of hamsters, and the process of healing of damaged oral mucositis was examined by measuring the size of the mucositis. Azulene ointment did not reduce the size of the mucositis compared with the vaseline-treated control group. Polaprezinc-sodium alginate suspension significantly improved the recovery from 5-fluorouracil-induced damage. In contrast, local treatment with dexamethasone exacerbated the mucositis markedly. These results suggested the healing effect of polaprezinc-sodium alginate suspension and the risk of steroids to severe oral mucositis induced by chemotherapy. PMID:17046745

  10. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment.

    PubMed

    Köstler, W J; Hejna, M; Wenzel, C; Zielinski, C C

    2001-01-01

    Chemotherapy- and radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay the treatment plan, as well as increase therapeutic expenses. The pathogenesis of this debilitating side effect can be attributed to the direct mucosal toxicity of cytotoxic agents and ionizing radiation and to indirect mucosal damage caused by a concomitant inflammatory reaction exacerbated in the presence of neutropenia, and the emergence of bacterial, mycotic, and viral infections. The prophylactic and therapeutic armamentarium for the treatment of oral mucositis consists of locally and systemically applied nonpharmacological measures and pharmacotherapeutics. PMID:11577493

  11. 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

  12. [Evolving therapeutic targets in inflammatory Bowel Disease: mucosal healing as an emerging end point].

    PubMed

    Condino, Giovanna; Margagnoni, Giovanna; Aratari, Annalisa; Luchetti, Roberto; Papi, Claudio

    2015-11-01

    In the last years the therapeutic goals of inflammatory bowel disease have changed from control of symptoms only towards long term strategies aimed at modifying the natural history of the disease. In this setting mucosal healing has emerged as an important therapeutic goal both in clinical trials and in clinical practice. Growing evidence suggests that mucosal healing may be associated with lower relapse rates, reduced hospitalizations and reduced need of surgery both in ulcerative colitis and in Crohn's disease. However, a validated definition of mucosal healing is lacking: as a consequence, although several drugs are capable of inducing and maintaining mucosal healing in different clinical settings, the effect size of different treatments is difficult to assess. One of the most important question for clinical practice is if we should systematically assess mucosal healing in all patients and target our treatment strategies to achieve mucosal healing. This review focuses on the definition of mucosal healing and on the ability of different medications to induce and maintain mucosal healing in inflammatory bowel disease. The significance of mucosal healing as a surrogate end point of disease outcome is also discussed. PMID:26668042

  13. Spatial distribution of ventilation and perfusion: mechanisms and regulation.

    PubMed

    Glenny, Robb W; Robertson, H Thomas

    2011-01-01

    With increasing spatial resolution of regional ventilation and perfusion, it has become more apparent that ventilation and blood flow are quite heterogeneous in the lung. A number of mechanisms contribute to this regional variability, including hydrostatic gradients, pleural pressure gradients, lung compressibility, and the geometry of the airway and vascular trees. Despite this marked heterogeneity in both ventilation and perfusion, efficient gas exchange is possible through the close regional matching of the two. Passive mechanisms, such as the shared effect of gravity and the matched branching of vascular and airway trees, create efficient gas exchange through the strong correlation between ventilation and perfusion. Active mechanisms that match local ventilation and perfusion play little if no role in the normal healthy lung but are important under pathologic conditions. PMID:23737178

  14. 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...

  15. Pulmonary ventilation and perfusion studies in lung cancer

    SciTech Connect

    Narabayashi, I.; Otsuka, N.

    1984-02-01

    In 46 patients with bronchogenic carcinoma, the diagnostic significance of pulmonary ventilation images by the continuous inhalation of Kr-81m gas, which has an extremely short half life, was studied in comparison with pulmonary perfusion images with Tc-99m MAA. The data were processed using digital analysis techniques. There were 15 cases with discrepancies between ventilation and perfusion. The V/Q ratios of the affected lung among the 43 patients showed values above 1.2 in nine cases and below 0.8 in six cases. The Kr-81m ventilation and Tc-99m perfusion images were compared before and after radiation therapy in eight patients. It was possible to assess the therapeutic effect on regional ventilation and regional perfusion, which could not be evaluated by chest x-ray alone, under the same conditions of normal breathing.

  16. Arterial Perfusion Imaging–Defined Subvolume of Intrahepatic Cancer

    SciTech Connect

    Wang, Hesheng; Farjam, Reza; Feng, Mary; Hussain, Hero; Ten Haken, Randall K.; Lawrence, Theodore S.; Cao, Yue

    2014-05-01

    Purpose: To assess whether an increase in a subvolume of intrahepatic tumor with elevated arterial perfusion during radiation therapy (RT) predicts tumor progression after RT. Methods and Materials: Twenty patients with unresectable intrahepatic cancers undergoing RT were enrolled in a prospective, institutional review board–approved study. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed before RT (pre-RT), after delivering ∼60% of the planned dose (mid-RT) and 1 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 to 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 compared with the responsive tumors (P=.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% to 65%), whereas the progressive tumors had an increase of the subvolumes (median, 57%; range, −7% to 165%) (P=.003). Receiver operating characteristic analysis of the percentage change in the subvolume for predicting tumor progression post-RT had an area under the curve 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

  17. 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

  18. Mucosal barrier, bacteria and inflammatory bowel disease: possibilities for therapy.

    PubMed

    Merga, Yvette; Campbell, Barry J; Rhodes, Jonathan M

    2014-01-01

    The mucosal barrier has three major components, the mucus layer, the epithelial glycocalyx and the surface epithelium itself, whose integrity largely depends on tight junction function. In health, there is relatively little direct interaction between the luminal microbiota and the epithelium - the continuous mucus layer in the colon keeps the surface epithelium out of contact with bacteria and the ileo-caecal valve ensures that the distal small intestine is relatively microbe free. Most interaction takes place at the Peyer's patches in the distal ileum and their smaller colonic equivalents, the lymphoid follicles. Peyer's patches are overlain by a 'dome' epithelium, 5% of whose cells are specialised M (microfold) epithelial cells, which act as the major portal of entry for bacteria. There are no goblet cells in the dome epithelium and M cells have a very sparse glycocalyx allowing easy microbial interaction. It is intriguing that the typical age range for the onset of Crohn's disease (CD) is similar to the age at which the number of Peyer's patches is greatest. Peyer's patches are commonly the sites of the initial lesions in CD and the 'anti-pancreatic' antibody associated with CD has been shown to have as its epitope the glycoprotein 2 that is the receptor for type-1 bacterial fimbrial protein (fimH) on M cells. There are many reasons to believe that the mucosal barrier is critically important in the pathogenesis of inflammatory bowel disease (IBD). These include (i) associations between both CD and ulcerative colitis (UC) with genes that are relevant to the mucosal barrier; (ii) increased intestinal permeability in unaffected relatives of CD patients; (iii) increased immune reactivity against bacterial antigens, and (iv) animal models in which altered mucosal barrier, e.g. denudation of the mucus layer associated with oral dextran sulphate in rodents, induces colitis. Whilst some IBD patients may have genetic factors leading to weakening of the mucosal barrier

  19. A perfusion chamber for physiological studies with acutely dissociated neurons.

    PubMed

    Wonderlin, W F; Weinreich, D

    1987-11-01

    We describe a recording chamber that immobilizes acutely dissociated neurons on an ultra-fine mesh grid positioned above a moving stream of perfusate. This chamber is easily fabricated and has two attributes for single-electrode voltage-clamp or patch-clamp recording: (1) shallow immersion (less than 20 micron) of the neurons, and (2) stable recording with rapid perfusion rates. PMID:3695568

  20. Perfusion of nonventilated lung: failure of hypoxic vasoconstriction

    SciTech Connect

    Sostman, H.D.; Neumann, R.D.; Gottschalk, A.; Greenspan, R.H.

    1983-07-01

    Alveolar hypoxia is a well established cause of regional vasoconstriction such that nonventilated segments are not perfused. The paradoxical situation of retained perfusion of nonventilated lung has seldom been discussed. Three clinical examples are illustrated. In each case coexistent chronic obstructive lung disease may have contributed to this unexpected finding by reducing pulmonary vascular capacity such that blood flow diversion from hypoxic segments was not possible.

  1. Evaluation of Microvascular Perfusion and Resuscitation after Severe Injury.

    PubMed

    Lee, Yann-Leei L; Simmons, Jon D; Gillespie, Mark N; Alvarez, Diego F; Gonzalez, Richard P; Brevard, Sidney B; Frotan, Mohammad A; Schneider, Andrew M; Richards, William O

    2015-12-01

    Achieving adequate perfusion is a key goal of treatment in severe trauma; however, tissue perfusion has classically been measured by indirect means. Direct visualization of capillary flow has been applied in sepsis, but application of this technology to the trauma population has been limited. The purpose of this investigation was to compare the efficacy of standard indirect measures of perfusion to direct imaging of the sublingual microcirculatory flow during trauma resuscitation. Patients with injury severity scores >15 were serially examined using a handheld sidestream dark-field video microscope. In addition, measurements were also made from healthy volunteers. The De Backer score, a morphometric capillary density score, and total vessel density (TVD) as cumulative vessel area within the image, were calculated using Automated Vascular Analysis (AVA3.0) software. These indices were compared against clinical and laboratory parameters of organ function and systemic metabolic status as well as mortality. Twenty severely injured patients had lower TVD (X = 14.6 ± 0.22 vs 17.66 ± 0.51) and De Backer scores (X = 9.62 ± 0.16 vs 11.55 ± 0.37) compared with healthy controls. These scores best correlated with serum lactate (TVD R(2) = 0.525, De Backer R(2) = 0.576, P < 0.05). Mean arterial pressure, heart rate, oxygen saturation, pH, bicarbonate, base deficit, hematocrit, and coagulation parameters correlated poorly with both TVD and De Backer score. Direct measurement of sublingual microvascular perfusion is technically feasible in trauma patients, and seems to provide real-time assessment of microcirculatory perfusion. This study suggests that in severe trauma, many indirect measurements of perfusion do not correlate with microvascular perfusion. However, visualized perfusion deficiencies do reflect a shift toward anaerobic metabolism. PMID:26736167

  2. Simulation in perfusion: where do we go from here?

    PubMed

    Fernandez, Adam

    2010-01-01

    Simulation is a common training modality used in aviation, the nuclear industry and by many medical specialties. The adoption of simulation by introductory perfusion education for beginning students and continuing medical education by cardiovascular perfusion has not kept pace with other fields and this paper explores issues connected with simulation in other professions, including training as it currently exists, access to simulator technology, and what could be achieved by utilizing simulator technology. PMID:20159937

  3. Sodium influxes in internally perfused squid giant axon during voltage clamp.

    PubMed

    Atwater, I; Bezanilla, F; Rojas, E

    1969-05-01

    1. An experimental method for measuring ionic influxes during voltage clamp in the giant axon of Dosidicus is described; the technique combines intracellular perfusion with a method for controlling membrane potential.2. Sodium influx determinations were carried out while applying rectangular pulses of membrane depolarization. The ratio ;measured sodium influx/computed ionic flux during the early current' is 0.92 +/- 0.12.3. Plots of measured sodium influx and computed ionic flux during the early current against membrane potential are very similar. There was evidence that the membrane potential at which the sodium influx vanishes is the potential at which the early current reverses. PMID:5767887

  4. Isolation and characterization of a mucosal triacylglycerol pool undergoing hydrolysis

    SciTech Connect

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

    1989-12-01

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

  5. Organ culture of mucosal biopsies of human small intestine.

    PubMed

    Browning, T H; Trier, J S

    1969-08-01

    In vitro experiments of small intestinal mucosal function and metabolism utilizing excised tissue have been limited to a few hours by rapid epithelial cell necrosis which occurs with current incubation methods. We describe a method for culturing human mucosal biopsies for up to 24 hr employing organ culture methodology and demonstrate its potential application to studies of mucosal function. Peroral biopsies were placed in organ culture plates and maintained with modified Trowell's medium in 95% O(2)-5% CO(2) at 37 degrees C for 6-24 hr. To study cell proliferation, 2 muc of thymidine-(3)H was added per ml of medium. To study fat absorption, biopsies were exposed to micellar solutions of linolenic acid, monoolein, and taurodeoxycholate in Krebs-Ringer buffer for 15 min after culture in vitro for 24 hr. After 24 hr of culture, villi were shorter and wider. Cells in the lamina were reduced in number. Light and electron microscopic morphology of epithelial cells compared favorably to those of control biopsies except in occasional areas of partial necrosis. Some absorptive cells were more cuboidal and contained more lysosomes; many appeared entirely normal. Most crypt cells appeared normal; some contained increased glycogen and lysosomes. Mitoses were present, and labeled cells were abundant in crypts of biopsies after 6 hr of incubation with thymidine-(3)H-containing medium. By 24 hr. labeled cells migrated to the base of the villi. When biopsies cultured in vitro were subsequently exposed to micellar lipid, numerous lipid droplets were identified in the cytoplasm of absorptive cells. Thus, after 24 hr in vitro under these culture conditions, many human small intestinal epithelial cells maintain near normal morphology, epithelial cell proliferation proceeds, and fat absorption occurs. PMID:5796354

  6. 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. PMID:12405726

  7. Impact of Mucosal Inflammation on Oral Simian Immunodeficiency Virus Transmission

    PubMed Central

    Chen, Hui-Ling; Hodara, Vida L.; Chu, Lianrui; Parodi, Laura M.; Smith, Lisa M.; Sexton, Valerie; Cappelli, David; Sodora, Donald L.

    2013-01-01

    Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus (HIV). There is epidemiological evidence that genital mucosal inflammation leads to enhanced HIV type 1 (HIV-1) transmission. The objective of this study was to assess the influence of periodontal inflammation on oral HIV transmission using a nonhuman primate model of teeth ligature-induced periodontitis. Simian immunodeficiency virus (SIV) was nontraumatically applied to the gingiva after moderate gingivitis was identified through clinical and immunologic analyses (presence of inflammatory cytokines). Overall oral SIV infection rates were similar in the gingivitis-induced and control groups (5 infections following 12 SIV administrations for each), although more macaques were infected with multiple viral variants in the gingivitis group. SIV infection also affected the levels of antiviral and inflammatory cytokines in the gingival crevicular fluid, and a synergistic effect was observed, with alpha interferon and interferon-inducible protein 10 undergoing significant elevations following SIV infection in macaques with gingivitis compared to controls. These increases in antiviral and inflammatory immune modulators in the SIV-infected gingivitis macaques could also be observed in blood plasma, although the effects at both compartments were generally restricted to the acute phase of the infection. In conclusion, while moderate gingivitis was not associated with increased susceptibility to oral SIV infection, it resulted in elevated levels of cytokines in the oral mucosa and plasma of the SIV-infected macaques. These findings suggest a synergy between mucosal inflammation and SIV infection, creating an immune milieu that impacts the early stages of the SIV infection with potential implications for long-term pathogenesis. PMID:23175379

  8. 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. PMID:22461027

  9. 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

  10. 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

  11. Mucosal healing in inflammatory bowel diseases: is there a place for nutritional supplementation?

    PubMed

    Lan, Annaïg; Blachier, François; Benamouzig, Robert; Beaumont, Martin; Barrat, Christophe; Coelho, Desire; Lancha, Antonio; Kong, Xiangfeng; Yin, Yulong; Marie, Jean-Claude; Tomé, Daniel

    2015-01-01

    Advanced mucosal healing (MH) after intestinal mucosal inflammation coincides with sustained clinical remission and reduced rates of hospitalization and surgical resection, explaining why MH is increasingly considered as a full therapeutic goal and as an endpoint for clinical trials. Intestinal MH is a complex phenomenon viewed as a succession of steps necessary to restore tissue structure and function. These steps include epithelial cell migration and proliferation, cell differentiation, restoration of epithelial barrier functions, and modulation of cell apoptosis. Few clinical studies have evaluated the needs for specific macronutrients and micronutrients and their effects on intestinal MH, most data having been obtained from animal and cell studies. These data suggest that supplementation with specific amino acids including arginine, glutamine, glutamate, threonine, methionine, serine, proline, and the amino acid-derived compounds, polyamines can favorably influence MH. Short-chain fatty acids, which are produced by the microbiota from undigested polysaccharides and protein-derived amino acids, also exert beneficial effects on the process of intestinal MH in experimental models. Regarding supplementation with lipids, although the effects of ω-3 and ω-6 fatty acids remain controversial, endogenous prostaglandin synthesis seems to be necessary for MH. Finally, among micronutrients, several vitamin and mineral deficiencies with different frequencies have been observed in patients with inflammatory bowel diseases and supplementation with some of them (vitamin A, vitamin D3, vitamin C, and zinc) are presumed to favor MH. Future work, including clinical studies, should evaluate the efficiency of supplementation with combination of dietary compounds as adjuvant nutritional intervention for MH of the inflamed intestinal mucosa. PMID:25208104

  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. Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

    PubMed

    Lee, I-C; Baek, H-S; Kim, S-H; Moon, C; Park, S-H; Kim, S-H; Shin, I-S; Park, S-C; Kim, J-C

    2015-03-01

    This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities. PMID:24972622

  14. Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease.

    PubMed

    Kruidenier, Laurens; Kuiper, Ineke; Van Duijn, Wim; Mieremet-Ooms, Marij A C; van Hogezand, Ruud A; Lamers, Cornelis B H W; Verspaget, Hein W

    2003-09-01

    Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non-inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up-regulation of Mn-SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM-mediated damage, these changes should be coordinately counterbalanced by an increased H(2)O(2)-neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H(2)O(2)-related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H(2)O(2)-metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H(2)O(2)-mediated damage seemed to be restrained by the increasing numbers of CAT- and MPO-positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro-inflammatory effects. In the epithelium, the number of

  15. Systemic and Mucosal Immune Responses to Cryptosporidium—Vaccine Development

    PubMed Central

    Ludington, Jacob G.; Ward, Honorine D.

    2015-01-01

    Cryptosporidium spp is a major cause of diarrheal disease worldwide, particularly in malnourished children and untreated AIDS patients in developing countries in whom it can cause severe, chronic and debilitating disease. Unfortunately, there is no consistently effective drug for these vulnerable populations and no vaccine, partly due to a limited understanding of both the parasite and the host immune response. In this review, we will discuss our current understanding of the systemic and mucosal immune responses to Cryptosporidium infection, discuss the feasibility of developing a Cryptosporidium vaccine and evaluate recent advances in Cryptosporidium vaccine development strategies PMID:26279971

  16. Familial occurrence of congenital incomplete prepyloric mucosal diaphragm.

    PubMed Central

    Gahukamble, D B

    1998-01-01

    Incomplete prepyloric mucosal diaphragm (IPMD) is an uncommon congenital anomaly that leads to gastric outlet obstruction in infancy and childhood. This report describes the occurrence of IPMD in six children in a closely knit tribal family from a geographically isolated desert town with a small population in the Sahara. Their records showed similarities of clinical, radiological, operative, and histopathological features. These features, as well as its occurrence in brothers, sisters, and cousins, suggest that this unusual anomaly is transmitted as an autosomal recessive trait. Images PMID:9863605

  17. Transepithelial transport of glutathione in isolated perfused small intestine

    SciTech Connect

    Hagen, T.M.; Jones, D.P.

    1986-03-01

    Uptake of GSH was studied in isolated perfused segment of jejunum in the adult rat. Krebs-Henseleit buffer was infused through the superior mesenteric artery and fractions were collected from the portal vein. The maintenance of vascular and epithelial integrity was established by lack of transfer of /sup 14/C-inulin or /sup 14/C-polyethylene glycol from the lumen to the perfusate. (glycine-2-/sup 3/H)GSH was introduced in the lumen and perfusate fractions collected every min. With 1 mM GSH and 10 mM Gly in the lumen, transport into the perfusate was 220 nmol/min. Analysis by HPLC showed that 80% was at the intact tripeptide, GSH. No cysteinylgylcine was detected in the perfusate. Pretreatment of the segment with 0.25 mM acivicin and 1 mM buthionine sulfoximine had no significant effect on GSH transport rate, thus showing that degradation and resynthesis of GSH did not contribute to the appearance of GSH in the perfusate. GSH transport was inhibited 50% by replacing lumenal NaCl with choline Cl. Addition of 10 mM ..gamma..-Clu-Glu or 10 mM ophthalmic acid decreased the rat of transport by 60-70%. These results establish that transepithelial transport of intact GSH occurs in rat small intestine. This may allow utilization of dietary GSH or reutilization of biliary GSH. In addition, the results suggest that oral GSH may be of therapeutic benefit.

  18. A pump-free membrane-controlled perfusion microfluidic platform.

    PubMed

    Goral, Vasiliy N; Tran, Elizabeth; Yuen, Po Ki

    2015-09-01

    In this article, we present a microfluidic platform for passive fluid pumping for pump-free perfusion cell culture, cell-based assay, and chemical applications. By adapting the passive membrane-controlled pumping principle from the previously developed perfusion microplate, which utilizes a combination of hydrostatic pressure generated by different liquid levels in the wells and fluid wicking through narrow strips of a porous membrane connecting the wells to generate fluid flow, a series of pump-free membrane-controlled perfusion microfluidic devices was developed and their use for pump-free perfusion cell culture and cell-based assays was demonstrated. Each pump-free membrane-controlled perfusion microfluidic device comprises at least three basic components: an open well for generating fluid flow, a micron-sized deep chamber/channel for cell culture or for fluid connection, and a wettable porous membrane for controlling the fluid flow. Each component is fluidically connected either by the porous membrane or by the micron-sized deep chamber/channel. By adapting and incorporating the passive membrane-controlled pumping principle into microfluidic devices, all the benefits of microfluidic technologies, such as small sample volumes, fast and efficient fluid exchanges, and fluid properties at the micro-scale, can be fully taken advantage of with this pump-free membrane-controlled perfusion microfluidic platform. PMID:26392835

  19. Integrating evidence-based perfusion into practices: the International Consortium for Evidence-Based Perfusion.

    PubMed

    Likosky, Donald S

    2006-12-01

    There is surmounting pressure for clinicians domestically and abroad not only to practice evidence-based perfusion, but also to supplement practice with documentation thereof. In this editorial, I shall describe an international initiative aimed at embracing this dictum from patients, regulatory bodies, and payers. "Research is the only hope that the future will be different than the past"- Daniel Mintz, MD "Practical men who believe themselves to be quite exempt from any intellectual influences are usually the slaves of some defunct economist.... It is ideas not vested interests which are dangerous for good or evil."-John Maynard Keynes. PMID:17312899

  20. Integrating Evidence-Based Perfusion Into Practices: The International Consortium for Evidence-Based Perfusion

    PubMed Central

    Likosky, Donald S.

    2006-01-01

    Abstract: There is surmounting pressure for clinicians domestically and abroad not only to practice evidence-based perfusion, but also to supplement practice with documentation thereof. In this editorial, I shall describe an international initiative aimed at embracing this dictum from patients, regulatory bodies, and payers. “Research is the only hope that the future will be different than the past”—Daniel Mintz, MD “Practical men who believe themselves to be quite exempt from any intellectual influences are usually the slaves of some defunct economist…. It is ideas not vested interests which are dangerous for good or evil.”—John Maynard Keynes PMID:17312899

  1. Perfusion Angiography in Acute Ischemic Stroke.

    PubMed

    Scalzo, Fabien; 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 T max, 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

  2. 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

  3. Myocardial perfusion echocardiography and coronary microvascular dysfunction.

    PubMed

    Barletta, Giuseppe; Del Bene, Maria Riccarda

    2015-12-26

    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. 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

  6. In Vitro Perfused Human Capillary Networks

    PubMed Central

    Moya, Monica L.; Hsu, Yu-Hsiang; Lee, Abraham P.; Hughes, Christopher C.W.

    2013-01-01

    Replicating in vitro the complex in vivo tissue microenvironment has the potential to transform our approach to medicine and also our understanding of biology. In order to accurately model the 3D arrangement and interaction of cells and extracellular matrix, new microphysiological systems must include a vascular supply. The vasculature not only provides the necessary convective transport of oxygen, nutrients, and waste in 3D culture, but also couples and integrates the responses of organ systems. Here we combine tissue engineering and microfluidic technology to create an in vitro 3D metabolically active stroma (∼1 mm3) that, for the first time, contains a perfused, living, dynamic, interconnected human capillary network. The range of flow rate (μm/s) and shear rate (s−1) within the network was 0–4000 and 0–1000, respectively, and thus included the normal physiological range. Infusion of FITC dextran demonstrated microvessels (15–50 μm) to be largely impermeable to 70 kDa. Our high-throughput biology-directed platform has the potential to impact a broad range of fields that intersect with the microcirculation, including tumor metastasis, drug discovery, vascular disease, and environmental chemical toxicity. PMID:23320912

  7. The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis

    PubMed Central

    van Vliet, Michel J.; Harmsen, Hermie J. M.; de Bont, Eveline S. J. M.; Tissing, Wim J. E.

    2010-01-01

    Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, thereby promoting bacterial translocation. According to this five-phase model, the intestinal microbiota plays no role in the pathophysiology of mucositis. However, research has implicated a prominent role for the commensal intestinal microbiota in the development of several inflammatory diseases like inflammatory bowel disease, pouchitis, and radiotherapy-induced diarrhea. Furthermore, chemotherapeutics have a detrimental effect on the intestinal microbial composition (strongly decreasing the numbers of anaerobic bacteria), coinciding in time with the development of chemotherapy-induced mucositis. We hypothesize that the commensal intestinal microbiota might play a pivotal role in chemotherapy-induced mucositis. In this review, we propose and discuss five pathways in the development of mucositis that are potentially influenced by the commensal intestinal microbiota: 1) the inflammatory process and oxidative stress, 2) intestinal permeability, 3) the composition of the mucus layer, 4) the resistance to harmful stimuli and epithelial repair mechanisms, and 5) the activation and release of immune effector molecules. Via these pathways, the commensal intestinal microbiota might influence all phases in the Sonis model of the pathogenesis of mucositis. Further research is needed to show the clinical relevance of restoring dysbiosis, thereby possibly decreasing the degree of intestinal mucositis. PMID:20523891

  8. Craniofacial mucosal immune system: importance of its unique organogenesis and function in the development of a mucosal vaccine.

    PubMed

    Okada, Kazunari; Yamasoba, Tatsuya; Kiyono, Hiroshi

    2011-01-01

    Mucosa-associated lymphoid tissues (MALT) play a critical role as inductive sites for the initiation of antigen-specific protective immunity against pathogens penetrating the mucus membranes. Nasopharynx-associated lymphoid tissue (NALT), situated at the bottom of the rodent nasal cavity, is thought to be an important site for the induction of antigen-specific immune response to inhaled antigens. In addition, we have recently shown that tear duct-associated lymphoid tissue (TALT), present in the murine tear duct bridging the ocular and nasal cavities, is involved in the induction and regulation of both nasal and ocular immunity. Interestingly, cellular requirements for the organogenesis of NALT and TALT are quite different from those of other MALT (e.g. Peyer's patches; PPs) and peripheral lymphoid tissues. Moreover, mucosal imprinting molecules of NALT and TALT inducer cells are totally independent of currently known chemokines and adhesion molecules in PPs and lymph nodes, such as the CXCR5-CXCL13, α4β1 integrin-vascular cell adhesion molecule-1 (VCAM1), and CCR9-CCL25 axes. NALT and TALT lymphocytes are also independent of these tissue-specific migration molecules. Together with already-characterized conjunctiva-associated lymphoid tissue (CALT ), which has been demonstrated to play a critical role in ocular defense, the MALT associated with the head region seems to be coordinately organizing the unique craniofacial mucosal immune system of the ocular, nasal, oral-pharynx mucus membranes. Clarification of the immunological network of this unique craniofacial immune system will facilitate the development of a safe and effective mucosal vaccine against respiratory and ocular infections. PMID:21865684

  9. 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

  10. [Extended hypothermic heart-lung preservation system for cardiopulmonary preservation with retrograde coronary sinus perfusion and lung immersion].

    PubMed

    Senoo, Y; Bando, K; Tago, M; Seno, S; Teraoka, H; Teramoto, S

    1990-09-01

    One major restriction of clinical heart-lung transplantation has been the inability to provide extended hypothermic organ preservation. We examined whether core-cooling, retrograde heart perfusion and lung immersion could provide adequate cardiopulmonary preservation. Hence, donor dogs were placed on cardiopulmonary bypass, and rapidly cooled to 15 degrees C. Then heterotopic heart unilateral left lung transplantations were performed. In control group I (n = 5), hearts and lungs were harvested following core-cooling and cardioplegic arrest, and transplanted immediately. In experimental group II (n = 5), heart-lung blocks were similarly excised but stored at 4 degrees C for 12 hours and then transplanted. During preservation, the lungs were immersed in the extracellular solution. For the heart, non-recirculating retrograde coronary sinus perfusion was performed with oxygenated intracellular solution containing perfluorochemicals. Myocardial function determined by the ratio of end-systolic pressure to end-systolic dimension in the experimental group was similar to that in controls. Although pulmonary vascular resistance and extravascular lung water of the experimental group was higher than those in control group, arterial oxygenation was similar in both groups. Thus, extended heart-lung preservation with core-cooling, retrograde heart perfusion and lung immersion technique could be achieved for heart-lung transplantation. PMID:2246529

  11. Optic Nerve Head Blood Flow Response to Reduced Ocular Perfusion Pressure by alteration of either the Blood Pressure or Intraocular Pressure

    PubMed Central

    Wang, Lin; Cull, Grant A; Fortune, Brad

    2015-01-01

    Purpose To test the hypothesis that blood flow autoregulation in the optic nerve head has less reserve to maintain normal blood flow in the face of blood pressure-induced ocular perfusion pressure decrease than a similar magnitude intraocular pressure-induced ocular perfusion pressure decrease. Materials and Methods Twelve normal nonhuman primates were anesthetized by continuous intravenous infusion of pentobarbital. Optic nerve blood flow was monitored by laser speckle flowgraphy. In the first group of animals (n=6), the experimental eye intraocular pressure was maintained at 10 mmHg using a saline reservoir connected to the anterior chamber. The blood pressure was gradually reduced by a slow injection of pentobarbital. In the second group (n=6), the intraocular pressure was slowly increased from 10 mmHg to 50 mmHg by raising the reservoir. In both experimental groups, optic nerve head blood flow was measured continuously. The blood pressure and intraocular pressure were simultaneously recorded in all experiments. Results The optic nerve head blood flow showed significant difference between the two groups (P = 0.021, repeat measures analysis of variance). It declined significantly more in the blood pressure group compared to the intraocular pressure group when the ocular perfusion pressure was reduced to 35 mmHg (P<0.045) and below. There was also a significant interaction between blood flow changes and the ocular perfusion pressure treatment (P=0.004, adjusted Greenhouse & Geisser univariate test), indicating the gradually enlarged blood flow difference between the two groups was due to the ocular perfusion pressure decrease. Conclusions The results show that optic nerve head blood flow is more susceptible to an ocular perfusion pressure decrease induced by lowering the blood pressure compared with that induced by increasing the intraocular pressure. This blood flow autoregulation capacity vulnerability to low blood pressure may provide experimental evidence

  12. 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.

  13. Host-Microbiome Cross-talk in Oral Mucositis.

    PubMed

    Vasconcelos, R M; Sanfilippo, N; Paster, B J; Kerr, A R; Li, Y; Ramalho, L; Queiroz, E L; Smith, B; Sonis, S T; Corby, P M

    2016-07-01

    Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen-related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the potential to contribute to the development of OM and may even prolong the existence of already established ulcerations, affecting tissue healing. Additional comprehensive and disciplined clinical investigation is needed to carefully characterize the relationship between the clinical trajectory of OM, the local levels of inflammatory changes (both clinical and molecular), and the ebb and flow of the oral microbiota. Answering such questions will increase our knowledge of the mechanisms engaged by the oral immune system in response to mucositis, facilitating their translation into novel therapeutic approaches. In doing so, directed clinical strategies can be developed that specifically target those times and tissues that are most susceptible to intervention. PMID:27053118

  14. T-bet as a key regulator of mucosal immunity.

    PubMed

    Mohamed, Rami; Lord, Graham M

    2016-04-01

    Initially understood to be a key regulator of interferon-γ-producing helper T cells, our knowledge of T-bet's functional roles has expanded to encompass a growing range of cellular lineages. In addition to regulating other interferon-γ-producing adaptive immune cells, it is now clear that T-bet plays a fundamental role in the regulation of innate immune responses across mucosal surfaces. This homeostatic role is demonstrated by the spontaneous colitis that occurs when T-bet is deleted from innate immune cells in RAG(-/-) mice. Using this model as a focal point, we review our understanding of T-bet's regulation of adaptive and innate immune systems, focusing particularly on mucosal populations including innate lymphoid cells, dendritic cells and intraepithelial lymphocytes. With the increasingly diverse effects of T-bet on different lineages, the classical binding-centric paradigm of T-bet's molecular functionality has increasingly struggled to account for the versatility of T-bet's biological effects. Recent recognition of the synergistic interactions between T-bet and other canonical transcription factors has led to a co-operative paradigm that has provided greater explanatory power. Synthesizing insights from ChIP-seq and comparative biology, we expand the co-operative paradigm further and suggest a network approach as a powerful way to understand and model T-bet's diverse functionality. PMID:26726991

  15. Oral mucosal lesions associated with use of quid.

    PubMed

    Avon, Sylvie Louise

    2004-04-01

    Quid is a mixture of substances that is placed in the mouth or actively chewed over an extended period, thus remaining in contact with the mucosa. It usually contains one or both of 2 basic ingredients, tobacco and areca nut. Betel quid or paan is a mixture of areca nut and slaked lime, to which tobacco can be added, all wrapped in a betel leaf. The specific components of this product vary between communities and individuals. The quid habit has a major social and cultural role in communities throughout the Indian subcontinent, Southeast Asia and locations in the western Pacific. Following migration from these countries to North America, predominantly to inner city areas, the habit has remained prevalent among its practitioners. Many dentists are unaware of the prevalence of the quid or paan habit in the Asian patient population. The recognition of the role of such products in the development of oral precancer and cancer is of great importance to the dental practitioner. A variety of oral mucosal lesions and conditions have been reported in association with quid and tobacco use, and the association of these conditions with the development of oral cancer emphasizes the importance of education to limit the use of quid. In most cases, cessation of the habit produces improvement in mucosal lesions as well as in clinical symptoms. PMID:15120019

  16. 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

  17. Epidemiology of the most common oral mucosal diseases in children.

    PubMed

    Rioboo-Crespo, Maria del Rosario; Planells-del Pozo, Paloma; Rioboo-García, Rafael

    2005-01-01

    Dentists who treat children must be alert to the possibility of finding diseases of the oral mucosa, especially in younger children. The present study aimed to review the most updated information and the experience of our group in order to yield epidemiological data that assist diagnosis of the most common diseases of the oral mucosa in children. Recent epidemiologic studies have shown a wide variability in the prevalence of oral mucosal lesions in different regions of the world and have led researchers to draw disparate conclusions. Moreover, studies have not been designed using standard criteria, further explaining the wide variability in the percentage of different groups of children with oral lesions, which ranges from 4.1 to 52.6%. The lesions most frequently considered by authors and that most often appear in the different studies are: recurrent aphthous stomatitis (0.9-10.8%), labial herpes (0.78-5.2%), fissured tongue (1.49-23%), geographic tongue (0.60-9.8%), oral candidiasis (0.01-37%) and traumatic injury (0.09%-22.15%). Dentists must be able to detect any of the numerous possible disorders and perform the correct differential diagnosis, key to the treatment plan. The aim of this paper, based on a review of the different national and international studies, is to contribute data on the most important oral mucosal diseases in the paediatric population in terms of prevalence and differential diagnosis. PMID:16264385

  18. Mucosal immune function comparison between amenorrheic and eumenorrheic distance runners.

    PubMed

    Shimizu, Kazuhiro; Suzuki, Natsumi; Nakamura, Mariko; Aizawa, Katsuji; Imai, Tomoko; Suzuki, Satomi; Eda, Nobuhiko; Hanaoka, Yukichi; Nakao, Kikuko; Suzuki, Naoto; Mesaki, Noboru; Kono, Ichiro; Akama, Takao

    2012-05-01

    This study examined the effects of amenorrhea on mucosal immune function and susceptibility to upper respiratory tract infection (URTI) in elite female distance runners. Based on their menstrual cycles during the prior year, 21 elite, collegiate, female distance runners were designated as eumenorrheic runners (ERs; n = 8; 19.9 ± 0.8 years) or amenorrheic runners (ARs; n n = 13; 20.0 ± 0.3 years). Resting saliva and blood samples were collected in the morning. The secretory immunoglobulin A (SIgA) concentration was measured using enzyme-linked immunosorbent assay. The SIgA secretion rate was calculated. Serum 17β-estradiol concentrations and serum progesterone concentrations were measured using radioimmunoassay. Subjects reported the appearance of URTI symptoms (sore throat, headache, runny nose, coughing, or fever), if any, during the prior month. The serum estradiol concentration and salivary SIgA secretion rate were significantly lower for ARs than for ERs (p < 0.05). Serum progesterone concentration was not significantly different between groups. Higher frequencies of headache, runny nose, coughing, and fever were observed in ARs than in ERs. Results show that athletic amenorrhea with low estrogen might accelerate downregulation of mucosal immune function in athletes and enhance susceptibility to infection. PMID:22516912

  19. [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. PMID:21879172

  20. 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. PMID:27356011

  1. Altered Esophageal Mucosal Structure in Patients with Celiac Disease.

    PubMed

    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

  2. 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

  3. Kinetics of glucose transport by the perfused mid-gut of the freshwater prawn Macrobrachium rosenberg ii.

    PubMed Central

    Ahearn, G A; Maginniss, L A

    1977-01-01

    1. Mucosal influx of [3H]glucose was examined in the mid-gut of a freshwater prawn, Macrobrachium rosenbergii, using an in vitro perfusion technique. 2. [3H]glucose transfer across the apical cell membrane of the epithelium exhibited Michaelis-Menten kinetics (Jmax.in = 0-15 mumole glucose equiv/g. min, Kt = 0-17 mM). Under Na-free conditions, glucose influx was significantly reduced and a linear function of substrate concentration, indicative of either slow cellular diffusion (KD = 7-6 X 10(3) mumole glucose equiv/g. min. mM) or a facilitated process with a low carrier affinity for the sugar. 3. Phlorizin was a potent competitive inhibitor of glucose influx (K1 = 3-6 X10(-3) mM), galactose and 3-O-methylglucose (3-O-MG) were weak inhibitors, and fructose had no evident effect on glucose uptake. Azide, but not iodoacetate (IAA), significantly depressed influx. 4. Absorbed [3H]glucose was rapidly metabolized by the mid-gut. The majority of accumulated activity within the tissue was in the form of phosphorylated compounds and tritiated water (THO), while only 0-3% was recovered as a free-glucose. 5. Preliminary studies examining transmural [3-H]glucose transport, however, demonstrated a significant net mucosal to serosal free-glucose flux across the prawn mid-gut which was Na-dependent and IAA- and phlorizin-sensitive. Two alternative interpretations of the data are advanced as possible mechanisms for transepithelial glucose transport: (1) group translocation, or (2) the operation of an energized, high affinity, baso-lateral sugar transport carrier. Images Plate 1 PMID:925985

  4. Draft Genome Sequence of Pedobacter sp. Strain Hv1, an Isolate from Medicinal Leech Mucosal Castings

    PubMed Central

    Ott, Brittany M.; Beka, Lidia; Graf, Joerg

    2015-01-01

    The Pedobacter sp. Hv1 strain was isolated from the medicinal leech, Hirudo verbana, mucosal castings. These mucosal sheds have been demonstrated to play a role in horizontal symbiont transmission. Here, we report the draft 4.9 Mbp genome sequence of Pedobacter sp. strain Hv1. PMID:26679583

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

    PubMed

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

    2012-06-01

    Porcine reproductive and respiratory syndrome (PRRS) is an economically important infectious disease of swine. Constant emergence of variant strains of PRRS virus (PPRSV) and virus-mediated immune evasion followed by viral persistence result in increased incidence and recurrence of PRRS in swine herds. Current live and killed PRRSV vaccines administered by a parenteral route are ineffective in inducing complete protection. Thus, new approaches in design and delivery of PRRSV vaccines are needed to reduce the disease burden of the swine industry. Induction of an effective mucosal immunity to several respiratory pathogens by direct delivery of a vaccine to mucosal sites has proven to be effective in a mouse model. However, there are challenges in eliciting mucosal immunity to PRRS due to our limited understanding of safe and potent mucosal adjuvants, which could potentiate the mucosal immune response to PRRSV. The purpose of this review is to discuss methods for induction of protective mucosal immune responses in the respiratory tract of pigs. The manuscript also discusses how PRRSV modulates innate, adaptive and immunoregulatory responses at both mucosal and systemic sites of infected and/or vaccinated pigs. This information may help in the design of innovative mucosal vaccines to elicit superior cross-protective immunity against divergent field strains of PRRSV. PMID:22717576

  6. Branch pattern of starch internal structure influences the glucogenesis by mucosal Nt-maltase-glucoamylase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To produce sufficient amounts of glucose from food starch, both alpha-amylase and mucosal alpha-glucosidases are required. We found previously that the digestion rate of starch is influenced by its susceptibility to mucosal alpha-glucosidases. In the present study, six starches and one glycogen were...

  7. Host responses to Candida albicans: Th17 cells and mucosal candidiasis

    PubMed Central

    Conti, Heather R.; Gaffen, Sarah L.

    2010-01-01

    Candida albicans causes mucosal and disseminated candidiasis, which represent serious problems for the rapidly expanding immunocompromised population. Until recently, Th1-mediated immunity was thought to confer the primary protection, particularly for oral candidiasis. However, emerging data indicate that the newly-defined Th17 compartment appears to play the predominant role in mucosal candidiasis. PMID:20381638

  8. Mucoadhesive propolis gel for prevention of radiation-induced oral mucositis.

    PubMed

    Noronha, Vladimir R A S; Araujo, Gustavo S; Gomes, Rafael T; Iwanaga, Samara H; Barbosa, Maralice C; Abdo, Evandro N; Ferreira e Ferreira, Efigenia; Viana Campos, Ana C; Souza, Alexandre A; Abreu, Sheila R L; Santos, Vagner R

    2014-01-01

    The objective of this phase II study was to determine the effectiveness of a mucoadhesive propolis gel in the prevention of radiation-induced oral mucositis. Twenty-four patients who were selected to undergo radiation therapy for oral cancer were included in this open-label trial. They were advised to use a mucoadhesive gel containing propolis 5,0% w/v three times a day starting one day before the course of radiation therapy and concluding after 2 weeks of radiation therapy. A weekly follow-up for evaluation of food intake, pain and grading of mucositis was performed. In order to confirm the absence of Candida-related mucositis in patients who developed mucositis, it was performed exfoliative cytology of buccal mucosa, palate and tongue and the material for Candifast(®) Candida species identification. At the end of the study was made the compliance of patients, quality, appreciation and acceptance of product evaluation. Twenty patients did not develop mucositis, two patients developed grade 1 mucositis and two patients developed grade 2 mucositis. None of the patients discontinued food intake and no pain was observed during the study. Candidosis was not detected in any patient. Mucoadhesive propolis gel could be considered as a potential topical medication for preventing radiation-induced oral mucositis. However, comparative phase III study with larger number of patients should be done for confirmation of the efficacy of the product. PMID:24502424

  9. Antigen targeting to M cells for enhancing the efficacy of mucosal vaccines

    PubMed Central

    Kim, Sae-Hae; Jang, Yong-Suk

    2014-01-01

    Vaccination is one of the most successful applications of immunology and for a long time has depended on parenteral administration protocols. However, recent studies have pointed to the promise of mucosal vaccination because of its ease, economy and efficiency in inducing an immune response not only systemically, but also in the mucosal compartment where many pathogenic infections are initiated. However, successful mucosal vaccination requires the help of an adjuvant for the efficient delivery of vaccine material into the mucosa and the breaking of the tolerogenic environment, especially in oral mucosal immunization. Given that M cells are the main gateway to take up luminal antigens and initiate antigen-specific immune responses, understanding the role and characteristics of M cells is crucial for the development of successful mucosal vaccines. Especially, particular interest has been focused on the regulation of the tolerogenic mucosal microenvironment and the introduction of the luminal antigen into the lymphoid organ by exploiting the molecules of M cells. Here, we review the characteristics of M cells and the immune regulatory factors in mucosa that can be exploited for mucosal vaccine delivery and mucosal immune regulation. PMID:24626171

  10. Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally co-administered with an antigen to pigs. Detoxified E. coli enterotoxins LTK63 and LTR72 enhanced mucosal and systemic immunity to the model peptide, exhibiting their efficacy as mucosal adjuvants for...

  11. Oropharyngeal mucositis in cancer therapy. Review of pathogenesis, diagnosis, and management.

    PubMed

    Epstein, Joel B; Schubert, Mark M

    2003-12-01

    Oropharyngeal mucositis is a common and treatment-limiting side effect of cancer therapy. Severe oral mucositis can lead to the need to interrupt or discontinue cancer therapy and thus may have an impact on cure of the primary disease. Mucositis may also increase the risk of local and systemic infection and significantly affects quality of life and cost of care. Current care of patients with mucositis is essentially palliative and includes appropriate oral hygiene, nonirritating diet and oral care products, topical palliative mouth rinses, topical anesthetics, and opioid analgesics. Systemic analgesics are the mainstay of pain management. Topical approaches to pain management are under investigation. The literature supports use of benzydamine for prophylaxis of mucositis caused by conventional fractionationated head and neck radiotherapy, and cryotherapy for short-half-life stomatoxic chemotherapy, such as bolus fluorouracil. Continuing studies are investigating the potential use of biologic response modifiers and growth factors, including topical and systemic delivery of epithelial growth factors and agents. Progress in the prevention and management of mucositis will improve quality of life, reduce cost of care, and facilitate completion of more intensive cancer chemotherapy and radiotherapy protocols. In addition, improved management of mucositis may allow implementation of cancer treatment protocols that are currently excessively mucotoxic but may produce higher cure rates. Continuing research related to the pathogenesis and management of mucositis will undoubtedly lead to the development of potential interventions and improved patient care. PMID:14723014

  12. Efficient Mucosal Delivery of Vaccine Using the FcRn-Mediated IgG Transfer Pathway

    PubMed Central

    Ye, Lilin; Zeng, Rongyu; Bai, Yu; Roopenian, Derry C.; Zhu, Xiaoping

    2011-01-01

    Vaccine strategies to prevent invasive mucosal pathogen