Sample records for acute mucosal pathogenesis

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

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


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

  2. Mucosal Immunity and acute viral gastroenteritis.

    Rose, Markus A


    Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq(®) and Rotarix(®) are excellent examples for their unique features and principles of mucosal immunization. We elaborate on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants' acute gastroenteritis.

  3. Acute pancreatitis: Etiology and common pathogenesis

    Guo-Jun Wang; Chun-Fang Gao; Dong Wei; Cun Wang; Si-Qin Ding


    Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux. Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed. However, little is known about the other acute pancreatitis. We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis. Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure, active trypsin reflux, and subsequent unregulated activation of trypsin within pancreatic acinar cells. Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation. Once the hypothesis is confirmed, traditional therapeutic strategies against acute pancreatitis may be improved. Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.

  4. Prevention of acute gastric mucosal lesions by Solcoseryl.

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


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

  5. Relative defects in mucosal immunity predict acute graft-versus-host disease.

    August, Keith J; Chiang, K-Y; Qayed, Muna; Dulson, Ashley; Worthington-White, Diana; Cole, Conrad R; Horan, John T


    Impairment of gut mucosal immunity by the transplant process could facilitate translocation of commensal bacteria and thereby augment the graft-versus-host response. To begin to assess the influence of gut mucosal immunity on the development of acute graft-versus-host disease (GVHD), we conducted a prospective study in 24 pediatric allogeneic hematopoietic cell transplant recipients, assessing 4 fecal markers of mucosal immunity: calprotectin, soluble CD8 (sCD8), soluble intracellular adhesion molecule 1, and β-defensin-2. Stool samples were collected prospectively on transplant days 0, +5, +10, and +15 and analyzed by ELISA. Lower levels on day +5 (calprotectin and β-defensin-2) and day +10 (calprotectin, β-defensin-2, and sCD8) were associated with subsequent acute GVHD. The most striking difference was with calprotectin on day +10. Patients with levels below 424 mg/kg had an incidence of 77.8%, whereas those with levels above this threshold had a cumulative incidence of 0% (P = .002). Relative defects in gut mucosal immunity may be important in the pathogenesis of acute GVHD.

  6. Effects of Mycotoxins on mucosal microbial infection and related pathogenesis.

    Park, Seong-Hwan; Kim, Dongwook; Kim, Juil; Moon, Yuseok


    Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation of activated lymphocytes, impairing phagocytic function of macrophages, and suppressing cytokine production, but some induce hypersensitive responses in different dose regimes. The present review describes various mycotoxin responses to infectious pathogens that trigger mucosa-associated diseases in the gastrointestinal and respiratory tracts of humans and other animals. In particular, it focuses on the effects of mycotoxin exposure on invasion, pathogen clearance, the production of cytokines and immunoglobulins, and the prognostic implications of interactions between infectious pathogens and mycotoxin exposure.

  7. Pathogenesis of Acute Respiratory Distress Syndrome

    A. M. Golubev


    Full Text Available Acute respiratory distress syndrome (ARDS is a common complication of many diseases. Its polyetiological pattern determines the specific features of lung morphological changes and the clinical course of ARDS. Objective: to analyze the pathogenesis of ARDS in the context of the general pathological processes underlying its development. Material and methods. More than 200 lungs from the people who had died from severe concomitant injury or ARDS-complicated pneumonia were investigated. More than 150 rat experiments simulated various types of lung injury: ventilator-induced lung injury with different ventilation parameters; reperfusion injuries (systemic circulation blockade due to 12-minute vascular fascicle ligation, followed by the recovery of cardiac performance and breathing; microcirculatory disorder (injection of a thromboplastin solution into the jugular vein; blood loss; betaine-pepsin aspiration; and closed chest injury. Different parts of the right and left lungs were histologically examined 1 and 3 hours and 1 and 3 days after initiation of the experiment. Lung pieces were fixed in 10% neutral formalin solution and embedded in paraffin. Histological sections were stained with hematoxylin and eosin and using the van Gieson and Weigert procedures; the Schiff test was used. Results. The influence of aggression factors (trauma, blood loss, aspiration, infection, etc. results in damage to the lung and particularly air-blood barrier structures (endothelium, alveolar epithelium, their basement membrane. In turn the alteration of cellular and extracellular structures is followed by the increased permeability of hemomicrocirculatory bed vessels, leading to the development of non-cardiogenic (interstitial, alveolar pulmonary edema that is a central component in the pathogenesis of ARDS. Conclusion. The diagnosis of the early manifestations of ARDS must account for the nature of an aggression factor, the signs confirming the alteration of the lung

  8. Pathogenesis of acute lung injury in severe acute pancreatitis

    SHI Lei; YUE Yuan; ZHANG Mei; PAN Cheng-en


    Objective:To study the pathogenesis of acute lung injury in severe acute pancreatitis (SAP). Methods:Rats were sacrificed at 1, 3, 5, 6, 9 and 12 h after establishment of inducing model. Pancreas and lung tissues were obtained for pathological study, microvascular permeability and MPO examination. Gene expressions of TNF-α and ICAM-1 in pancreas and lung tissues were detected by RT-PCR. Results:After inducing SAP model, the injury degree of the pancreas and the lung increased gradually, accompanied with gradually increased MPO activity and microvascular permeability. Gene expressions of TNF-α and ICAM-1 in pancreas rose at 1 h and reached peak at 7 h. Relatively, their gene expressions in the lungs only rose slightly at 1 h and reached peak at 9-12 h gradually. Conclusion:There is an obvious time window between SAP and lung injury, when earlier protection is beneficial to prevent development of acute lung injury.

  9. Pathogenesis of severe acute respiratory syndrome

    ZHANG Ding-mei; LU Jia-hai; ZHONG Nan-shan


    Severe acute respiratory syndrome (SARS) first emerged in Guangdong province,China in November2002.During the following 3 months,it spread rapidly across the world,resulting in approximately 800 deaths.In 2004,subsequent sporadic cases emerged in Singapore and China.A novel coronavims,SARS-CoV,was identified as the etiological agent of SARS.1,2 This virus belongs to a family of large,positive,single-stranded RNA viruses.Nevertheless,genomic characterization shows that the SARS-CoV is only moderately related to other known coronaviruses.3 In contrast with previously described coronaviruses,SARS-CoV infection typically causes severe symptoms related to the lower respiratory tract.The SARS-CoV genome includes 14 putative open reading frames encoding 28 potential proteins,and the functions of many of these proteins are not known.4 A number of complete and partial autopsies of SARS patients have been reported since the first outbreak in 2003.The predominant pathological finding in these cases was diffuse alveolar damage (DAD).This severe pulmonary injury of SARS patients is caused both by direct viral effects and immunopathogenetic factors.5 Many important aspects of the pathogenesis of SARS have not yet been fully clarified.In this article,we summarize the most important mechanisms involved in the complex pathogenesis of SARS,including clinical characters,host and receptors,immune system response and genetic factors.

  10. the Pathogenesis of acute on Chronic Hepatitis B liver Failure


    Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would beneift for the prognosis and raise the survival rate of patients.

  11. Acute appendicitis following endoscopic mucosal resection of cecal adenoma.

    Nemoto, Yukako; Tokuhisa, Junya; Shimada, Nagasato; Gomi, Tatsuya; Maetani, Iruru


    Endoscopic mucosal resection (EMR) allows the removal of flat or sessile lesions, laterally spreading tumors, and carcinoma of the colon or the rectum limited to the mucosa or the superficial submucosa. Acute appendicitis is the most common abdominal emergency requiring emergency surgery, and it is also a rare complication of diagnostic colonoscopy and therapeutic endoscopy, including EMR. In the case presented here, a 53-year-old female underwent colonoscopy due to a positive fecal occult blood test and was diagnosed with cecal adenoma. She was referred to our hospital and admitted for treatment. The patient had no other symptoms. EMR was performed, and 7 h after the surgery, the patient experienced right -lower abdominal pain. Laboratory tests performed the following day revealed a WBC count of 16000/mm(3), a neutrophil count of 14144/mm(3), and a C-reactive protein level of 2.20 mg/dL, indicating an inflammatory response. Computed tomography also revealed appendiceal wall thickening and swelling, so acute appendicitis following EMR was diagnosed. Antibiotics were initiated leading to total resolution of the symptoms, and the patient was discharged on the sixth post-operative day. Pathological analysis revealed a high-grade cecal tubular adenoma. Such acute appendicitis following EMR is extremely rare, and EMR of the cecum may be a rare cause of acute appendicitis.

  12. Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection.

    Tincati, Camilla; Douek, Daniel C; Marchetti, Giulia


    Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies. Results from studies addressing the pathogenesis of microbial translocation have improved our knowledge of the damage of the gastrointestinal epithelial barrier occurring in HIV infection. However, the extent to which mucosal impairment translates directly to increased gastrointestinal permeability remains an open issue. In this respect, novel work has established a role for IL-17 and IL-22-secreting T cell populations in limiting microbial translocation and systemic T-cell activation/inflammation, thus representing a possible target of immune-therapeutic interventions shown to be promising in the animal model. Further, recent reports have not only confirmed the presence of a dysbiotic intestinal community in the course of HIV infection but have also shown that it may be linked to mucosal damage, microbial translocation and peripheral immune activation. Importantly, technical advances have also shed light on the metabolic activity of gut microbes, highlighting the need for novel therapeutic approaches to correct the function, as well as the composition, of the gastrointestinal microbiota.

  13. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    Minmin Li


    Full Text Available The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2 and cyclooxygenase- (COX- 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  14. Current concept of pathogenesis of severe acute pancreatitis

    Xie Ning Wu


    @@ The pathogenesis of severe acute pancreatitis is very complicated. It is a multifactorial as well as multifaceted disease. First of all, the etiologic agents initiate the pancreatic acinar injury by release of pancreatic enzymes and overstimulation of macrophages and neutrophils, then the cytokines and inflammatory mediators are liberated. There is also interaction between neutrophils and endothelial cells producing free radicals, the cytokines cause increasing vascular permeability, activating complement component, resulting in microcirculatory impairment and imbalance of thrombo-fibrinolytic system. Many of these events occur not only in the pancreas itself, but also in the other vital organs and tissues, leading to severe acute pancreatitis and complications. The sequencial events are as follows.

  15. Pathogenesis of pancreatic encephalopathy in severe acute pancreatitis

    Xi-Ping Zhang; Hua Tian


    BACKGROUND:Pancreatic encephalopathy (PE) is a serious complication of severe acute pancreatitis (SAP). In recent years, more and more PE cases have been reported worldwide, and the onset PE in the early stage was regarded as a poor prognosis sign of SAP, but the pathogenesis of PE in SAP still has not been clariifed in the past decade. The purpose of this review is to elucidate the possible pathogenesis of PE in SAP. DATA SOURCES:The English-language literature concern-ing PE in this review came from the Database of MEDLINE (period of 1991-2005), and the keywords of severe acute pancreatitis and pancreatic encephalopathy were used in the searching. RESULTS:Many factors were involved in the pathogenesis of PE in SAP. Pancreatin activation, excessive release of cytokines and oxygen free radicals, microcirculation abnormalities of hemodynamic disturbance, ET-1/NO ratio, hypoxemia, bacterial infection, water and electrolyte imbalance, and vitamin B1 deifciency participated in the development of PE in SAP. CONCLUSIONS:The pathogenesis of PE in SAP has not yet been fully understood. The development of PE in SAP may be a multi-factor process. To ifnd out the possible inducing factor is essential to the clinical management of PE in SAP.

  16. The role of endotoxin in the pathogenesis of gastric mucosal damage in cirrhotic rats with portal hypertensive gastropathy

    ChengLan; XiaoningSun; LiweiDong; BailiHuang; SuYuan; KeliWu


    Objective:To study the role and the mechanism of endotoxin in the pathogenesis of gastric mucosa during portal vein hypertension gastrography (PHG) in the rats with cirrhosis. Methods:Rat model for PHG was established by injection of tetrachloride. The animals were injected with endotoxin i.p. at 3 mg/kg and endotoxin antagonist BPI21 i.v. at 2.0 mg/kg. The plasma level of endotoxin as well as the gastric mucosal level of tumor necrosis factor alpha (TNF-α) was measured with azobenzene and ELISA respectively. Furthermore, the pathological changes of the gastric mucosa were studied with HE stainning. Results:In rats with PHG, increased endotoxin and TNF-αas well as the gastric pathological lesion were observed. Injection of endotoxin remarkably increased plasma level of endotoxin as well as the gastric mucosal level of tumor necrosis TNF-αand induced more serious gastric lesion. Animals injected with endotoxin antagonist BPI21 showed improved gastric mucosal lesion, accompanied by the declining TNF-αlevel. Conclusions:Our results suggestes that endotoxin may play a pathogenetic role in PHG by inducing the expression of TNF-α.

  17. The Adaptor Protein Myd88 Is a Key Signaling Molecule in the Pathogenesis of Irinotecan-Induced Intestinal Mucositis.

    Deysi V T Wong

    Full Text Available Intestinal mucositis is a common side effect of irinotecan-based anticancer regimens. Mucositis causes cell damage, bacterial/endotoxin translocation and production of cytokines including IL-1 and IL-18. These molecules and toll-like receptors (TLRs activate a common signaling pathway that involves the Myeloid Differentiation adaptor protein, MyD88, whose role in intestinal mucositis is unknown. Then, we evaluated the involvement of TLRs and MyD88 in the pathogenesis of irinotecan-induced intestinal mucositis. MyD88-, TLR2- or TLR9-knockout mice and C57BL/6 (WT mice were given either saline or irinotecan (75 mg/kg, i.p. for 4 days. On day 7, animal survival, diarrhea and bacteremia were assessed, and following euthanasia, samples of the ileum were obtained for morphometric analysis, myeloperoxidase (MPO assay and measurement of pro-inflammatory markers. Irinotecan reduced the animal survival (50% and induced a pronounced diarrhea, increased bacteremia, neutrophil accumulation in the intestinal tissue, intestinal damage and more than twofold increased expression of MyD88 (200%, TLR9 (400%, TRAF6 (236%, IL-1β (405%, IL-18 (365%, COX-2 (2,777% and NF-κB (245% in the WT animals when compared with saline-injected group (P<0.05. Genetic deletion of MyD88, TLR2 or TLR9 effectively controlled the signs of intestinal injury when compared with irinotecan-administered WT controls (P<0.05. In contrast to the MyD88-/- and TLR2-/- mice, the irinotecan-injected TLR9-/- mice showed a reduced survival, a marked diarrhea and an enhanced expression of IL-18 versus irinotecan-injected WT controls. Additionally, the expression of MyD88 was reduced in the TLR2-/- or TLR9-/- mice. This study shows a critical role of the MyD88-mediated TLR2 and TLR9 signaling in the pathogenesis of irinotecan-induced intestinal mucositis.

  18. A critical role of gastric mucosal ascorbic acid in the progression of acute gastric mucosal lesions induced by compound 48/80 in rats

    Yoshio Kamiya; Yoshiji Ohta; Yoichiro Imai; Tomiyasu Arisawa; Hiroshi Nakano


    AIM: To study the role of gastric mucosal ascorbic acid(AA) in the progression of acute gastric mucosal lesions induced by compound 48/80 (C48/80), a mast cell degranulator, in rats.METHODS: C48/80 (0.75 mg/kg) was intraperitoneally injected to fasted Wistar rats. Oral administration of AA (10, 50 or 100 mg/kg) was performed 0.5 h after C48/80treatment. Determinations for gastric mucosal lesion severity and blood flow, and assays for gastric mucosal total AA, reduced AA, oxidized AA, vitamin E, thiobarbituric acid reactive substances (TBARS), adherent mucus, nitrite/nitrate (NOx), non-protein SH (NPSH), and myeloperoxidase(MPO), and serum total AA, reduced AA, oxidized AA,and NOx were conducted 0.5 and 3 h after C48/80treatment.RESULTS: Gastric mucosal lesions occurred 0.5 h after C48/80 treatment and progressed at 3 h. Gastric mucosal blood flow decreased 0.5 h after C48/80 treatment but the decrease was recovered at 3 h. Gastric mucosal total AA, reduced AA, vitamin E, and adherent mucus concentrations decreased 3 h after C48/80 treatment.Gastric mucosal oxidized AA concentration remained unchanged after C48/80 treatment. Gastric mucosal NPSH concentration decreased 0.5 h after C48/80 treatment,but the decrease was recovered at 3 h. Gastric mucosal TBARS concentration and MPO activity increased 0.5 h after C48/80 treatment and further increased at 3 h.Serum total AA and reduced AA concentrations increased 0.5 h after C48/80 treatment and further increased at 3 h, while serum oxidized AA concentration increased at 0.5 h. Serum and gastric mucosal NOx concentrations increased 3 h after C48/80 treatment. AA administration to C48/80-treated rats at 0.5 h after the treatment prevented the gastric mucosal lesion progression and the changes in gastric mucosal total AA, reduced AA, vitamin E, adherent mucus, NOx, and TBARS concentrations and MPO activity and serum NOx concentration found at 3 h after the treatment dose-dependently. The AA administration to C48/80-treated

  19. Acute effects of high-dose intragastric nicotine on mucosal defense mechanisms

    Lindell, G; Bukhave, Klaus; Lilja, I;


    Peptic ulcer disease is overrepresented among smokers; they also heal slowly and relapse frequently. Data are accumulating that smoking is detrimental to gastroduodenal mucosal cytoprotection. This study was designed to assess acute effects of high-dose intragastric nicotine, as it has been shown...

  20. [Pathogenesis and target therapy of acute respiratory distress syndrome].

    Moroz, V V; Vlasenko, A V; Golubev, A M


    The paper summarizes results of experimental studies and clinical observations of the pathogenesis and effectiveness of respiratory, non-respiratory and pharmacological treatment methods for acute respiratory distress syndrome caused by direct and indirect damaging factors. The article deals with differences and peculiarities of morphological changes and lung functional disorders, clinical, laboratory and instrumental signs of various origins in ARDS and justifies necessity of differential diagnosis and differential treatment of ARDS, depending on the reasons for its development. Furthermore the article discusses an algorithm for differential diagnosis and differential treatment for ARDS caused by direct and indirect damaging factors.

  1. [Significance of deficient bacterial colonization in the pathogenesis of mucosal lesions in experimental blind loop syndrome].

    Menge, H; Germer, C T; Stössel, R; Simes, G; Wagner, J; Hahn, H; Riecken, E O


    A complete evaluation of the bacterial flora in jejunal self-filling blind loops was performed. The results show a significant increase in bacteria of the genera E. coli, Streptococcus and Bacteroides. In further experiments, jejunal self-filling blind loops were created in germ-free animals. In spite of the germ-free state the mucosa displayed marked hyperplasia. The same was true when the blind loops had been contaminated with aerobic bacteria. These results demonstrate that other factors in addition to bacterial overgrowth contribute to the mucosal damage observed in self-filling blind loops.

  2. Depletion of mucosal substance P in acute otitis media

    Cayé-Thomasen, Per; Schmidt, Peter Thelin; Hermansson, Ann;


    OBJECTIVE: The neuropeptide substance P (SP) is an inducer of neurogenic inflammation and bone resorption in the middle ear. Resorption of the bone tissue structures surrounding the middle ear cavity is a distinct feature of the initial stage of acute otitis media (AOM), which may be due to nerve...


    赵超; 肖文; 叶光福; 周建平; 周其璋


    Emergency endoscopy studies have shown that the most of seriously ill patients develop acute stress-related mucosal damage and ulceration within 24 hours of admission, which manifest the upper gastrointestinal tract

  4. Acute effects of Helicobacter pylori extracts on gastric mucosal blood flow in the mouse

    Johanna Henriksn(a)s; Christer Atuma; Mia Phillipson; Stellan Sandler; Lars Engstrand; Lena Holm


    AIM: To investigate the mechanisms underlying the reduction in gastric blood flow induced by a luminal water extract of Helicobacter pylori (HPE). METHODS: The stomachs of isoflurane-anesthetized mice were exteriorized, and the mucosal surface exposed. Blood flow was measured with the laser Doppler technique, and systemic arterial blood pressure monitored. C57BL/6 mice were exposed to water extract produced from H pylori strain 88-23. To investigate the role of a nerve- or iNOS-mediated pathway, we used intraluminal lidocaine and iNOS-/-mice. Blood flow response to the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine (ADMA) was also assessed. RESULTS: In wild-type mice, HPE decreased mucosal blood flow by approximately 30%. This reduction was abolished in iNOS-deficient mice, and by pre-treatment with lidocaine. Luminally applied ADMA resulted in reduction in blood flow similar to that observed in wildtype mice exposed to HPE. CONCLUSION: A H pylori water extract reduces gastric mucosal blood flow acutely through iNOS- and nerve-mediated pathways.


    Anna Falanga


    Full Text Available Acute promyelocytic leukemia (APL is a distinct subtype of myeloid leukemia characterized by t(15;17 chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha. APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta and tumor necrosis factor (TNF-alpha], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.

  6. Effects of traditional Chinese medicine on intestinal mucosal permeability in early phase of severe acute pancreatitis

    CHEN Hong; LI Fei; JIA Jian-guo; DIAO Yong-peng; LI Zong-xin; SUN Jia-bang


    Background Traditional Chinese medicine has been used widely for many years in China to treat acute pancreatitis.We have investigated the effects of Dachengqi decoction on intestinal mucosal permeability and outcome in patients with severe acute pancreatitis (SAP).Methods Forty patients with sustained SAP that required admission to the surgical intensive care unit were enrolled prospectively in the study. All of these patients were divided randomly into the Dachengqi decoction group (n=20) and control group (n=20) on admission. Intestinal permeability was assessed by measuring absorption of two metabolically inert markers, lactulose (L) and mannitol (M), which were administered orally. Serum concentrations of endotoxin (lipopolysaccharide, LPS) and the ratio of lactulose to mannitol in urine (L/M) were detected in all patients.Results Compared with those in the control group, urinary L/M ratio decreased significantly in the Dachengqi decoction group on the 7th day after admission (P=0.001). Also, serum concentrations of LPS were reduced on the 5th and 7th day after admission (P=0.006, P=0.008, respectively). Incidence of multiple organ dysfunction syndrome (MODS) and pancreatic infection was significantly lower in the Dachengqi decoction group compared with those in the control group (P=0.038, P=0.025, respectively).Conclusion Dachengqi decoction may promote the recovery of intestinal mucosal permeability and decrease the incidence of MODS and pancreatic infection in patients with SAP.

  7. [Changes of Intestinal Mucosal Barrier and Intestinal Flora in Rats with Severe Acute Pancreatitis].

    Li, Yan; Wu, Hao; Deng, Yiyun; Liao, Ruyi; Xi, Lili; Yao, Ping


    This paper is to explore changes of intestinal mucosal barrier, intestinal flora, and bacterial translocation in rats with severe acute pancreatitis (SAP). Twenty four male SD rats were randomly divided into the control group (n = 10) and the experimental group (n = 14). The model of severe acute pancreatitis of rats was induced by the method of injecting adversely 5% sodium taurocholate into the common biliary-pancreatic duct. All of the rats were killed after 24 hours and the level of the serum amylase and the plasma endotoxin was determined after that. The pathological changes of pancreas and small intestine were observed through hematoxylin-eosin staining (HE staining) and the abdominal viscera bacterial translocation rates were tested. With the method of real-time polymerase chain reaction (RT-PCR) the quantity of the intestinal flora was analyzed. In the control group, the level of Escherichia coli, Lactobacillus and Bifidobacterium were 2.08 ± 1.29, 11.04 ± 7.55 and 12.21 ± 4.95, respectively. On the contrast, the level of Escherichia coli in the cecum contents was much higher (9.72 ± 3.58, P intestines were also significantly higher (P intestinal mucosal barrier was severely damaged and the dysbacteriosis occurs in the intestinal canal. And these might relate to the occurrence and development of multiple organ infection.

  8. Role of viruses in the pathogenesis of acute otitis media.

    Heikkinen, T


    To date there is ample evidence suggesting a crucial role for respiratory viruses in the pathogenesis of AOM. Respiratory viral infection appears to initiate the cascade of events that finally leads to development of AOM (Fig. 1). The pathogenesis of AOM is complicated, involving a network of factors, some probably not yet identified, which affect each other in a time-dependent manner. Increased knowledge of the detailed mechanisms of viral infection, the host inflammatory response during URI and the interaction between viruses and bacteria could lead to major advances in the prevention of AOM.

  9. Effects of Atractylodis Rhizoma Pharmacopuncture on an Acute Gastric Mucosal Lesion Induced by Compound 48/80 in Rats

    Lee Yun-Kyu


    Full Text Available Objectives: This study was designed to investigate the protective effects of Atractylodis Rhizoma pharmacopuncture (ARP against acute gastric mucosal lesions induced by compound 48/80 in rats. Methods: The ARP was injected in Joksamni (ST36 and Jungwan (CV12 1 hr before treatment with compound 48/80. The animals were sacrificed under anesthesia 3 hrs after treatment with compound 48/80. The stomachs were removed, and the amounts of gastric adherent mucus, gastric mucosal hexosamine, thiobarbituric acid reactive substances (TBARS, xanthine oxidase (XO, and superoxide dismutase (SOD were measured. Also, histological examination were performed. Results: Gastric adherent mucus, gastric mucosal hexosamine and histological defects of gastric mucosa declined significantly after ARP treatment. Changes in gastric mucosal TBARS were also reduced by ARP treatment, but this result was not statistically significant. ARP treatment did not change the XO and the SOD activities. Conclusions: ARP showed protective effects for acute gastric mucosal lesions induced by compound 48/80 in rats. These results suggest that ARP may have protective effects for gastritis.

  10. Effect of adjuvant lactulose enema therapy on outcome and intestinal mucosal barrier function in patients with acute pancreatitis

    Ling Gao; Ming-Quan Li


    Objective:To analyze the effect of adjuvant lactulose enema therapy on outcome and intestinal mucosal barrier function in patients with acute pancreatitis.Methods: A total of 98 patients with acute pancreatitis were randomly divided into observation group and control group, control group received conventional symptomatic treatment, observation group received symptomatic treatment + adjuvant lactulose enema therapy, and differences in levels of inflammatory cytokines, RAAS system-related molecules and mucosal barrier function-related indexes in serum as well as intestinal flora quantity in stool samples were compared between two groups after treatment.Results:Serum inflammatory cytokines IL-1β, IL-6, IL-8, PCT and TNF-α levels of enema group were significantly lower than those of control group; serum RAAS system molecules R, AngI, AngII and ALD levels were significantly lower than those of control group; serum mucosal barrier function indexes D-lactate, LPS, I-FABP and DAO levels were significantly lower than those of control group; the quantity of bifidobacterium and lactobacillus in stool samples were significantly more than those of control group while the quantity of enterobacterium, enterococcus and E. coli were significantly lower than those of control group.Conclusion:Adjuvant lactulose enema therapy can promote the improvement of acute pancreatitis, and restore patients’ intestinal mucosal barrier function.

  11. Oral hygiene care of patients with oral cancer during postoperative irradiation. An alleviating effect on acute radiation mucositis

    Katsura, Kouji; Masuko, Noriko; Hayashi, Takafumi [Niigata Univ. (Japan). School of Dentistry; Sugita, Tadashi; Sakai, Kunio; Tsuchida, Emiko; Matsumoto, Yasuo; Sasamoto, Ryuta


    To evaluate the effect of oral hygiene care of patients with oral cancer on alleviating acute radiation mucositis. Eighteen patients receiving postoperative radiotherapy for tongue and oral floor cancer were evaluated. Radiotherapy was given in 2 Gy per fraction, 5 times a week for a total dose of 50 Gy in most patients. Radiation field included the tongue and oral floor. During radiotherapy, 8 patients were treated by dento-maxillofacial radiologists with special concern on oral hygiene (oral hygiene group) and the remaining 10 patients were treated with routine dental care (standard medication group). Mucositis were evaluated using JCOG grade and EORTC/RTOG score by radiotherapists or dento-maxillofacial radiologists at 10 Gy intervals. Oral hygiene plans comprised motivation to maintain oral hygiene and establishing the habits of oral self care 4 times per day. Once a week, oral hygiene and oral cleaning of patients were checked by dento-maxillofacial radiologists. Oral self care included mechanical tooth brushing and a chemical mouthwash. No patients with grade 3 and score 4 mucositis were noted in the oral hygiene group. Severe mucositis occurred less frequently in the oral hygiene group than in the standard medication group. Interruption of radiotherapy due to severe mucositis did not occur in the oral hygiene group. On the other hand, interruption of radiotherapy occurred in four patients in the standard medication group, and in three it was due to severe oral pain. Our results suggested that our method of oral hygiene was more effective for alleviating acute radiation mucositis than other methods so far reported. In addition, our method is considered to be useful in preventing rampant dental caries and severe periodontitis due to the xerostomia induced by radiotherapy. (author)

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

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


    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 fullthickness 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 2.23 mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24 h 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.

  13. Pathogenesis of Acute and Delayed Corneal Lesions after Ocular Exposure to Sulfur Mustard Vapor


    had poor outcomes. Using a rabbit corneal vapor exposure model, we previously demonstrated a clinical progression with acute and chronic sequelae...can cause a permanent reduction in visual acuity or complete loss of eyesight [6]. The pathogenesis of MGK has been clinically described as a chronic

  14. Prediction of Acute Radiation Mucositis using an Oral Mucosal Dose Surface Model in Carbon Ion Radiotherapy for Head and Neck Tumors.

    Atsushi Musha

    Full Text Available To evaluate the dose-response relationship for development of acute radiation mucositis (ARM using an oral mucosal dose surface model (OMDS-model in carbon ion radiotherapy (C-ion RT for head and neck tumors.Thirty-nine patients receiving C-ion RT for head and neck cancer were evaluated for ARM (once per week for 6 weeks according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0, and the Radiation Therapy Oncology Group (RTOG scoring systems. The irradiation schedule typically used was 64 Gy [relative biological effectiveness (RBE] in 16 fractions for 4 weeks. Maximum point doses in the palate and tongue were compared with ARM in each patient.The location of the ARM coincided with the high-dose area in the OMDS-model. There was a clear dose-response relationship between maximum point dose and ARM grade assessed using the RTOG criteria but not the CTCAE. The threshold doses for grade 2-3 ARM in the palate and tongue were 43.0 Gy(RBE and 54.3 Gy(RBE, respectively.The OMDS-model was useful for predicting the location and severity of ARM. Maximum point doses in the model correlated well with grade 2-3 ARM.

  15. Divergent mucosal and systemic responses in children in response to acute otitis media.

    Verhoeven, D; Pichichero, M E


    Acute otitis media (AOM), induced by respiratory bacteria, is a significant cause of children seeking medical attention worldwide. Some children are highly prone to AOMs, suffering three to four recurrent infections per year (prone). We previously determined that this population of children could have diminished anti-bacterial immune responses in peripheral blood that could fail to limit bacterial colonization in the nasopharynx (NP). Here, we examined local NP and middle ear (ME) responses and compared them to peripheral blood to examine whether the mucosa responses were similar to the peripheral blood responses. Moreover, we examined differences in effector cytokine responses between these two populations in the NP, ME and blood compartments at the onset of an AOM caused by either Streptococcus pneumoniae or non-typeable Haemophilus influenzae. We found that plasma effector cytokines patterned antigen-recall responses of CD4 T cells, with lower responses detected in prone children. ME cytokine levels did not mirror blood, but were more similar to the NP. Interferon (IFN)-γ and interleukin (IL)-17 in the NP were similar in prone and non-prone children, while IL-2 production was higher in prone children. The immune responses diverged in the mucosal and blood compartments at the onset of a bacterial ME infection, thus highlighting differences between local and systemic immune responses that could co-ordinate anti-bacterial immune responses in young children.

  16. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats

    Mehmet Kanter; Halit Demir; Cengiz Karakaya; Hanefi Ozbek


    AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an experimental model.METHODS: Male Wistar albino rats were assigned into 4groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis.RESULTS: NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue.CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity.

  17. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis.

    Whibley, Natasha; Tritto, Elaine; Traggiai, Elisabetta; Kolbinger, Frank; Moulin, Pierre; Brees, Dominique; Coleman, Bianca M; Mamo, Anna J; Garg, Abhishek V; Jaycox, Jillian R; Siebenlist, Ulrich; Kammüller, Michael; Gaffen, Sarah L


    Antibodies targeting IL-17A or its receptor, IL-17RA, are approved to treat psoriasis and are being evaluated for other autoimmune conditions. Conversely, IL-17 signaling is critical for immunity to opportunistic mucosal infections caused by the commensal fungus Candida albicans, as mice and humans lacking the IL-17R experience chronic mucosal candidiasis. IL-17A, IL-17F, and IL-17AF bind the IL-17RA-IL-17RC heterodimeric complex and deliver qualitatively similar signals through the adaptor Act1. Here, we used a mouse model of acute oropharyngeal candidiasis to assess the impact of blocking IL-17 family cytokines compared with specific IL-17 cytokine gene knockout mice. Anti-IL-17A antibodies, which neutralize IL-17A and IL-17AF, caused elevated oral fungal loads, whereas anti-IL-17AF and anti-IL-17F antibodies did not. Notably, there was a cooperative effect of blocking IL-17A, IL-17AF, and IL-17F together. Termination of anti-IL-17A treatment was associated with rapid C. albicans clearance. IL-17F-deficient mice were fully resistant to oropharyngeal candidiasis, consistent with antibody blockade. However, IL-17A-deficient mice had lower fungal burdens than anti-IL-17A-treated mice. Act1-deficient mice were much more susceptible to oropharyngeal candidiasis than anti-IL-17A antibody-treated mice, yet anti-IL-17A and anti-IL-17RA treatment caused equivalent susceptibilities. Based on microarray analyses of the oral mucosa during infection, only a limited number of genes were associated with oropharyngeal candidiasis susceptibility. In sum, we conclude that IL-17A is the main cytokine mediator of immunity in murine oropharyngeal candidiasis, but a cooperative relationship among IL-17A, IL-17AF, and IL-17F exists in vivo. Susceptibility displays the following hierarchy: IL-17RA- or Act1-deficiency > anti-IL-17A + anti-IL-17F antibodies > anti-IL-17A or anti-IL-17RA antibodies > IL-17A deficiency.

  18. Mucosal immunization with PsaA protein, using chitosan as a delivery system, increases protection against acute otitis media and invasive infection by Streptococcus pneumoniae.

    Xu, J-H; Dai, W-J; Chen, B; Fan, X-Y


    As infection with Streptococcus pneumoniae (mainly via the mucosal route) is a leading cause of acute otitis media, sinus and bacterial pneumonia, the mucosal immunity plays an important role in the prevention of pneumococcal diseases. Therefore, intranasal vaccination may be an effective immunization strategy, but requires appropriate mucosal vaccine delivery systems. In this work, chitosan was used as a mucosal delivery system to form chitosan-PsaA nanoparticles based on ionotropic gelation methods and used to immunize BALB/c mice intranasally. Compared to mice immunized with naked PsaA, levels of IFN-γ, IL-17A and IL-4 in spleen lymphocytes, the systemic (IgG in serum) and mucosal (IgA in mucosal lavage) specific antibodies were enhanced significantly in mice inoculated with chitosan-PsaA. Furthermore, increased protection against acute otitis media following middle ear challenge with pneumococcus serotype 14, and improved survival following intraperitoneal challenge with pneumococcus serotype 3 or serotype 14, was found in the mice immunized with chitosan-PsaA nanoparticles. Thus, intranasal immunization with chitosan-PsaA can successfully induce mucosal and systemic immune responses and increase protection against pneumococcal acute otitis media and invasive infections. Hence, intranasal immunization with PsaA protein, based on chitosan as a delivery system, is an efficient immunization strategy for preventing pneumococcal infections.

  19. Ligustrazine alleviates gastric mucosal injur y in a rat model of acute necrotizing pancreatitis

    Sheng-Chun Dang; Jian-Xin Zhang; Jian-Guo Qu; Xue-Qing Wang; Xin Fan


    BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inlfammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inlfammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group C);ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood lfow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score;meanwhile, the levels of serum interleukin-1β(IL-1β) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood lfow in group P was signiifcantly lower than that in group C (P CONCLUSIONS: Decreased gastric blood lfow and increased inlfammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.

  20. CELECOXIB - Chemoradiation therapy for reducing mucositis and other acute side effects in advance head and neck carcinoma

    Izadi Sh


    Full Text Available "nBackground: Chemo-radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay or interruption of treatment plan, cyclo-oxygenase 2 (COX2 is an inducible enzyme primarily expressed in inflamed and tumoral tissues. COX-2 inhibitors have shown promise to reduce chemoradiation induce toxicities. We conducted a phase III, randomized double blind clinical trial to evaluate the toxicity and efficacy of celecoxib, a selective COX2 inhibitor, administered concurrently with chemoradiation for locally advanced head and neck cancer. Here in we report the first report about the role of COX-2 inhibitor in acute toxicicities. "nMethods: Patients with stage III/IV (locally advance head and neck carcinoma who referred to department of radiation-oncology were eligible. Patients were treated with chemotherapy with cisplatin concurrently with radiation (60-70Gy. Celecoxib (100mg qid was started at the first day of radiotherapy and was given for a total of 8 weeks. Acute toxicities were evaluated every week by WHO scale. "nResults: One hundred twenty two patients were enrolled into the study, (61 patients for each group. In repeated mesurment analysis of variance there is a significant difference in the time of onset of grade II acute toxicities between the two groups; The mucositis, dysphagia, epidermitis and oral pain score changed significantly over the typical five weeks in two groups but these changes were more sever in placebo group (p=0.0001. In the analysis of the overall changes in the following laboratory parame-ters: WBC, hemoglobin and platelet showed that these parameters decreased over time in both groups without a significant difference between groups. "nConclusion: The results of these study showed that the use of a COX-2 inhibitor (celecoxib that is a safe and inexpensive drug may reduce acute toxicities of chemoradiation specially

  1. Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

    R Anuradha

    Full Text Available Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+ or without (CP Ag- active infection; with clinically asymptomatic infections (INF; and in those without infection (endemic normal [EN]. Comparisons between the two actively infected groups (CP Ag+ compared to INF and those without active infection (CP Ag- compared to EN were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein, acute phase proteins (haptoglobin and serum amyloid protein-A, and inflammatory cytokines (IL-1β, IL-12, and TNF-α are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

  2. Protective effect of Matricaria chamomilla on ethanol-induced acute gastric mucosal injury in rats.

    Cemek, Mustafa; Yilmaz, Ezgi; Büyükokuroğlu, Mehmet Emin


    The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity.

  3. Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia:a case-control study

    Dorina Lauritano; Massimo Petruzzi; Dario Di Stasio; Alberta Lucchese


    The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P50.002), duration of mucositis (P50.003) and the average grade of mucositis (P50.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.

  4. Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs


    Background One of the major causes of death in severe acute pancreatitis (SAP) is severe infection owing to bacterial translocation. Some clinical studies suggested that ecoimmunonutrition (EIN) as a new strategy had better treatment effect on SAP patients. But the experiment studies on the precise mechanism of the effect of EIN were less reported. In this study, we mainly investigated the effects of EIN on bacterial translocation in SAP model of dogs.Methods SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in healthy hybrid dogs. The SAP dogs were supported with either parenteral nutrition (PN) or elemental enteral nutrition (EEN) or EIN. The levels of serum amylase, serum aminotransferase and plasma endotoxin were detected before and after pancreatitis induction. On the 7th day after nutrition supports, peritoneal fluid, mesenteric lymph nodes (MLN), liver, and pancreas were collected for bacterial culture with standard techniques to observe the incidence of bacterial translocation. Pathology changes of pancreas were analyzed by histopathologic grading and scoring of the severity of pancreas, and the degree of intestinal mucosal damage was assessed by measuring mucosal thickness, villus height, and crypt depth of ileum.Results Compared with PN and EEN, EIN significantly decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin, and the incidence of bacterial translocation. Furthermore, compared with the others, the histology scores of inflammation in pancreas and the ileum injury (ileum mocosa thickness, villus height, and crypt depth) were significantly alleviated by EIN (P<0.05). Moreover, concerning liver function, the serum levels of alanine aminotransferase, aspartate aminotransferase and albumin were ameliorating significantly in the EIN group.Conclusion Our results suggested that EIN could maintain the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation

  5. Palifermin and Chlorhexidine Mouthwashes in Prevention of Chemotherapy-Induced Mucositis in Children with Acute Lymphocytic Leukemia: a Randomized Controlled Trial

    Narges Gholizadeh


    Full Text Available Statement of the Problem: Over the past three decades, significant improvements have been achieved in the survival of children with cancer. However, the considerable morbidity which occurs as a result of chemotherapy often restricts the treatment intensity. One of the important dose-limiting and costly adverse effects of cancer therapy is mucositis. Children with hematological malignancies are greatly at risk of developing mucositis. Purpose: This study aimed to assess the effectiveness of palifermin in preventing mucositis in children with acute lymphocytic leukemia (ALL who undergo chemotherapy. Materials and Method: In this clinical trial, 90 children with ALL were randomized to receive chlorhexidine (n=45 or palifermin (n=45. One group received 60 μg/ kg/ day palifermin as an intravenous bolus once daily for 3 days before and 3 days after the chemotherapy. Chlorhexidine mouthwash was administered once daily for 3 days before and 3 days after the chemotherapy. The world health organization (WHO oral toxicity scale was employed for grading the mucositis. The data were analyzed by using two-way ANOVA. Results: The two groups were matched for age and gender. The study groups were significantly different in terms of mucositis grading (P values after 1 and 2 week therapy were 0.00. Palifermin decreased the incidence and severity of chemotherapy-induced mucositis. Conclusion: Palifermin reduces the oral mucositis in children with ALL. Several mechanisms of action are suggested for keratinocyte growth factor (such as palifermin including promotion of cell proliferation and cytoprotection, restraining the apoptosis, and changing the cytokine profile. Keywords ● Oral Mucositis ● Palifermin ● Leukemia

  6. Acute fatty liver of pregnancy: An update on pathogenesis and clinical implications

    Jamal A Ibdah


    Acute fatty liver of pregnancy (AFLP) is a serious maternal illness occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. Till recently, it has been considered a mysterious illness. In this editorial, we review the recent advances in understanding the pathogenesis of AFLP and discuss the studies documenting a fetal-maternal interaction with a causative association between carrying a fetus with a defect in mitochondrial fatty acid oxidation and development of AFLP.Further, we discuss the impact of these recent advances on the offspring born to women who develop AFLP, such that screening for a genetic defect can be life saving to the newborn and would allow genetic counseling in subsequent pregnancies.The molecular basis and underlying mechanism for this unique fetal-maternal interaction causing maternal liver disease is discussed.

  7. Role of platelet-activating factor in pathogenesis of acute pancreatitis

    Li-Rong Liu; Shi-Hai Xia


    Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides with diverse pathological and physiological effects. This bioactive phospholipid mediates processes as diverse as wound healing,physiological inflammation, angiogenesis, apoptosis,reproduction and long-term potentiation. PAF acts by binding to a specific G protein-coupled receptor to activate multiple intracellular signaling pathways.Since most cells both synthesize and release PAF and express PAF receptors, PAF has potent biological actions in a broad range of cell types and tissues.Inappropriate activation of this signaling pathway is associated with many diseases in which inflammation is thought to be one of the underlying features. Acute pancreatitis (AP) is a common inflammatory disease.The onset of AP is pancreatic autodigestion mediated by abnormal activation of pancreatic enzyme caused by multiple agents, which subsequently induce pancreatic and systemic inflammatory reactions. A number of experimental pancreatitis and clinical trials indicate that PAF does play a critical role in the pathogenesis of AP. Administration of PAF receptor antagonist can significantly reduce local and systemic events that occur in AP. This review focuses on the aspects that are more relevant to the pathogenesis of AP.

  8. Host immune response and acute disease in a zebrafish model of francisella pathogenesis

    Vojtech, L.N.; Sanders, G.E.; Conway, C.; Ostland, V.; Hansen, J.D.


    Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebraflsh were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebraflsh following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebraflsh mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-l?? (IL-1??), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebraflsh to heat-killed bacteria demonstrated that the significant induction of IL-?? was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebraflsh share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach. Copyright ?? 2009, American Society for Microbiology. All Rights Reserved.

  9. Higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by Streptococcus pneumoniae in young children.

    Xu, Q; Casey, J R; Pichichero, M E


    Mucosal immunity has a crucial role in controlling human respiratory tract infections. This study characterizes the naturally acquired mucosal antibody levels to three Streptococcus pneumoniae (Spn) protein antigens, pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and pneumolysin (Ply), and assesses the association of the mucosal antibody levels with occurrence of acute otitis media (AOM) caused by Spn. Both nasopharyngeal (NP) immunoglobulin G (IgG) and IgA levels to all three proteins slightly decreased in children from 6 to 9 months of age and then gradually increased through 24 months of age. Spn NP colonization was associated with higher mucosal antibody levels to all three proteins. However, children with Spn AOM had 5-8-fold lower IgG and 3-6-fold lower IgA levels to the three proteins than children without AOM but asymptomatically colonized with Spn. Antigen-specific antibody levels in the middle ear fluid (MEF) were correlated with antibody levels in the NP. Children with AOM caused by Spn had lower antibody levels in both the MEF and NP than children with AOM caused by other pathogens. These results indicate that higher naturally acquired mucosal antibody levels to PhtD, PcpA and Ply are associated with reduced AOM caused by Spn.

  10. Mucosal invasion by fusobacteria is a common feature of acute appendicitis in Germany, Russia, and China

    Alexander Swidsinski


    Full Text Available Background/Aim: To investigate the geographic occurrence of mucosa-invading Fusobacteria in acute appendicitis. Patients and Methods: Carnoy- and formalin-fixated appendices from Germany, Russia, and China were comparatively investigated. Bacteria were detected using fluorescent in situ hybridization. Cecal biopsies from patients with inflammatory bowel disease and other conditions were used as disease controls. Results: Fusobacteria represented mainly by Fusobacterium nucleatum were the major invasive component in bacterial infiltrates in acute appendicitis but were completely absent in controls. The occurrence of invasive Fusobacteria in Germany, Russia, and China was the same. The detection rate in Carnoy-fixated material was 70-71% and in formalin-fixated material was 30-36%. Conclusions: Acute appendicitis is a polymicrobial infectious disease in which F. nucleatum and other Fusobacteria play a key role.

  11. Role of platelet activating factor in pathogenesis of acute pancreatitis in rats.

    Konturek, S J; Dembinski, A; Konturek, P J; Warzecha, Z; Jaworek, J; Gustaw, P; Tomaszewska, R; Stachura, J


    The importance of platelet activating factor in acute pancreatitis was examined by determining the tissue content of endogenous platelet activating factor and the protective effects of TCV-309, a highly selective platelet activating factor blocker, against caerulein induced pancreatitis in rats. Infusion of caerulein (10 micrograms/kg/h) for five hours resulted in about 70% increase in pancreatic weight, 22% rise in protein content, 50% reduction in tissue blood flow, nine fold increase in tissue level of platelet activating factor and 165% rise in plasma amylase as well as histological evidence of acute pancreatitis. Such infusion of caerulein in chronic pancreatic fistula rats caused a marked increase in protein output from basal secretion of 10 mg/30 minutes to 40 mg/30 minutes in the first hour of infusion followed by a decline in protein output to 15-20 mg/30 minutes in the following hours of the experiment. Exogenous platelet activating factor (50 micrograms/kg) injected ip produced similar alterations in weight, protein content, blood flow, and histology of the pancreas but the increment in serum amylase was significantly smaller and pancreatic secretion was reduced below the basal level. TCV-309 (50 micrograms/kg) given ip before caerulein or platelet activating factor administration significantly reduced the biochemical and morphological alterations caused by caerulein and abolished those induced by exogenous platelet activating factor. These results indicate that platelet activating factor plays an important role in the pathogenesis of acute pancreatitis probably by reducing the blood flow and increasing vascular permeability in the pancreas. PMID:1385272

  12. Pathogenesis of acute radiation effects in the urinary bladder. Experimental results

    Doerr, W.; Eckhardt, M.; Ehme, A.; Koi, S. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Technische Univ. Dresden (Germany)


    Purpose: The present review summarizes experimental studies of the pathogenesis of acute radiation-induced changes in urinary bladder function. Material and methods: Transurethral cystometry was used for longitudinal assessment of bladder function in mice. With this technique, radition-induced changes in storage capacity can be quantified. In histological studies, changes in urothelial cell density and in urothelial protein expression during the acute radiation response were determined. Acetylsalicylic acid (ASA) was used for the treatment of acute functional changes. Results: The histological studies did not reveal any systematic fluctuations in urothelial cell density during the time of the acute radiation response. However, characteristic changes in the expression of proteins associated with urothelial cell function, differentiation and cell contact were observed, which correlated with the functional impairment. By local or systemical application of ASA, a significant restoration of bladder function compared to placebo treatment could be achieved. Conclusion: Acute functional radiation effects in the urinary bladder are not based on urothelial denudation. However, changes in protein expression indicate an impairment of the urothelial barrier function. The results of ASA treatment demonstrate that prostaglandins are involved in the response. Alterations in urothelial or endothelial prostaglandin metabolism may be primarily radiation-induced or secondary because of the impaired urothelial barrier. (orig.) [Deutsch] Ziel: Die vorliegende Arbeit soll tierexperimentelle Ergebnisse zur Pathogenese akuter Funktionsstoerungen der Harnblase nach Bestrahlung zusammenfassen. Material und Methoden: Transurethrale zystometrische Messungen dienen zur longitudinalen Erfassung der Harnblasenfunktion bei der Maus. Mit dieser Methode koennen strahlenbedingte Stoerungen der Speicherkapazitaet quantifiziert werden. In histologischen Untersuchungen wurden Veraenderungen in der

  13. Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats

    Fatih Mehmet Birdane; Mustafa Cemek; Yavuz Osman Birdane; (I)lhami Gül(c)in; Mehmet Emin Büyükokuro(g)lu


    AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats.METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated;whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid,retinol and β-carotene levels were measured in all the groups.RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage.This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 ± 2.81 vs 13.15 ± 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid,retinol and β-carotene levels.CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

  14. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis.

    Jose L Nieto-Torres


    Full Text Available Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV envelope (E gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS

  15. 从肠黏膜免疫系统损害探讨AIDS脾虚病机%Discuss the spleen deficiency of AIDS pathogenesis from the point of view intestinal mucosal immune system damage

    王春芳; 李真; 徐立然


    HIV/AIDS patients with intestinal mucosal immune system damage promoting the immunodeficiency of body and the incidence of opportunistic infections, which is consistent with the evolution of spleen deficiency pathogenesis point of view of TCM. This paper discusses the spleen deficiency of AIDS pathogenesis from the point of view intestinal mucosal immune system damage, and proposed strengthening the spleen to improve immune function of intestinal mucosa of AIDS.%HIV/AIDS患者肠黏膜免疫系统损害促进了机体免疫功能的缺失和机会性感染的发生,AIDS以脾虚为主的中医病机演变过程,与HIV感染所致以肠黏膜损伤为重要表现的全身免疫损伤过程相符合.文章从肠黏膜免疫系统损害角度探讨AIDS脾虚病机,提出健脾扶正以改善肠黏膜免疫功能的中医药治疗AIDS思路.

  16. Intercellular Adhension Molecule-1 in the Pathogenesis of Heroin-induced Acute Lung Injury in Rats

    周琼; 白明; 邹世清


    The expression of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of heroin-induced acute lung injury (ALI) in rats was investigated. The model of ALI was established by intravenous injection of heroin into tail vein in rats. Thirty-six rats were randomly divided into heroin-treated groups (1 h, 2 h, 4 h, 6 h and 24 h) and normal control group. Changes in histopathologic morphology and biological markers of ALI were measured. The expression of ICAM-1in lung tissue was detected by using immunohistochemistry and RT-PCR. The results showed that the W/D ratio and protein contents in BALF of the heroin-treated groups were significantly higher than that of the control group (P<0.01). The histopathological changes in the lung tissue were more obvious in heroin-treated groups. The ICAM-1 protein and mRNA expression in the lung tissue of heroin-treated groups were significantly increased as compared with that of the control group (P<0.01), and correlated with the ALI parameters in a time-dependent manner. Increasing of ICAM-1 expression was involved in the formation of heroin-induced lung injury. Furthermore, the level of expression was positively correlated with the severity of lung injury.

  17. The role of tubuloglomerular feedback in the pathogenesis of acute kidney injury.

    Singh, Prabhleen; Okusa, Mark D


    The mechanisms involved in reduction in glomerular filtration rate (GFR) in prerenal and intrarenal acute kidney injury (AKI) are not mutually exclusive and prerenal mechanisms continue to play a role in the pathogenesis of established intrarenal AKI. In nearly all forms of AKI, glomeruli are morphologically normal; therefore, the investigative efforts have focused on systemic and intrarenal mechanisms that lead to the failure of filtration at the glomerulus. There is observed and/or deductive evidence supporting the role of tubuloglomerular feedback in mediating the reduction in GFR in various forms of AKI. In prerenal AKI, the activation of various neurohormonal renal vasoconstrictors can increase the sensitivity and responsiveness of tubuloglomerular feedback. In different forms of intrarenal AKI, the varying degree of tubular injury is linked to filtration failure directly by mechanisms such as tubular obstruction or tubular backleak of solutes, or indirectly via the activation of tubuloglomerular feedback. Tubular obstruction or backleak of solutes, while readily understood, do not appear to be consistent features in experimental AKI and have a limited role in explaining the degree of impairment of GFR in human AKI. The functional connection between tubular damage and filtration failure mediated by tubuloglomerular feedback via alterations in nephron plasma flow and glomerular capillary hydrostatic pressure is more consistently observed or deduced from experimental data. It also explains the principal abnormality of increased preglomerular resistances, a pathogenic characteristic of both experimental and human AKI.

  18. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection.

    Saurabh Mehandru


    Full Text Available BACKGROUND: During acute and early HIV-1 infection (AEI, up to 60% of CD4(+ T cells in the lamina propria of the lower gastrointestinal (GI tract are lost as early as 2-4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART is well established. However, the extent of immune reconstitution in the GI tract is unknown. METHODS AND FINDINGS: Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1-7 y of uninterrupted therapy. Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%-60% depletion of lamina propria lymphocytes despite 1-7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO+ HLA-DR+, returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4+ T cell depletion despite therapy. Rare HIV-1 RNA-expressing cells were detected by in situ hybridization. CONCLUSIONS: Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T

  19. The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy


    T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. Small molecule gamma secretase inhibitors (GSIs) can effectively inhibit oncogenic NOTCH1 and are in clinical testing for the treatme...

  20. Effect of acid secretion blockade on acute gastric mucosal lesions induced by Tityus serrulatus scorpion toxin in anaesthetized rats.

    Melo, Júnio Rios; de Araújo, Gnana Keith Marques; da Luz, Magda Maria Profeta; da Conceição, Sérgio Alexandre; Lisboa, Felipe Assis; Moraes-Santos, Tasso; Cunha-Melo, José Renan


    Scorpion venom (TX) promotes gastric acid and pepsin secretion leading to acute gastric mucosal lesions (AGML), when injected in animals. The goal of the present study was to observe the effects of acid gastric secretion blockers over the incidence of TX-induced AGML in vivo. To verify this model, we used male albino rats, fasted 18-20 h (n=122) and anaesthetized with urethane (1.4 g/kg, i.p.). Their trachea and left femoral vein were both cannulated; the first to avoid airway obstructions during scorpion intoxication and the second for administration of saline, TX and acid blockers. Following the surgical procedure, the animals were divided in 10 groups of at least 10 animals each. Control groups were injected with NaCl 0.9% 1 ml/kg (n=10) or TX 375 microg/kg (n=32). Test groups (n=10, each) received atropine 5 mg/kg, cimetidine 10mg/kg, ranitidine 2.5mg/kg, ranitidine 5mg/kg, omeprazol 1 mg/kg, omeprazol 4 mg/kg, octreotide 80 and octreotide 100 microg/kg 10 min before the TX was injected. After 1h of intoxication, the stomach was resected for macroscopic study and the gastric secretion was collected for volume, pH and acid output assessment. We observed that all blockers were able to completely or partially prevent the TX-induced acid secretion as well as the AGML (p<0.05). Our data suggest the TX-induced AGML can be prevented by different class of acid blockers injected before the intoxication.

  1. Preventive effect of tetramethylpyrazine on intestinal mucosal injury in rats with acute necrotizing pancreatitis

    Jian-Xin Zhang; Sheng-Chun Dang; Jian-Guo Qu; Xue-Qing wang


    AIM: To evaluate the role of microcirculatory disorder(MCD) and the therapeutic effectivenessof tetramethylpyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 192 Sprague-Dawley rats were randomly divided into three groups: normal control group (C group), ANP group not treated with TMP (Pgroup), ANP group treated with TMP (T group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 mL/kg).C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP (10 mL/kg) via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase (MPO) expressed intracellularly in azurophilic granules of neutrophils.RESULTS: The blood flow was significantly lower in P group than in C group (P < 0.01). The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes.The intestinal MPO activities were significantly higher in P group than in C group (P < 0.01). The blood flow of intestine was significantly higher in T group than in P group after 2 h (P < 0.01). The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group (P <0.01 or P < 0.05). There was a negative correlation between intestinal blood flow and MPO activity (r = -0.981,P < 0.01) as well as between intestinal blood flow and pathologic scores (r = -0.922, P < 0.05).CONCLUSION: MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.

  2. Influence of live combined bifidobacterium, lactobacillus and enterococcus capsules inflammation factors and intestinal mucosal barrier function of severe acute pancreatitis patients

    Ping-Ping Shi; Ling-Yun Wu; Jian-Jun Wang


    Objective:To explore the influence of inflammation factors and intestinal mucosal barrier function on severe acute pancreatitis patients treated with bifidobacterium triple viable capsules.Methods:88 cases severe acute pancreatitis patients were divided into observation group and control group according to admission order, 44 cases in each group, all patients were given conventional treatment, on this base, patients in observation group were treated by oral bifidobacterium triple viable capsules, they were treated for one week, detected the serum inflammatory factors: the tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and C-reactive protein (CRP) and intestinal mucosal barrier function index: endotoxin, diamine oxidase (DAO), D-lactic acid, urinary lactulose/mannitol (L/M) in the two groups before and after treatment.Results:The levels of TNF-α, IL-6 and CRP in two groups after treatment were significantly reduced than before treatment, and after treatment the levels of TNF-α, IL-6 and CRP in observation group was significantly lower than that of the control group, all the difference was statistically significant; The levels of endotoxin, DA, D-lactic acid, L/M in two groups after treatment were significantly reduced than before treatment, and the levels of endotoxin, DA, D-lactic acid,L/M after treatment in observation group was significantly lower than that of the control group, the difference was statistically significant.Conclusion: Based on conventional treatment combined bifidobacterium triple viable capsules can significantly reduce inflammation in patients with severe acute pancreatitis, it can protect the intestinal mucosal barrier function, and has important clinical significance.

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

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


    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

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

    Shahram Golbabapour


    Full Text Available 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.

  5. Role of mucosal immunity in pathogenesis of asthma and allergic rhinitis%黏膜免疫在支气管哮喘及变应性鼻炎发病中的作用

    李风森; 徐丹; 杜丽娟


    目的 探讨黏膜免疫在哮喘、变应性鼻炎发病过程中的作用,寻找两种病发病时共同的联系物质,以揭示哮喘与变应性鼻炎发病之间的关联性.方法 收集急性发作期哮喘患者82例(其中单纯哮喘44例,哮喘合并鼻炎38例),单纯变应性鼻炎患者30例,正常对照组30例.分别采集受检者唾液、痰液、鼻腔分泌物各2 ml,用ELISA法测定分泌型免疫球蛋白A(sIgA)的变化.采肘静脉血各2 ml,用流式细胞仪检测CD4+、CD8+淋巴细胞,荧光酶联免疫法检测血清嗜酸性阳离子蛋白(eosinophil cationic protein,ECP)、总免疫球蛋白E(total immunoglobulin E,T-IgE).结果 痰液中sIgA含量在单纯哮喘组、哮喘合并鼻炎组、单纯变应性鼻炎组均较正常组降低(P<0.01);唾液sIgA含量在哮喘组、合并组较正常组有降低趋势但差异无统计学意义.鼻腔分泌物中sIgA各组比较,哮喘组与合并组均高于正常组(P<0.05)及鼻炎组(P<0.01),而鼻炎组与正常组之间差异无统计学意义.血液中CD4+细胞在哮喘组、合并组均高于正常组(P<0.05);血液中CD8+细胞在各组间差异无统计学意义;CD4+/CD8+在哮喘组较正常组和鼻炎组增高(P<0.05).血清T-IgE在合并组及鼻炎组均较正常组增高(P<0.01).正常组血清ECP检出率极低;哮喘组血清ECP高于鼻炎组(P<0.05),而哮喘组与合并组、鼻炎组与合并组差异无统计学意义.哮喘组ECP与T-IgE正相关(r=0.467,P<0.05),合并组与鼻炎组ECP与T-IgE无相关性.结论 哮喘和变应性鼻炎都与黏膜免疫有密切关系,黏膜免疫可能是其发病过程中相同的病理特征在不同部位的体现.而sIgA、CD4+、CD8+、ECP、T-IgE等免疫介质可能是黏膜免疫的物质基础之一.%Objective To explore the role of mucosal immunity in the pathogenesis of asthma and allergic rhinitis and to search for common materials for the two conditions, so as to reveal the relationship of asthma and allergic

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

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


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

  7. Systematic review of diet in the pathogenesis of acute pancreatitis: A tale of too much or too little?

    Tudor Thomas


    Full Text Available Background/Aim: The role of diet as the cause of acute pancreatitis (AP has been suggested. The aim of the current review was to determine if there exists sufficient evidence linking nutrition, or the lack of it, to the pathogenesis of AP. Patients and Methods: A systematic search of the scientific literature was carried out using Embase, PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials for the years 1965 - 2011 to obtain access to studies involving dietary factors and the pathogenesis of AP. Results: A total of 17 studies were identified describing diet and AP. These included 12 human and 5 animal studies. 8 reports were found to link malnutrition and/or refeeding to the pathogenesis of AP. Two studies found an increased consumption of fats and proteins in patients with alcohol-related AP while 1 study noted a lesser intake of carbohydrate in patients. However, none of these differences attained statistical significance. A recent prospective case-control study found a significantly higher risk for AP amongst patients eating par-boiled rice and fresh water fish. Conclusions: Evidence from literature does not appear to support the role of diet as a single bolus meal as a cause for AP. Prolonged consumption of diets rich in proteins and fats may work synergistically with gallstones / alcohol to trigger an attack of AP indicating a possible role of diet as a cofactor in the development of AP possibly by lowering the threshold needed by these other agents to lead to the attack of AP.

  8. Swine-origin influenza-virus-induced acute lung injury:Novel or classical pathogenesis?

    Naoyoshi; Maeda; Toshimitsu; Uede


    Influenza viruses are common respiratory pathogens in humans and can cause serious infection that leads to the development of pneumonia.Due to their hostrange diversity,genetic and antigenic diversity,and potential to reassort genetically in vivo,influenza A viruses are continual sources of novel influenza strains that lead to the emergence of periodic epidemics and outbreaks in humans.Thus,newly emerging viral diseases are always major threats to public health.In March 2009,a novel influenza virus suddenly emerged and caused a worldwide pandemic.The novel pandemic influenza virus was genetically and antigenically distinct from previous seasonal human influenza A/H1N1 viruses;it was identified to have originated from pigs,and further genetic analysis revealed it as a subtype of A/H1N1,thus later called a swine-origin influenza virus A/H1N1.Since the novel virus emerged,epidemiological surveys and research on experimental animal models have been conducted,and characteristics of the novel influenza virus have been determined but the exact mechanisms of pulmonary pathogenesis remain to be elucidated.In this editorial,we summa-rize and discuss the recent pandemic caused by the novel swine-origin influenza virus A/H1N1 with a focus on the mechanism of pathogenesis to obtain an insight into potential therapeutic strategies.

  9. Pathogenesis of Septic Acute Lung Injury and Strategies for Immuno-Pharmacological Therapy.


    obtained from septic-NO animals revealed a qualitative reduction in alveolar and septal edema . Although qualitative in nature, parenchyma of septic-NO...pulmonary edema in a model of acute lung injury. Am. Rev. Respir. Dis. 142:1083- 1087. 18. McDonald, R. J. 1991. Pentoxifylline reduces injury to isolated...patients with uncomplicated sepsis and septic shock--comparison with cardiogenic shock. Thromb. Haemost. 58:709-713. 60. Carvalho, A. C., S. DeMarinis

  10. Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin.

    Ikezoe, Takayuki


    Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia characterized by the proliferation of blasts with distinct morphology, a specific balanced reciprocal translocation t(15;17), and life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL, although hemorrhage-related death during the early phase of therapy remains a serious problem. Moreover, population-based studies have shown that the incidence of early death during induction chemotherapy is nearly 30 %, and the most common cause of death is associated with hemorrhage. Thus, development of a novel treatment strategy to alleviate abnormal coagulation in APL patients is urgently required. Recombinant human soluble thrombomodulin (rTM) comprises the active extracellular domain of TM, and has been used for treatment of DIC since 2008 in Japan. Use of rTM in combination with remission induction chemotherapy, including ATRA, produces potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL. This review article discusses the pathogenesis and features of DIC caused by APL, as well as the possible anticoagulant and anti-leukemic action of rTM in APL patients.

  11. A rare aggravation of severe mucositis post chemotherapy in a child with acute lymphoblastic leukemia [v1; ref status: indexed,

    Adlette Inati


    Full Text Available Oral mucositis is a debilitating manifestation in children undergoing chemotherapy and radiotherapy. Children with mucositis should be properly managed in order to prevent further exacerbation and adverse complications. We hereby present the first report of a severe chemotherapy-induced mucositis, plausibly aggravated by improper dental hygiene leading to shedding of the ventral part of the tongue in a child with pre-B acute lymphoblastic leukemia (ALL. The patient steadily and gradually recovered her oral maneuvers and ability to speak several months later. Her tongue underwent hypertrophy as a compensatory mechanism. We recommend that critical and regular assessment of the oral mucosa and proper dental care and oral hygiene be emphasized in all pediatric patients receiving chemotherapy. Families of affected children need to be educated about the benefits and modes of optimal oral hygiene for their children and the need to seek immediate care for mouth pain and or lesions. Optimal treatment for mucositis needs to be instituted without delay in this high risk pediatric population. Such a preventive and therapeutic approach may prevent associated life threatening oral and systemic complications, promote rapid and complete mucosal healing, alleviate pain and improve quality of life in children with cancer.

  12. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

    María Jesús Tu(n)ón; Marcelino Alvarez; Jesús M Culebras; Javier González-Gallego


    Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by meansof the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.

  13. Pneumococcal conjugate vaccination does not induce a persisting mucosal IgA response in children with recurrent acute otitis media.

    Bogaert, D.; Veenhoven, R.H.; Ramdin, R.; Luijendijk, I.H.; Rijkers, G.T.; Sanders, E.A.M.; Groot, R. de; Hermans, P.W.M.


    AIM: In a prospective controlled study in young children with a history of recurrent acute otitis media, we analyzed the salivary IgA and IgG antibody titers upon vaccination with a 7-valent pneumococcal conjugate vaccine (PCV) given once or twice, followed by a 23-valent polysaccharide booster vacc

  14. Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium.

    Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Karuppagounder, Vengadeshprabhu; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Miyashita, Shizuka; Nomoto, Mayumi; Harima, Meilei; Suzuki, Hiroshi; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi


    The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1β, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.

  15. Israeli acute paralysis virus: epidemiology, pathogenesis and implications for honey bee health.

    Yan Ping Chen


    Full Text Available Israeli acute paralysis virus (IAPV is a widespread RNA virus of honey bees that has been linked with colony losses. Here we describe the transmission, prevalence, and genetic traits of this virus, along with host transcriptional responses to infections. Further, we present RNAi-based strategies for limiting an important mechanism used by IAPV to subvert host defenses. Our study shows that IAPV is established as a persistent infection in honey bee populations, likely enabled by both horizontal and vertical transmission pathways. The phenotypic differences in pathology among different strains of IAPV found globally may be due to high levels of standing genetic variation. Microarray profiles of host responses to IAPV infection revealed that mitochondrial function is the most significantly affected biological process, suggesting that viral infection causes significant disturbance in energy-related host processes. The expression of genes involved in immune pathways in adult bees indicates that IAPV infection triggers active immune responses. The evidence that silencing an IAPV-encoded putative suppressor of RNAi reduces IAPV replication suggests a functional assignment for a particular genomic region of IAPV and closely related viruses from the Family Dicistroviridae, and indicates a novel therapeutic strategy for limiting multiple honey bee viruses simultaneously and reducing colony losses due to viral diseases. We believe that the knowledge and insights gained from this study will provide a new platform for continuing studies of the IAPV-host interactions and have positive implications for disease management that will lead to mitigation of escalating honey bee colony losses worldwide.

  16. Efficacy of a Solution Composed by Verbascoside, Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate in the Treatment of Chemotherapy-induced Oral Mucositis in Children With Acute Lymphoblastic Leukemia.

    Bardellini, Elena; Amadori, Francesca; Schumacher, Richard Fabian; D'Ippolito, Carmelita; Porta, Fulvio; Majorana, Alessandra


    The aim of this study was to assess the efficacy of a solution composed by verbascoside, polyvinylpyrrolidone, and sodium hyaluronate (Mucosyte) in the treatment of chemotherapy-induced oral mucositi (OM). Patients between 5 and 18 years receiving chemotherapy for acute lymphoblastic leukemia and with OM grade 1 or 2 were randomized in group A (treated with Mucosyte, 3 mouthwashes/d per 8 d) and group B (treated with placebo, ie, an inert water-based solution, 3 mouthwashes/d per 8 d). The OM scoring was performed at day 1 (diagnosis of OM-T0), after 3 days of treatment (T1), and at day 8 (T2). Pain was evaluated through the visual analog scale with the same timing of OM measurement. A total of 56 patients were included (28 patients per group). Group A experienced a statistically significant decline of OM at T2 (P=0.0038); a statistically significant difference in pain reduction between 2 groups both at T1 and at T2 (P<0.005) was observed. The use of Mucosyte mouthwashes in children with chemotherapy-induced OM may be recommended as supportive therapy.

  17. Spectral-Domain Optical Coherence Tomography Features of Acute Syphilitic Posterior Placoid Chorioretinitis: The Role of Autoimmune Response in Pathogenesis

    Pedro Brito


    Full Text Available Purpose: Syphilis is an infectious disease that can cause a wide variety of ocular signs. One of the rarest manifestations of ocular syphilis is acute syphilitic posterior placoid chorioretinitis (ASPPC. We report on the spectral-domain optical coherence tomography (SD-OCT features of a case diagnosed with unilateral ASPPC. Methods: A 64-year-old man presented with a sudden loss of visual acuity (VA in the right eye. His only clinical sign was a large, geographic, yellow-white lesion centered on the right fovea. Our patient was studied with SD-OCT on presentation and during follow-up, as well as with fluorescein and indocyanine green angiography, electrophysiological study, and serologic and autoimmune screening. Results: Laboratory workup revealed positive serology for active syphilis and elevated anti-beta2 glycoprotein I antibodies. SD-OCT showed a marked distortion of both the choroidal and outer retinal architecture. After treatment, best-corrected VA improved to 20/25. Pattern electroretinography displayed a severe reduction of P50 amplitude, which improved in late follow-up. Six months after presentation, VA was 20/25 and anti-beta2 glycoprotein I antibodies returned to normal levels. Conclusions: Our findings are compatible with immunologically mediated temporary physiological impairment of the neuroretina, since the changes seen by SD-OCT could not have normalized if they were due to anatomical injury. The results of our study provide clues to understanding the pathogenesis of this disease and allow us to define a characteristic temporal sequence of events in ASPPC.

  18. 小鼠急性乙醇性胃黏膜损伤模型的制备%Establishment of animal model of ethanol-induced acute gastric mucosal lesions in mice

    叶惠惠; 刘河霞; 张咏梅; 吴克俭


    Objective To investigate the optimal ethanol concentration and capacity contributing to ethanol -induced acute gastric mucosal injury and to establish the stable model of ethanol - induced acute gastric mucosal injury in mice. Methods Eighty Kunming mice were randomly divided into control group, normal saline gavage group, 75% ethanol gavage group, and 99.5% ethanol gavage group, followed by sacrifice of animals at 1 h and 4 h for removal of their stomachs and observation of the gastric mucosal lesions. Results The gastric mucosal lesions were evident following gavage of ethanol at the time point of 1 h in mice and 99.5% ethanol at 0.2 ml/10 g gavage induced much sever damage. The gastric mucosal lesions at 1 h were attenuated as compared to 4 h following 99.5% ethanol at 0.2 ml/10 g gavage. There wasn't significant change of survival rates with the concentration and duration of ethanol gavage in mice. Conclusion Ethanol gavage can induce acute gastric mucosal injury in mice, with 99.5% ethanol at 0.2 ml/10 g as the optimal choice to establish the model of acute gastric mucosal injury.%目的 研究引起小鼠急性乙醇性胃黏膜损伤的最佳乙醇浓度与容量,以建立稳定的小鼠急性乙醇性胃黏膜损伤模型.方法 80只昆明小鼠随机分成正常对照组、生理盐水灌胃组、75%乙醇灌胃组、99.5%乙醇灌胃组,然后分别在1 h、4 h处死小鼠取胃,观察小鼠胃黏膜损伤情况.结果 乙醇灌胃1 h后,胃黏膜出现不同程度的损伤,其中99.5%乙醇0.2 ml/10 g对小鼠胃黏膜的损伤较重.99.5%乙醇0.2 ml/10 g灌胃4 h与1 h相比,胃黏膜损伤指数有所下降.随着乙醇浓度的增加与乙醇灌胃时间的延长小鼠的生存率并无显著变化.结论 乙醇灌胃可致小鼠急性胃黏膜损伤,且以99.5%乙醇0.2 ml/10 g灌胃用来制备小鼠急性乙醇性胃黏膜损伤模型最佳.

  19. [Preventive effects of troxipide on a newly developed model of acute gastric mucosal lesion (AGML) induced by ischemia/reperfusion plus ammonia in the rat].

    Momo, K; Hoshina, K; Ishibashi, Y; Saito, T


    We have developed a unique rat AGML model produced by ischemia/reperfusion plus 0.2% ammonia (I/R.NH3), either treatment which would not induce mucosal injury when used alone. The effects of troxipide and other gastric mucosal defensive drugs were investigated with this I/R.NH3-induced AGML model and other AGML models in rats. The following results were obtained: 1) Like allopurinol, troxipide at 50-200 mg/kg, p.o. dose-dependently prevented I/R.NH3-induced development of AGML and also the ischemia/reperfusion-induced increase of gastric mucosal thiobarbituric acid (TBA)-reactive substances; 2) Troxipide at 10(-6)-10(-4) M, like allopurinol, inhibited concentration-dependently in vitro xanthine oxidase activity in gastric mucosal homogenates; 3) Troxipide at 50-200 mg/kg, p.o. inhibited AGMLs induced by bleeding plus 0.2% ammonia and by 1.0% ammonia alone; and 4) Troxipide and sofalcone were similar in preventing all AGMLs tested and also the increase of mucosal TBA-reactive substances, but somewhat differed from teprenone, cetraxate hydrochloride, azulene plus L-glutamine and sucralfate. These findings suggest that troxipide may inhibit I/R.NH3-induced AGML development by preventing generation of oxygen free radicals and by protecting against mucosal fragility due to reduced energy metabolism from poor blood flow and also against ammonia-induced disruption of the gastric mucosal barrier. Therefore, troxipide may be highly effective for various AGMLs with multifactor involvement.

  20. In Vivo and Cadaver Studies of the Canalicular/Lacrimal Sac Mucosal Folds

    Yongsheng You


    Full Text Available Purpose. The study aimed to investigate canalicular/lacrimal sac mucosal folds (CLS-MFs in vivo and in cadavers in order to explore their functional roles in the lacrimal drainage system. Method. The observations of CLS-MFs in vivo were performed on 16 patients with chronic dacryocystitis after undergoing an endonasal endoscopic dacryocystorhinostomy (EE-DCR. The lacrimal sacs and common canaliculi of 19 adult cadavers were dissected. The opening/closing of an orifice and mucosal fold was recorded. All of the specimens were subjected to a histological examination. Results. The upper and lower lacrimal canaliculi in all of the samples united to form a common canaliculus that opened to the lacrimal sac. CLS-MFs were observed in 10 of the 16 patients (62.5% and 9 of the 19 cadavers (47.4%. The orifices or mucosal folds could be opened or closed when related muscles contracted or relaxed. Histological sections showed a mucosal fold at one side of an orifice. Conclusion. Common canaliculus is the most common type that the canaliculus opens to lacrimal sac. CLS-MFs exist in a certain ratio that can be opened/closed with the movement of the orifices. They may be involved in the drainage of tears or the pathogenesis of acute dacryocystitis or lacrimal sac mucocele.

  1. Oral mucositis - self-care

    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 ...

  2. Protective effects of alginate-chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. (Zuojin Pill) against ethanol-induced acute gastric mucosal injury in rats.

    Wang, Qiang-Song; Zhu, Xiao-Ning; Jiang, Heng-Li; Wang, Gui-Fang; Cui, Yuan-Lu


    Zuojin Pill (ZJP), a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in a ratio of 6:1 (w/w) and was first recorded in "Danxi's experiential therapy" for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss.) Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the mucoadhesive microspheres loaded with alkaloids reduce the inflammatory response by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), downregulating the mRNA expression of inducible nitric oxide synthase, TNF-α, and IL-1β in gastric mucosa. All the results indicate that mucoadhesive microspheres loaded with alkaloids could not only increase the residence time of alkaloids in rat stomach, but also exert gastroprotective effects through reducing the inflammatory response on ethanol-induced gastric mucosal damage. Thus, these

  3. Research Progress in Pathogenesis of Acute Promyelocytic Leukemia%急性早幼粒细胞白血病发病机制研究新进展

    鞠满凯; 张磊


    There has been deep research about the pathogenesis of acute promyelocytic leukemia .The classical pathogenesis is due to the translocation of chromosome t (15;17),the formation of promyelocyti-cleukemia (PML)/retinoic acid receptor α(RARα) fusion gene and then the generation of PML/RARαfusion protein which leads to the occurrence of the disease.In recent years,with the development of the re-search,more fusion genes are discovered,with relatively different natures.Although the classic PML/RARαaccounts for the majority of acute promyelocytic leukemia,other types have lots of differences in drug sensitiv-ity,so the pathogenesis should be made clear so as to instruct the treatment.%急性早幼粒细胞白血病的发病机制已有较深入研究,经典的发病机制是由于染色体 t (15;17)易位形成PML/维甲酸受体α(RARα)融合基因,进而产生PML/RARα融合蛋白导致疾病的发生。近年来随着研究的进展,更多的融合基因被发现,且有相对各异的性质。虽然经典的 PML/RARα占急性早幼粒细胞白血病的大多数,但其他类型基因对药物敏感性却各有不同,应明确其发病机制,指导治疗。

  4. Fluconzole in treatment of acute radiation-induced oral mucositis with fungal infection%氟康唑治疗急性放射性口腔粘膜炎继发的真菌感染

    姚原; 吴国华; 蒋马伟; 林清; 陆冬青; 翁霞


    目的:研究头颈部肿瘤放射治疗中急性放射性口腔粘膜反应与真菌感染的关系及氟康唑治疗的有效性。方法:71例口腔粘膜受到大面积照射的肿瘤病人:男性42例,女性29例;年龄52 a± s 41 a(11~76 a),在病人的口腔粘膜反应最严重的时候,做口腔粘膜真菌学检查,32例有真菌感染的病人,用氟康唑胶囊100 mg,po, qd×5 d或氟康唑注射液150 mg,iv,gtt×3 d治疗。结果:真菌的检出率为45%,以白念珠菌感染为主。有真菌感染和无真菌感染的2组病人,在急性放射性粘膜反应上差异有显著意义(P<0.05);有真菌感染的病人用氟康唑治疗,治疗前后的粘膜反应差异有显著意义(P<0.05)。结论:严重的急性放射性粘膜反应与真菌感染有密切的关系;有真菌感染的放射性口腔粘膜反应用氟康唑治疗可以明显减轻放射性粘膜反应。%AIM: To study the relation of acute radiation-induced oral mucositis to fungal infection and evaluate the effect of fluconazole in the treatment of patients with fungal infection. METHODS: Seventy-one patients (M 42, F 29; 52 a± s 41 a,11-76 a) with large area of oral mucosas irradiated were into this study. When most serious mucositis, the patients' oral mucosas were checked, 32 patients with fungal infection were treated with fluconazole (fluconazole 100 mg, po, qd×5 d or 150 mg,iv,gtt×3 d). RESULTS: The rate of fungal infection was 45%, the most of patients were infected by candida albicans. Degrees of mucositis between the patients with fungal infection to the patients without fungal infection were significantly different (P<0.05). The patients with fungal infection were treated with fluconazole. Degree of mucositis between the pretreated patients and post-treated patients were significantly different (P<0.05). CONCLUSION: The serious acute radiation-induced oral mucositis has significantly related with fungal infection. The patients

  5. Enhanced gastric mucosal haemostasis after upper gastrointestinal haemorrhage.

    Allison, M C; Fullarton, G M; Brown, I.L.; Crean, G P; McColl, K E


    An endoscopic technique for the measurement of gastric mucosal bleeding time has been developed to study gastric haemostasis in patients with acute upper gastrointestinal haemorrhage. The relation of gastric mucosal bleeding time to skin bleeding time and nonsterodial anti-inflammatory drug usage was examined in 61 control patients and in 47 patients presenting with bleeding peptic ulcers or erosions. Gastric mucosal bleeding time was shorter in patients with haemorrhage (median 2 minutes, ra...

  6. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. (Zuojin Pill against ethanol-induced acute gastric mucosal injury in rats

    Wang QS


    Full Text Available Qiang-Song Wang,1,2,* Xiao-Ning Zhu,1,* Heng-Li Jiang,1,* Gui-Fang Wang,3 Yuan-Lu Cui1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, 3Pharmacy Department, Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Zuojin Pill (ZJP, a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. in a ratio of 6:1 (w/w and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss. Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the

  7. Mucosal healing and fibrosis after acute or chronic inflammation in wild type FVB-N mice and C57BL6 procollagen α1(I-promoter-GFP reporter mice.

    Shengli Ding

    Full Text Available BACKGROUND: Injury and intestinal inflammation trigger wound healing responses that can restore mucosal architecture but if chronic, can promote intestinal fibrosis. Intestinal fibrosis is a major complication of Crohn's disease. The cellular and molecular basis of mucosal healing and intestinal fibrosis are not well defined and better understanding requires well characterized mouse models. METHODS: FVB-N wild type mice and C57BL6 procollagen α1(I-GFP reporter mice were given one (DSS1 or two (DSS2 cycles of 3% DSS (5 days/cycle followed by 7 days recovery. Histological scoring of inflammation and fibrosis were performed at DSS1, DSS1+3, DSS1+7, DSS2, DSS2+3, and DSS2+7. Procollagen α1(I-GFP activation was assessed in DSS and also TNBS models by whole colon GFP imaging and fluorescence microscopy. Colocalization of GFP with α-smooth muscle actin (α-SMA or vimentin was examined. GFP mRNA levels were tested for correlation with endogenous collagen α1(I mRNA. RESULTS: Males were more susceptible to DSS-induced disease and mortality than females. In FVB-N mice one DSS cycle induced transient mucosal inflammation and fibrosis that resolved by 7 days of recovery. Two DSS cycles induced transmural inflammation and fibrosis in a subset of FVB-N mice but overall, did not yield more consistent, severe or sustained fibrosis. In C57BL6 mice, procollagen α1(I-GFP reporter was activated at the end of DSS1 and through DSS+7 with more dramatic and transmural activation at DSS2 through DSS2+7, and in TNBS treated mice. In DSS and TNBS models GFP reporter expression localized to vimentin(+ cells and much fewer α-SMA(+ cells. GFP mRNA strongly correlated with collagen α1(I mRNA. CONCLUSIONS: One DSS cycle in FVB-N mice provides a model to study mucosal injury and subsequent mucosal healing. The procollagen α1(I-GFP transgenic provides a useful model to study activation of a gene encoding a major extracellular matrix protein during acute or chronic

  8. Medical Recapitulate%Role of Nrf-2 Gene in the Pathogenesis of Brain Damage Following Acute Carbon Monoxide Poison-ing

    郑然(综述); 李琴; 邹勇(审校)


    Acute brain damage and delayed encephalopathy are two main clinical manifestations of brain damage after carbon monoxide(CO) exposure,and seriously affect the life quality and prognosis of patients with CO poisoning.Hyperbaric oxygen is considered as the main therapy for brain damage after acute CO poi-soning.However,there are many controversies on its clinical application .The pathogenesis of brain damage after acute CO poisoning is poorly elucidated.The activation of nuclear factor erythrocyte two related factors-2 ( Nrf-2) may benefit the therapy for inflammatory and apoptosis mechanism triggered by CO poisoning .Thus, research on the role of Nrf-2 gene in the pathogenesis of brain damage following acute CO poisoning can pro-vide new ideas for the targeted therapy for the acute brain damage and delayed encephalopathy following CO poisoning.%一氧化碳中毒后的急性脑损伤和迟发型脑病严重影响患者的预后及生存质量。高压氧作为临床治疗一氧化碳中毒性脑损伤的主要方法争议颇多,而一氧化碳中毒性脑损伤的发病机制目前也尚未明确。核因子红细胞2相关因子2(Nrf-2)的激活可能对一氧化碳中毒引发的炎症、凋亡等发挥较好的治疗作用。因此,研究Nrf-2在一氧化碳中毒性脑损伤发病机制中的作用可为一氧化碳中毒后急性脑损伤和迟发型脑病的靶向治疗提供新思路。

  9. Pathogenesis of helicobacter pylori infection: Bacterium and host relationship

    Sokić-Milutinović Aleksandra


    Full Text Available Helicobacter pylori (H. pylori colonizes the gastric mucosa of a half of the mankind. Duodenal ulcer is found in 15-25%, t gastric ulcer in 13%, while gastric adenocarcinoma develops in 1% of all infected individuals. Pathogenesis of H. pylori infection is related to the virulence factors of the bacterium, environmental (dietary habits, hygiene, stress and host factors (age, sex, blood type. Colonization of the gastric mucosa is related to the motility of the bacterium, presence of lipopolysacharide (LPS and various bacterial enzymes. Gastric mucosal injury is the result of H. pylori LPS, vacuolization cytotoxin (vacA, cytotoxin associated protein (cagA, heat shock proteins and factors responsible for neutrophil chemotaxis and activity. H. pylori colonizes the gastric mucosa and zones of ectopic gastric epithelium. H. pylori infection is transmitted via oral-oral, fecal-oral and iatrogenic way (during endoscopy. Higher prevalence of the infection is associated with lower socioeconomic level, lack of drinking water, and living in a community. Acute H. pylori gastritis is superficial pangastritis progressing into the chronic phase after 7-10 days. Gastric mucosal atrophy and intestinal metaplasia can develop during the course of H. pylori infection. Clearly defined factors that influence the outcome of H. pylori infection include bacterial strain, distribution of gastritis, acid secretion and gastric mucosal atrophy.

  10. Transgenic Killer Commensal Bacteria as Mucosal Protectants

    Luciano Polonelli


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

  11. Israeli acute paralysis virus: epidemiology, pathogenesis and implications for honey bee health and Colony Collapse Disorder (CCD)

    Israeli acute paralysis virus (IAPV) is a widespread RNA virus that was linked with honey bee Colony Collapse Disorder (CCD), the sudden and massive die-off of honey bee colonies in the U.S. in 2006-2007. Here we describe the transmission, prevalence and genetic diversity of IAPV, host transcripti...

  12. Phase 3 Trial of Domiciliary Humidification to Mitigate Acute Mucosal Toxicity During Radiation Therapy for Head-and-Neck Cancer: First Report of Trans Tasman Radiation Oncology Group (TROG) 07.03 RadioHUM Study

    Macann, Andrew, E-mail: [Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Fua, Tsien [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Milross, Chris G. [Department of Radiation Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales (Australia); Porceddu, Sandro V. [Oncology Services, Princess Alexandra Hospital, Woolloongabba, Queensland (Australia); Penniment, Michael [Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia (Australia); Wratten, Chris [Radiation Oncology, Calvary Mater Newcastle, Waratah, New South Wales (Australia); Krawitz, Hedley [Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Poulsen, Michael [Department of Radiation Oncology, Radiation Oncology Mater Centre, South Brisbane, Queensland (Australia); Tang, Colin I. [Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); Morton, Randall P. [Department of Otorhinolaryngology, Middlemore Hospital, Otahuhu, Auckland (New Zealand); Hay, K. David [Department of Oral Health, Auckland City Hospital, Auckland (New Zealand); Thomson, Vicki [Department of Otorhinolaryngology, Auckland City Hospital, Auckland (New Zealand); Bell, Melanie L.; King, Madeleine T. [Psycho-oncology Cooperative Research Group, Univerity of Sydney, Sydney, New South Wales (Australia); Fraser-Browne, Carol L. [Adult Oncology Research Centre, Auckland City Hospital, Auckland (New Zealand); Hockey, Hans-Ulrich P. [Biometrics Matters Ltd, Hamilton (New Zealand)


    Purpose: To assess the impact of domicile-based humidification on symptom burden during radiation therapy (RT) for head-and-neck (H and N) cancer. Methods and Materials: From June 2007 through June 2011, 210 patients with H and N cancer receiving RT were randomized to either a control arm or to receive humidification using the Fisher and Paykel Healthcare MR880 humidifier. Humidification commenced on day 1 of RT and continued until Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, clinical mucositis (CMuc) grade ≤1 occurred. Forty-three patients (42%) met a defined benchmark for humidification compliance and contributed to per protocol (PP) analysis. Acute toxicities, hospitalizations, and feeding tube events were recorded prospectively. The McMaster University Head and Neck Radiotherapy Questionnaire (HNRQ) was used for patient-reported outcomes. The primary endpoint was area under the curve (AUC) for CMuc grade ≥2. Results: There were no significant differences in AUC for CMuc ≥2 between the 2 arms. Humidification patients had significantly fewer days in hospital (P=.017). In compliant PP patients, the AUC for CTCAE functional mucositis score (FMuc) ≥2 was significantly reduced (P=.009), and the proportion who never required a feeding tube was significantly greater (P=.04). HNRQ PP analysis estimates also in the direction favoring humidification with less symptom severity, although differences at most time points did not reach significance. Conclusions: TROG 07.03 has provided efficacy signals consistent with a role for humidification in reducing symptom burden from mucositis, but the influence of humidification compliance on the results moderates recommendations regarding its practical utility.

  13. Human LINE1 endonuclease domain as a putative target of SARS-associated autoantibodies involved in the pathogenesis of severe acute respiratory syndrome

    HE Wei-ping; SHU Cui-li; LI Bo-an; ZHAO Jun; CHENG Yun


    Background Severe acute respiratory syndrome(SARS)is a disease with a mortality of 9.56%.Although SARS is etiologically linked to a new coronavirus(SARS-CoV)and functional cell receptor has been identified,the pathogenesis of the virus infection is largely unclear.Methods The clinical specimens were processed and analyzed using an indirect enzyme-linked immunosorbent assay (ELISA) in-house.Further investigations of target antigen included reviews of phage display technique,rapid amplification of cDNA ends(RACE)technique,protein expression and purification,Western blotting validation,serological and immunohistochemical staining in postmortem tissue.Results A type of medium or low titer anti-lung tissue antibodies were found in the sera of SARS patients at the early stage of the disease.Human long interspersed nuclear element 1(LINE1)gene endonuclease(EN)domain protein was one of the target autoantigens and it was aberrantly expressed in the lung tissue of SARS patients.Anti-EN antibody was positive in the sera of 40.9% of SARS patients.Conclusions Human LINE1 endonuclease domain was identified as a putative target of SARS-associated autoantibodies,which were presented in the serum of SARS patients and may be involved in the pathogenesis of SARS.

  14. Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications

    Takahashi Shinichiro


    Full Text Available Abstract FLT3 is a type III receptor tyrosine kinase. Mutations of FLT3 comprise one of the most frequently identified types of genetic alterations in acute myeloid leukemia. One-third of acute myeloid leukemia patients have mutations of this gene, and the majority of these mutations involve an internal tandem duplication in the juxtamembrane region of FLT3, leading to constitutive activation of downstream signaling pathways and aberrant cell growth. This review summarizes the current understanding of the effects of the downstream molecular signaling pathways after FLT3 activation, with a particular focus on the effects on transcription factors. Moreover, this review describes novel FLT3-targeted therapies, as well as efficient combination therapies for FLT3-mutated leukemia cells.

  15. Pathogenesis of Cardiorenal Syndrome Type 1 in Acute Decompensated Heart Failure : Workgroup Statements from the Eleventh Consensus Conference of the Acute Dialysis Quality Initiative (ADQI)

    Haase, Michael; Mueller, Christian; Damman, Kevin; Murray, Patrick T.; Kellum, John A.; Ronco, Claudio; McCullough, Peter A.; McCullough, PA; Kellum, JA; Mehta, RL; Murray, PT; Ronco, C


    Pathophysiological mechanisms of cardiorenal syndromes (CRS) types 1-5 are still sparsely characterized. In an attempt to address this issue, a consensus conference on CRS was held in Venice, Italy, in November 2012 under the auspices of the Acute Dialysis Quality Initiative (ADQI). Working group 1

  16. Current concept on the pathogenesis of inflammatory bowel disease-crosstalk between genetic and microbial factors: Pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take "toll"?

    Peter Laszlo Lakatos; Simon Fischer; Laszlo Lakatos; Istvan Gal; Janos Papp


    The pathogenesis of inflammatory bowel disease (IBD)is only partially understood. Various environmental and host (e.g. genetic-, epithelial-, immune and nonimmune) factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity.Some genes are associated with IBD itself, while others increase the risk of ulcerative colitis (UC) or Crohn's disease (CD) or are associated with disease location and/or behaviour. This review addresses recent advances in the genetics of IBD. The article discusses the current information on the crosstalk between microbial and genetic factors (e.g. NOD2/CARD15, SLC22A46A5 and DLG5). The genetic data acquired in recent years help in understanding the pathogenesis of IBD and can identify a number of potential targets for therapeutic intervention.In the future, genetics may help more accurately diagnose and predict disease course in IBD.



    Abstract. Amounts of several neutrophil enzymes (elastase, myeloperoxidase (MPO), MMP-2) and their local inhibitors, i.e., Clara cell protein (CC16) and HSP-70, have been determined in blood plasma from fifty-two patients with various forms of influenza A/H1N1. Sixteen patients have developed acute respiratory distress syndrome (ARDS). In cases of uncomplicated influenza, elastase and MPO levels were shown to be increased, while MMP-2 levels did not change, along with higher contents of HSP-7...

  18. Role of lysosomal enzymes released by alveolar macrophages in the pathogenesis of the acute phase of hypersensitivity pneumonitis

    J. L. Pérez-Arellano


    Full Text Available Hydrolytic enzymes are the major constituents of alveolar macrophages (AM and have been shown to be involved in many aspects of the inflammatory pulmonary response. The aim of this study was to evaluate the role of lysosomal enzymes in the acute phase of hypersensitivity pneumonitis (HPs. An experimental study on AM lysosomal enzymes of an HP-guinea-pig model was performed. The results obtained both in vivo and in vitro suggest that intracellular enzymatic activity decrease is, at least partly, due to release of lysosomal enzymes into the medium. A positive but slight correlation was found between extracellular lysosomal activity and four parameters of lung lesion (lung index, bronchoalveolar fluid total (BALF protein concentration, BALF LDH and BALF alkaline phosphatase activities. All the above findings suggest that the AM release of lysosomal enzymes during HP is a factor involved, although possibly not the only one, in the pulmonary lesions appearing in this disease.

  19. Radiation induced oral mucositis

    P S Satheesh Kumar


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


    E. V. Prutkina


    Full Text Available Abstract. Amounts of several neutrophil enzymes (elastase, myeloperoxidase (MPO, MMP-2 and their local inhibitors, i.e., Clara cell protein (CC16 and HSP-70, have been determined in blood plasma from fifty-two patients with various forms of influenza A/H1N1. Sixteen patients have developed acute respiratory distress syndrome (ARDS. In cases of uncomplicated influenza, elastase and MPO levels were shown to be increased, while MMP-2 levels did not change, along with higher contents of HSP-70 and unchanged CC16 amounts. Upon development of influenza-associated pneumonia, elastase and MPO concentrations became elevated, whereas MMP-2 levels were decreased, along with unchanged amounts of CC16 and HSP-70. In cases of ARDS development, CC16 amounts exhibited a sharp decrease. Meanwhile, contents of other proteins remained at the levels shown for pneumonia patients. It has been shown that increased concentrations of neutrophil elastase and MPO with a relative CC16 deficiency and decreased MMP-2 may represent a mechanism of pneumonia development. Decreased CC16 concentration may serve as a risk predictor of ARDS development.

  1. Pathogenesis of Hepatic Encephalopathy

    Irena Ciećko-Michalska


    Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

  2. Moving towards a new era in the research of tonsils and mucosal barriers.

    Yamanaka, Noboru


    The palatine and nasopharyngeal tonsils (adenoids) are lymphoepithelial tissues located in strategic anatomical areas of the oral pharynx and nasopharynx. These immunocompetent tissues represent the first line of defense against ingested or inhaled foreign proteins such as bacteria, viruses, or food antigens. Accompanying the advances being made in the field of medicine today, the role of the tonsils in immunocompetence is becoming extremely important. Upper respiratory tract infections such as acute otitis media, acute rhinosinusitis and acute pharyngo-tonsillitis are diseases that occur with extremely high frequency, and the antimicrobial agents used to treat these diseases account for a large proportion of health care costs. The increasingly refractory nature of upper respiratory tract infections caused by drug-resistant bacteria has become a major worldwide concern. The elucidation of the immune functions of the tonsils and mucosal membranes of the upper respiratory tract is considered to have important significance. The tonsils are also considered to play an important role as one of the causes of sleep apnea syndrome, and have been reported to be intimately involved in the manifestation of IgA nephropathy and palmoplantar pustulosis, a kind of skin disorder. Interest has continued to grow in this symposium with each session ever since it was first held in Kyoto, Japan in 1987. Since then, the symposium has been held every 3-4 years; in Pavia in 1991, in Sapporo in 1995, in Ghent in 1999, in Wakayama in 2003, and in Siena in 2006. Since the 5th symposium in Wakayama, the topics were extended to mucosal barriers of upper airways including the mucosal immune system, innate immunity, and mucosal vaccine. Recent fine technologies and information on molecular biological approaches for upper airways will continue to advance our understanding of epidemiology, etiology, pathogenesis, diagnosis and management of tonsil-related disorders and various upper respiratory

  3. 重症急性胰腺炎相关肾损伤的发病机制及治疗进展%Pathogenesis and treatment progress of associated renal injury in severe acute pancreatitis

    罗刚; 杨旭


    Severe acute pancreatitis(SAP) is a acute abdomen caused by a variety of reasons.Its major characteristic is pancreatic enzyme activation and digestion of pancreatic tissue itself.It is with or without other organ function change.Among them,acute renal failure(acute renal failure,ARF) is one of the important causes of death in SAP patients.Because the pathogenesis of the disease has not been fully elucidated,the treatment methods need further exploration.In this paper,the author reviews the pathogenesis and treatment progress of associated renal function injury in severe acute pancreatitis in recent years.%重症急性胰腺炎(SAP)是由多种原因引起的胰酶激活和胰腺组织的自身消化为主要特征的伴或不伴其他器官功能改变的急腹症。其中,急性肾衰竭(Acute renal failure,ARF)是导致 SAP 患者死亡的重要原因之一。由于该病的发病机制尚未完全阐明,治疗方法有待进一步探索。本文就近年来 SAP 相关肾功能损害的发病机制及治疗进展进行综述。

  4. Effects of psychiatric disorders on Type A acute aortic dissection pathogenesis and analysis of follow-up results

    Paolo Nardi


    Full Text Available Aims: A connection between psychiatric disorders (PDs and Type A acute aortic dissection (AAD has not been shown. The aim of this study was to define the psychological profile of patients treated for AAD, and to analyze the prevalence of PDs in their medical histories, in the immediate postoperative period, and at a mid-term follow-up. Patients and Methods: From March 2005 to October 2014, 240 consecutive patients underwent surgery for AAD. 60 patients (mean age 60+/-13 years; 43 males underwent psychiatric consultation postoperatively, and they represent the subjects of our retrospective study. Ascending aorta +/- arch replacement was performed in 43 patients, whereas the Bentall procedure +/- arch replacement was performed in 17. Data were retrospectively analyzed. Follow-ups were completed in 59 patients (mean duration 35+/-23 months. Results: PDs were present in the medical histories of 34 patients. Postoperatively, in 28 cases, a definitive diagnosis of PD (group PD was made in agreement with the diagnostic and statistical manual of mental disorders-IV criteria, including: Major depression (n=13, anxious-depressive syndrome (n=6, bipolar disorder Type 2 (n=4, panic attacks (n=2, paranoid schizophrenia (n=1, and anxiety (n=2. 32 patients without a definitive psychiatric diagnosis were classified as Group non-PD. In the postoperative period, clinical manifestations of PDs, including delirium, persistent spatio-temporal disorientation, and psychomotor agitation were evident in 22 patients (78% in group PD versus 8 patients (25% in group non-PD (P<0.0001. During follow-up, only one death for non-cardiac reasons occurred in group PD. There were no suicides; only 10 patients of group PD required PD treatment (P<0.0001 vs. early postoperative findings; 4 patients in group non-PD required PD treatment. Conclusion: Our findings suggest a strong relationship between PD and AAD. Because the psychiatric conditions appeared to be largely stable after

  5. 肥大细胞在急性应激性肠黏膜屏障损伤中的作用机制%Mechanism of Mast Cells in Acute Stress Induced Intestinal Mucosal Barrier Injury

    唐宇; 马洪升


    背景:应激所致肠黏膜屏障损伤的机制以及肥大细胞(MC)在其中的作用尚未明确.目的:探讨肠黏膜MC(IMMC)在急性应激性肠黏膜屏障损伤中的作用机制.方法:Sprague-Dawley(SD)大鼠随机分为正常对照组(N组)、应激组(S组),S组给予急性冷束缚应激建立模型,按照应激结束后处死时间进一步分为S2h、S4h、S8h、S16h、S24h组.取回肠末端观察组织病理学改变,以Chiu's评分评估肠黏膜组织损伤程度,以甲苯胺蓝染色计数IMMC,以透射电镜观察肠黏膜组织和IMMC超微结构,以ELISA法检测肠黏膜组织组胺含量.结果:S组的Chiu's评分均显著高于N组(P0.05).IMMC计数与Chiu's评分无相关性(P>0.05).S组肠黏膜超微结构破坏明显,IMMC胞质大量脱颗粒.S2h、S4h、S8h 组的肠黏膜组织组胺含量较N组显著降低(P0.05).肠黏膜组织组胺含量与Chiu's评分呈负相关(P=0.03).结论:急性应激状态下,IMMC脱颗粒释放炎性介质是导致肠黏膜屏障损伤的重要机制.%Background: The mechanism of stress induced intestinal barrier injury and the mechanistic role of mast cells ( MC ) have not yet been clarified. Aims: To investigate the mechanistic role of intestinal mucosal MC ( IMMC ) in acute stress induced intestinal mucosal barrier injury. Methods: Sprague-Dawley ( SD ) rats were randomly divided into normal control group ( N group ) and stress group ( S group ). Rats in S group were given acute cold/restraint stress and were further divided into S2h, S4h, S8h, S16h and S24h subgroups according to the time point of sacrificing after stress. Histological change of terminal ileum tissue was observed and the degree of damage was evaluated by Chiu s scoring system. IMMC number was counted by toluidine blue staining. The ultrastructure of intestinal tissue and IMMC was observed by transmission electron microscopy. The content of histamine in intestinal tissue was determined by ELISA. Results: Chiu s score in S

  6. 急性出血坏死性胰腺炎大鼠肠道免疫功能的改变%Intestinal mucosal immune barrier injury of rats with acute hemorrhagic necrotic pancreatiti

    金英朝; 王海宽; 张弘超; 李小东; 刘大伟


    ObjectiveTo observe intestinal mucosal immune barrier relative factors TNF-α in serum, sIgA levels of intestinal juice, and CD3+ and CD4+ cell change of intestinal tissue in rats with acute hemorrhagic necrotic pancreatitis. To investigate the change of intestinal mucosal immune barrier injury in this model.Methods36 wistar rats were randomly divided into three groups: SAP model group(A group), the sham operation control group (B group) (N = 18). Abdominal aortic and Portal vein blood were collected, and stored in refrigerator for next assays. Intestinal juice were collected and stored in refrigerator for next assays. The intestinal tissue were ifxed in 4% neutral formaldehyde buffer. TNF-α concentration of blood and sIgA levels of intestinal juice were evaluated by ELISA method. Immunohistochemistry was adopted to detect intestinal tissue CD3+ and CD4+ expression. Endotoxin levels of portal vein blood was detected following the kit instruction.ResultsTesting the indicators after model building of each group,we have the following ifndings: In group A, Blood TNF-a and sIgA levels of intestinal juice are signiifcantly lower than that in the group B, while endotoxin levels of portal vein blood signiifcantly higher. The expression of CD3+ and CD4+ T immune cell are signiifcantly lower in group A.ConclusionThis study conifrmed the participation of the intestinal mucosal immune barrier function injury are important inlfammatory disorders in acute pancreatitis in rats with acute hemorrhagic necrotic pancreatitis.%目的:探讨分析急性出血坏死性胰腺炎(AHNP)大鼠肠道黏膜免疫功能的变化情况。方法选取成年的Wistar雄性大鼠,随机分成AHNP组、假手术组。分别于造模后24 h取标本检测(主要包括内毒素的含量、CD3、CD4及CD8的阳性T淋巴细胞的比例、盲肠内容物sIgA的浓度,血清肿瘤坏死因子-α(TNF-α)的水平等。结果 AHNP组各时间段的门静脉血内毒素含量均有显著

  7. Nasal mucosal biopsy

    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 ...

  8. Live bacterial delivery systems for development of mucosal vaccines

    Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.


    By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

  9. The Effects of Combined Adiponectin-Metformin on Glucose and Lipids Levels in Mice and Acute Toxicity and Anti-Ulcerogenic Activity of Adiponectin Against Ethanol-Induced Gastric Mucosal Injuries in Rat

    Mohammed A. Alshawsh


    Full Text Available Adiponectin is a protein hormone secreted entirely by abdominal fat tissue. It exhibits various biological activities. The present study was performed to evaluate the effects of metformin alone or in combination with adiponectin on blood glucose, TG (triglyceride, CHOL (Total cholesterol, LDL (Low density lipoprotein and HDL (High density lipoprotein levels in mice and also to evaluate the anti-ulcerogenic activity of adiponectin against ethanol induced gastric mucosal injury in rats. Three groups of mice were gavaged with 1% volume/body weight high fat-sucrose. Metformin at a dosage of 250 mg/kg was added to the feed and a dosage of 2.5 mg/kg adiponectin was injected intraperitoneally (i.p. Blood glucose was measured at one hour intervals for five hours. Blood concentrations of TG, CHOL, LDL and HDL were also measured at the end of the fifth hour of the experiment. On the other hand, four groups of adult healthy rats were i.p. injected with distilled water, omeprazole 20 mg/kg, 2.5 mg/kg and 5 mg/kg adiponectin one hour before oral administration of absolute ethanol to generate gastric mucosal injury. After an additional hour the rats were sacrificed and the ulcer areas of the gastric walls were determined. Furthermore, an acute toxicity study has indicated no mortality with 5 mg/kg dose of adiponectin injected i.p in rats and no major clinical signs of toxicity were observed. The results indicate that the effect of a combination of metformin and adiponectin on blood glucose and HDL is quite effective. Histology of the gastric wall of negative control rats revealed severe damage of gastric mucosa, along with edema and leucocyte infiltration of the submucosal layer compared to rats pre-treated with either omeprazole or adiponectin extract where there was marked gastric protection along with reduction or inhibition of edema and leucocytes infiltration. The results suggest that combination of metfomin and adiponectin give a promising antidiabetic

  10. Migraine Pathogenesis

    Nabih M. M.D. Ramadan


    @@Introduction Various theories of migraine pathogenesis have been developed over the years. To this date, none fully explains all the migraine phenomena. A complete description of each proposed theory is beyond the scope of this chapter. Nonetheless, a brief description of the arguments for and against the leading theories is noteworthy

  11. 鱼油对重症急性胰腺炎大鼠肠黏膜屏障的影响%Fish oil protects the intestinal mucosal barrier in rats with severe acute pancreatitis

    张波; 刘燕燕; 刘丛丛; 武华


    目的:探讨 -3鱼油脂肪乳剂对重症急性胰腺炎(SAP)大鼠早期肠黏膜功能屏障的影响.方法:♂Wistar大鼠30只随机分为:假手术组(So组,n=10),鱼油治疗组(F组,n=10)和生理盐水治疗组(N组,n=10).通过胰管逆行注射法建成SAP模型,并分别尾静脉注射 -3鱼油脂肪乳剂和生理盐水治疗.检测大鼠血浆D-乳酸和肠脂肪酸结合蛋白(I-FABP)的水平,观察小肠黏膜组织和胰腺组织并进行病理学评分.0.23,均P<0.05或0.01).结论:ω-3鱼油脂肪乳剂能降低D-乳酸和I-FABP的浓度,从而降低肠黏膜的通透性,减轻全身炎症反应,保护大鼠的肠黏膜屏障.%AIM: To evaluate the protective effect of omega-3 fish oil on the intestinal mucosal barrier in serious acute pancreatitis (SAP) rats.METHODS: Thirty male Wistar rats were randomly divided into three groups: sham-operated group (n = 10), fish oil group (n = 10), and normal saline group (n = 10).SAP was induced in rats of the fish oil group and normal saline group by retrograde injection of 5% sodium cholate (1 mL/kg) into the pancreatic duct.These two groups were then intravenously given fish oil supplement (2 mL/kg) and normal saline (2mL/kg), respectively.The sham-operated group was subjected to sham operation.After treatment, plasma D-lactate and serum intestinal fatty acid binding protein (I-FABP) were measured, and the severity of pancreatitis and intestinal changes was evaluated by histopathological scoring.RESULTS: Plasma D-lactate (mmol/L), serum I-FABP (μg/L), and histopathological scores of intestinal changes and pancreatitis in the normal saline group were markedly lower than those in the sham-operated group and fish oil group (0.43 ± 0.12 vs 0.07 ±0.02, 0.26 ± 0.05; 1 510.00 ± 72.72 vs 80.50 ± 5.60, 904.00 + 61.50; 2.60 ± 0.32 vs 0.20 ± 0.10, 1.85 ± 0.34; 8.60 ± 0.31 vs 0.30 ± 0.12, 7.30 ± 0.23; all P < 0.05 or 0.01).CONCLUSION: Omega-3 fish oil supplementation reduces plasma D-lactate and

  12. Mucosal vaccination of fish

    Rombout, J.H.W.M.; Kiron, V.


    Among the novel vaccination methods, mucosal vaccination seems to possess all the desired criteria. The chapter reviews the state-of-the-art knowledge regarding this type of vaccination with a focus on their uptake, immune stimulation, and where possible, discusses their potential as future vaccines

  13. 大黄素对急性放射性肠炎肠黏膜屏障的保护作用%Protective effects of emodin on intestinal mucosal barrier in acute radiation enteritis

    王玉; 周冬枝; 夏欣欣; 韩萍萍; 曹丽君


    Objective To investigate the effects and mechanisms of emodin on acute radiation enteritis models and intestinal mucosal barrier. Methods Totally 50 healthy male SD rats were randomly divided into normal group, model group, emodin prevention group, emodin treatment group and SiMiDa group. Emodin prevention group had been given emodin for 3 consecutive days in advance. Except normal group, the others were given a single dose of 10 Gy 6 MV of higher-energy X-rays on the abdominal region to establish acute radiation enteritis models. After 6 h, emodin prevention group, emodin treatment group and SiMiDa group were given intragastric administration for 4 days. The morphologic indexes were measured by light microscopy and the image analysis system. Intestinal diamine oxidase (DAO) activities as well as bacteria translocation rates of liver, spleen and mesenteric lymph node were measured. Intestinal tumor necrosis factor alpha (TNF-α) was measured by ELISA and nitric oxide (NO) level was measured by spectrophotometer. Results Emodin prevention group, emodin treatment group and SiMiDa group had significantly higher levels of villus height, crypt depth, thickness of mucosa and entire wall as well as DAO activities than model group (P0.05). Conclusion Emodin could significantly increase villus height of the small intestine, crypt depth and mucosal layer thickness, enhance intestinal tissue DAO activities, protect the intestinal mucosa, reduce bacterial translocation rate, and reduce TNF-α expression in the intestinal tissue and NO generation. There are no significant differences between prophylaxis and treatment administration of emodin.%目的 探讨大黄素对急性放射性肠炎疗效及对肠黏膜屏障保护的疗效机制.方法 SD大鼠50只,随机分为正常组、模型组、大黄素预防组、大黄素治疗组、思密达组.大黄素预防组提前灌胃给药3d,除正常组外的各组采用X射线照射建立急性放射性肠炎模型,照射后6h

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

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


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

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

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


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

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

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


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

  17. Pathogenesis of mucosal injury in the blind loop syndrome.

    Jonas, A; Krishnan, C; Forstner, G


    Bacterial extracts were prepared from cultures originating in chronic self-filling intestinal blind loops in rats. Their ability to remove active maltase molecules from isolated brush border membranes was studied in vitro. Twelve strains in 51 tested, belonging to one of three species, Bacteroides fragilis, Clostridium perfringens, and Streptococcus fecalis, possessed maltase-releasing activity. The ability to remove maltase correlated well with the ability to hydrolyze p-nitrophenyl-tert-butyloxycarbonyl-l-alaninate (NBA), an ester substrate rapidly hydrolyzed by elastase, but not with substrated favored by tryhsin and chymotrypsin. Maltase-releasing activity from C. perfringens was strongly inhibited by soybean trypsin inhibitor and to a lesser extent by lima bean trypsin inhibitor. Of four chloromethylketone active-site directed inhibitors tested with specificities for elastase, trypsin, and chymotrypsin, inhibition was maximal with elastase-specific inhibitors. In two species, activity was shown to be heat sensitive, and to be inhibited by concentration of the extract. In one species maltase-releasing activity was shown to be due to an enzyme of molecular weight at least 66,000 with the capacity to remove lactase, sucrase, and alkaline phosphatase, as well as maltase. The results indicate that anaerobic or facultatively anaerobic species, previously identified with the pathology of of the blind loop syndrome, contain proteases which are capable of removing components of the intestinal surface membrane. These proteases appear to have elastase-like substrate specificity and may be involved in the etiology of disaccharidase deficiency in bacterial overgrowth syndromes.

  18. Contrastive study of Dahuanggancao Decoction on intestinal mucosal barrier function in severe acute pancreatitis%大黄甘草汤对重症急性胰腺炎肠黏膜屏障功能的对照研究

    陈小鹏; 樊勇; 王跃斌; 陈罗飞; 王琛


    目的:探讨大黄甘草汤对重症急性胰腺炎(SAP)肠黏膜屏障功能的影响。方法将45只清洁级健康雄性SD大鼠采用随机数字表法随机分为大黄甘草汤治疗组(D组)、SAP模型组(P组)和假手术组(S组),每组15只。采用逆行注射5%牛黄胆酸钠(0.5 mL/100 g)制备大鼠SAP模型。D组给予大黄甘草汤(2.0 mL/100 g),P、S组给予0.9%氯化钠溶液(2.0 mL/100 g)。分别于建模后12、24、36 h经腹主动脉采集血标本检测血淀粉酶、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、IL-10、D-乳酸水平等。结果 D组大鼠血淀粉酶、TNF-α、IL-6、D-乳酸水平明显低于P组,IL-10水平明显高于P组,差异均有统计学意义(P<0.05)。结论大黄甘草汤对SAP大鼠肠黏膜屏障功能具有保护作用,治疗SAP疗效较好。%Objective To explore the effect of Dahuanggancao Decoction on the intestinal mucosal barrier function of se-vere acute pancreatitis(SAP). Methods Forty-five clean class SD healthy male rats were randomly divided into the Dahuanggancao Decoction group(D,n=15),SAP model group(P,n=15)and sham operation group(S,n=15). The SAP rat model was induced by the retrograde injection of 5%sodium taurocholate(0.5 mL/100 g). The group D was given Dahuanggancao Decoction(2.0 m/100 g), while the group P and S was given 0.9%sodium chloride solution(2.0 mL/100 g). The blood samples were collected from inferior vena cava at 12,24,36 h after model construction and serum amylase,TNF-α,IL-6,IL-10 and D-lactic acid levels were detected. Results The serum amylase,TNF-α,IL-6 and D-lactic acid levels in the group D were significantly lower than those in the group P,while the IL-10 level was significantly higher than that in the group P,the difference was statistically significant(P<0.05). Conclusion Dahuanggancao Decoction has a protective effect on the intestinal mucosal barrier function of SAP rats and has good effect in

  19. 重症急性胰腺炎并发胰腺脑病的发病机制研究进展%Advanced on the pathogenesis of severe acute pancreatitis complicated with pancreatic encephalopathy

    刘补报; 李得溪


    胰腺脑病是重症急性胰腺炎的严重并发症,病死率高,预后差。目前关于胰腺脑病的发病机制主要有胰酶学说、细胞因子学说、营养缺乏学说、细菌和真菌感染学说、低氧血症与微循环障碍和组织代谢紊乱学说等,但尚未有哪一种学说能独立阐明其发病机制。笔者主要综述近几年来发展的各种学说。%Pancreatic encephalopathy (PE) is a severe complication of severe acute pancreatitis, and has the characteristics of the high mortality and poor prognosis. Although about the pathogenesis of pancreatic encephalopathy mainly include theory of pancreatic enzyme, the theory of cytokines, the theory of alimentary deficiency, the theory of bacterial and fungal infection, the theory of hypoxemia and microcirculation dysfunction, the theory of tissue metabolism disorder and so on, the pathogenesis of pancreatic encephalopathy still unclear at present. The author mainly reviews the development of the pathogenesis of pancreatic encephalopathy in recent years.

  20. 急性早幼粒细胞白血病的发病机制及治疗进展%Advance in the pathogenesis and treatment of acute promyelocytic leukemia

    谢琴芬; 金洁; 黄健


    急性早幼粒细胞白血病(APL)是目前发病机制了解最清楚的血液系统恶性肿瘤.维甲酸和三氧化二砷直接针对PML-RARα融合蛋白的治疗使得该疾病成为肿瘤靶向治疗的第一个模型,各种新型治疗方案也得到了广泛的关注.现对APL的发病机制及最新的临床治疗进展进行总结和讨论.%Pathogenesis of acute promyelocytic leukemia is one of the best understood disease among human hematological malignancies. Becasue of retinoic acid (RA) and arsenic trioxide which directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARα) fusion protein, this disease became the first model for oncogene-targeted therapies.And other new therapy methods also gain great concern. The complexity of recent views of acute promyelocytic leukemia pathogenesis, as well as latest progress in clinical treatment were summarized and discussed in this review.

  1. Buccal Mucosal Graft Urethroplasty

    Angela M. Arlen


    Full Text Available At our institution, the majority of buccal mucosal graft urethroplasties are performed using a two-team approach with an otolaryngologic surgeon. We report our two-surgeon experience with buccal mucosal grafting for reconstruction of all anterior urethral strictures. Twenty-four men underwent autologous buccal mucosal graft urethroplasty between October 2001 and September 2008 for recurrent urethral stricture disease. Twenty-two underwent a single-stage repair and two underwent a two-stage repair. Medical charts were retrospectively reviewed for demographics, comorbidities, etiology, location and length of stricture, and prior interventions in order to identify predictors of buccal urethroplasty success, defined as no evidence of stricture recurrence. All patients underwent retrograde urethrogram and cystoscopy. Operative and anesthesia times were evaluated. We determined an overall success rate of 83.3% (20 of 24 cases. Mean anesthesia time for single-stage urethroplasty was 155 min and mean operative time was 123 min. One of the two two-stage urethroplasties experienced stricture recurrence (50%. The single-stage buccal graft success rate was 86.4% (19 of 22 cases. Two of the four who developed recurrent stricture disease that required intervention had undergone a previous mesh urethroplasty. Complications developed in four of 24 patients (16.6%, including superficial wound infection (one, superficial wound dehiscence (two, and abscess/fistula formation requiring reoperation (one. The buccal mucosa is an ideal tissue for both single- and two-stage substitution urethroplasty for patients with recurrent stricture disease. Our two-surgeon technique minimizes anesthesia and operative times, and contributes to the overall high success rate and relatively low complication rate.

  2. [Roxatidine in the treatment of gastroduodenal mucosal lesions in hepatic cirrhosis].

    Sardini, C; Ventura, P; Abbati, G L; Rigo, G; Cioni, G; Cristani, A; Tincani, E; Ventura, E


    In about 50% of patients with liver cirrhosis, upper digestive bleeding is not due to oesaphageal varices rupture, but to a group of peculiar mucosal lesions usually referred as "congestive gastropathy" and "hepatogenic ulcer". The pathogenesis of such mucosal damage is still unclear: an important causative role is commonly thought to be played by portal hypertension, but the role of peptical pathway and of the mucosal barrier impairment must not be underscored as well. Aim of this study was to evaluate the effect of roxatidine in the long-term treatment of mucosal damage in 19 patients with liver cirrhosis. Patients showed a good tolerance and no side effects. The improvement of endoscopic pattern after a three months period of roxatidine therapy was statistically significant; moreover there was no occurrence of digestive bleeding. In conclusion, H2 antagonist may be considered as the drug of choice for the treatment of mucosal damage in patients with liver cirrhosis, for both its safety and effectiveness.

  3. Anthrax Pathogenesis.

    Moayeri, Mahtab; Leppla, Stephen H; Vrentas, Catherine; Pomerantsev, Andrei P; Liu, Shihui


    Anthrax is caused by the spore-forming, gram-positive bacterium Bacillus anthracis. The bacterium's major virulence factors are (a) the anthrax toxins and (b) an antiphagocytic polyglutamic capsule. These are encoded by two large plasmids, the former by pXO1 and the latter by pXO2. The expression of both is controlled by the bicarbonate-responsive transcriptional regulator, AtxA. The anthrax toxins are three polypeptides-protective antigen (PA), lethal factor (LF), and edema factor (EF)-that come together in binary combinations to form lethal toxin and edema toxin. PA binds to cellular receptors to translocate LF (a protease) and EF (an adenylate cyclase) into cells. The toxins alter cell signaling pathways in the host to interfere with innate immune responses in early stages of infection and to induce vascular collapse at late stages. This review focuses on the role of anthrax toxins in pathogenesis. Other virulence determinants, as well as vaccines and therapeutics, are briefly discussed.

  4. Hydrophobicity of mucosal surface and its relationship to gut barrier function.

    Qin, Xiaofa; Caputo, Francis J; Xu, Da-Zhong; Deitch, Edwin A


    Loss of the gut barrier has been implicated in the pathogenesis of the multiple organ dysfunction syndrome, and, thus, understanding the intestinal barrier is of potential clinical importance. An important, but relatively neglected, component of the gut barrier is the unstirred mucus layer, which through its hydrophobic and other properties serves as an important barrier to bacterial and other factors within the gut lumen. Thus, the goal of this study was to establish a reproducible method of measuring mucosal hydrophobicity and test the hypothesis that conditions that decrease mucosal hydrophobicity are associated with increased gut permeability. Hydrophobicity was measured in various segments of normal gut by measuring the contact angle of an aqueous droplet placed on the mucosal surface using a commercial goniometer. Second, the effect of the mucolytic agent N-acetyl cysteine on mucosal hydrophobicity and gut permeability was measured, as was the effects of increasing periods of in vivo gut ischemia on these parameters. Gut ischemia was induced by superior mesenteric artery occlusion, and gut permeability was measured by the mucosal-to-serosal passage of fluoresceine isothiocyanate-dextran (4.3 kDa) (FD4) across the everted sacs of ileum. Intestinal mucosal hydrophobicity showed a gradual increase from the duodenum to the end of the ileum and remained at high level in the cecum, colon, and rectum. Both N-acetyl cysteine treatment and ischemia caused a dose-dependent decrease in mucosal hydrophobicity, which significantly correlated increased gut permeability. Mucosal hydrophobicity of the intestine can be reproducibly measured, and decreases in mucosal hydrophobicity closely correlate with increased gut permeability. These results suggest that mucosal hydrophobicity can be a reliable method of measuring the barrier function of the unstirred mucus layer and a useful parameter in evaluating the pathogenesis of gut barrier dysfunction.

  5. The Influence of Different Periods Aerosol Inhalation Treatment on Acute Oral Mucositis Caused by Radiotherapy%不同雾化吸入时机对放射性急性口腔黏膜炎治疗效果的影响



    Objective To observe the influence of different periods aerosal inhalation treatment on acute o-ral mucositis caused by radiotherapy.Methods Totally 60 patients hospitalized with head and neck cancer and undergoing radiotherapy were randomly divided into observation group and control group,with 30 ca-ses in each group.The observation group received aerosol inhalation while the radiotherapy started,while the control group only received aerosol inhalation while the acute oral mucositis appeared.The incidence rate of acute oral mucositis caused by radiotherapy,inj ury of oral mucosa and pain degree were compared between two groups.Results During the radiotherapy,the incidence rate of acute oral mucositis caused by radiotherapy,inj ury of oral mucosa and pain degree in observation group were less or lower than which in control group (P<0.05 or P<0.01).Conclusion Giving inhalation treatment at the beginning of radio-therapy can reduces the incidence rate of acute oral mucositis caused by radiotherapy,and the inj ury level of oral mucosa,and also ease the pain,which guarantees the success of radiotherapy,and thus to improve pa-tient’s quality of life.%目的:了解不同雾化吸入开始时间对放射性急性口腔黏膜炎治疗效果的影响.方法便利抽样法选择2012年10月至2013年7月,上海交通大学附属第六人民医院肿瘤放疗科收治的头颈部恶性肿瘤行根治性放射治疗的患者60例,按入院先后将其分为观察组和对照组各30例,观察组患者放疗开始即给予雾化吸入,对照组患者放疗过程中出现放射性急性口腔黏膜炎后再给予雾化吸入,评价并比较两组患者放射性急性口腔黏膜炎的发生情况、口腔黏膜损伤及疼痛程度.结果放疗期间,观察组患者放射性急性口腔黏膜炎的发生率、口腔黏膜损伤及疼痛程度均低于或轻于对照组患者,差异均有统计学意义(P<0.05或P<0.01).结论放疗开始即给予雾化

  6. Pathogenesis of Takotsubo syndrome

    Daniele Masarone


    Full Text Available Takotsubo syndrome (TTS is an enigmatic disease with a multifactorial and still unresolved pathogenesis. Postulated mechanisms include catecholamine excess, coronary artery spasm, and microvascular dysfunction, however catecholamines seem to play a central role in the pathophysiology of TTS. In facts catecholamines have relevant effects on the vasculature and myocardium. Toxic direct effects of catecholamine on myocardium are mediated by multiple pathway including functional hypoxia, metabolic changes and changes in membrane permeability leading to various electrolytic imbalances. Recently report of familial cases has suggested a genetic component. Further research is required to help clarify the proposed hypotheses and to increase our understanding of the cardiovascular responses to acute stress and the pathophysiology underpinning TTS.

  7. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis.

    Michel J van Vliet


    Full Text Available 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.

  8. 急性呼吸窘迫综合征的发病机制和诊断%Pathogenesis and diagnosis of the acute respiratory distress syndrome



    急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是临床各科均可发生的急危重症,其病死率极高。自1967年Ashbaugh等在《Lancet》杂志首先报道成人急性呼吸窘迫(acute respiratory distress in adult)以来,引起了国内外广大学者的高度重视,相继出现了大量的临床与实验研究报道,对急性肺损伤(acute lung injury.ALI)和ARDS的本质及发病机制有了较为深刻的认识.对ARDS的命名、定义逐渐规范,提出了ALI/ARDS临床诊断标准和治疗原则。

  9. Cutaneous and mucosal pain syndromes

    Siddappa K


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

  10. Alteration of the redox state with reactive oxygen species for 5-fluorouracil-induced oral mucositis in hamsters.

    Fumihiko Yoshino

    Full Text Available Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis.

  11. DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease

    Renner, Marcus; Bergmann, Gaby; Krebs, Inge


    BACKGROUND & AIMS: Impaired mucosal defense plays an important role in the pathogenesis of Crohn's disease (CD), one of the main subtypes of inflammatory bowel disease (IBD). Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein with predominant...

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

    Ming-hua Cao

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

  13. 高迁移率族蛋白B1与急性胰腺炎肠黏膜屏障损伤关系的研究%Study on the Relationship between High Mobility Group Box 1 and Intestinal Mucosal Barrier Injury in Acute Pancreatitis

    张伟杰; 徐桂芳; 田志强; 吴国忠; 邹晓平


    背景:急性胰腺炎(AP)是临床常见的急腹症,肠黏膜屏障损伤引起继发感染是AP患者死亡的主要原因之一.近年动物模型研究发现高迁移率族蛋白B1(HMGB1)在AP肠黏膜屏障损伤中发挥重要作用.目的:研究HMGB1与AP患者肠黏膜屏障损伤的关系.方法:纳入2007年12月~2009年3月南京大学医学院附属鼓楼医院和中国人民解放军第101医院收治、确诊的AP患者80例,其中重症急性胰腺炎(SAP) 38例,轻症急性胰腺炎(MAP) 42例,选取30名同期健康体检者作为正常对照组.检测患者血清HMGB1含量,分析其与AP病情严重程度、血清内毒素含量、二胺氧化酶(DAO)含量、尿液乳果糖/甘露醇(L/M)比值的关系.结果:SAP组和MAP组血清HMGB1含量、内毒素含量、DAO含量和尿液L/M比值与对照组相比显著升高(P<0.05).患者血清HMGB1含量与血清内毒素含量、DAO含量、尿液L/M比值以及Ranson评分、24 h APACHEⅡ评分、Balthazar CT评分均呈正相关(P<0.001).结论:血清HMGB1含量可反映AP病情严重程度,并可作为判断AP患者肠黏膜屏障损伤的参考指标.%Background: Acute pancreatitis (AP) is a common acute abdomen of digestive system, secondary infection induced by intestinal mucosal barrier injury is one of the main causes of death in AP. Recent experimental studies have shown that high mobility group box 1 ( HMGB1) plays an important role in the intestinal mucosal barrier injury of AP. Aims: To define the relationship between HMGB1 and intestinal mucosal barrier injury of AP patients. Methods: A total of 80 AP patients from Dec. 2007 to Mar. 2009 at Drum Tower Hospital of Nanjing University Medical School and 101th Hospital of People's Liberation Army were enrolled, 38 cases were severe acute pancreatitis (SAP) and 42 were mild acute pancreatitis (MAP). Thirty healthy subjects were served as controls. Serum levels of HMGB1, endotoxin, diamine oxidase (DAO) and urine lactose/mannitol ( L

  14. 急性呼吸窘迫综合征研究进展%Advance in the pathogenesis of acute respiratory distress syndrome



    急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是一种常见的对患者影响极大的急性肺损伤(ALI)综合征,近年来已对其定义得到了更一致的认识。并且在发病机制和治疗研究方面取得了很大进步,设计和试验出了很多新的方案。这里仅对其定义、发病机制进行阐述,并扼要讨论其在治疗方面的进展。

  15. Reverse Genetics for Fusogenic Bat-Borne Orthoreovirus Associated with Acute Respiratory Tract Infections in Humans: Role of Outer Capsid Protein σC in Viral Replication and Pathogenesis.

    Takahiro Kawagishi


    Full Text Available Nelson Bay orthoreoviruses (NBVs are members of the fusogenic orthoreoviruses and possess 10-segmented double-stranded RNA genomes. NBV was first isolated from a fruit bat in Australia more than 40 years ago, but it was not associated with any disease. However, several NBV strains have been recently identified as causative agents for respiratory tract infections in humans. Isolation of these pathogenic bat reoviruses from patients suggests that NBVs have evolved to propagate in humans in the form of zoonosis. To date, no strategy has been developed to rescue infectious viruses from cloned cDNA for any member of the fusogenic orthoreoviruses. In this study, we report the development of a plasmid-based reverse genetics system free of helper viruses and independent of any selection for NBV isolated from humans with acute respiratory infection. cDNAs corresponding to each of the 10 full-length RNA gene segments of NBV were cotransfected into culture cells expressing T7 RNA polymerase, and viable NBV was isolated using a plaque assay. The growth kinetics and cell-to-cell fusion activity of recombinant strains, rescued using the reverse genetics system, were indistinguishable from those of native strains. We used the reverse genetics system to generate viruses deficient in the cell attachment protein σC to define the biological function of this protein in the viral life cycle. Our results with σC-deficient viruses demonstrated that σC is dispensable for cell attachment in several cell lines, including murine fibroblast L929 cells but not in human lung epithelial A549 cells, and plays a critical role in viral pathogenesis. We also used the system to rescue a virus that expresses a yellow fluorescent protein. The reverse genetics system developed in this study can be applied to study the propagation and pathogenesis of pathogenic NBVs and in the generation of recombinant NBVs for future vaccines and therapeutics.

  16. Study on the pathogenesis of hyponatremia following acute stroke in the elderly patients%老年急性脑卒中患者并发低钠血症的机制探讨

    陈观保; 陈双喜


    Objective To investigate the incidence, clinical characters and pathogenesis of hyponatremia following acute stroke in the elderly patients.Methods The clinical,serum natrium and CT data of 41 cases with hyponatremia following acute stroke in the elderly patients were retrospectively analysed.Results The incidence of hyponatremia following acute stroke in the elderly patients was 16.02% (taking hemorrhagic stroke),the occurrence of the patients' coma induced by hyponatremia and the fatality rate were higher than the controls (P<0.05);Hyponatremia correlated closely with the localization of lesions in CT, the focus in brain ganglion (induding thalamus) and hematocele in the ventricles of brain caused easily hyponatremia.Conclusion Dysfunction of hypothalamus-pituitarium was one of the risk factors in causing hyponatremia following acute stoke in the elderly patients.%目的探讨老年急性脑卒中患者并发低钠血症的发生率、临床特点及发生机制。方法回顾分析41例老年急性脑卒中并发低钠血症患者的临床、血清钠及CT资料。结果老年急性脑卒中并发低钠血症的发生率占同期住院老年脑卒中患者的16.02%,以出血性脑卒中为多见,并发低钠血症者发生昏迷和病死率均高于对照组(均P<0.05);低钠血症的发生与CT所见的病灶分布密切相关,病灶位于基底节区(含丘脑)及脑室内积血更易发生低钠血症。结论下丘脑-垂体功能紊乱是引起老年急性脑卒中并发低钠血症的主要原因之一。

  17. Studies on the pathogenesis of acute inflammation. I. The inflammatory reaction to thermal injury as observed in the rabbit ear chamber.



    A special adaptation of the rabbit ear chamber has been devised to study in vivo, under high magnification, the acute inflammatory reaction to thermal injury. Systematic observations of the cellular response have led to the following conclusions. 1. Contrary to the commonly accepted view, vasodilatation does not always precede the adherence of leucocytes to vascular endothelium. 2. The fact that leucocytes often adhere to one another as well as to the endothelium indicates that the increased adhesiveness characteristic of the early stages of inflammation is not limited to the surfaces of the endothelial cells. 3. The sharing of erythrocytes and platelets in this increased stickiness suggests that a "plasma factor" is involved. There is indirect but as yet inconclusive evidence that the plasma factor may concern the clotting mechanism of the blood. 4. The adherence of leucocytes to the endothelium is usually first noted on the side of the vessel closest to the site of injury. This previously undescribed phenomenon of "unilateral sticking" is in keeping with the concept that the vascular reaction is caused by products of cellular damage which diffuse to the vessel from the site of injury. 5. Leucocytes always become adherent to the endothelium before penetrating the vessel wall. They often migrate about for some time on the endothelial surface before undergoing diapedesis. 6. Although no definite stomata are at any time visible in the endothelium, penetrating leucocytes may leave behind temporary defects through which other leucocytes and even erythrocytes may pass. 7. The diapedesis of leucocytes appears to depend primarily upon cellular motility. It may occur in static vessels where there is presumably little if any hydrostatic pressure. 8. The diapedesis of erythrocytes, on the other hand, is a passive process depending upon intravascular pressure. Its occurrence is greatly exaggerated in areas in which intravascular pressure becomes elevated. Such elevations

  18. Helicobacter pylori virulence and cancer pathogenesis.

    Yamaoka, Yoshio; Graham, David Y


    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

  19. Pathogenesis of arenavirus hemorrhagic fevers.

    Moraz, Marie-Laurence; Kunz, Stefan


    Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments.

  20. 选择性剖宫产儿急性呼吸窘迫综合征发病机制研究进展%Progress in the pathogenesis of acute respiratory distress syndrome in neonate by caesarean section



    Acute respiratory distress syndrome is one of the common respiratory diseases in neonates. It is more common in neonates by elective cesarean section. The pathogenesis is complicated, while delayed lung fluid clearance is considered playing a role in it. Meconium aspiration, delayed establishment of respiratory reflex, gestational age, contractions before onset, male baby, perinatal asphyxia, maternal diabetes or asthma are thought to be risk factors.%新生儿急性呼吸窘迫综合征是新生儿较常见的呼吸道疾病,多见于选择性剖宫产儿,具体发病机制复杂,肺液清除延迟是其主要发病机制,同时胎粪吸入、呼吸反射建立延迟、胎龄、宫缩发动、男性患儿、围生期窒息、母亲有糖尿病或哮喘是其危险因素。

  1. Psoriatic arthritis: genetics and pathogenesis

    A. Mathieu


    Full Text Available Psoriatic arthritis is a complex disease affecting primarily peripheral and axial joints and entheses together with the skin. The pathogenesis is characterized by a genetic background and by inflammatory mechanisms which may be triggered by environmental factors. Several susceptibility genes have been investigated; they include HLA genes, genes within the HLA region and genes outside the HLA region. T cells, including the recently described subset Th17, are thought to play an important role in the acute and chronic phases of the disease. Some of these findings allowed novel therapeutic interventions or opened new promising approaches in treatment. The most relevant data of the literature are summarized and discussed.

  2. Pathogenesis of cardiac injury with severe acute pancreatitis%重症急性胰腺炎心脏损伤的发病机制

    许建彪; 程若川; 张建明


    In early stage of the severe acute pancreatitis, mediators of inflammation make the permeability of the microcirculation blood vessel increasing and more fluidify aggregates in tissue space. Pancreatic tissue is dropsical and necrotic ; a great quantity of body fluid accumulates in abdominal cavity, which induce utility circulation volume and returned blood volume decreasing rapidly. As more and more utility circulation volume decreases, the blood current of the coronary arterY is insufficient and the cardiac muscle cell is ischemic, the cardiac muscle is suffering injury to different extent. The cardiac load is overweight relatively. The cardiac muscle fiber is prolonged and interchanged idand cardiac muscle cellular membrane is damaged. The chain reaction and magnification of the mediators of inflammation let body delivery generous cell factors such as TNF-α,interleukin, oxygen free radical and so on, which make cardiac muscle cell's integrality damage,apoptosis,cardiac functional disturbance even exhaustion. In addition, abdominal compartment syndrome,pancreatitis associated ascetic fluid and electrolyte disturbances etc are also the important factors that affect the development of the disease.%重症急性胰腺炎早期炎症介质使微循环血管通透性增加,组织间隙积液,胰腺组织水肿、坏死,腹腔内大量体液积蓄,二者导致有效循环血量急剧下降,回心血量下降.随着有效循环血量进行性下降,冠脉血流不足,心肌细胞缺血,心肌受到不同程度的损伤,心脏负担相对过重,心肌纤维被动拉长易位,导致心肌细胞膜的损伤.炎症介质连锁反应和放大效应使机体大量释放细胞因子如TNF-α、细胞介素、氧自由基等活性物质,导致心肌细胞的完整性受损,心肌细胞凋亡,心脏功能障碍甚至衰竭.此外,腹腔间隔综合征、胰腺炎相关性腹水、电解质紊乱等也是参与其发生的重要因素.

  3. Mucosal immunity and the microbiome.

    Neish, Andrew S


    By definition, the mucosal immune system is responsible for interfacing with the outside world, specifically responding to external threats, of which pathogenic microbes represent a primary challenge. However, it has become apparent that the human host possesses a numerically vast and taxonomically diverse resident microbiota, predominantly in the gut, and also in the airway, genitourinary tract, and skin. The microbiota is generally considered symbiotic, and has been implicated in the regulation of cellular growth, restitution after injury, maintenance of barrier function, and importantly, in the induction, development, and modulation of immune responses. The mucosal immune system uses diverse mechanisms that protect the host from overt pathogens, but necessarily has coevolved to monitor, nurture, and exploit the normal microbiota. As a whole, mucosal immunity encompasses adaptive immune regulation that can involve systemic processes, local tissue-based innate and inflammatory events, intrinsic defenses, and highly conserved cell autonomous cytoprotective responses. Interestingly, specific taxa within the normal microbiota have been implicated in roles shaping specific adaptive, innate, and cell autonomous responses. Taken together, the normal microbiota exerts profound effects on the mucosal immune system, and likely plays key roles in human physiology and disease.

  4. 血小板在急性呼吸窘迫综合征发病中的作用%Impact of platelets in the pathogenesis of acute respiratory distress syndrome

    范晓枝; 刘宏


    Acute respiratory distress syndrome (ARDS ) is a commonly seen critical illness among different clinical departments but unfortunately its detailed pathogenesis still remains unclear .Recent studies have found that platelets are closely related to the pathogenesis of ARDS .On one hand ,ARDS fosters platelet activation :when ARDS happens ,changes in volume ,structure ,function ,biochemistry and other aspects would occur in platelets ;on the other hand ,platelets also reinforce the progress of ARDS .When ARDS happens ,the activated platelet deposits on damaged lung microvascular system would trigger and aggravate lung injuries .ARDS can also be resulted from the interactive effects of platelets with leukocytes ,endothelial cells and cytokines .Alternatively ,signal transduction may also lead to ARDS .This article reviews the structure and functions of platelets ,changes of platelet in ARDS and its mechanisms ,and the mechanism of platelet which causes ARDS .%急性呼吸窘迫综合征(ARDS )是临床各科常见危重病症,其具体发病机制尚不完全清楚。近年研究发现,血小板与ARDS的发病密切相关。一方面,ARDS促进血小板的活化。ARDS时,血小板在数量、结构、功能、生化等方面都会发生改变。另一方面,血小板促进ARDS的发病过程。ARDS时,活化的血小板沉积在受损的肺微血管系统内,有助于引发和加剧肺泡损伤;血小板与白细胞、内皮细胞、细胞因子相互作用促进ARDS的发病,也可通过信号转导促进ARDS的发病。本文对血小板的结构和功能、ARDS时血小板的变化及其机制和血小板引起 ARDS的机制加以阐述。

  5. Effects of dexmedetomidine on sufentanil pretreatment rats with acute gastric mucosal lessions induced by water-immersion-restraint stress%右美托咪定或(和)舒芬太尼预处理对浸水束缚应激大鼠急性胃黏膜损害的影响

    曹明; 屠伟峰; 刘晓燕; 郄文斌


    目的:探讨右美托咪定(DEX)预处理或(和)舒芬太尼(SUF)预处理对浸水束缚应激(WIRS)大鼠急性胃黏膜损害的影响.方法:30只Wistar大鼠随机分成正常对照组(NC组,n=6)、WIRS对照组(WC组,n=6)、DEX预处理组(DP组,n=6)、SUF预处理组(SP组,n=6)、DEX复合SUF预处理组(DSP组,n=6).DP组:腹腔注射7.5 μg/kg 10 min后进行WIRS; SP组:腹腔注射10 μg/kg2 min后进行WIRS;DSP组:腹腔注射7.5 μg/kg DEX 8 min后再注射SUF 10 μg/kg,2 min后进行WIRS;以等容积生理盐水腹腔注射后10 min进行WIRS作为WC组.所有实验大鼠于WIRS 6 h后给予10%水合氯醛3 mL/kg腹腔注射麻醉,剖腹取出全胃后先进行胃液pH测定、胃黏膜损伤指数(GI)评定,然后按要求留取胃黏膜组织标本以检测胃黏膜组织超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)和一氧化氮合酶(NOS)的含量和病理学检查.结果:DEX预处理后,MDA、MPO升高幅度都较WC组明显降低,pH、SOD下降幅度明显减少,GI和胃黏膜损伤病理改变较WC组减轻(P< 0.05),但NOS的变化没有统计学意义(P>0.05);与SP组比较,DSP组SOD、MDA、GI、pH、MPO、NOS的变化无统计学意义(P>0.05).结论:DEX预处理可有效减轻WIRS诱发的急性胃黏膜损伤,其确切机制尚不清楚,可能与控制伤害性应激反应、降低氧化应激、降低胃酸和抑制炎症反应有关,但并没有使舒芬太尼对胃黏膜损伤的保护作用增强.%Objectives To explore the effects of dexmedetomidine on sufentanil pretreatment rats with acute gastric mucosal lesions induced by water-immersion-restraint stress. Methods Thirty wistar rats were randomly assigned to normal control group (Group NC, n = 6); WIRS controlled group (Group WC, n = 6, intraperitoneal infusion of saline 10 min before WIRS); DEX pretreatment group (Group DP, n = 6, intraperitoneal infusion of dexmedetomidine at 7.5 μg/kg 10 min before WIRS); SF pretreatment group (Group SP, n

  6. Is rhabdomyolysis an additional factor in the pathogenesis of acute renal failure in leptospirosis? É a rabdomiólise um fator adicional na patogônese da insuficiencia renal aguda na leptospirose?

    Reinaldo Martinelli


    Full Text Available Leptospirosis is an important cause of acute renal failure in our environment. Although several mechanisms are implicated, the role of rhabdomyolysis in the pathogenesis of acute renal failure in leptospirosis has not been analysed. Sixteen patients with the diagnosis of leptospiroses consecutively admitted to the hospital were prospectively studied. The disease was characterized by sudden onset in all patients and, at admission, jaundice, conjunctival suffusion and myalgias. Mild to moderate proteinuria with unremarkable urinary sediment was recorded in 37.5% of the patients and abnormal levels of urea creatinine were found in 87.5% and 74.0%, respectively. Increased levels of aminotranspherase were documented in all 12 and CPK in all 10 patients studied. Serum myoglobin levels greater than 120µg/l recorded in 56.2%. A correlation between myoglobin and renal failure or severity of disease, however, could not be established.Leptospirose é uma importante causa de insuficiência renal aguda, em nosso ambiente. Embora vários sejam os mecanismos implicados, o papel da rabdomiólise na patogênese da insuficiência renal aguda na leptospirose ainda não foi analisado. Com esse objetivo, 16 pacientes com o diagnóstico da forma icterohemorrágica da leptospirose consecutivamente admitidos no Hospital Couto Maia, Salvador, Bahia, foram prospectivamente estudados. A doença foi caracterizada por início súbito e, à admissão, ictericia, sufusões hemorrágicas conjuntivais e mialgias. Proteinúria de intensidade média a moderada com sedimento urinário inexpressivo foi observada em 37,5% dos pacientes e níveis séricos elevados de uréia e creatinina em 78,5% e 74,0%, respectivamente. Níveis aumentados de aminotransferase foram documentados em todos os 12 e de CPK em todos os 10 pacientes avaliados para essas enzimas. Níveis séricos maiores que 120µg/l foram observados em 56,2% dos pacientes. Não foram encontradas correlações, entretanto

  7. Effects of dosmalfate, a new cytoprotective agent, on acute and chronic trinitrobenzene sulphonic acid-induced colitis in rats.

    Villegas, Isabel; La Casa, Carmen; Orjales, Aurelio; Alarcón de la Lastra, Catalina


    Activated neutrophils and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) are clearly involved in the pathogenesis of bowel disease. Increased expression of epidermal growth factor-receptor (EGF receptor) has been reported for the colon mucosa surrounding areas of ulceration, suggesting a pivotal role in mucosal defence and repair. In this study, we examined the effects of dosmalfate, a new flavonoid derivative compound (diosmin heptakis) with antioxidant and cytoprotective properties, on acute and chronic experimental trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. The inflammation response was assessed by neutrophil infiltration as evaluated by histology and myeloperoxidase activity. Mucosal TNF-alpha production and histological analysis of the lesions was also carried out. In addition, we studied the expression of the EGF receptor inmunohistochemically during the healing of TNBS-induced chronic colitis. A 2-day treatment with 400 or 800 mg/kg of dosmalfate ameliorated the colon damage score and the incidence of adhesions. It also significantly (P<0.05) decreased myeloperoxidase activity and colonic mucosal production of TNF-alpha. Chronic treatment (14 days) with 800 mg/kg/day of dosmalfate also had significant protective effects on TNBS-induced colitis which were reflected by significant attenuation (P<0.05) of the damage score while the inflammatory indicators were not improved. The chronic beneficial effect of dosmalfate was apparently related to the enhancement of EGF receptor expression. These findings confirm the protective effects of dosmalfate in acute and chronic experimental colitis.

  8. Mucosal immunity in liver autoimmunity: a comprehensive review.

    Trivedi, Palak J; Adams, David H


    Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) all nestle within the umbrella term of autoimmune liver disease, in which the end result is immune-mediated hepatocellular or hepatobiliary injury. All three conditions are associated with gut inflammation; PSC and AIH being strongly linked to inflammatory bowel disease (IBD) and PBC to coeliac disease. This clinical observation has stimulated several intriguing pathogenic concepts in which gut commensals, pathogens and intestinal antigens are all implicated in causing liver injury. Th17-cells have also been linked to AIH, PBC and more recently PSC. Given that the intestine is a key regulator of immunopathogenic Th17 responses, this may underpin a common disease mechanism and open up novel treatment avenues based on rational targeting of immune pathways. Moreover, the discovery of long-lived mucosal memory T-cells being recruited to the liver in response to aberrantly expressed endothelial-cell adhesion molecules and chemokines, which are normally 'gut-restricted,' could plausibly explain why these diseases are associated with site-restricted tissue distributions and pave the way for therapeutic strategies based on modulating tissue specific lymphocyte homing. That particular gene-polymorphisms have been found which confer combined PSC/IBD susceptibility underscores the fundamental role of mucosal immunogenicity in disease pathogenesis. Mucosal lymphocytes may also play a pivotal role in graft versus host disease affecting the liver, and there is increasing evidence to support dysregulated mucosal immunity as being responsible for the hepatic manifestations of gluten-sensitive enteropathy, graft versus host disease, as wells as the pancreatobiliary manifestations of IgG4-related disease.

  9. Protective and therapeutic effects of electroacupuncture on gastric motor disorders and acute gastric mucosal lesions under psychological stress in rats%心理性应激状态下针刺对大鼠DMV放电、胃电和胃粘膜损伤的影响

    王景杰; 黄裕新; 郭庆东; 秦明; 高巍; 王庆莉


    AIM To test the protective and therapeutic effects of electroacupuncture on gastric motor disorders and acute gastric mucosal lesions under psychological stress in rats. METHODS Ninety-six male Sprague-Dauley rats were randomly divided into three groups: control group (CG, n=32), psychological stress group (PSG, n=32) and electroacupuncture group (EAG, n=32). Every group was randomly divided into four subgroups (CG, n=32, n=8; PSG, n=32, n=8; EAG, n=32, n=8). Animal model was constructed with impulsive stimulator of high voltage and stable currency stimulating the Chusanli with electroacupuncture. Then spontaneous electroactivity of dorsal motor nucleus of the vagus nerve (DMV) was recorded extracellularly and EGG with the serosa method, and the gastric mucosa injury index was calculated. RESULTS The spontaneous electroactivity from DMV was rarely observed in normal rats. EGG was regular with frequency 3 per minute and amplitude 360~370 μV. Gastric mucosa was normal. Under psychological stress, spontaneous electroactivity from DMV was irregular which did not significantly correlate with time and degree of psychological stress. But we observed that increasing frequency of spontaneous electroactivity from DMV was predominant. EGG was disorderly and irregular. There was no difference in frequency and amplitude of EGG between C group and A group on the 2nd day, the 4th day, the 6th day, the 8th day after psychological stress with stimulating chusanli by electroacupuncture under psychological stress. Gastric mucosal lesion appeared, even did ulcer. The degree of gastric mucosal lesion became more and more serious, and lesion index increased gradually with the continues psychological stress. But gastric mucosal lesion alleviated significantly under psychological stress with electroacupuncture stimulation. And the effect was more significant with the continues electroacupuncture stimulation. There was significant difference in lesion index between C group and B

  10. Pathogenesis and Prevention of Acute Renal Failure


    364,343 were clearly dose-dependent, with greater = natriuresis and diuresis at the 5.0 microgram/minute dose than at the 0.5 microgram/minute dose...has not appreciably altered the course or outcome of ARF (11-13). A combination of dopamine and furosemide was reported to produce a diuresis if used...peptides (containing 19 to 33 amino acids), isolated from atrial myocytes, which produce vasodilation and * natriuresis . Micropuncture studies suggest

  11. Citrulline as a Marker for Chemotherapy Induced Mucosal Barrier Injury in Pediatric Patients

    van Vilet, Michel J.; Tissing, Wim J. E.; Rings, Edmond H. H. M.; Koetse, Harma A.; Stellaard, Frans; Kamps, Willem A.; de Bont, Eveline S. J. M.


    Background. The Currently used National Cancer Institute (NCI) adverse events criteria for mucosal barrier injury (MBI) are insufficient for use in children. We searched for objective, easily measurable indicators for MBI in children with cancer. Purpose. In children with acute myeloid leukemia, var

  12. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation

    Campbell, Eric L.; Bruyninckx, Walter J.; Kelly, Caleb J; Louise E. Glover; McNamee, Eóin N.; Bowers, Brittelle E.; Bayless, Amanda J.; Scully, Melanie; Saeedi, Bejan J.; Golden-Mason, Lucy; Ehrentraut, Stefan F.; Curtis, Valerie F; Burgess, Adrianne; Garvey, John F; Sorensen, Amber


    Acute intestinal inflammation involves early accumulation of neutrophils (PMN) followed by either resolution or progression to chronic inflammation. Based on recent evidence mucosal metabolism influences disease outcomes, we hypothesized that transmigrating PMN influence the transcriptional profile of the surrounding mucosa. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by PMN-epithelial crosstalk. Transmigrating PMN rapidly depleted microenvironmental O2 sufficie...

  13. Serum zinc levels in 368 patients with oral mucosal diseases: A preliminary study

    Bao, Zhe-Xuan; Yang, Xiao-Wen; Shi, Jing


    Background The aim of this study was to assess the serum zinc levels in patients with common oral mucosal diseases by comparing these to healthy controls. Material and Methods A total of 368 patients, which consisted of 156 recurrent aphthous stomatitis (RAS) patients, 57 oral lichen planus (OLP) patients, 55 burning mouth syndrome (BMS) patients, 54 atrophic glossitis (AG) patients, 46 xerostomia patients, and 115 sex-and age-matched healthy control subjects were enrolled in this study. Serum zinc levels were measured in all participants. Statistical analysis was performed using a one-way ANOVA, t-test, and Chi-square test. Results The mean serum zinc level in the healthy control group was significantly higher than the levels of all other groups (p < 0.001). No individual in the healthy control group had a serum zinc level less than the minimum normal value. However, up to 24.7% (13/54) of patients with AG presented with zinc deficiency, while 21.2% (33/156) of patients with RAS, 16.4% (9/55) of patients with BMS, 15.2% (7/46) of patients with xerostomia, and 14.0% (8/57) of patients with OLP were zinc deficient. Altogether, the zinc deficiency rate was 19.02% (70/368) in the oral mucosal diseases (OMD) group (all patients with OMD). The difference between the OMD and healthy control group was significant (p <0.001). Gender differences in serum zinc levels were also present, although not statistically significant. Conclusions Zinc deficiency may be involved in the pathogenesis of common oral mucosal diseases. Zinc supplementation may be a useful treatment for oral mucosal diseases, but this requires further investigation; the optimal serum level of zinc, for the prevention and treatment of oral mucosal diseases, remains to be determined. Key words:Oral mucosal diseases, Zinc deficiency, pathogenesis. PMID:27031065

  14. The Development of an AIDS Mucosal Vaccine

    Xian Tang


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

  15. Voice disorders in mucosal leishmaniasis.

    Ana Cristina Nunes Ruas

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

  16. Neisseria prophage repressor implicated in gonococcal pathogenesis.

    Daou, Nadine; Yu, Chunxiao; McClure, Ryan; Gudino, Cynthia; Reed, George W; Genco, Caroline A


    Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, can infect and colonize multiple mucosal sites in both men and women. The ability to cope with different environmental conditions requires tight regulation of gene expression. In this study, we identified and characterized a gonococcal transcriptional regulatory protein (Neisseria phage repressor [Npr]) that was previously annotated as a putative gonococcal phage repressor protein. Npr was found to repress transcription of NGNG_00460 to NGNG_00463 (NGNG_00460-00463), an operon present within the phage locus NgoΦ4. Npr binding sites within the NGNG_00460-00463 promoter region were found to overlap the -10 and -35 promoter motifs. A gonococcal npr mutant demonstrated increased adherence to and invasion of human endocervical epithelial cells compared to a wild-type gonococcal strain. Likewise, the gonococcal npr mutant exhibited enhanced colonization in a gonococcal mouse model of mucosal infection. Analysis of the gonococcal npr mutant using RNA sequence (RNA-seq) analysis demonstrated that the Npr regulon is limited to the operon present within the phage locus. Collectively, our studies have defined a new gonococcal phage repressor protein that controls the transcription of genes implicated in gonococcal pathogenesis.

  17. A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface.

    Xiaoxiao Li

    Full Text Available Aberrant interactions between the host and the intestinal bacteria are thought to contribute to the pathogenesis of many digestive diseases. However, studying the complex ecosystem at the human mucosal-luminal interface (MLI is challenging and requires an integrative systems biology approach. Therefore, we developed a novel method integrating lavage sampling of the human mucosal surface, high-throughput proteomics, and a unique suite of bioinformatic and statistical analyses. Shotgun proteomic analysis of secreted proteins recovered from the MLI confirmed the presence of both human and bacterial components. To profile the MLI metaproteome, we collected 205 mucosal lavage samples from 38 healthy subjects, and subjected them to high-throughput proteomics. The spectral data were subjected to a rigorous data processing pipeline to optimize suitability for quantitation and analysis, and then were evaluated using a set of biostatistical tools. Compared to the mucosal transcriptome, the MLI metaproteome was enriched for extracellular proteins involved in response to stimulus and immune system processes. Analysis of the metaproteome revealed significant individual-related as well as anatomic region-related (biogeographic features. Quantitative shotgun proteomics established the identity and confirmed the biogeographic association of 49 proteins (including 3 functional protein networks demarcating the proximal and distal colon. This robust and integrated proteomic approach is thus effective for identifying functional features of the human mucosal ecosystem, and a fresh understanding of the basic biology and disease processes at the MLI.

  18. The Pathogenesis of Autism

    Watts, Timothy John


    Autism is well known as a complex developmental disorder with a seemingly confusing and uncertain pathogenesis. The definitive mechanisms that promote autism are poorly understood and mostly unknown, yet available theories do appear to focus on the disruption of normal cerebral development and its subsequent implications on the functional brain unit. This mini-review aims solely to discuss and evaluate the most prominent current theories regarding the pathogenesis of autism. The main conclusi...

  19. Mucosal immunity and probiotics in fish.

    Lazado, Carlo C; Caipang, Christopher Marlowe A


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

  20. Modulation of gut mucosal biofilms.

    Kleessen, Brigitta; Blaut, Michael


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

  1. Emerging evidence on the pathobiology of mucositis.

    Al-Dasooqi, N.; Sonis, S.T.; Bowen, J.M.; Bateman, E.; Blijlevens, N.M.; Gibson, R.J.; Logan, R.M.; Nair, R.G.; Stringer, A.M.; Yazbeck, R.; Elad, S.; Lalla, R.V.


    BACKGROUND: Considerable progress has been made in our understanding of the biological basis for cancer therapy-induced mucosal barrier injury (mucositis). The last formal review of the subject by MASCC/ISOO was published in 2007; consequently, an update is timely. METHODS: Panel members reviewed th

  2. Biology and mucosal immunity to myxozoans.

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


    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.

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

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


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

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

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


    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.

  5. Current perspectivesin pathogenesis and antimicrobial resistance of enteroaggregative Escherichia coli.

    Kong, Haishen; Hong, Xiaoping; Li, Xuefen


    Enteroaggregative Escherichia coli (EAEC) is an emerging pathogen that causes acute and persistent diarrhea in children and adults. While the pathogenic mechanisms of EAEC intestinal colonization have been uncovered (including bacterial adhesion, enterotoxin and cytotoxin secretion, and stimulation of mucosal inflammation), those of severe extraintestinal infections remain largely unknown. The recent emergence of multidrug resistant EAEC represents an alarming public health threat and clinical challenge, and research on the molecular mechanisms of resistance is urgently needed.

  6. Intestinal mucosal atrophy and adaptation

    Darcy Shaw; Kartik Gohil; Marc D Basson


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

  7. Etiology and Pathogenesis of Idiopathic Achalasia.

    Pressman, Amanda; Behar, Jose


    This review examines the etiology and pathogenesis of idiopathic achalasia. This disease is clinically characterized by dysphagia of solids and liquids due to the presence of simultaneous or absent esophageal contractions and impaired or absent relaxation of the lower esophageal sphincter. It includes a review of (a) etiology and pathogenesis of this inflammatory process that damage the ganglion cells of the Auerbach plexus that is limited to the esophagus; (b) genetic abnormalities and polymorphisms associated with this disease that may help explain its heterogeneity expressed by the different motility abnormalities of its phenotypes as well as differences in its clinical progression. These different genetic abnormalities may be responsible for the slow progression of types I or II phenotypes; (c) indirect evidence of viruses present in these patients that may initiate its development; (d) the abnormalities of the muscle layer that may be responsible for the dilation of the body of the esophagus that ultimately causes the sigmoid-like esophagus in the very last phase of this disease. This progression to the end-stage phase tends to occur in about 5% of patients. And, (e) the chronic inflammatory abnormalities in the squamous mucosa that may be the cause of the dysplastic and neoplastic changes that may lead to squamous cell carcinoma whose incidence in this disease is increased. These mucosal abnormalities are usually present in patients with markedly dilated body of the esophagus and severe food stasis.

  8. Circumferential mucosal dissection and esophageal perforation in a patient with eosinophilic esophagitis

    Gennaro Liguori; Maurizio Cortale; Fabrizio Cimino; Michele Sozzi


    A young man with a previous history of episodes of mild solid food dysphagia was admitted with a total dysphagia.The esophagogastroduodenoscopy (EGDS) showed an extensive disruption of mucosal layer with a cul-de-sac in the lower part of the esophagus.Soon after the procedure,the patient suffered from an acute chest pain and subsequent CT scan demonstrated an intramural circumferential dissection of thoracic esophagus,and a mediastinal emphysema.An emergency right thoracotomy was performed,followed by a total esophagectomy with esophagogastroplasty and jejunostomy.The histopathology confirmed that mucosal and submucosal layers were circumferentially detached from muscular wall and showed an eosinophilic infiltration of the whole organ with necrosis and erosions of mucosal,submucosal and muscular layers.The diagnosis was esophageal perforation in eosinophilic esophagitis.

  9. An NK Cell Perforin Response Elicited via IL-18 Controls Mucosal Inflammation Kinetics during Salmonella Gut Infection.

    Anna A Müller


    Full Text Available Salmonella Typhimurium (S.Tm is a common cause of self-limiting diarrhea. The mucosal inflammation is thought to arise from a standoff between the pathogen's virulence factors and the host's mucosal innate immune defenses, particularly the mucosal NAIP/NLRC4 inflammasome. However, it had remained unclear how this switches the gut from homeostasis to inflammation. This was studied using the streptomycin mouse model. S.Tm infections in knockout mice, cytokine inhibition and -injection experiments revealed that caspase-1 (not -11 dependent IL-18 is pivotal for inducing acute inflammation. IL-18 boosted NK cell chemoattractants and enhanced the NK cells' migratory capacity, thus promoting mucosal accumulation of mature, activated NK cells. NK cell depletion and Prf-/- ablation (but not granulocyte-depletion or T-cell deficiency delayed tissue inflammation. Our data suggest an NK cell perforin response as one limiting factor in mounting gut mucosal inflammation. Thus, IL-18-elicited NK cell perforin responses seem to be critical for coordinating mucosal inflammation during early infection, when S.Tm strongly relies on virulence factors detectable by the inflammasome. This may have broad relevance for mucosal defense against microbial pathogens.

  10. An NK Cell Perforin Response Elicited via IL-18 Controls Mucosal Inflammation Kinetics during Salmonella Gut Infection.

    Müller, Anna A; Dolowschiak, Tamas; Sellin, Mikael E; Felmy, Boas; Verbree, Carolin; Gadient, Sandra; Westermann, Alexander J; Vogel, Jörg; LeibundGut-Landmann, Salome; Hardt, Wolf-Dietrich


    Salmonella Typhimurium (S.Tm) is a common cause of self-limiting diarrhea. The mucosal inflammation is thought to arise from a standoff between the pathogen's virulence factors and the host's mucosal innate immune defenses, particularly the mucosal NAIP/NLRC4 inflammasome. However, it had remained unclear how this switches the gut from homeostasis to inflammation. This was studied using the streptomycin mouse model. S.Tm infections in knockout mice, cytokine inhibition and -injection experiments revealed that caspase-1 (not -11) dependent IL-18 is pivotal for inducing acute inflammation. IL-18 boosted NK cell chemoattractants and enhanced the NK cells' migratory capacity, thus promoting mucosal accumulation of mature, activated NK cells. NK cell depletion and Prf-/- ablation (but not granulocyte-depletion or T-cell deficiency) delayed tissue inflammation. Our data suggest an NK cell perforin response as one limiting factor in mounting gut mucosal inflammation. Thus, IL-18-elicited NK cell perforin responses seem to be critical for coordinating mucosal inflammation during early infection, when S.Tm strongly relies on virulence factors detectable by the inflammasome. This may have broad relevance for mucosal defense against microbial pathogens.

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

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


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

  12. Mucosal Immunology of HIV Infection

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


    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 inflicti...

  13. Gestosis pathogenesis (review

    Prigorodov M.V.


    Full Text Available Literature review contains the analysis of information concerning disturbances in hemostasis system in case of arterial hypertension, frequency rate, risk factors, causes and mechanisms of occurrence. The review states the causes of complications, inadequate treatment effects and arterial hypertension pathogenesis

  14. Inflammatory bowel disease: pathogenesis.

    Zhang, Yi-Zhen; Li, Yong-Yu


    Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. Of the four components of IBD pathogenesis, most rapid progress has been made in the genetic study of gut inflammation. The latest internationally collaborative studies have ascertained 163 susceptibility gene loci for IBD. The genes implicated in childhood-onset and adult-onset IBD overlap, suggesting similar genetic predispositions. However, the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD, as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation. Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms, including the innate and adaptive immunity, and the interactions between genetic factors and microbial and environmental cues. In this review, we provide an update on the major advances that have occurred in above areas.

  15. Brain neuropeptides in gastric mucosal protection.

    Gyires, Klára; Zádori, Zoltán S


    The centrally induced gastroprotective effect of neuropeptides has been intensively studied. Besides many similarities, however, differences can also be observed in their gastroprotective actions. The gastroprotective dose-response curve proved to be either sigmoid, or bell-shaped. Additional gastrointestinal effects of neuropeptides can contribute to their mucosal protective effect. Part of the neuropeptides induces gastroprotection by peripheral administration as well. Besides vagal nerve the sympathetic nervous system may also be involved in conveying the central effect to the periphery. Better understanding of the complex mechanism of the maintenance of gastric mucosal integrity may result in the development of new strategy to enhance gastric mucosal resistance against injury.

  16. Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function.

    Taché, Y; Perdue, M H


    Central corticotrophin releasing-factor (CRF) signalling pathways are involved in the endocrine, behavioural and visceral responses to stress. Recent studies indicate that peripheral CRF-related mechanisms also contribute to stress-induced changes in gut motility and intestinal mucosal function. Peripheral injection of CRF or urocortin inhibits gastric emptying and motility through interaction with CRF2 receptors and stimulates colonic transit, motility, Fos expression in myenteric neurones and defecation through activation of CRF1 receptors. With regard to intestinal epithelial cell function, intraperitoneal CRF increases ion secretion and mucosal permeability to macromolecules. The motility and mucosal changes induced by peripheral CRF mimic those induced by acute stress. In addition, CRF receptor antagonists given peripherally prevent acute restraint and water avoidance stress-induced delayed gastric emptying, stimulation of colonic motor function and mucosal permeability. Similarly, early trauma enhanced intestinal mucosal dysfunction to an acute stressor in adult rats and the response is prevented by peripheral injection of CRF antagonist. Chronic psychological stress results in reduced host defence and initiates intestinal inflammation through mast cell-dependent mechanisms. These findings provide convergent evidence that activation of peripheral CRF receptors and mast cells are important mechanisms involved in stress-related alterations of gut physiology.

  17. Role of inducible nitric oxide synthase pathway on methotrexate-induced intestinal mucositis in rodents

    Siqueira Francisco JWS


    Full Text Available Abstract Background Methotrexate treatment has been associated to intestinal epithelial damage. Studies have suggested an important role of nitric oxide in such injury. The aim of this study was to investigate the role of nitric oxide (NO, specifically iNOS on the pathogenesis of methotrexate (MTX-induced intestinal mucositis. Methods Intestinal mucositis was carried out by three subcutaneous MTX injections (2.5 mg/kg in Wistar rats and in inducible nitric oxide synthase knock-out (iNOS-/- and wild-type (iNOS+/+ mice. Rats were treated intraperitoneally with the NOS inhibitors aminoguanidine (AG; 10 mg/Kg or L-NAME (20 mg/Kg, one hour before MTX injection and daily until sacrifice, on the fifth day. The jejunum was harvested to investigate the expression of Ki67, iNOS and nitrotyrosine by immunohistochemistry and cell death by TUNEL. The neutrophil activity by myeloperoxidase (MPO assay was performed in the three small intestine segments. Results AG and L-NAME significantly reduced villus and crypt damages, inflammatory alterations, cell death, MPO activity, and nitrotyrosine immunostaining due to MTX challenge. The treatment with AG, but not L-NAME, prevented the inhibitory effect of MTX on cell proliferation. MTX induced increased expression of iNOS detected by immunohistochemistry. MTX did not cause significant inflammation in the iNOS-/- mice. Conclusion These results suggest an important role of NO, via activation of iNOS, in the pathogenesis of intestinal mucositis.

  18. Microbiota and mucosal immunity in amphibians

    Bruno M Colombo


    Full Text Available We know that animals live in a world dominated by bacteria. In the last twenty years we have learned that microbes are essential regulators of mucosal immunity. Bacterias, 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.

  19. A regenerative approach towards mucosal fenestration closure.

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


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

  20. Exploiting Mucosal Immunity for Antiviral Vaccines.

    Iwasaki, Akiko


    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.

  1. Microbiota and mucosal immunity in amphibians.

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


    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.

  2. Effect of ageing on colonic mucosal regeneration

    Ferenc Sipos; Katalin Leiszter; Zsolt Tulassay


    The physiologic and pathologic cellular and molecular changes occurring with age in the human colon affect both the inflammatory process leading to mucosal injury and the regenerative capacity of the epithelium. On the one hand, age-related telomere shortening and inflamm-ageing may lead to the development of colonic inflammation, which results in epithelial damage. On the other hand, the altered migration and function of regenerative stem cells, the age-related methylation of mucosal healing-associated genes, together with the alterations of growth factor signaling with age, may be involved in delayed mucosal regeneration. The connections of these alterations to the process of ageing are not fully known. The understanding and customtailored modification of these mechanisms are of great clinical importance with regard to disease prevention and modern therapeutic strategies. Here, we aim to summarize the age-related microscopic and molecular changes of the human colon, as well as their role in altered mucosal healing.

  3. Deletion of the complement C5a receptor alleviates the severity of acute pneumococcal otitis media following influenza A virus infection in mice.

    Hua Hua Tong

    Full Text Available There is considerable evidence that influenza A virus (IAV promotes adherence, colonization, and superinfection by S. pneumoniae (Spn and contributes to the pathogenesis of otitis media (OM. The complement system is a critical innate immune defense against both pathogens. To assess the role of the complement system in the host defense and the pathogenesis of acute pneumococcal OM following IAV infection, we employed a well-established transtympanically-induced mouse model of acute pneumococcal OM. We found that antecedent IAV infection enhanced the severity of acute pneumococcal OM. Mice deficient in complement C1qa (C1qa-/- or factor B (Bf -/- exhibited delayed viral and bacterial clearance from the middle ear and developed significant mucosal damage in the eustachian tube and middle ear. This indicates that both the classical and alternative complement pathways are critical for the oto-immune defense against acute pneumococcal OM following influenza infection. We also found that Spn increased complement activation following IAV infection. This was characterized by sustained increased levels of anaphylatoxins C3a and C5a in serum and middle ear lavage samples. In contrast, mice deficient in the complement C5a receptor (C5aR demonstrated enhanced bacterial clearance and reduced severity of OM. Our data support the concept that C5a-C5aR interactions play a significant role in the pathogenesis of acute pneumococcal OM following IAV infection. It is possible that targeting the C5a-C5aR axis might prove useful in attenuating acute pneumococcal OM in patients with influenza infection.

  4. Lymphocyte Trafficking to Mucosal Tissues

    Mikhak, Zamaneh; Agace, William Winston; Luster, Andrew D.


    Lymphocytes are the key cells of the adaptive immune system that provide antigen-specific responses tailored to the context of antigen exposure. Through cytokine release and antibody production, lymphocytes orchestrate and amplify the recruitment and function of other immune cells and contribute...... to host defense against invading pathogens and the pathogenesis of many inflammatory diseases. Lymphocyte function is critically dependent on their ability to traffic into the correct anatomic locations at the appropriate times. This process is highly regulated and requires that lymphocytes interact...

  5. The development of an AIDS mucosal vaccine

    Xian Tang; Zhiwei Chen


    It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, ...

  6. Molecular Pathogenesis of Spondyloarthritis

    Carlsen, Thomas Gelsing

    This dissertation includes a presentation of knowledge on the molecular pathogenesis of spondyloarthritis achieved through a PhD programme at Aalborg University from 1.12.2011 - 1.12.2014. Work was carried out in the Laboratory of Medical Mass Spectrometry, headed by: Professor Svend Birkelund...... and Immunology in San Diego, USA. Research was conducted on biological material from patients suffering from spondyloarthritis and healthy donors, to whom I dedicate this work....

  7. Pathogenesis of hepatitis B virus infection


    Infection with hepatitis B virus (HBV) leads to a wide spectrum of clinical presentations ranging from an asymptomatic carrier state to self-limited acute or fulminant hepatitis to chronic hepatitis with progression to cirrhosis and hepatocellular carcinoma. Infection with HBV is one of the most common viral diseases affecting man. Both viral factors as well as the host immune response have been implicated in the pathogenesis and clinical outcome of HBV infection. In this review, we will discuss the impact of virus-host interactions for the pathogenesis of HBV infection and liver disease. These interactions include the relevance of naturally occurring viral variants for clinical disease, the role of virus-induced apoptosis for HBV-induced liver cell injury and the impact of antiviral immune responses for outcome of infection.

  8. Mucosal surface morphology and histological changes in the duodenum of the rat following administration of cysteamine

    Poulsen, Steen Seier; Szabo, S


    Acute duodenal ulcer can be produced in the rat by subcutaneous or oral administration of cysteamine. Development of this ulcer on the intestinal mucosal surface was followed from precursory stages to perforation using low power semimacroscopical and conventional histological techniques. The proc......Acute duodenal ulcer can be produced in the rat by subcutaneous or oral administration of cysteamine. Development of this ulcer on the intestinal mucosal surface was followed from precursory stages to perforation using low power semimacroscopical and conventional histological techniques....... The process started in the epithelium of the apical parts of the villi where segments of surface epithelial cells exfoliated and the lamina propria seemed to retract. As the process continued the villi gradually became lower eventually forming an avillous surface. Subsequently defects in the epithelium...

  9. Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

    Lee, Robert J.; Workman, Alan D.; Carey, Ryan M.; Chen, Bei; Rosen, Phillip L.; Doghramji, Laurel; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Cohen, Noam A.


    Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6–12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases. PMID:27623953

  10. Clonal repertoires of virus-specific CD8+ T lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys.

    Sircar, Piya; Furr, Kathryn L; Dorosh, Lauren A; Letvin, Norman L


    Because it is thought that mucosal tissues play a fundamental role in early HIV/SIV infection, it is crucial to understand the virus-specific responses in mucosal tissues to facilitate devising strategies to prevent and control these infections. We have employed TCR repertoire analyses to define the clonal composition of a dominant SIV epitope-specific CD8(+) T cell population in mucosal and systemic compartments of SIV-infected rhesus monkeys during both acute and chronic infection. We show that the CD8(+) T cell repertoire in mucosal tissues of uninfected rhesus monkeys is oligoclonal, whereas the CD8(+) T cell repertoire in blood is polyclonal. Early postinfection, the SIV-specific CD8(+) T cell clonal repertoire is distinct in mucosal compartments and peripheral blood. However, we observed a narrowing of the virus-specific CD8(+) T cell clonal repertoire in all sampled anatomic compartments as infection progressed from acute to chronic, and there was comparable clonal diversity in all anatomic compartments. We showed during chronic infection that the same clonal populations of virus-specific CD8(+) T cells are present in all compartments. These data indicate that the SIV-specific CD8(+) T cells in systemic and mucosal sites have a shared clonal origin and are, therefore, capable of both responding to infection in the systemic circulation and trafficking to mucosal tissues.

  11. 大鼠口腔黏膜急性排斥反应外周血CD68水平与巨噬细胞浸润的相关性研究%Correlation between the CD68 proportion of peripheral blood mononuclear cell and macrophage infiltration during acute rejection of rat oral mucosal xenotransplantation

    左雯鑫; 王红; 李晓宇; 陶小安; 程斌


    Objective To investigate the role of the dynamic process of peripheral blood CD68 mononuclear cells proportion and macrophages inflitration and possible correlation between them during acute rejection of rat oral mucosal xenotransplantation. Methods Thirty-six female wistar rats were divided into three groups randomly, including xenotransplantation group( n = 15 ), trauma control group( n = 12) and normal control group ( n = 9). The rat oral mucosa xenotransplantation model was established. The flow cytometry was used to evaluate the peripheral blood CD68 mononuclear cell and immunohistochemical assay performed to detect the macrophages infiltration one week (W1), two weeks (W2)and four weeks (W4) after xenotransplantation. Results The peripheral blood CD68 mononuclear cells percentage of each xenotransplantation group presented a rise and fall tendency at the three time points, and the peak value appeared at W4(43. 1% ), and the nadir at W2( 10.4% ). The macrophage counts achieved peak value in xenotransplantation group at W1 [ 580.0 (195.5) cell/high power field ], and then reduced with time. Conclusions The mononuclear cells and macrophage were capable of recognizing the xenograft and directly participated the acute rejection of rat oral mucosal xenotransplantation. The peripheral blood mononuclear cells percentage could reflect macrophage infiltrating condition at the early stage of the acute rejection.%目的 探讨大鼠外周血CD68单核细胞比例和颊黏膜巨噬细胞浸润变化及二者相关性在口腔黏膜急性排斥反应中的作用和意义.方法 36只雌性Wistar大鼠按随机数字表随机分为移植组(15只)、创伤对照组(12只)及正常对照组(9只),建立口腔黏膜异种移植模型,分别于术后1、2、4周采用流式细胞术检测各组大鼠外周血CD68单核细胞百分数,免疫组化SP法检测颊黏膜巨噬细胞CD68的表达.结果 移植组3个时点外周血CD68单核细胞百分数呈高低起伏的变

  12. Inside the mucosal immune system.

    Jerry R McGhee

    Full Text Available An intricate network of innate and immune cells and their derived mediators function in unison to protect us from toxic elements and infectious microbial diseases that are encountered in our environment. This vast network operates efficiently by use of a single cell epithelium in, for example, the gastrointestinal (GI and upper respiratory (UR tracts, fortified by adjoining cells and lymphoid tissues that protect its integrity. Perturbations certainly occur, sometimes resulting in inflammatory diseases or infections that can be debilitating and life threatening. For example, allergies in the eyes, skin, nose, and the UR or digestive tracts are common. Likewise, genetic background and environmental microbial encounters can lead to inflammatory bowel diseases (IBDs. This mucosal immune system (MIS in both health and disease is currently under intense investigation worldwide by scientists with diverse expertise and interests. Despite this activity, there are numerous questions remaining that will require detailed answers in order to use the MIS to our advantage. In this issue of PLOS Biology, a research article describes a multi-scale in vivo systems approach to determine precisely how the gut epithelium responds to an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α, given by the intravenous route. This article reveals a previously unknown pathway in which several cell types and their secreted mediators work in unison to prevent epithelial cell death in the mouse small intestine. The results of this interesting study illustrate how in vivo systems biology approaches can be used to unravel the complex mechanisms used to protect the host from its environment.

  13. Honey and a mixture of honey, beeswax, and olive oil-propolis extract in treatment of chemotherapy-induced oral mucositis: a randomized controlled pilot study.

    Abdulrhman, Mamdouh; Elbarbary, Nancy Samir; Ahmed Amin, Dina; Saeid Ebrahim, Rania


    In spite of being one of the most investigated subjects among supportive care in cancer, no therapy has been found effective in treatment of chemotherapy-induced oral mucositis. Based on the observations that honey bees products have anti-inflammatory and wound healing effects, the present study tried to evaluate the effect of topical application of honey and a mixture of honey, olive oil-propolis extract, and beeswax (HOPE) in treatment of oral mucositis. This was a randomized controlled clinical trial conducted on 90 patients with acute lymphoblastic leukemia and oral mucositis grades 2 and 3. The mean age of enrolled patients was 6.9 years. The patients were assigned into 3 equal treatment groups: Honey, HOPE, and control groups. Topical treatment for each patient consists of honey, HOPE, and benzocaine gel for honey, HOPE, and control groups, respectively. Recovery time in grade 2 mucositis was significantly reduced in the honey group as compared with either HOPE or controls (P < .05). In grade 3 mucositis, recovery time did not differ significantly between honey and HOPE (P = 0.61) but compared with controls, healing was faster with either honey or HOPE (P < .01). Generally, in both grades of mucositis, honey produced faster healing than either HOPE or controls (P < .05). Based on our results that showed that honey produced faster healing in patients with grade 2/3 chemotherapy-induced mucositis, we recommend using honey and possibly other bee products and olive oil in future therapeutic trials targeting chemotherapy-induced mucositis.

  14. The effect of prebiotics on intestinal mucosal barrier protein occludin in model rats acutely exposed to high altitude%添加益生元对急进高原大鼠肠黏膜屏障紧密连接蛋白Occludin的作用研究

    段云; 张方信; 单体栋; 邵珂; 张盼


    Objective To investigate the effect of prebioties on the expression of occludin intestinal mueosal barrier in model rats acutely exposed to high altitude.Method Forty-eight rat medels in radical plateau hypoxia environment were established(3 848 m).These rats were randomly divided into hypoxia control group (n =24) and prebiotics group ( n = 24), then further randomly divided into six groups ( n = 8) by 2 d, 4 d and 6 d time points, respectively.The expression of occludin protein in intestinal mucosa was analyzed by immunohistochemistry method, and Tumor necrosis factorα (TNF-α) and interleukin-10 (IL-10) in ileum tissue were determined with ELISA.Result At each time point, occludin protein in all hypoxia control groups were significantly lower than in prebiotica group (P < 0.01 ), while TNF-α was significantly increased and serum IL-10 was remarkably reduced(P <0.05).Conclusion Prebiotics has the effect of maintaining the integrity of epithelial cells by increasing occludin protein expression and reducing the damage of intestinal mucosal barrier caused by hypoxia.%目的 探讨通过灌胃的方式给予益生元(低聚半乳糖)对急进高原大鼠肠黏膜屏障紧密连接Occludin蛋白的表达及作用.方法 在3 848米建立高原缺氧模型大鼠共48只,随机选24只为高原缺氧对照组,另24只为添加益生元组,再按2 d,4 d和6 d时间点,分为6组,每组8只.采用免疫组织化学法检测Occludin蛋白表达,用ELISA法测定回肠组织肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10).结果 和高原缺氧组各时间点比较,添加益生元组Occludin蛋白表达显著升高(P<0.01),TNF-α水平降低、IL-10水平升高(P<0.05).结论 益生元可以增加急进高原缺氧大鼠肠黏膜紧密连接蛋白Occludin的表达,改善高原缺氧对大鼠肠黏膜屏障的破坏.

  15. Mucosal Immunity and the Onset of Allergic Disease

    Yusei Ohshima


    Full Text Available Mucosal barriers encounter an environment that is rich in pathogens that possess mechanisms for invading mucosal tissues. These barriers also encounter innocuous antigens, such as foods, airborne antigens, and microbiota. The mucosa has developed a sophisticated immune system that can mount robust immune responses against pathogenic antigens, while maintaining mucosal tolerance against non-pathogenic antigens. Accumulating evidence indicates that the mucosal epithelium, dendritic cells, and a subtype of T cells with regulatory properties play important roles in the development and maintenance of mucosal tolerance. Moreover, the micribiota also contribute to regulating the mucosal immune system. A failure to develop or the breakdown of mucosal tolerance can result in allergic diseases, such as food allergy and asthma. By taking advantage of the unique characteristics of the mucosal immune system, strategies that induce regulatory cells in vivo and, thereby, reconstitute mucosal tolerance may be used to develop novel therapies that are suitable for treating or preventing of allergic diseases.

  16. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?

    Zhonghui Wen


    Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

  17. Establishment of a Single Dose Radiation Model of Oral Mucositis in Mice

    Ryu, Seung Hee; Moon, Soo Young; Choi, Eun Kyung; Kim, Jong Hoon; Ahn, Seung Do; Song, Si Yeol; Park, Jin Hong; Noh, Young Ju; Lee, Sang Wook [Ulsan University College of Medicine, Seoul (Korea, Republic of)


    Oral mucositis induced by radiotherapy to the head and neck area, is a common acute complication and is considered as the most severe symptom for cancer patients in the early stages of treatment. This study was proposed to establish the oral mucositis mouse model induced by a single dose of radiation for the facility of testing therapeutic candidates which can be used for the oral mucositis treatments. Materials and Methods: Fifty-five BALB/c mice were divided into four groups: control, 16 Gy, 18 Gy, and 20 Gy. Oral mucositis was induced by a single dose of radiation to the head and neck using 6 MV x-Ray from linear accelerator. After irradiation, body weight and physical abnormalities were checked daily. Tongue tissues from all groups were taken on days 1, 2, 3, 5, 7, 9, and 14, respectively and H and E staining was conducted to examine morphological changes. Results: Body weight dramatically decreased after day 5 in all irradiated mice. In the 16 Gy treatment group, body weight was recovered on day 14. The histology data showed that the thickness of the epithelial cell layer was decreased by the accumulated time after radiation treatment, up to day 9. Severe ulceration was revealed on day 9. Conclusion: A single dose of 16 Gy is sufficient dose to induce oral mucositis in Balb/C mice. Significant changes were observed in the Balb/C mice on days 7 and 9 after radiation. It is suggested that this mouse model might be a useful standard tool for studying oral mucositis induced by radiation.

  18. Pathogenesis of Tourette's syndrome.

    Leckman, J F; Peterson, B S; Anderson, G M; Arnsten, A F; Pauls, D L; Cohen, D J


    This review presents a models of disease pathogenesis in the context of CNS development. It begins with an exploration of the clinical features and natural history of Tourette's syndrome. This is followed by a consideration of the role of genetic and nongenetic factors. An effort is then made to review the anatomical organization of the basal ganglia and related cortical sites. These circuits are intimately involved in the normal processing of sensorimotor, cognitive, and emotionally laden information. Evidence implicating these circuits in the pathobiology of Tourette's syndrome is then considered. The review closes with the prospects for advances in interdisciplinary research and therapeutics using this model as a guide.


    Chernekhovskaya, N E; Povalayev, A V; Layshenko, G A


    In review today conceptions of view to aetiology and pathogenesis gastro-duodenales ulcerative lesions in elderly. Atherosclerosis, ischemic disease of the heart and hypertension are reasons of acute ulcers and erosions in elderly. The breaking of microcirculation are very importance.

  20. Probiotics the Good Neighbor: Guarding the Gut Mucosal Barrier

    R. K. Rao


    Full Text Available Problem statement: The disruption of gut barrier function plays a crucial role in the pathogenesis of not only gastrointestinal diseases, but also the diseases of liver and other organs. Mucosal protective factors that preserve the gut barrier integrity are beneficial in the prevention and treatment of such diseases. Probiotics is a group of helpful bacteria that protect the gastrointestinal mucosa from a variety of insults. Therefore, understanding the mechanism of probiotic-mediated protection of gut barrier function is an important area of investigation. Approach: Several studies had addressed the role of probiotics in the protection of gut barrier integrity. In a recent study, we investigated the role of Lactobacillus rhamnosus GG and two soluble proteins, p40 and p75, in the protection of gut barrier function in Caco-2 cell monolayer, a model of the intestinal epithelium. Results: Studies demonstrated that live or dead Lactobacillus rhamnosus GG prevents oxidative stress-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. The isolated soluble proteins of this probiotic, p40 and p75, also prevent hydrogen peroxide-induced tight junction disruption. This protective effect of probiotic proteins was mediated by the activation of ERK1/2 and protein kinase C isoforms, PKCβI and PKCε. Conclusion: Lactobacillus rhamnosus GG prevent oxidative stress-induced disruption of intestinal epithelial tight junctions and barrier function, suggesting that preservation of epithelial barrier function is one of the mechanisms involved in the mucosal protective role of probiotics in the gut.

  1. Alterations of the Ileal and Colonic Mucosal Microbiota in Canine Chronic Enteropathies.

    Eric Cassmann

    Full Text Available The intestinal microbiota is increasingly linked to the pathogenesis of chronic enteropathies (CE in dogs. While imbalances in duodenal and fecal microbial communities have been associated with mucosal inflammation, relatively little is known about alterations in mucosal bacteria seen with CE involving the ileum and colon.To investigate the composition and spatial organization of mucosal microbiota in dogs with CE and controls.Tissue sections from endoscopic biopsies of the ileum and colon from 19 dogs with inflammatory bowel disease (IBD, 6 dogs with granulomatous colitis (GC, 12 dogs with intestinal neoplasia, and 15 controls were studied by fluorescence in situ hybridization (FISH on a quantifiable basis.The ileal and colonic mucosa of healthy dogs and dogs with CE is predominantly colonized by bacteria localized to free and adherent mucus compartments. CE dogs harbored more (P < 0.05 mucosal bacteria belonging to the Clostridium-coccoides/Eubacterium rectale group, Bacteroides, Enterobacteriaceae, and Escherichia coli versus controls. Within the CE group, IBD dogs had increased (P < 0.05 Enterobacteriaceae and E. coli bacteria attached onto surface epithelia or invading within the intestinal mucosa. Bacterial invasion with E. coli was observed in the ileal and colonic mucosa of dogs with GC (P < 0.05. Dogs with intestinal neoplasia had increased (P < 0.05 adherent (total bacteria, Enterobacteriaceae, E. coli and invasive (Enterobacteriaceae, E. coli, and Bacteroides bacteria in biopsy specimens. Increased numbers of total bacteria adherent to the colonic mucosa were associated with clinical disease severity in IBD dogs (P < 0.05.Pathogenic events in canine CE are associated with different populations of the ileal and colonic mucosal microbiota.

  2. Role of gastric blood flow, neutrophil infiltration, and mucosal cell proliferation in gastric adaptation to aspirin in the rat.

    Konturek, S J; Brzozowski, T; Stachura, J; Dembinski, A; Majka, J


    Gastric mucosa exhibits the ability to adapt to ulcerogenic action of aspirin but the mechanism of this phenomenon is unknown. In this study, acute gastric lesions were produced by single or repeated doses of acidified aspirin in rats with intact or resected salivary glands and with intact or suppressed synthase of nitric oxide. A single oral dose of aspirin produced a dose dependent increase in gastric lesions accompanied by considerable blood neutrophilia and mucosal neutrophil infiltration, significant reduction in gastric blood flow, and almost complete suppression of biosynthesis of prostaglandins. After rechallenge with aspirin, the mucosal damage became smaller and progressively declined with repeated aspirin insults. Gastric adaptation to aspirin was accompanied by a significant rise in gastric blood flow, reduction in both blood neutrophilia and mucosal neutrophil infiltration, and a remarkable increase in mucosal cell regeneration and mucosal content of epidermal growth factor. Salivectomy, which reduced the mucosal content of epidermal growth factor, aggravated the initial mucosal damage induced by the first exposure to acidified aspirin but did not prevent the adaptation of this mucosa to repeated aspirin insults. Pretreatment with NG-nitro-L-arginine (L-NNA), a specific inhibitor of nitric oxide synthase, eliminated the hyperaemic response to repeated aspirin but did not abolish the development of adaptation to aspirin showing that the maintenance of the gastric blood flow plays little part in this adaptation. In conclusion, the stomach adapts readily to repeated aspirin insults and this is accompanied by a considerable reduction in blood neutrophilia and the severity of neutrophil infiltration and by an extensive proliferation of mucosal cells possibly involving epidermal growth factor. PMID:7525421

  3. Pathogenesis of Raynaud's phenomenon.

    Herrick, A L


    The pathogenesis of Raynaud's phenomenon is not fully understood. However, the last 20 yr have witnessed enormous increases in our understanding of different mechanisms which, singly or in combination, may contribute. A key point is that Raynaud's phenomenon can be either primary (idiopathic) or secondary to a number of underlying conditions, and that the pathogenesis and pathophysiology vary between these conditions. This review concentrates upon those subtypes of Raynaud's phenomenon of most interest to rheumatologists: systemic sclerosis-related Raynaud's phenomenon, primary Raynaud's phenomenon and Raynaud's phenomenon secondary to hand-arm vibration syndrome. In this review, I shall discuss the main mechanisms thought to be important in pathophysiology under the three broad headings of 'vascular', 'neural' and 'intravascular'. While these are false distinctions because all interrelate, they facilitate discussion of the key elements: the blood vessel wall (particularly the endothelium), the neural control of vascular tone, and the many circulating factors which can impair blood flow and/or cause endothelial injury. Vascular abnormalities include those of both structure and function. Neural abnormalities include deficiency of the vasodilator calcitonin gene-related peptide (released from sensory afferents), alpha(2)-adrenoreceptor activation (possibly with up-regulation of the normally 'silent' alpha(2C)-adrenoreceptor) and a central nervous system component. Intravascular abnormalities include platelet activation, impaired fibrinolysis, increased viscosity and probably oxidant stress. As our understanding of the pathophysiology of Raynaud's phenomenon increases, so do our possibilities for identifying effective treatments.

  4. Pemphigus: Epidemiology and Pathogenesis

    Yelda Karıncaoğlu


    Full Text Available Pemphigus, a group of bullous diseases affecting the oral mucosa and the skin, is caused by antibody-mediated autoimmune reaction to desmogleins (Dsg, desmosomal transmembrane glycoproteins, leading to acantholysis. Pemphigus has a worldwide distribution but the incidence in patients of Jewish origin is higher. The disease has a peak incidence of occurrence between the 4th and 6th decades. While various environmental factors have been implicated as triggering agents, HLA association is probably the most important predisposing factor. Pemphigus, is caused by antibody-mediated autoimmune reaction to desmosomal cadherins, Dsg1, and Dsg3. Recent molecular studies have shown that acantholysis can occur also in the presence of antibodies against 9a nicotinic acetylcholine receptor. Pemphigus is currently divided into three distinct varieties, i.e., pemphigus vulgaris (PV, pemphigus foliaceus (PF and other variants of pemphigus, depending on clinical features, the level of separation in the epidermis, and immunologic characteristics of auto-antigens. Blistering pathogenesis differ for each of the types of pemphigus. PV is characterized by IgG autoantibodies against Dsg 3, whereas the target of PF is Dsg1, although about 50% of PV patients also have Dsg1 autoantibodies. Lesion distribution is related to the location of the antigen (Dgs 3 and/or Dgs 1 in the epithelium and specific autoantibody production. This article reviews the epidemiology and pathogenesis of pemphigus.

  5. Irritable bowel syndrome: Diagnosis and pathogenesis

    Magdy El-Salhy


    Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life.It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients.The diagnosis of IBS is based on symptom assessment and the Rome Ⅲ criteria.A combination of the Rome Ⅲ criteria,a physical examination,blood tests,gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis.Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS.The pathogenesis of IBS seems to be multifactorial,with the following factors playing a central role in the pathogenesis of IBS:heritability and genetics,dietary/intestinal microbiota,low-grade inflammation,and disturbances in the neuroendocrine system (NES) of the gut.One hypothesis proposes that the cause of IBS is an altered NES,which would cause abnormal GI motility,secretions and sensation.All of these abnormalities are characteristic of IBS.Alterations in the NES could be the result of one or more of the following:genetic factors,dietary intake,intestinal flora,or low-grade inflammation.Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases.Patients with PI-and IBD-IBS exhibit low-grade mucosal inflammation,as well as abnormalities in the NES of the gut.

  6. 重症急性胰腺炎大鼠肠粘膜免疫屏障功能损伤及早期腹腔引流对其影响的实验研究%Research of Intestinal Mucosal Immune Barrier Injury to Rats with Severe Acute Pancreatitis and Impact on It by Early Catheter Drainage

    郑晓博; 邹洪; 伍松; 唐均成; 文艺; 冯梨; 陈振宇; 张少华; 汤礼军


    目的:探讨早期腹腔引流对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠肠粘膜免疫屏障功能损伤的影响及作用机制。方法将72只Wistar大鼠随机分为3组:SAP组(A组)、SAP引流组(B组)、假手术对照组(C组)。观察术后12、24 h大鼠死亡率,各时相点腹水量。分别于术后的第6、12、24 h采集血液、腹水、肠液、肠组织、胰腺标本,冻存以备检测。采用全自动生化分析仪检测血清及腹水淀粉酶活性,ELISA法测定血清及腹水IL-6、TNF-a浓度,胰腺组织冰冻切片HE染色观察病理变化,ELISA法检测肠液sIgA水平,肠组织作CD4+T淋巴细胞免疫组化染色。结果分别于术后6、12、24 h,通过各项指标的检测,有以下发现:①术后同时相点A、B两组大鼠血清及腹水淀粉酶、IL-6、TNF-a水平均显著高于C组大鼠水平,且术后同时相点A、B两组大鼠胰腺组织水肿及出血坏死程度均较C组大鼠显著加重。②对肠液sIgA的检测发现,术后各时相点A、B两组大鼠均显著低于C组大鼠水平,且A、B两组大鼠肠组织中CD4+T淋巴细胞浸润程度也均显著低于C组。③术后同时相点B组大鼠血清及腹水淀粉酶、IL-6、TNF-a水平均显著低于A组大鼠水平;B组大鼠胰腺组织水肿及出血坏死程度较A组明显减轻。④术后同时相点B组肠液sIgA水平显著高于A组水平;且B组肠组织中CD4+T淋巴细胞浸润程度较A组显著增加。结论SAP发病早期,通过腹腔置管引流将富含诸如IL-6、TNF-a等炎性因子的腹水引流出体外,对肠粘膜免疫屏障功能起到显著的保护作用。%Objective To investigate the impact and mechanism of the catheter drainage on the rats with intestinal mucosal immune barrier in-jury by severe acute pancreatitis(SAP).Methods 72 wistar rats were randomly divided into three groups:SAP model group(A group),SAP drainage group (B group

  7. Novel vaccine development strategies for inducing mucosal immunity.

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


    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.

  8. NOD样受体通路在急性腹腔感染早期对大鼠肠屏障的作用机制初探%Effect mechanism of NOD like receptor signaling pathway on intestinal mucosal barrier of rat during early phase of acute intra-abdominal infection

    肖元廷; 李国逊; 王西墨


    Objective To initially investigate the expressing regularity and effect of enterocyte NOD like receptors on gut mucosal barrier during early phase of acute intra-abdominal infection.Methods Sprague-Dawley (SD) rats were randomly allocated into control group (n=6) and experimental group (n=24).Acute intra-abdominal infection model was induced by cecal ligation and puncture (CLP).The level of NOD2 and NOD like receptor 3 (NLRP3) mRNA expression in gut mucosa was determined using fluorescent polymerase chain reaction (PCR) ; the expression of caspase-1 and tight junction protein was determined by Western blotting; the activity of nuclear factor-κB (NF-κB) was determined by electrophoretic mobility shift assay (EMSA) ; the level of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was determined by enzyme linked immunosorbent assay (ELISA).The dead cell percentage of enterocyte was observed by terminaldeoxynucleoitidyl transferase mediated nick end labeling,and the gut mucosal permeability using an in situ loop preparation of gut with fluorescence isothiocyanate-conjugated dextran was determined.Results NOD2 mRNA expression was quickly increased to a very high apex at 2 hours after operation,compared with the control group,the difference was statistically significant (75.50 ± 13.03 vs.1.00 ± 0.00,P<0.01),and quickly descended at 6 hours,and then slowing descended.The expression of NLRP3 mRNA was decreased at 2 hours after the operation,then increased gradually,and peaked at 12 hours,which was significantly higher than that in control group (4.03 ± 0.71 vs.1.00 ± 0.00,P<0.05).The level of caspase-1 was significantly higher than that in control group at 2 hours (3.56 ± 0.14 vs.2.10 ± 0.11,P<0.01) and then gradually increased.The levels of Occludin,ZO-1 and Claudin-4 were obviously lowered than that in control group at 2-6 hours (2 hours Occludin:7.24 ± 1.13 vs.12.72 ± 1.34,6 hours ZO-1:0.47 ± 0.09 vs.1.57 ± 0.17,2 hours Claudin-4:1.63

  9. Electrochemotherapy of mucosal head and neck tumors

    Plaschke, Christina Caroline; Gothelf, Anita; Gehl, Julie


    with head and neck cancer treated across the mucosal surface with electrochemotherapy. The search resulted in 11 studies with a total of 72 patients. RESULTS: Overall complete response was reported as good, especially in primary small tumors. Side effects were minor in primary tumors whereas large......, recurrent tumors displayed more frequent side effects and some serious adverse events. Design and structure of the studies differed considerably, making general comparisons difficult. CONCLUSION: Few studies concerning electrochemotherapy on mucosal head and neck tumors are available and they are not easily...

  10. Endoscopic, assisted, modified turbinoplasty with mucosal flap.

    Puterman, M M; Segal, N; Joshua, B-Z


    A variety of surgical methods have been developed to reduce the volume of the inferior turbinates, in order to create a more patent nasal airway. We describe a technique used in our department since February 2002 for all patients undergoing inferior turbinectomy. We resect with endoscopic assistance the lateral mucosa and bony inferior turbinate. This technique can reduce a large volume of the turbinate while preserving the mucosal continuity and the submucosa by covering the raw surface with a mucosal flap. We believe our method minimises post-operative side effects and complications such as dryness, infection, bleeding and pain.

  11. Oral mucosal diseases: evaluation and management.

    Stoopler, Eric T; Sollecito, Thomas P


    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.

  12. [Etiology and pathogenesis of inflammatory bowel diseases].

    Lukáš, Milan


    Zdenek Mařatka has been the first physician, who had brought a new information for the Czech medical community with topic of inflammatory bowel diseases, which had been systematic studied for him. He had prepared an original theory - two component hypothesis about origin of ulcerative colitis, which had been developed and innovated by him for long time. From the international point of view, Mařatka has had an extraordinary impact and significant contribution for recognition of ulcerative colitis and Crohn´s disease. Despite the fact that the true origin of ulcerative colitis and Crohn´s disease (UC) still remain elusive, basic as well as clinical research bring many new data on etiology and pathogenesis of this inflammatory condition. It seems clear that IBD originate from interaction of several intrinsic and extrinsic factors that contribute individually in a particular patient. Among internal factors the genes play an important role, because its influence on the mucosal immunity system and immunological response. Among the external factors importance are recognized the gut microbiota content, cigarette smoking and psychological stress.

  13. Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut.

    Michielan, Andrea; D'Incà, Renata


    The pathogenesis of inflammatory bowel disease (IBD) is multifactorial with data suggesting the role of a disturbed interaction between the gut and the intestinal microbiota. A defective mucosal barrier may result in increased intestinal permeability which promotes the exposition to luminal content and triggers an immunological response that promotes intestinal inflammation. IBD patients display several defects in the many specialized components of mucosal barrier, from the mucus layer composition to the adhesion molecules that regulate paracellular permeability. These alterations may represent a primary dysfunction in Crohn's disease, but they may also perpetuate chronic mucosal inflammation in ulcerative colitis. In clinical practice, several studies have documented that changes in intestinal permeability can predict IBD course. Functional tests, such as the sugar absorption tests or the novel imaging technique using confocal laser endomicroscopy, allow an in vivo assessment of gut barrier integrity. Antitumor necrosis factor-α (TNF-α) therapy reduces mucosal inflammation and restores intestinal permeability in IBD patients. Butyrate, zinc, and some probiotics also ameliorate mucosal barrier dysfunction but their use is still limited and further studies are needed before considering permeability manipulation as a therapeutic target in IBD.

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

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


    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,

  15. Sucralfate for the treatment of radiation induced mucositis; Einsatz von Sucralfat in der Radioonkologie

    Belka, C. [Univ. Tuebingen (Germany). Abt. fuer Strahlentherapie; Hoffmann, W. [Univ. Tuebingen (Germany). Abt. fuer Strahlentherapie; Paulsen, F. [Univ. Tuebingen (Germany). Abt. fuer Strahlentherapie; Bamberg, M. [Univ. Tuebingen (Germany). Abt. fuer Strahlentherapie


    Purpose: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. Patients and Method: The results of available studies are analysed and discussed. Results: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. Conclusion: Nevertheless sucralfate is a save, cheap and active drug for the prevention and treatment of radiation mucositis especially in patients with pelvic irradiation. (orig.) [Deutsch] Hintergrund: Schleimhautreaktionen stellen eine wesentliche akute und chronische Nebenwirkung radioonkologischer Therapieverfahren dar. Klinisch im Vordergrund stehen Schmerzen, Ernaeherungsprobleme und Durchfaelle. Da bislang keine kausalen Therapie- oder Prophylaxemassnahmen bekannt sind, erfolgt die Behandlung symptomorientiert. Hierbei kommen insbesondere lokale und systemische

  16. Molecular Pathogenesis of NASH

    Alessandra Caligiuri


    Full Text Available Nonalcoholic steatohepatitis (NASH is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression.

  17. Pathogenesis of Lassa fever.

    Yun, Nadezhda E; Walker, David H


    Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host's immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.

  18. Pathogenesis of Lassa Fever

    David H. Walker


    Full Text Available Lassa virus, an Old World arenavirus (family Arenaviridae, is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.

  19. Molecular Pathogenesis of NASH

    Caligiuri, Alessandra; Gentilini, Alessandra; Marra, Fabio


    Nonalcoholic steatohepatitis (NASH) is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression. PMID:27657051

  20. [Pathogenesis of rheumatoid arthritis].

    Branimir Anić; Miroslav Mayer


    Rheumatoid arthritis (RA) is an autoimmune systemic disease that primarily affects joints. Etiology and the pathogenesis of RA are complex, involving many types of cells, among others macrophages, T and B cells, fibro- blasts, chondrocytes and dendritic cells. Despite well documented role of many genes and epigenetic modifications in the development and evolution of the disease, in most RA patients there is no clear predisposing factor present. Environmental factors involved in RA pathogenesis are cigarette smoke, industrial pollutants like silica crystals, disturbances of intestinal, lung, and oral microbiota and some specific bacterial and viral infectious agents and their components. In the initial disease stage there are qualitative and quantitative disturbances ofpeptide citrulination as well as other protein modifications, followed by antigen presenting cell (APC) (macrophages and dendritic cells) and fibroblast like synoviocytes (FLS) activation. Some microbes foster this processes by APC and FLS direct and indirect activation. In the second stage APC's elicit specific humoral B cell re- sponse resulting in specific antibodies production and T cell autoreactivity. Inherited and acquired defects in T and B cell responses caused by repeated activation of innate immunity as well as loss of tolerance, elicit chronic autoimmune inflammation, primarily of synovial membranes, and development of cellular panus. Pathologic activation of the osteoclasts and release of the immune system effector molecules and the proteolytic enzymes damage the cartilage, bone and tendons composition and structure. Persistent inflammation through its complex mechanisms results in many systemic and extraarticular RA manifestations of almost all organ systems, resulting in severe complications and comorbidities such as rheumatoid lung, carditis, vasculitis, cahexia, anemia, accelerated atherosclerosis, myocardial and cerebrovascular vascular disease, lymphoma, osteoporosis, depression etc

  1. Transition Metal Ions at the Crossroads of Mucosal Immunity and Microbial Pathogenesis

    Vladimir eDiaz-Ochoa


    Full Text Available Transition metal ions are essential micronutrients for all living organisms. In mammals, these ions are often protein-bound and sequestered within cells, limiting their availability to microbes. Moreover, in response to infection, mammalian hosts further reduce the availability of metal nutrients by activating epithelial cells and recruiting neutrophils, both of which release metal-binding proteins with antimicrobial function. Microorganisms, in turn, have evolved sophisticated systems to overcome these limitations and acquire the metal ions essential for their growth. Here we review some of the mechanisms employed by the host and by pathogenic microorganisms to compete for transition metal ions, with a discussion of how evading nutritional immunity benefits pathogens. Furthermore, we provide new insights on the mechanisms of host-microbe competition for metal ions in the mucosa, particularly in the inflamed gut.

  2. Pathogenesis of mucosal injury in the blind loop syndrome. Brush border enzyme activity and glycoprotein degradation.

    Jonas, A; Flanagan, P R; Forstner, G G


    The effect of intestinal bacterial over-growth on brush border hydrolases and brush border glycoproteins was studied in nonoperated control rats, control rats with surgically introduced jejunal self-emptying blind loops, and rats with surgically introduced jejunal self-filling blind loops. Data were analyzed from blind loop segments, segments above and below the blind loops, and three corresponding segments in the nonoperated controls. Rats with self-filling blind loops had significantly greater fat excretion than controls and exhibited significantly lower conjugated:free bile salt ratios in all three segments. Maltase, sucrase, and lactase activities were significantly reduced in homogenates and isolated brush borders from the self-filling blind loop, but alkaline phosphatase was not affected. The relative degradation rate of homogenate and brush border glycoproteins was assessed by a double-isotope technique involving the injection of d-[6-(3)H]glucosamine 3 h and d-[U-(14)C]glucosamine 19 h before sacrifice, and recorded as a (3)H:(14)C ratio. The relative degradation rate in both homogenate and brush border fractions was significantly greater in most segments from rats with self-filling blind loops. In the upper and blind loop segments from rats with self-filling blind loops, the (3)H:(14)C ratios were higher in the brush border membrane than in the corresponding homogenates, indicating that the increased rates of degradation primarily involve membrane glycoproteins. Incorporation of d-[6-(3)H]glucosamine by brush border glycoproteins was not reduced in rats with self-filling blind loops, suggesting that glycoprotein synthesis was not affected. Polyacrylamide gel electrophoresis of brush border glycoproteins from the contaminated segments indicated that the large molecular weight glycoproteins, which include many of the surface hydrolases, were degraded most rapidly. Brush border maltase, isolated by immunoprecipitation, had (3)H:(14)C ratios characteristic of the most rapidly degraded glycoproteins. The results indicate that bacteria enhance the destruction of intestinal surface glycoproteins including disaccharidases. Since alkaline phosphatase, a glycoprotein, is not affected, the destruction is selective and presumably involves only the most exposed membrane components.

  3. Concomitant early mucosal and cutaneous leishmaniasis in Brazil.

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


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

  4. Can the oral microflora affect oral ulcerative mucositis?

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


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

  5. Mucosal Vaccination and Therapy with Genetically Modified Lactic Acid Bacteria

    Wells, J.


    Lactic acid bacteria (LAB) have proved to be effective mucosal delivery vehicles that overcome the problem of delivering functional proteins to the mucosal tissues. By the intranasal route, both live and killed LAB vaccine strains have been shown to elicit mucosal and systemic immune responses that

  6. Measuring mucosal damage induced by cytotoxic therapy.

    Blijlevens, N.M.A.; Land, B. van 't; Donnelly, J.P.; Rabet, L. M'; Pauw, B.E. de


    We scored oral mucositis and gut toxicity and measured sugar permeability testing among 56 recipients of a haematopoietic stem cell transplant (HSCT) given myeloablative conditioning with idarubicin, cyclophosphamide and TBI, and a group of 18 patients given cytotoxic chemotherapy for newly diagnose

  7. Topical morphine for oral mucositis in children

    Nielsen, Bettina Nygaard; Aagaard, Gitte; Henneberg, Steen W;


    Systemic opioids for painful chemotherapy-induced oral mucositis in children often result in unsatisfactory pain relief and a high frequency of side effects. Opioids applied topically can produce analgesia by binding to opioid receptors on peripheral terminals of sensory neurons. These receptors...

  8. Nutrition and Gut Mucositis in Pediatric Oncology

    Pontoppidan, Peter Erik Lotko

    and differential regulation of miRNA-155 and -146a. This was sustained during the first three weeks after transplantation, along with increased spontaneous production of inflammatory cytokines by early trafficking of leukocytes. In conclusion, we successfully induced oral and intestinal mucositis in piglets...

  9. Documentation of radiation-induced oral mucositis. Scoring Systems

    Riesenbeck, D. [Klinik und Poliklinik fuer Strahlentherapie - Radioonkologie, Westfaelische Wilhelms-Universitaet Muenster (Germany); Doerr, W. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Technische Universitaet Dresden (Germany)


    Background: Radiation therapy of tumors in the head and neck region is frequently associated with severe side effects in the oral mucosa which often necessitate interruption of the prescribed treatment protocol. In order to compare therapeutic strategies and, more important, in order to perform multicenter studies, generally accepted scoring systems have to be applied for uniform documentation of the oral mucosal response. Methods: Different scoring protocols are found in the literature. The scoring protocols most widely accepted are the CTC classification and the RTOG/EORTC classification. These are compared with more detailed systems. Results: In the CTC classification, grading of stomatitis is included in the responses of the gastrointestinal tract and emphasizes dietary effects. For effects of radiation alone or of radiochemotherapy, the RTOG/EORTC system, focusing on therapeutic interventions, has been established. However, there are only minor differences in the grading of mucositis between these 2 protocols. Based on the RTOG/EORTC classification, Maciejewski et al. introduced a classification system with inclusion of the area affected, but also changed the sensitivity of the scores. The latter may be confusing if the source of the system used is not cited in a report. An alternative system was proposed by Dische, which in addition to objective morphologic criteria also includes the symptoms induced by the mucosal response, and hence includes some subjective aspects reported by the patient. Conclusions: For routine documentation of acute radiation side effects in the oral cavity, the German version of the RTOG/EORTC classification can be recommended. In studies with particular interest in oral mucositis, a more sensitive scoring system may be applied. In any publication concerning mucositis, a table or a detailed description of the system used should be included. (orig.) [Deutsch] Hintergrund: Die Strahlentherapie von Tumoren der Kopf-Hals-Region ist haeufig

  10. S_3神经根电刺激改善急性完全性脊髓损伤后肠黏膜屏障功能%Role of electrical stimulation of S_3 nerve root in improvement of intestinal mucosal barrier function after acute complete spinal cord injury in rabbits

    白春宏; 安洪; 王莎莉; 蒋电明; 范伟; 聂海


    目的 探讨S_3神经根电刺激对急性完全性脊髓损伤后肠黏膜屏障功能障碍的作用. 方法 建立兔脊髓损伤性截瘫模型,以截瘫后行S_3神经根电刺激为实验组,不做刺激截瘫兔为对照组,正常白兔为正常组.无菌条件下,采集门静脉血进行内毒素定量测定和细菌培养,采集肝、脾、肠系膜淋巴结作细菌培养并进行菌种鉴定.取实验组和对照组各动物的肝、脾、肠系膜淋巴结、小肠进行病理切片HE染色检查,取小肠进行电镜检查. 结果 对照组肠黏膜屏障及其他器官破坏严重,血清内毒素水平较实验组和正常组明显增高,肠道菌群移位发生率较高;实验组电刺激S_3神经根使失神经肠道蠕动增强,排出的肠内容物明显增加,同时肠黏膜破坏较轻,其他脏器损伤也较对照组轻,血清内毒素水平较对照组明显减轻并且与正常组差异无统计学意义,细菌移位率明显下降. 结论 急性脊髓损伤后电刺激S_3神经根能较好地促进肠道蠕动,促进肠内容物的排出,良好地改善肠黏膜屏障功能,进而减轻内毒素血症和肠道细菌移位;有利于减少SIRS和MODS的产生.%Objective To investigate the effect of electrical stimulation of S_3 nerve root on improvement of intestinal mucosal barrier function in rabbits with acute complete spinal cord injury. Methods Model of paraplegia was built by injuring spinal cord in rabbits. Then, the rabbits with electrical stimulation of S_3 nerve root were set as experimental group and those without set as control group. Normal rabbits were set as normal group. Under aseptic condition, portal vein blood was collected for quantitative determination of endotoxin and bacterial culture ; and liver, spleen and mesenteric lymph nodes were collected for bacterial culture and strain identification. Liver, spleen, mesenteric lymph nodes and small intestines were collected from experimental group and control group for

  11. Management of radiation therapy-induced mucositis in head and neck cancer patients. Part II: supportive treatments

    Wei Cheong Ngeow


    Full Text Available Oropharyngeal mucositis is the acute inflammatory and ulcerative reaction of the oral mucosa following radiation therapy to the head and neck region. It is such a common problem that nearly all head and neck cancer patients develop some degree of mucositis. This complication is usually transient in nature but it also represents an important clinical problem as it is a painful, debilitating, dose-dependent side effect for which there is no widely acceptable prophylaxis or effective treatment. As several authoritative groups have recently either undertaken systematic reviews or issued guidelines on the management of mucositis, it is the aim of this review instead, to provide an overview of all the remedies and pharmaceutical agents available, as well as highlighting to researchers the gaps that need to be filled.

  12. Strategies of mucosal immunotherapy for allergic diseases

    Yi-Ling Ye; Ya-Hui Chuang; Bor-Luen Chiang


    Incidences of allergic disease have recently increased worldwide.Allergen-specific immunotherapy (SIT) has long been a controversial treatment for allergic diseases.Although beneficial effects on clinically relevant outcomes have been demonstrated in clinical trials by subcutaneous immunotherapy (SCIT),there remains a risk of severe and sometimes fatal anaphylaxis.Mucosal immunotherapy is one advantageous choice because of its non-injection routes of administration and lower side-effect profile.This study reviews recent progress in mucosal immunotherapy for allergic diseases.Administration routes,antigen quality and quantity,and adjuvants used are major considerations in this field.Also,direct uses of unique probiotics,or specific cytokines,have been discussed.Furthermore,some researchers have reported new therapeutic ideas that combine two or more strategies.The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation,which includes continuous searching for efficient adjuvants,collecting more information about dominant T-cell epitopes of allergens,and having the proper combination of each.In clinics,when compared to other mucosal routes,sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration,although local and systemic side effects have been reported.Additionally,not every allergen has the same beneficial effect.Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults.Data collected from large,well-designed,double-blind,placebo-controlled,and randomized trials,with post-treatment follow-up,can provide robust substantiation of current evidence.

  13. A mucosal model to study microbial biofilm development and anti-biofilm therapeutics

    Anderson, Michele J.; Parks, Patrick J.; Peterson, Marnie L.


    Biofilms are a sessile colony of bacteria which adhere to and persist on surfaces. The ability of bacteria to form biofilms is considered a virulence factor, and in fact is central to the pathogenesis of some organisms. Biofilms are inherently resistant to chemotherapy and host immune responses. Clinically, biofilms are considered a primary cause of a majority of infections, such as otitis media, pneumonia in cystic fibrosis patients and endocarditis. However, the vast majority of the data on biofilm formation comes from traditional microtiter-based or flow displacement assays with no consideration given to host factors. These assays, which have been a valuable tool in high-throughput screening for biofilm-related factors, do not mimic a host-pathogen interaction and may contribute to an inappropriate estimation of the role of some factors in clinical biofilm formation. We describe the development of a novel ex vivo model of biofilm formation on a mucosal surface by an important mucosal pathogen, methicillin resistant S. aureus (MRSA). This model is being used for the identification of microbial virulence factors important in mucosal biofilm formation and novel anti-biofilm therapies. PMID:23246911

  14. Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets.

    van Unen, Vincent; Li, Na; Molendijk, Ilse; Temurhan, Mine; Höllt, Thomas; van der Meulen-de Jong, Andrea E; Verspaget, Hein W; Mearin, M Luisa; Mulder, Chris J; van Bergen, Jeroen; Lelieveldt, Boudewijn P F; Koning, Frits


    Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease. We distinguished 142 immune subsets and through computational applications found distinct immune subsets in peripheral blood mononuclear cells and intestinal biopsies that distinguished patients from controls. In addition, mucosal lymphoid malignancies were readily detected as well as precursors from which these likely derived. These findings indicate that an integrated high-dimensional analysis of the entire immune system can identify immune subsets associated with the pathogenesis of complex intestinal disorders. This might have implications for diagnostic procedures, immune-monitoring, and treatment of intestinal diseases and mucosal malignancies.

  15. Protective role of Rheum tanguticum polysaccharide 1 on the radiation-induced acute intestinal mucosal injury%唐古特大黄多糖组分1对大鼠急性放射性肠损伤的保护作用

    刘琳娜; 张甜; 石磊; 张志培; 李诗草; 关波; 张文娟


    Objective To investigate the protective role of Rheum tanguticum polysaccharides 1 ( RTP1 ) on the ra-diation-induced acute intestinal mucosal injury in rats .Methods Rats in RTP1 group were treated with 200 , 400 or 800 mg/kg RTP1 by intragastric administration for 7 days.At the 7th day, rats in IC group and RTP1 groups received a single dose of 10 .0 Gy for the abdomianl regions .At the 4 th day of radiation , the small intestinal samples were collected for pathology analysis and levels of SOD , MDA, GSH were also detected .The levels of DAO , D-lactate and endotoxin in blood plasma were measured .Results Compared with the IC group , the mucosa structure of small intestine in the RTP1 group was greatly improved .RTP1 pretreatment decreased the levels of MDA , the plasma levels of DAO D-lactate and endotoxin (P<0.05);enhanced the activity of SOD and the level of GSH (P<0.05).Conclusion RTP1 can promote the recovery of intestinal mucosa damage , which may be related to its inhibition of intestinal epithelial injury and intracellular reactive oxygen species production caused by radiation .%目的:探讨唐古特大黄多糖组分1( Rheum tanguticum polysaccharides , RTP1)对辐射所致大鼠急性肠黏膜损伤的保护作用。方法 RTP1灌胃给药(剂量200、400、800 mg/kg)7 d后,除正常组大鼠外,其余各组均接受10.0 Gy/只一次性全腹均匀X射线照射1次,3d后处死动物,观察小肠黏膜病理形态改变,测定肠黏膜屏障功能、小肠组织氧化还原酶活性及血浆内毒素水平。结果RTP1预处理后可以改善肠黏膜损伤,升高SOD活性及GSH含量,降低MDA水平,抑制血浆中DAO、D-乳酸及内毒素水平,与IC组比较,差异具有统计学意义(P<0.05)。结论 RTP1通过减轻肠黏膜屏障功能损害,增强抗氧化能力保护辐射所致肠黏膜损伤。

  16. NRAS and BRAF mutation frequency in primary oral mucosal melanoma.

    Buery, Rosario Rivera; Siar, Chong Huat; Katase, Naoki; Gunduz, Mehmet; Lefeuvre, Mathieu; Fujii, Masae; Inoue, Masahisa; Setsu, Kojun; Nagatsuka, Hitoshi


    Oral mucosal melanoma (OMM) is a fatal sarcoma of unknown etiology. Histological morphology and genetic events are distinct from those of its cutaneous counterpart. Mutation and up-regulation of c-kit has been identified in OMM which may activate downstream molecules such as RAS and RAF. These molecules are involved in the mitogen-activated protein kinase (MAPK) pathway leading to tremendous cell proliferation and survival. NRAS and BRAF mutation and protein expression have been studied in other melanoma subtypes. The purpose of this study was to determine RAS protein expression and NRAS and BRAF mutation in 18 primary OMM cases using immunohistochemistry and mutation analysis. Results showed that RAS is intensely expressed in both in situ and invasive OMMs. However, NRAS mutation was only observed in 2/15 polymerase chain reaction (PCR) amplified cases both of which were silent mutations. On the other hand, BRAF missense mutations were observed only in 1/15 cases with PCR amplification. NRAS and BRAF mutations were independent from previously reported c-kit mutations. The classical V600E BRAF mutation was not found; instead a novel V600L was observed suggesting that the oncogenic event in OMM is different from that in skin melanoma. The low frequency of NRAS and BRAF mutations indicate that these genes are not common, but probable events in OMM pathogenesis, most likely independent of c-kit mutation.

  17. Recent progress in melasma pathogenesis.

    Lee, Ai-Young


    Melasma is a common skin pigmentation condition. Given therapeutic difficulty as one of the biggest concerns, understanding of the etiology and pathogenesis of melasma becomes essential. UV irradiation, female sex hormones, and inflammatory processes are addressed as triggering factors with genetic predisposition. The mechanism of UV-induced melanogenesis has been extensively investigated as a model system to study melasma pathogenesis. Hitherto, treatment modalities for melasma are similar to other hyperpigmentation disorders. However, individual triggering factors induce a separate pigmentation disease, whose pathogenic mechanisms and clinical phenotypes are different from the ones encountered in melasma. Fortunately, there have been ongoing updates on melasma pathogenesis with regard to major triggering factors. Presence of certain factors working independently of UV exposure and role of dermal factors and microRNAs are being identified as novel discoveries about melasma pathogenesis. In this review, the melasma pathogenesis is reviewed in association with updated and new findings.

  18. A mouse model of otitis media identifies HB-EGF as a mediator of inflammation-induced mucosal proliferation.

    Keigo Suzukawa

    Full Text Available Otitis media is one of the most common pediatric infections. While it is usually treated without difficulty, up to 20% of children may progress to long-term complications that include hearing loss, impaired speech and language development, academic underachievement, and irreversible disease. Hyperplasia of middle ear mucosa contributes to the sequelae of acute otitis media and is of important clinical significance. Understanding the role of growth factors in the mediation of mucosal hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae.From a whole genome gene array analysis of mRNA expression during acute otitis media, we identified growth factors with expression kinetics temporally related to hyperplasia. We then tested these factors for their ability to stimulate mucosal epithelial growth in vitro, and determined protein levels and histological distribution in vivo for active factors.From the gene array, we identified seven candidate growth factors with upregulation of mRNA expression kinetics related to mucosal hyperplasia. Of the seven, only HB-EGF (heparin-binding-epidermal growth factor induced significant mucosal epithelial hyperplasia in vitro. Subsequent quantification of HB-EGF protein expression in vivo via Western blot analysis confirmed that the protein is highly expressed from 6 hours to 24 hours after bacterial inoculation, while immunohistochemistry revealed production by middle ear epithelial cells and infiltrating lymphocytes.Our data suggest an active role for HB-EGF in the hyperplasia of the middle ear mucosal epithelium during otitis media. These results imply that therapies targeting HB-EGF could ameliorate mucosal growth during otitis media, and thereby reduce detrimental sequelae of this childhood disease.

  19. PIKA Provides an Adjuvant Effect to Induce Strong Mucosal and Systemic Humoral Immunity Against SARS-CoV

    Wei-wei Gai; Yan Zhang; Di-han Zhou; Yao-qing Chen; Jing-yi Yang; Hui-min Yan


    Severe Acute Respiratory Syndrome(SARS)is a deadly infectious disease caused by SARS Coronavirus(SARS-CoV).Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV.However,safe and potent adjuvants,especially with more efficient and economical needle-free vaccination are always needed more urgently in a pandemic.The development of a safe and effective mucosal adjuvant and vaccine for prevention of emergent infectious diseases such as SARS will be an important advancement.PIKA,a stabilized derivative of Poly(I:C),was previously reported to be safe and potent as adjuvant in mouse models.In the present study,we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly(I:C)derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus.Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites,co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity.When intranasal immunization was used,PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response.Overall,PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.

  20. 5-Fluorouracil induced intestinal mucositis via nuclear factor-κB activation by transcriptomic analysis and in vivo bioluminescence imaging.

    Chung-Ta Chang

    Full Text Available 5-Fluorouracil (5-FU is a commonly used drug for the treatment of malignant cancers. However, approximately 80% of patients undergoing 5-FU treatment suffer from gastrointestinal mucositis. The aim of this report was to identify the drug target for the 5-FU-induced intestinal mucositis. 5-FU-induced intestinal mucositis was established by intraperitoneally administering mice with 100 mg/kg 5-FU. Network analysis of gene expression profile and bioluminescent imaging were applied to identify the critical molecule associated with 5-FU-induced mucositis. Our data showed that 5-FU induced inflammation in the small intestine, characterized by the increased intestinal wall thickness and crypt length, the decreased villus height, and the increased myeloperoxidase activity in tissues and proinflammatory cytokine production in sera. Network analysis of 5-FU-affected genes by transcriptomic tool showed that the expression of genes was regulated by nuclear factor-κB (NF-κB, and NF-κB was the central molecule in the 5-FU-regulated biological network. NF-κB activity was activated by 5-FU in the intestine, which was judged by in vivo bioluminescence imaging and immunohistochemical staining. However, 5-aminosalicylic acid (5-ASA inhibited 5-FU-induced NF-κB activation and proinflammatory cytokine production. Moreover, 5-FU-induced histological changes were improved by 5-ASA. In conclusion, our findings suggested that NF-κB was the critical molecule associated with the pathogenesis of 5-FU-induced mucositis, and inhibition of NF-κB activity ameliorated the mucosal damage caused by 5-FU.

  1. Pathogenesis of achalasia cardia

    Uday C Ghoshal; Sunil B Daschakraborty; Renu Singh


    Achalasia cardia is one of the common causes of motor dysphagia.Though the disease was first described more than 300 years ago,exact pathogenesis of this condition still remains enigmatic.Pathophysiologically,achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus.In the initial stage,degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine,resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achaiasia).Since the initial description,several studies have attempted to explore initiating agents that may cause the disease,such as viral infection,other environmental factors,autoimmunity,and genetic factors.Though Chagas disease,which mimics achalasia,is caused by an infective agent,available evidence suggests that infection may not be an independent cause of primary achalasia.A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins,siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down's syndrome and Parkinson's disease.Polymorphisms in genes encoding for nitric oxide synthase,receptors for vasoactive intestinal peptide,interleukin 23 and the ALADIN gene have been reported.However,studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained.Currently,the disease is believed to be multi-factorial,with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.

  2. Adverse prognostic influence of diabetes mellitus and hyperglycemia on the clinical course of brain infarct: a review of its causes with special reference to the pathogenesis of hyperglycemia in the acute phase of stroke

    Charles André


    Full Text Available In non-diabetic patients, the appearance of hyperglycemia in the acute phase of stroke is related to the extension of cellular injury, and hence to the physiologic stress response. In animal models of ischemic insult, the deleterious effects of hyperglycemia depend heavily on the production of lactic acid «via» activation of the glycolitic anaerobic pathway. The abnormal production of lactic acid and consequent tissular acidosis appear mainly in the early post-reperfusion period, or in states of marked but partial reduction of blood flow. A direct reduction of cerebral blood flow and, perhaps, the production of a hyperosmolar state may contribute to worsening of the ischemic injury. In diabetic patients, previous hemoreologic and microcirculatory changes, and a greater susceptibility to infections may additionally reduce the chances of complete recovery after stroke.

  3. 急性早幼粒细胞白血病发生机制及治疗研究进展%The progress of acute promyelocytic leukemia in pathogenesis and therapy

    梁雪; 孔佩艳


    急性早幼粒细胞白血病是一种预后凶险的白血病,约占成人急性髓系白血病的10%。该型白血病出血倾向严重,易并发弥漫性血管内凝血(diffuse intravascular eoagulation,DIC),尤其在化疗时易发生,常导致患者早期死亡,急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)是临床上第一个应用诱导分化和针对肿瘤特异性标志分子进行治疗并取得显著疗效的人类恶性肿瘤。

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

    Logan Richard M


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

  5. Mucosal Schwann cell "Hamartoma": A new entity?

    Paola Pasquini; Andrea Baiocchini; Laura Falasca; Dante Annibali; Guido Gimbo; Francesco Pace; Franca Del Nonno


    Schwannoma is a well-described, benign nerve sheath tumor of the soft tissue, but is rare in the gastrointestinal tract. Gastrointestinal schwannomas are often incidentally discovered as small polypoid intraluminal lesions. In this report, we describe the clinicopathologic and immunohistochemical features of a distinctive neural mucosal polyp composed of a diffuse cellular proliferation of uniform bland spindled cells in the lamina propria that entraps the colonic crypts. Immunohistochemical analysis revealed strong and diffuse positivity for the S-100 protein. To avoid confusion of these solitary colorectal polyps containing pure spindled Schwann cell proliferation in the lamina propria with neural lesions that have significant association with inherited syndromes, it is better to use the designation "mucosal Schwann hamartoma".

  6. Probiotics as Antifungals in Mucosal Candidiasis.

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


    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.

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

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


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

  8. The microbiome and regulation of mucosal immunity.

    McDermott, Andrew J; Huffnagle, Gary B


    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.

  9. Peptic activity and gastroduodenal mucosal damage.

    Raufman, J P


    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 t...

  10. Antioxidant agents: a future alternative approach in the prevention and treatment of radiation-induced oral mucositis?

    de Freitas Cuba, Letícia; Salum, Fernanda Gonçalves; Cherubini, Karen; de Figueiredo, Maria Antonia Zancanaro


    Radiotherapy is a therapeutic modality frequently employed for patients with head and neck cancer (HNC). It destroys tumor cells, but it is not selective, also affecting healthy tissues and producing adverse effects. One that stands out is oral mucositis because of the morbidity that it is capable of causing. This lesion is characterized by the presence of erythema, ulcerations, pain, opportunistic infections, and weight loss. These side effects can lead to serious situations that require the interruption of the antineoplastic treatment and can result in hospitalization and even death. The complex mechanisms linked to the pathogenesis of oral mucositis were recently established, and since then, the control of oxidative stress (OS) has been tied to the prevention and management of this disease. The authors have carried out a review of the literature about the use of antioxidant agents in the prevention and treatment of radiation-induced oral mucositis, using the PubMed database. This review has shown that the research on use of antioxidants (AOX) has proved insufficient to justify suggesting the products in treatment protocols. Results are promising, however, and AOX may represent a future alternative in the prevention and treatment of oral mucositis.

  11. 儿童急性胰腺炎的诊断、治疗及病因分析%The diagnosis, pathogenesis, and treatment of acute pancreatitis in children

    王晓晔; 谢艺; 崔华雷


    Objective To analyze the characteristics of the clinical presentations,etiologies,diagnosis,and treatment of pediatric pancreatitis.Methods Sixty-three patients (39 males and 24 females) with diagnosis of pancreatitis were studied from March 2007 to March 2010.All patients were treated by abrosia,gastrointestinal decompression and intravenous hydration therapy,ulinastatin and octreotide acetate were also used to inhibit pancreatic enzyme secretion.Only 5 cases underwent abdominal cavity drainage.Results The morbidity of acute pancreatitis increased with age,especially from 9 to 14 years old.And the obese children were also susceptible to acute pancreatitis.The antibiotic therapy and the inhibition of pancreatic enzymes were effective for children with acute pancreatitis.All patients were cured.Conclusions The implement of antibiotic therapy and the inhibition of pancreatic enzymes in early phage are very important,surgical therapy should be adopted in severe cases.%目的 通过对63例确诊为急性胰腺炎患儿诊治过程的总结,分析近年来儿童急性胰腺炎的疾病特点,总结治疗经验.方法 2007年3月至2010年3月我院收治63例急性胰腺炎患儿,男39例,女24例,分析致病因素,经症状体征、化验检查、影像学检查确诊后,均予禁食、胃肠减压,静脉补液抗感染,应用抑制胰酶分泌药物(醋酸奥曲肽)及抗炎抑酶药物(乌司他丁)治疗,58例患儿经保守治疗痊愈,5例重症患儿经保守治疗无效行开腹腹腔引流术后治愈.结果 急性胰腺炎发病率逐年增高,年龄集中在9~14岁,肥胖儿发病率增高,全身抗感染结合抑制胰酶分泌治疗有效,63例患儿均治愈,其中5例急性重症患儿保守治疗无效后经手术治疗治愈.结论 及时应用抗生素及胰酶抑制剂治疗小儿急性胰腺炎有良好的治疗效果,急性重症胰腺炎应积极手术治疗,为防治疾病应做好健康宣教.

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

    Shanahan, F


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

  13. Hitting the mucosal road in tolerance induction.

    Wiedermann, Ursula


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

  14. Advances in the pathogenesis of cardiorenal syndrome type 3.

    Clementi, Anna; Virzì, Grazia Maria; Brocca, Alessandra; de Cal, Massimo; Pastori, Silvia; Clementi, Maurizio; Granata, Antonio; Vescovo, Giorgio; Ronco, Claudio


    Cardiorenal syndrome (CRS) type 3 is a subclassification of the CRS whereby an episode of acute kidney injury (AKI) leads to the development of acute cardiac injury or dysfunction. In general, there is limited understanding of the pathophysiologic mechanisms involved in CRS type 3. An episode of AKI may have effects that depend on the severity and duration of AKI and that both directly and indirectly predispose to an acute cardiac event. Experimental data suggest that cardiac dysfunction may be related to immune system activation, inflammatory mediators release, oxidative stress, and cellular apoptosis which are well documented in the setting of AKI. Moreover, significant derangements, such as fluid and electrolyte imbalance, metabolic acidosis, and uremia, which are typical features of acute kidney injury, may impair cardiac function. In this review, we will focus on multiple factors possibly involved in the pathogenesis issues regarding CRS type 3.

  15. Advances in the Pathogenesis of Cardiorenal Syndrome Type 3

    Anna Clementi


    Full Text Available Cardiorenal syndrome (CRS type 3 is a subclassification of the CRS whereby an episode of acute kidney injury (AKI leads to the development of acute cardiac injury or dysfunction. In general, there is limited understanding of the pathophysiologic mechanisms involved in CRS type 3. An episode of AKI may have effects that depend on the severity and duration of AKI and that both directly and indirectly predispose to an acute cardiac event. Experimental data suggest that cardiac dysfunction may be related to immune system activation, inflammatory mediators release, oxidative stress, and cellular apoptosis which are well documented in the setting of AKI. Moreover, significant derangements, such as fluid and electrolyte imbalance, metabolic acidosis, and uremia, which are typical features of acute kidney injury, may impair cardiac function. In this review, we will focus on multiple factors possibly involved in the pathogenesis issues regarding CRS type 3.

  16. Pathogenesis of Thromboembolism and Endovascular Management

    Sasan Behravesh


    Full Text Available Venous thromboembolism (VTE, a disease that includes deep venous thrombosis (DVT and pulmonary embolism (PE, is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted.

  17. Pathogenesis of Thromboembolism and Endovascular Management

    Behravesh, Sasan; Hoang, Peter; Nanda, Alisha; Wallace, Alex; Sheth, Rahul A.; Deipolyi, Amy R.; Memic, Adnan; Naidu, Sailendra


    Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted. PMID:28154761

  18. Protein contact dermatitis: allergens, pathogenesis, and management.

    Levin, Cheryl; Warshaw, Erin


    Protein contact dermatitis is an allergic skin reaction induced principally by proteins of either animal or plant origin. The clinical presentation is that of a chronic dermatitis, and it is often difficult to differentiate between allergic contact dermatitis and other eczematous dermatoses. One distinguishing clinical feature is that acute flares of pruritus, urticaria, edema, or vesiculation are noted minutes after contact with the causative substances. Additionally, the patch-test result is typically negative, and the scratch- or prick-test result is positive. The pathogenesis of protein contact dermatitis is unclear but may involve a type I (immunoglobulin E [IgE], immediate) hypersensitivity reaction, type IV (cell-mediated delayed) hypersensitivity reaction, and/or a delayed reaction due to IgE-bearing Langerhans' cells. Management involves avoidance of the allergen.

  19. Pathogenesis of and unifying hypothesis for idiopathic pouchitis.

    Coffey, J Calvin


    Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients\\' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.

  20. Current concepts of the pathogenesis of inflammatory bowel disease.

    Shanahan, F


    Although the cause of inflammatory bowel disease is not known, the pathogenesis involves an immune-mediated tissue damage that is the result of an interaction among genetic predisposing factors, exogenous triggers and endogenous modifying influences. Multiple genes are involved and operate at the level of the immune response and at the target organ. Exogenous triggers include the enteric microflora which might stimulate the mucosal immune system in genetically predisposed individuals. Endogenous modifying factors such as the psychoneuroendocrine system have regulatory effects on the immune system and the inflammatory response, and may influence the course of the disease. While autoimmune phenomena do occur, particularly in ulcerative colitis, there is no evidence that they are directly responsible for the tissue damage. It appears more likely, particularly in Crohn\\'s disease, that tissue injury may occur as an indirect or "bystander" effect of mucosal T-cell hyperactivation, perhaps in response to a normal enteric microbial antigen. Most of the immunologic and histologic features of Crohn\\'s disease can be explained by the effects of T-cell derived and other cytokines on the epithelium, the local immune system, the microvasculature, and the recruitment of auxiliary effector cells such as neutrophils.

  1. Pathogenesis of and unifying hypothesis for idiopathic pouchitis.

    Coffey, J Calvin


    Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients\\' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.

  2. Role of ammonia in the pathogenesis of brain edema.



    Full Text Available The role of hyperammonemia in the pathogenesis of cerebral edema was investigated using mongrel dogs to develop a treatment for cerebral edema in acute hepatic failure. Intravenous infusion of ammonium acetate alone into dogs did not induce brain edema, although blood ammonia reached unphysiologically high levels. However, ammonium acetate infusion during mannitol-induced reversible (osmotic opening of the blood-brain barrier (BBB effectively induced cytotoxic brain edema. Pretreatment with a branched-chain amino acid (BCAA; valine, leucine and isoleucine solution prevented an increase in intracranial pressure (ICP and brain water content, and caused a decrease in brain ammonia content and an increase in brain BCAA and glutamic acid. The results suggest that ammonia plays an important role in the pathogenesis of cerebral edema during acute hepatic failure and that BCAAs accelerate ammonia detoxification in the brain.

  3. [Pseudomembranous colitis: pathogenesis, prevention, treatment].

    Zakharova, N V; Fil', T S


    The article reviews a pathogenesis of Pseudomembranous colitis. Questions of prevention and treatment of Clostridium difficile--associated diarrhea are shown by the Evidence-based medicine. There is an accent on the rational prescription of antibiotics.

  4. Highlights in pathogenesis of vitiligo.

    Mohammed, Ghada F; Gomaa, Amal Ha; Al-Dhubaibi, Mohammed Saleh


    Vitiligo is a common pigmentary disorder. Many studies across decades and all over the world have attempted to illustrate the pathogenesis behind it; however, the pathogenesis of vitiligo remains elusive. This review article, we present the findings behind the most and updated theories behind this psychologically debilitating and disfiguring disease. The discussion begun with the role of genetic predisposition followed by neural theory first proposed in the 1950s. We highlight the autoimmune hypothesis, followed by the reactive oxygen species model, zinc-α2-glycoprotein deficiency hypothesis, viral theory, intrinsic theory and biochemical, molecular and cellular alterations accounting for loss of functioning melanocytes in vitiligo. Many theories were elaborated to clarify vitiligo pathogenesis. It is a multifactorial disease involving the interplay of several factors. Future research is needed to clarify the interaction of these factors for better understanding of vitiligo pathogenesis and subsequent successful treatment.

  5. Highlights in pathogenesis of vitiligo

    Ghada F. Mohammed; Gomaa, Amal HA; Al-Dhubaibi, Mohammed Saleh


    Vitiligo is a common pigmentary disorder. Many studies across decades and all over the world have attempted to illustrate the pathogenesis behind it; however, the pathogenesis of vitiligo remains elusive. This review article, we present the findings behind the most and updated theories behind this psychologically debilitating and disfiguring disease. The discussion begun with the role of genetic predisposition followed by neural theory first proposed in the 1950s. We highlight the autoimmune ...

  6. Molecular mechanisms of rosacea pathogenesis

    Davydova A.M.


    Full Text Available The article presents possible molecular mechanisms for rosacea pathogenesis from current domestic and foreign clinical observations and laboratory research: regulation and expression defects of antimicrobial peptides, vascular endothelial growth factor, the effect of serine proteases, oxidative stress, reactive oxygen species and ferritin on the occurrence and course of rosacea. New developments in molecular biology and genetics are advanced for researching the interaction of multiple factors involved in rosacea pathogenesis, as well as providing the bases for potentially new therapies.

  7. Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture


    Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatmen...

  8. Hemorrhagic fever with renal syndrome:pathogenesis and clinical picture


    Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatmen...

  9. Acute esophageal necrosis caused by alcohol abuse

    Tetsu Endo; Juichi Sakamoto; Ken Sato; Miyako Takimoto; Koji Shimaya; Tatsuya Mikami; Akihiro Munakata; Tadashi Shimoyama; Shinsaku Fukuda


    Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture.

  10. Frank hematuria as the presentation feature of acute leukemia

    Suriya Owais


    Full Text Available Muco-cutaneous bleeding is a common presenting feature of acute leukemias. Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur in any mucosal surface of the body. Hematuria as an isolated or main presenting feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19 year old male with acute lymphoblastic leukemia and a 52 year old male with acute myeloid leukemia, both presenting with gross hematuria. There was no demonstrable leukemic infiltration of the urinary tract on imaging studies. Hematuria in these patients was likely to be due to occult leukemic infiltration of the urinary system, aggravated by thrombocytopenia, as it subsided after starting chemotherapy. Our cases highlight that hematuria should be remembered as a rare presenting feature of acute leukemia.

  11. Probiotic supplements and debridement of peri-implant mucositis

    Hallström, Hadar; Lindgren, Susann; Widén, Cecilia


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

  12. Chitosan-Based Nanoparticles for Mucosal Delivery of RNAi Therapeutics

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


    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....

  13. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

    Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N


    Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.Mucosal Immunology advance online publication 2 November 2016. doi:10.1038/mi.2016.95.

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

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


    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.

  15. Scoring irradiation mucositis in head and neck cancer patients

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


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

  16. Mucosal and systemic adjuvant activity of alphavirus replicon particles

    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.


    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

  17. Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema

    Children with edematous severe acute malnutrition (SAM) produce less cysteine than do their nonedematous counterparts. They also have marked glutathione (GSH) depletion, hair loss, skin erosion, gut mucosal atrophy, and depletion of mucins. Because GSH, skin, hair, mucosal, and mucin proteins are ri...

  18. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Debashis Nandy


    Full Text Available Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF, insulin-like growth factor (IGF, platelet derived growth factor (PDGF, fibroblast growth factor (FGF, epidermal growth factor (EGF, and transforming growth factor (TGF in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  19. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)


    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  20. Efficacy of Enteral Supplementation Enriched with Glutamine, Fiber, and Oligosaccharide on Mucosal Injury following Hematopoietic Stem Cell Transplantation

    Satoshi Iyama


    Full Text Available The combination of glutamine, fiber and oligosaccharides (GFO is thought to be beneficial for alleviating gastrointestinal mucosal damage caused by chemotherapy. A commercial enteral supplementation product (GFO enriched with these 3 components is available in Japan. We performed a retrospective study to test whether oral GFO decreased the severity of mucosal injury following hematopoietic stem cell transplantation (HSCT. Of 44 HSCT patients, 22 received GFO and 22 did not. Severity of diarrhea/mucositis, overall survival, weight loss, febrile illness/documented infection, intravenous hyperalimentation days/hospital days, engraftment, acute and chronic GVHD, and cumulative incidence of relapse were studied. Sex, age, performance status, diagnosis, disease status, and treatment variables were similar in both groups. There were fewer days of diarrhea grade 3-4 in patients receiving GFO than in those who did not (0.86 vs. 3.27 days; the same was true for days of mucositis grade 3-4 (3.86 vs. 6.00 days. Survival at day 100 was 100% in the GFO group, but only 77.3% for the patients not receiving GFO (p = 0.0091, log-rank test. Weight loss and the number of days of intravenous hyperalimentation were better in the GFO group (p Enterococcus species developed in the GFO group (p = 0.0728 than in the non-GFO group. Other outcomes were not affected. To the best of our knowledge, this is the first comparative clinical study of GFO supplementation to alleviate mucosal injury after allo-HSCT. We conclude that glutamine, fiber and oligosaccharide supplementation is an effective supportive therapy to decrease the severity of mucosal damage in HSCT.

  1. Oral lichen planus and lichenoid mucositis.

    De Rossi, Scott S; Ciarrocca, Katharine


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

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

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


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

  3. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    Andersen, Jesper Bøje


    Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...... underlying the diversity of growth patterns of this malignancy remain a clinical concern. It is crucial to advance our present understanding of the molecular pathogenesis of CCA to improve current clinical strategies and patient outcome. This will facilitate the delineation of patient subsets...

  4. Genes contributing to prion pathogenesis

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V;


    incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1...

  5. [Asteatotic dermatitis: etiology and pathogenesis].

    Zhou, Li-juan; Lyu, Zhong-fa


    Asteatotic dermatitis (AsD) is a common skin disease characterized by dry skin, itching, erythema, peeling and other skin lesions. It results from the damage in cutaneous barrier related to age, seasonal climate and bathing habits, and presents dysfunction of sebaceous, sweat glands and the increase of transepidermal water loss. The pathogenesis of AsD is not clear. Previous studies mainly focused on the relationship between skin barrier damage and bathing habits, age or gender. Recently, more studies focus on its relationship with other systematic diseases and drugs. This paper reviews etiology and pathogenesis of AsD to provide new ideas for the diagnosis and treatment of AsD.

  6. Huntington disease: pathogenesis and treatment.

    Dayalu, Praveen; Albin, Roger L


    Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, culminating in death. It is caused by an expanded CAG repeat in the huntingtin gene. Even years before symptoms become overt, mutation carriers show subtle but progressive striatal and cerebral white matter atrophy by volumetric MRI. Although there is currently no direct treatment of HD, management options are available for several symptoms. A better understanding of HD pathogenesis, and more sophisticated clinical trials using newer biomarkers, may lead to meaningful treatments. This article reviews the current knowledge of HD pathogenesis and treatment.

  7. Acute genital ulcers.

    Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora


    Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers.

  8. Dexmedetomidine decreases the oral mucosal blood flow.

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


    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.

  9. Pathogenesis of anemia in Trypanosoma brucei-infected mice.

    Amole, B O; Clarkson, A B; Shear, H L


    The pathogenesis of anemia was studied in trypanosome-infected mice. A strain of Trypanosoma brucei, TREU 667, was used which first produces an acute phase marked by waves of parasitemia. Erythrocytes from infected animals were coated with immunoglobulin M during or just before the waves of anemia and parasitological crises. Erythrocytes from normal animals could be sensitized with "precrisis" sera presumably containing antigen and antibody. These data suggest that anemia during the acute phase is due to sensitization of erythrocytes with immunoglobulin M-antigen complexes. The anemia is partially compensated by a strong erythropoietic response. The acute phase is followed by a chronic phase marked by a constant high parasitemia and immunosuppression. The less marked anemia occurring during this latter phase is due to hemodilution and perhaps a low but significant immune response to the parasites, which causes continuing erythrocyte sensitization by immunoglobulin M-antigen complexes. PMID:7201455

  10. Acute otitis media and acute bacterial sinusitis.

    Wald, Ellen R


    Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future.

  11. A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis

    M Mehdipour


    Full Text Available "n Background and the Purpose of the Study: Patients undergoing high-dose chemotherapy for hematological malignancies are susceptible to development of oral mucositis, and no effective modality has been reported for its prophylaxis and treatment. The aim of this study was to evaluate the effectiveness of zinc mouthwash on chemotherapy-induced oral mucositis lesions. "nMethods: In this double-blind randomized trial, patients under chemotherapy for acute leukemia were divided into two test and control groups of 15 patients each. The groups were homogeneous with respect to medical history, tumor characteristics, and therapeutic details. The test group received 10ml 0.2% zinc sulfate mouthwash, and the control group received 10ml 0.2% chlorhexidine gluconate mouthwash, twice a day for a period of two weeks. Spijkervet scale was used to grade the severity of mucositis at every other week during eight weeks. The severity scores were analyzed with repeated measure ANOVA using SPSS 13.0 computer software. "nResults: Mean severity scores were generally lower in the test group compared to the controls at all four time intervals evaluated; but only, the differences in weeks of 2 and 3 were statistically significant (P=0.025. Conclusion: Zinc mouthwash used in conjunction with chemotherapy may reduce the severity of oral mucositis lesions in patients with leukaemia.

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

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


    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.

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

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


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

  14. Chemotherapy induced intestinal mucositis; from bench to bed

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


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

  15. Pathogenesis of motor neuron disease

    Xuefei Wang


    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  16. Biology and pathogenesis of Acanthamoeba

    Siddiqui Ruqaiyyah; Khan Naveed


    Abstract Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and ev...

  17. On the pathogenesis of IDDM

    Nerup, J; Mandrup-Poulsen, Thomas; Helqvist, S


    A model of the pathogenesis of insulin-dependent diabetes mellitus, i.e. the initial phase of beta-cell destruction, is proposed: in a cascade-like fashion efficient antigen presentation, unbalanced cytokine, secretion and poor beta-cell defence result in beta-cell destruction by toxic free radic...

  18. Erythropoietin-induced proliferation of gastric mucosal cells

    Kazuro Itoh; Masato Higuchi; Fumio Ishihata; Yushi Sudoh; Soichiro Miura; Yoshio Sawasaki; Kyoko Takeuchi; Shingo Kato; Nobuhiro Imai; Yoichiro Kato; Noriyuki Shibata; Makio Kobayashi; Yoshiyuki Moriguchi


    AIM: To analyze the localization of erythropoietin receptor on gastric specimens and characterize the effects of erythropoietin on the normal gastric epithelial proliferation using a porcine gastric epithelial cell culture model.METHODS: Erythropoietin receptor was detected by RT-PCR, Western blotting and immunohistochermistry.Growth stimulation effects of erythropoietin on cultured gastric mucosal cells were determined by ELISA using bromodeoxyuridine (BrdU).RESULTS: Erythropoietin receptor was detected on cultured porcine gastric mucosal epithelial cells.Erythropoietin receptor was also detected histochemically at the base of gastric mucosal epithelium. BrdU assay demonstrated a dose-dependent increase in growth potential of cultured porcine gastric mucosal epithelial cells by administration of erythropoietin, as well as these effects were inhibited by administration of antierythropoietin antibody (P< 0.01).CONCLUSION: These findings indicate that erythropoietin has a potential to proliferate gastric mucosal epithelium via erythropoietin receptor.

  19. Role of capsule and suilysin in mucosal infection of complement-deficient mice with Streptococcus suis.

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


    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.

  20. Some aspects of periodontitis pathogenesis in children

    Shcherbina I.N.


    Full Text Available Inflammatory processes in the tissues surrounding tooth root are frequent enough and develop as the direct complication of caries. As acute periodontitis is manifested with grinding toothache and violation of ph¬y¬sio¬logical act of chewing, symptoms of general intoxication, the continuous sluggish chronic periodontitis is harmful and dangerous to the organism as well. It forms the state of chronic оdontogenetic intoxication and chroneosepsis with wrong functioning of some internal organs and body systems. The like complications can cause significant disturbance to the function of kidneys, liver, heart, joints and their treatment without ablating focus of inflammation is often in- effective; this must be taken into account by doctors-interns. However, scanning of the oral cavity by conservative means has its difficulties mostly because of ignoring pathogenesis of such inflammation. That is why activity of ferments of blood dehydrogenases from the periapical tissues of the teeth affected with the chronic periodontitis was studied. The level of succinate dehydrogenase and alpha-glycerophosphate degydrogenase of lymphocytes of 110 schoolchildren aged 13-17 years old was studied. The main group of examined individuals included those of infected with tuber¬culousis – 50 individuals, and the control group (60 individuals – clinically healthy ones without tuberculousis desease. All schoolchildren had 1 or 2 teeth affected with chronic periodontitis of the apical localization. The researchers found that a significant inhibition of activity of succinate dehydrogenase and alpha-glycerophosphate degydrogenase ferments occurs in the inflammatory periodontal tissues, which indicates to local immunity decline, and as a consequence, pathogenic bacteria activation. In people infected with tuberculousis these violations were more developed. Such features of periodontitis pathogenesis must be taken into account when providing a combined treatment.

  1. Citrobacter rodentium-induced colitis: A robust model to study mucosal immune responses in the gut.

    Koroleva, Ekaterina P; Halperin, Sydney; Gubernatorova, Ekaterina O; Macho-Fernandez, Elise; Spencer, Cody M; Tumanov, Alexei V


    Citrobacter rodentium is a natural mouse pathogen which reproducibly infects mice and causes intestinal disease. The C. rodentium model of infection is very useful for investigating host-pathogen immune interactions in the gut, and can also be used to understand the pathogenesis of several important human intestinal disorders, including Crohn's disease, ulcerative colitis, dysbiosis and colon tumorigenesis. Both innate and adaptive immune responses play a critical role in protection against C. rodentium. Here, we summarize the role of immune components in protection against C. rodentium and describe techniques for the analysis of innate and adaptive mucosal immune responses, including setting up the infection, analysis of colonic hyperplasia and bacterial dissemination, evaluation of antibody responses, and purification and analysis of intestinal epithelial and lymphoid cells.

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

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


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

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

    Crissinger, K.D.; Granger, D.N. (Louisiana State Univ. Medical Center, Shreveport (USA))


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

  4. Gastric mucosal damage in water immersion stress:Mechanism and prevention with GHRP-6

    Shu Guo; Qian Gao; Qing Jiao; Wei Hao; Xue Gao; Ji-Min Cao


    reaching the gastric mucosa.FS alone also induced serious gastric injury,but SR could not induce gastric injury.Bilateral vagotomy or atropine prevented the WRS-induced mucosal lesion,indicating that increased outflow from the vagal center is a decisive factor in WRS-induced gastric injury.The mucosal lesions were prevented by prior injection of GHRP-6 via IP did,but not via ICV,suggesting that the protection is peripheral,although a sudden injection is not equivalent to a physiological release and uptake,which eventually may affect the vagal center.CONCLUSION:From the central nervous system,vagal nerves carry the cutaneous stimuli brought about by the immersion restraint,an experimental model for inducing acute gastric erosions.GHRP-6 prevents the occurrence of these lesions.

  5. Impact of colonic mucosal lipoxin A4 synthesis capacity on healing in rats with dextran sodium sulfate-induced colitis.

    Ağış, Erol R; Savaş, Berna; Melli, Mehmet


    Ulcerative colitis is a chronic inflammatory disease of the colon. This study evaluates the role of colonic mucosal lipoxin A4 (LXA4) synthesis in an experimental rat model of dextran sodium sulfate (DSS)-induced colitis. Wistar rats were randomly assigned to four groups: healthy controls, DSS-induced colitis with no or vehicle therapy, misoprostol or 5-aminosalicylic acid (5-ASA) therapy groups. Disease severity and colonic mucosal LXA4 synthesis was assessed specifically during the acute phase (day 5), chronic phase (day 15) and healing phases (day 19). Both misoprostol and 5-ASA reduced histopathologic score during the acute phase and reduced disease activity score at the healing phase. In addition, misoprostol reduced histopathologic score and colon weight/length ratio during the healing phase. Only misoprostol therapy increased colonic mucosal LXA4 synthesis. Furthermore, LXA4 levels correlated negatively with disease progression (R=-0.953). Collectively, our findings suggest that misoprostol-induced LXA4 synthesis may be favorable for the healing of ulcerative colitis.

  6. Mucosal biofilm detection in chronic otitis media

    Wessman, Marcus; Bjarnsholt, Thomas; Eickhardt-Sørensen, Steffen Robert


    The objectives of this study were to examine middle ear biopsies from Greenlandic patients with chronic otitis media (COM) for the presence of mucosal biofilms and the bacteria within the biofilms. Thirty-five middle ear biopsies were obtained from 32 Greenlandic COM patients admitted to ear...... of the patients served as controls. PNA-FISH showed morphological signs of biofilms in 15 out of 35 (43 %) middle ear biopsies. In the control skin biopsies, there were signs of biofilms in eight out of 23 biopsies (30 %), probably representing skin flora. PCR and 16s sequencing detected bacteria in seven out...... of 20 (35 %) usable middle ear biopsies, and in two out of ten (20 %) usable control samples. There was no association between biofilm findings and PCR and 16s sequencing. Staphylococci were the most common bacteria in bacterial culture. We found evidence of bacterial biofilms in 43 % of middle ear...

  7. Oral mucosal involvement in visceral leishmaniasis

    Sunny Garg; Richik Tripathi; Kamlakar Tripathi


    Leishmaniasis affects both the visceral and cutaneous tissues in body.OralMucosal involvement in leishmaniasis is rare and is often overlooked.We present a case17 year old boy from the north east region ofBihar who has a history of visceral leishmaniasis one year back, came to the department of oral surgery for treatment of persistent oral ulcers.Oral examination did not give any diagnostic information while systemic examination revealed enlarged spleen and low grade fever.Patient was screened for leishmaniasis by rK39 based immunochromatographic strip test which came to be positive.Biopsy of the ulcer as well as splenic and bone marrow aspirate confirmed the presence of leishmaniasis.Patient was administeredAmphotericinB for20 days following which significant clinical and haematological improvement followed.

  8. Mucosal immunity to pathogenic intestinal bacteria.

    Perez-Lopez, Araceli; Behnsen, Judith; Nuccio, Sean-Paul; Raffatellu, Manuela


    The intestinal mucosa is a particularly dynamic environment in which the host constantly interacts with trillions of commensal microorganisms, known as the microbiota, and periodically interacts with pathogens of diverse nature. In this Review, we discuss how mucosal immunity is controlled in response to enteric bacterial pathogens, with a focus on the species that cause morbidity and mortality in humans. We explain how the microbiota can shape the immune response to pathogenic bacteria, and we detail innate and adaptive immune mechanisms that drive protective immunity against these pathogens. The vast diversity of the microbiota, pathogens and immune responses encountered in the intestines precludes discussion of all of the relevant players in this Review. Instead, we aim to provide a representative overview of how the intestinal immune system responds to pathogenic bacteria.

  9. Role of polyamines in gastrointestinal mucosal growth

    Zhao Xiang Bian; Jian Hua Wang


    The polyamines [putrescine (PU), spermidine (SPD) and spermine (SPM)] are ubiquitous polycationiccompounds found in all prokaryotic and eukaryotic cells, are essentially involved in a variety of regulatorysteps during normal, adaptive, and malignant cell proliferation. Nearly four decades investigation about thepolyamines contributed to the synthesis and decomposition of polyamines and the active and passive enzymeswhich regulate them at different levels. This review focuses on the sources and homeostasis of intracellularpolyamines, the transport and role of the polyamines in the growth of the gastrointestinal mucosa and theirpossible mechanism. We tried to point out the gaps remaining in the story and give a working hypothesis forthe role of polyamines in gastrointestinal mucosal growth. We propose in the hypothesis that polyamine is a“key”to unlock the “door”of cell proliferation. How many “doors” between the “polyamine key” and the“real start” of proliferation? The polyamine might be the only key for cell proliferation. Another possibilityis that polyamine is the first key and its “unlocking-effect” resulting in getting another key for the next doorin the proliferation chain, for example, proto-oncogenes. To decide whether polyamine is an intermediatestep or just only one step of cell proliferation, the possible way is to keep polyamine to be a stimulus and finda way to deprive the function of proto-oncogene protein (or other possible gene expression product) to checkthe effect on the cell proliferation. Another important question is how polyamine can trigger the synthesis ofDNA in virtual. Arabinose operon model may give us some ideas to investigate about that. And furthermore,it is necessary to pay attention to the relationship between polyamine and other cell proliferation regulator,like growth factor, chalone, cAMP, cGMP, etc. Further studies are needed to investigate the mechanism ofpolyamine acted on the gastrointestinal mucosal

  10. Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis.

    van der Velden, Walter J F M; Herbers, Alexandra H E; Netea, Mihai G; Blijlevens, Nicole M A


    Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as 'febrile neutropenia', but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or 'mucositis'. MBI creates a port-de-entrée for resident micro-organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host-microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept 'febrile neutropenia' alone may no longer suffice and a new concept 'febrile mucositis' should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host-microbe interactions arising from cytotoxic therapy-induced tissue damage in order to reduce fever in neutropenic patients with cancer.

  11. Trypsinogen activation in acute and chronic pancreatitis: Is it a prerequisite?

    Sah, Raghuwansh P.; Saluja, Ashok K.


    Trypsinogen activation is sufficient to induce acute pancreatitis in an experimental model. However, whether it is a requirement for the pathogenesis of acute and chronic pancreatitis remains to be explored.

  12. Acquired bilateral nevus of ota-like macules with Mucosal involvement: A new variant of Hori′s nevus

    Ramesh M Bhat


    Full Text Available Acquired bilateral nevus of Ota-like macules (ABNOM or Hori′s nevus, a rare form of acquired dermal melanocytoses, presents as bilateral facial blue-gray macules without ocular or mucosal involvement. This condition is mostly found in women of Asian descent and usually appears in the fourth or fifth decade of life. Pathogenesis is unknown, though few theories have been proposed. Effective treatment has been found to be achieved with pigment-specific lasers. Herein, we report a case of Hori′s nevus with mucosal involvement. A 42-year-old male patient, presented to us with blue-gray discoloration on either side of his face, both eyes, and in the mouth since the age of one year. Histopathological examination showed clusters and singly dispersed pigmented melanocytes within the upper and mid-dermis regions. Special staining of melanocytes using Masson-Fontana stain was positive. Diagnosis of Hori′s nevus was made by correlating clinical and histopathological findings. Patient was informed of his treatment options, but refused treatment. A similar case of Hori′s nevus with mucosal involvement has not been reported so far.

  13. Acquired Bilateral Nevus of ota-like Macules with Mucosal Involvement: A New Variant of Hori's Nevus.

    Bhat, Ramesh M; Pinto, Hyacinth Peter; Dandekeri, Sukumar; Ambil, Srinath Madapally


    Acquired bilateral nevus of Ota-like macules (ABNOM) or Hori's nevus, a rare form of acquired dermal melanocytoses, presents as bilateral facial blue-gray macules without ocular or mucosal involvement. This condition is mostly found in women of Asian descent and usually appears in the fourth or fifth decade of life. Pathogenesis is unknown, though few theories have been proposed. Effective treatment has been found to be achieved with pigment-specific lasers. Herein, we report a case of Hori's nevus with mucosal involvement. A 42-year-old male patient, presented to us with blue-gray discoloration on either side of his face, both eyes, and in the mouth since the age of one year. Histopathological examination showed clusters and singly dispersed pigmented melanocytes within the upper and mid-dermis regions. Special staining of melanocytes using Masson-Fontana stain was positive. Diagnosis of Hori's nevus was made by correlating clinical and histopathological findings. Patient was informed of his treatment options, but refused treatment. A similar case of Hori's nevus with mucosal involvement has not been reported so far.

  14. Nutritional rickets: pathogenesis and prevention.

    Pettifor, John M


    Nutritional rickets remains a public health concern in many areas of the world despite cheap and effective means of preventing the disease. The roles of vitamin D deficiency, low dietary calcium intakes and the interrelationships between the two in the pathogenesis of the disease are discussed. It is now recognized that vitamin D deficiency in the pregnant and lactating mother predisposes to the development of rickets in the breastfed infant, and that cultural and social factors are important in the pathogenesis of the disease during the adolescent growth spurt. Prevention of rickets is dependent on the awareness of the medical profession and the general public of the need to ensure adequate intakes of vitamin D in at-risk populations, and of the importance of increasing dietary intakes of calcium using locally available and inexpensive foods in communities in which dietary calcium deficiency rickets is prevalent.

  15. Vitiligo: symptoms, pathogenesis and treatment.

    Ghafourian, A; Ghafourian, S; Sadeghifard, N; Mohebi, R; Shokoohini, Y; Nezamoleslami, S; Hamat, R A


    Vitiligo is an acquired cutaneous disorder of pigmentation, with an incidence of 0.5% to 2% worldwide. There are three major hypotheses for the pathogenesis of vitiligo that are not exclusive of each other: biochemical/cytotoxic, neural and autoimmune. Recent data provide strong evidence supporting an autoimmune pathogenesis of vitiligo. As vitiligo can have a major effect on quality of life, treatment can be considered and should preferably begin early when then disease is active. Current treatment modalities are directed towards stopping progression of the disease and achieving repigmentation. Therapies include corticosteroids, topical immunomodulators, photo(chemo)therapy, surgery, combination therapies and depigmentation of normally pigmented skin. It seems that traditional Chinese medicine could be more effective than the current treatment for vitligo.

  16. Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection

    Wu Li


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

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

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


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

  18. Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection.

    Li, Wu; Deng, Guangcun; Li, Min; Liu, Xiaoming; Wang, Yujiong


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

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

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


    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.

  20. Oral mucosal status and major salivary gland function

    Wolff, A.; Fox, P.C.; Ship, J.A.; Atkinson, J.C.; Macynski, A.A.; Baum, B.J. (National Institute of Dental Research, Bethesda, MD (USA))


    Normal salivary function is considered to be critical for the maintenance of healthy oral mucosa. However, few studies have examined mucosal changes in patients with objectively documented salivary gland performance. In the present report, the mucosal status of 298 subjects being evaluated in a dry mouth clinic was assessed. A complete oral examination was performed and unstimulated and stimulated salivary samples were collected separately from the parotid and submandibular/sublingual glands. Data were analyzed according to diagnosis and salivary output after the assignment of an oral mucosal rating to each subject. In general, the mucosal surfaces were well preserved and infections were not seen. Patients evaluated for Sjoegren's syndrome and radiation-induced xerostomia had the lowest salivary gland performance but displayed a mucosal status similar to denture-wearing healthy subjects or patients with normal salivary flow who had idiopathic xerostomia. However, those patients with a total lack of salivary flow rarely had normal-appearing oral mucosa. These results confirm a role for saliva in oral mucosal preservation and also suggest that other factors may act to maintain oral mucosal integrity.

  1. [Pathogenesis of invasive fungal infections].

    Garcia-Vidal, Carolina; Carratalà, Jordi


    Invasive fungal infections remain a life-threatening disease. The development of invasive fungal disease is dependent on multiple factors, such us colonization and efficient host immune response. We aimed to review the pathogenesis of invasive fungal infections, in particular, those caused by Candida and Aspergillus. For this we propose, to describe the fungal characteristics, to detail the host defence mechanisms against fungus and to analyse the host risk factors for invasive fungal infection.

  2. Microbial Pathogenesis and Host Defense.


    Ghio, S.,1 Levitus, G.,1 Chiale, p.,2 Hoebeke, j., 3 Van Regenmortel, M.H.V.,4 Levin, M.J., 1 1 Laboratorio de Biologia Molecular de la Enfermedad Biologia Molecular de la Enfermedad de Chagas, INGEBI-CONICET, FCEN-UBA, Buenos Aires, Argentina; tCardiovascular Division, Ramos Mejia Hospital... molecular genetic tools can facilitate the dissection of the mechanism of pathogenesis in an organism that was previously intractable. One session dealt

  3. Molecular biology and pathogenesis of hepatitis E virus

    Vivek Chandra; Shikha Taneja; Manjula Kalia; Shahid Jameel


    The hepatitis E virus (HEV) is a small RNA virus and the etiological agent for hepatitis E, a form of acute viral hepatitis. The virus has a feco-oral transmission cycle and is transmitted through environmental contamination, mainly through drinking water. Recent studies on the isolation of HEV-like viruses from animal species also suggest zoonotic transfer of the virus. The absence of small animal models of infection and efficient cell culture systems has precluded virological studies on the replication cycle and pathogenesis of HEV. A vaccine against HEV has undergone successful clinical testing and diagnostic tests are available. This review describes HEV epidemiology, clinical presentation, pathogenesis, molecular virology and the host response to HEV infection. The focus is on published literature in the past decade.

  4. Neuropeptides control the dynamic behavior of airway mucosal dendritic cells.

    Voedisch, Sabrina; Rochlitzer, Sabine; Veres, Tibor Z; Spies, Emma; Braun, Armin


    The airway mucosal epithelium is permanently exposed to airborne particles. A network of immune cells patrols at this interface to the environment. The interplay of immune cells is orchestrated by different mediators. In the current study we investigated the impact of neuronal signals on key functions of dendritic cells (DC). Using two-photon microscopic time-lapse analysis of living lung sections from CD11c-EYFP transgenic mice we studied the influence of neuropeptides on airway DC motility. Additionally, using a confocal microscopic approach, the phagocytotic capacity of CD11c(+) cells after neuropeptide stimulation was determined. Electrical field stimulation (EFS) leads to an unspecific release of neuropeptides from nerves. After EFS and treatment with the neuropeptides vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP), airway DC in living lung slices showed an altered motility. Furthermore, the EFS-mediated effect could partially be blocked by pre-treatment with the receptor antagonist CGRP(8-37). Additionally, the phagocytotic capacity of bone marrow-derived and whole lung CD11c(+) cells could be inhibited by neuropeptides CGRP, VIP, and Substance P. We then cross-linked these data with the in vivo situation by analyzing DC motility in two different OVA asthma models. Both in the acute and prolonged OVA asthma model altered neuropeptide amounts and DC motility in the airways could be measured. In summary, our data suggest that neuropeptides modulate key features motility and phagocytosis of mouse airway DC. Therefore altered neuropeptide levels in airways during allergic inflammation have impact on regulation of airway immune mechanisms and therefore might contribute to the pathophysiology of asthma.

  5. Epigenetics and Colorectal Cancer Pathogenesis

    Bardhan, Kankana; Liu, Kebin, E-mail: [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)


    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  6. HIV infection and specific mucosal immunity: workshop 4B.

    Challacombe, S J; Fidel, P L; Tugizov, S; Tao, L; Wahl, S M


    Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues-namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.

  7. Mucoadhesive formulation of Bidens pilosa L. (Asteraceae reduces intestinal injury from 5-fluorouracil-induced mucositis in mice

    Paulo Henrique Marcelino de Ávila


    Full Text Available Gastrointestinal mucositis induced during cancer treatment is considered a serious dose-limiting side effect of chemotherapy and/or radiotherapy. Frequently, interruption of the cancer treatment due to this pathology leads to a reduction in cure rates, increase of treatment costs and decrease life quality of the patient. Natural products such as Bidens pilosa L. (Asteraceae, represent a potential alternative for the treatment of mucositis given its anti-inflammatory properties. In this study, B. pilosa glycolic extract was formulated (BPF with poloxamer, a mucoadhesive copolymer, was used for treatment of 5-fluorouracil (5-FU-induced mucositis in mice. As expected, animals only treated with 5-FU (200 mg/kg presented marked weight loss, reduction of intestinal villi, crypts and muscular layer, which was associated with severe disruption of crypts, edema, inflammatory infiltrate and vacuolization in the intestinal tissue, as compared to the control group and healthy animals only treated with BPF. On the other hand, the treatment of intestinal mucositis-bearing mice with BPF (75, 100 or 125 mg/kg managed to mitigate clinical and pathologic changes, noticeably at 100 mg/kg. This dose led to the restoration of intestinal proliferative activity through increasing Ki-67 levels; modulated the expression of Bax, Bcl2 and p53 apoptotic markers protecting intestinal cells from cell death. Moreover, this treatment regulated lipid peroxidation and inflammatory infiltration. No acute toxic effects were observed with this formulation. This work demonstrated that BPF was safe and effective against 5-FU-induced intestinal mucositis in mice. Additional studies are already in progress to further characterize the mechanisms involved in the protective effects of this technological formulation toward the development of a new medicine for the prevention and treatment of intestinal injury in patients undergoing chemotherapy/radiotherapy.

  8. Suppressive effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant on ethanol-induced gastric mucosal injury in rats.

    Kim, Jeong-Hwan; Choi, Seok-Keun; Choi, Sang-Yun; Kim, Han-Kyeom; Chang, Hyo-Ihl


    Ethanol has been found to induce ulcerative gastric lesion in humans. The present study investigated the in vivo protective effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant against ethanol-induced gastric mucosal injury in rats. The rats were treated with 80% ethanol for 3 d after pretreatment with two doses of astaxanthin (5 and 25 mg/kg of body weight respectively) for 3 d, while the control rats received only 80% ethanol for 3 d. The oral administration of astaxanthin (5 and 25 mg/kg of body weight) showed significant protection against ethanol-induced gastric lesion and inhibited elevation of the lipid peroxide level in gastric mucosa. In addition, pretreatment with astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly indicated that the acute gastric mucosal lesion induced by ethanol nearly disappeared after pretreatment with astaxanthin.

  9. Oxidative Stress: Dual Pathway Induction in Cardiorenal Syndrome Type 1 Pathogenesis

    Grazia Maria Virzì; Anna Clementi; Massimo de Cal; Alessandra Brocca; Sonya Day; Silvia Pastori; Chiara Bolin; Giorgio Vescovo; Claudio Ronco


    Cardiorenal Syndrome Type 1 (Type 1) is a specific condition which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Even though its pathophysiology is complex and not still completely understood, oxidative stress seems to play a pivotal role. In this study, we examined the putative role of oxidative stress in the pathogenesis of CRS Type 1. Twenty-three patients with acute heart failure (AHF) were included in the study. Subsequently, 11 patients ...

  10. [Transthyretin: it's miracle function and pathogenesis].

    Ando, Yukio


    Transthyretin (TTR) was previously called prealbumin because the band it formed on agarose gel electrophoresis at pH 8.6 was at the prealbumin position. However, it has been well documented that TTR of rodents does not show a prealbumin position on electrophoresis. Now, its name describes its function, binding to retinol binding protein (RBP) and T4. The serum concentration of the protein is 20-40 mg/dl, and TTR forms a tetramer. The plasma half life of the protein is 1.9 days. TTR is synthesized by the liver, retina, pancreas, and choroid plexus. In cerebro-spinal fluid (CSF), it is the second most abundant protein, and is considered as an important protein in the pathogenesis of Alzheimer's disease, depression, and lead intoxication. In addition, TTR is a tryptophan-rich protein, it is used as one of the nutrition assessment proteins, it acts as an anti acute phase protein, and its plasma concentration decreases during inflammation and bacterial infection. Since TTR is a highly amyloidogenic protein because it contains a beta-sheet structure, it becomes a precursor protein in familial amyloidotic polyneuropathy(FAP). Moreover, TTR plays important roles in various CNS disorders, diabetes melitus, and lipid metabolism.

  11. Risk analysis, diagnosis and management of gastrointestinal mucositis in pediatric cancer patients

    Kuiken, Nicoline S. S.; Rings, Edmond H. H. M.; Tissing, Wim J. E.


    Mucositis is a complex inflammatory reaction of the mucous membranes of the alimentary tract upon chemotherapy and radiotherapy treatment in oncology patients. Mucositis can be subdivided in oral and gastrointestinal mucositis (GI mucositis). The damage to the gastrointestinal tract compromises the

  12. Activated protein C in the treatment of acute lung injury and acute respiratory distress syndrome

    A.D. Cornet; G.P. van Nieuw Amerongen; A. Beishuizen; M.J. Schultz; A.R.J. Girbes; A.B.J. Groeneveld


    Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) frequently necessitate mechanical ventilation in the intensive care unit. The syndromes have a high mortality rate and there is at present no treatment specifically directed at the underlying pathogenesis. Central in

  13. Chamomile Mouth Rinse Effects on Mucositis Reduction After Radiotherapy

    Talaipour AR


    Full Text Available In recent years many patients have been received radiotherapy for head and neck tumors and"na large number of them have been survived for some years."nThe side effects of radiotherapy in oral region are mucositis, ulcers, fungal and viral infections and"nsalivary glands dysfunction. Among these, mucositis is the most important one."nA randomized double blind clinical trial was performed in radiotherapy department of Tehran Imam"nKhomeini Hospital to determine chamomile mouth rinse effects on mucositis after radiotherapy."nThe patients are selected randomly from those with oral oropharyngeal or nasopharyngeal cancers."nData showed that chamomile administration could decrease mucositis rate significantly,


    Radha Bhati


    Full Text Available Oral mucosal drug delivery system is widely applicable as novel site for administration of drug for immediate and controlled release action by preventing first pass metabolism and enzymatic degradation due to GI microbial flora. Oral mucosal drug delivery system provides local and systemic action. In this review, attention is focused to give regarding physiology of oral mucosal including tissue permeability, barriers to permeation and route of permeation, biopharmaceutics of buccal and sublingual absorption, factors affecting drug absorption, detailed information of penetration enhancers, design of oral mucosal drug delivery system and role of mucoadhesion and various theories of bioadhesion. Evaluation techniques and selection of animal model for in-vivo studies are also discussed.

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

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian


    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......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...

  16. Pathogenesis of Nonsteroidal Anti-Inflammatory Drug Gastropathy: Clues to Preventative Therapy

    Salim MA Bastaki


    Full Text Available Gastric ulceration and bleeding are major impediments to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs. The development of effective therapies for prevention of these adverse effects requires better understanding of their pathogenesis. Several features of NSAIDs contribute to the development of damage in the stomach, including the topical irritant effects of these drugs on the epithelium, impairment of the barrier properties of the mucosa, suppression of gastric prostaglandin synthesis, reduction of gastric mucosal blood flow and interference with the repair of superficial injury. The presence of acid in the lumen of the stomach also contributes to the pathogenesis of NSAID-induced ulcers and bleeding in a number of ways. Acid impairs the restitution process, interferes with hemostasis and can inactivate several growth factors that are important in mucosal integrity and repair. Profound suppression of gastric acid secretion has been shown to be effective in preventing NSAID-induced ulceration. There is a strong possibility that new NSAIDs entering the market will have greatly reduced toxicity in the gastrointestinal tract.

  17. Limitations in assessment of mucosal healing in inflammatory bowel disease

    Hugh; James; Freeman


    An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that complete healing of the intestinal mucosa in inflammatory bowel diseases should result in reduced disease complications,reduced hospitalization and reduced surgical treatment.By implication,the natural history of inflammatory bowel disease might then be altered. Measurement of mucosal healing,how...




    Full Text Available Primary mucosal malignant melanomas of sinonasal tract are uncommon tumors comprising 0.3-2% of all malignant melanomas and 4% of all head and Neck melanomas. We are reporting a rare case of mucosal malignant melanoma in a 45 year old female arising from nasopharynx which was excised completely by trans palatal approach followed by irradiation. This case is being reported because of its isolated involvement of nasopharynx, and early age of presentation.

  19. The streptomycin mouse model for Salmonella diarrhea: functional analysis of the microbiota, the pathogen's virulence factors, and the host's mucosal immune response.

    Kaiser, Patrick; Diard, Médéric; Stecher, Bärbel; Hardt, Wolf-Dietrich


    The mammalian intestine is colonized by a dense microbial community, the microbiota. Homeostatic and symbiotic interactions facilitate the peaceful co-existence between the microbiota and the host, and inhibit colonization by most incoming pathogens ('colonization resistance'). However, if pathogenic intruders overcome colonization resistance, a fierce, innate inflammatory defense can be mounted within hours, the adaptive arm of the immune system is initiated, and the pathogen is fought back. The molecular nature of the homeostatic interactions, the pathogen's ability to overcome colonization resistance, and the triggering of native and adaptive mucosal immune responses are still poorly understood. To study these mechanisms, the streptomycin mouse model for Salmonella diarrhea is of great value. Here, we review how S. Typhimurium triggers mucosal immune responses by active (virulence factor elicited) and passive (MyD88-dependent) mechanisms and introduce the S. Typhimurium mutants available for focusing on either response. Interestingly, mucosal defense turns out to be a double-edged sword, limiting pathogen burdens in the gut tissue but enhancing pathogen growth in the gut lumen. This model allows not only studying the molecular pathogenesis of Salmonella diarrhea but also is ideally suited for analyzing innate defenses, microbe handling by mucosal phagocytes, adaptive secretory immunoglobulin A responses, probing microbiota function, and homeostatic microbiota-host interactions. Finally, we discuss the general need for defined assay conditions when using animal models for enteric infections and the central importance of littermate controls.

  20. Biology and pathogenesis of Acanthamoeba

    Siddiqui Ruqaiyyah


    Full Text Available Abstract Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens.

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

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


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

  2. Using Light to Treat Mucositis and Help Wounds Heal

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


    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.

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

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


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

  4. Hemolytic uremic syndrome: pathogenesis and update of interventions.

    Palermo, Marina S; Exeni, Ramón A; Fernández, Gabriela C


    The typical form of hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin-producing Escherichia coli infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, accounting for 20% of renal transplants in children and adolescents in Argentina. Despite extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in Argentinean contribution. The hope that a better understanding of transmission dynamics and pathogenesis of this disease will produce better therapies to prevent the acute mortality and the long-term morbidity of HUS is the driving force for intensified research.

  5. Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging.

    Ciccarelli, Olga; Barkhof, Frederik; Bodini, Benedetta; De Stefano, Nicola; Golay, Xavier; Nicolay, Klaas; Pelletier, Daniel; Pouwels, Petra J W; Smith, Seth A; Wheeler-Kingshott, Claudia A M; Stankoff, Bruno; Yousry, Tarek; Miller, David H


    The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many insights have been gained from such imaging studies: persisting inflammation in the absence of a damaged blood-brain barrier, activated microglia within and beyond lesions, increased mitochondrial activity after acute lesions, raised sodium concentrations in the brain, increased glutamate in acute lesions and normal-appearing white matter, different degrees of demyelination in different patients and lesions, early neuronal damage in grey matter, and early astrocytic proliferation and activation in lesions and white matter. Clinical translation of molecular and metabolic imaging and extension of these techniques will enable the assessment of novel drugs targeted at these disease mechanisms, and have the potential to improve health outcomes through the stratification of patients for treatments.

  6. Black esophagus: Acute esophageal necrosis syndrome

    Grigoriy; E; Gurvits


    Acute esophageal necrosis (AEN), commonly referred to as "black esophagus", is a rare clinical entity arising from a combination of ischemic insult seen in hemodynamic compromise and low-flow states, corrosive injury from gastric contents in the setting of esophago-gastroparesis and gastric outlet obstruction, and decreased function of mucosal barrier systems and reparative mechanisms present in malnourished and debilitated physical states. AEN may arise in the setting of multiorgan dysfunction, hypoperfusi...

  7. Protein profiles in mucosal and systemic compartments in response to Vibrio cholerae in a mouse pulmonary infection model.

    Kang, Seok-Seong; Baik, Jung Eun; Yang, Jae Seung; Cho, Kun; Yun, Cheol-Heui; Han, Seung Hyun


    We have recently shown that a mouse lung infection model resulting in acute pneumonia could be used for evaluating the protective immunity induced by mucosal vaccines against Vibrio cholerae. In order to gain insight and better understanding of the pathogenicity of V. cholerae infection, we identified and compared proteins induced by V. cholerae in nasal washes, bronchoalveolar lavages (BAL), and sera. Intranasal administration of V. cholerae increased the concentration of total proteins in nasal washes and BAL fluids, but not in sera. LTQ-Orbitrap hybrid Fourier transform mass spectrometry showed that cytoskeletal proteins, protease inhibitors and anti-inflammatory mediators were present in nasal washes from uninfected mice. The distinctly expressed proteins in nasal washes in response to V. cholerae mainly consisted of protease inhibitors, anti-inflammatory proteins, and anti-microbial proteins. A number of protease inhibitors and anti-inflammatory proteins were selectively expressed in BAL fluids from V. cholerae-infected mice, while cytoskeletal proteins and heat shock proteins were mainly observed in BAL fluids from uninfected mice. A large number of serum complements, protease inhibitors, and acute phase proteins were expressed in V. cholerae-infected mice. Collectively, these results suggest that intranasal administration of V. cholerae leading to acute pneumonia elicited alterations of protein profiles associated with immune homeostasis and host protection in both the mucosal and systemic compartments.

  8. Lower nasopharyngeal epithelial cell repair and diminished innate inflammation responses contribute to the onset of acute otitis media in otitis-prone children.

    Verhoeven, David; Nesselbush, Monica; Pichichero, Michael E


    About 30 % of young children experience excessive, frequent episodes of middle ear infection and are classified as acute otitis media prone (OP). Streptococcus pneumoniae (Spn) is a predominant otopathogen in OP and non-OP (NOP) children. The pathogenesis of middle ear infection involves otopathogen nasopharyngeal (NP) colonization followed by an upper respiratory viral infection that modifies the NP environment to allow a sufficient inoculum of bacteria to reflux via the Eustachian tube into the middle ear space. Here, we analyzed the NP mucosal repair response between age-matched stringently defined OP (sOP) and NOP children who progressed to middle ear infection caused by Spn. We found lower epidermal growth factor, epidermal growth factor receptor, and angiogenin cytokine concentrations in nasal washes of sOP compared with NOP children. Despite higher expression of TLR2/4 transcript expression in nasal epithelium and in polymorphonuclear cells present in nasal secretions in sOP children, sOP children had lower expression of proinflammatory cytokines such as IL-6 and IL-8 in the NP. Chemotaxis-associated cytokine expression at onset of AOM in sOP children was also lower compared with NOP children, possibly indicating a lower capacity to signal the innate immune system. We conclude that lower epithelial cell repair responses during viral infection in the NP combined with diminished innate inflammatory responses potentiate Spn pathogenesis in the sOP child.

  9. Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV.

    Eric A Weaver

    Full Text Available 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.

  10. Gastric mucosal electrical potential difference, pH, blood flow, and morphology during hypoxia and selective gastric ischaemia with and without allopurinol pretreatment in anaesthetized dogs

    Højgaard, L; Bülow, J B; Madsen, J


    Ischaemia has been implicated in the pathogenesis of gastric mucosal disorders. The aim of this investigation was to study the gastric mucosal electrical potential difference (PD), pH, blood flow and morphology during hypoxia, gastric ischaemia, and gastric ischaemia following inhibition of free...... radical formation with allopurinol. PD and pH were measured simultaneously with an intragastric microelectrode, and the PD values were corrected for the liquid junction potentials created by the intragastric pH variation. Blood flow was measured by the radiolabelled microsphere technique in 18...... anaesthetized dogs. Short general hypoxia and short ischaemia caused reversible declines in PD, increases in pH, and no morphological damage. Ischaemia for 1 h caused a significant decline in PD persistent after reperfusion, an increase in pH, and morphological PD, but after reperfusion PD was normalized. Gross...

  11. New advances in the pathogenesis and therapy of essential thrombocythemia.

    Levine, Ross L; Heaney, Mark


    Essential thrombocythemia (ET) is a hematopoietic disorder that manifests clinically as thrombocytosis, and patients with ET are at increased risk for developing thrombosis, myelofibrosis, and transformation to acute myeloid leukemia. Although ET was recognized as a distinct clinical syndrome more than 6 decades ago and was classified as a myeloproliferative neoplasm (MPN) by William Dameshek in 1951, the molecular pathogenesis of ET remained unknown until 2005, when activating mutations in the JAK2 tyrosine kinase (JAK2V617F) were identified in a significant proportion of patients with ET, polycythemia vera (PV) and primary myelofibrosis (PMF). In addition, subsequent studies have identified gain-of-function mutations in the thrombopoietin receptor (MPL) in a subset of patients with JAK2V617F-negative ET, suggesting that JAK2 activation by distinct mechanisms contributes to the pathogenesis of ET. Despite these important observations, important questions remain regarding the role of JAK2/MPL mutations in ET pathogenesis, the etiology of JAK2/MPL negative ET, the factors that distinguish ET from other MPNs with the JAK2V617F mutation, and the role of JAK2-targeted therapies for the treatment of these MPNs.

  12. Prospective small bowel mucosal assessment immediately after chemoradiotherapy of unresectable locally advanced pancreatic cancer using capsule endoscopy: a case series.

    Yamashina, Takeshi; Takada, Ryoji; Uedo, Noriya; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ioka, Tatsuya; Ishihara, Ryu; Teshima, Teruki; Nishiyama, Kinji; Iishi, Hiroyasu


    In this case series, three consecutive patients with unresectable locally advanced pancreatic cancer (ULAPC) underwent capsule endoscopy (CE) before and after chemoradiotherapy (CRT) to evaluate duodenal and jejunal mucosa, and to examine the relationship between CE findings and dose distribution. CE after CRT showed duodenitis and proximal jejunitis in all three patients. The most inflamed region was the third part of the duodenum, and in dose distribution, this was the closest region to the center of irradiation. This case series shows that CE can safely diagnose acute duodenitis and proximal jejunitis caused by CRT for ULAPC, and that dose distribution is possible to predict the degree of duodenal and jejunal mucosal injuries.

  13. Innate Immune Signaling in the Pathogenesis of Necrotizing Enterocolitis

    David J. Hackam


    Full Text Available Necrotizing enterocolitis (NEC is a challenging disease to treat, and caring for patients afflicted by it remains both frustrating and difficult. While NEC may develop quickly and without warning, it may also develop slowly, insidiously, and appear to take the caregiver by surprise. In seeking to understand the molecular and cellular processes that lead to NEC development, we have identified a critical role for the receptor for bacterial lipopolysaccharide (LPS toll like receptor 4 (TLR4 in the pathogenesis of NEC, as its activation within the intestinal epithelium of the premature infant leads to mucosal injury and reduced epithelial repair. The expression and function of TLR4 were found to be particularly elevated within the intestinal mucosa of the premature as compared with the full-term infant, predisposing to NEC development. Importantly, factors within both the enterocyte itself, such as heat shock protein 70 (Hsp70, and in the extracellular environment, such as amniotic fluid, can curtail the extent of TLR4 signaling and reduce the propensity for NEC development. This review will highlight the critical TLR4-mediated steps that lead to NEC development, with a focus on the proinflammatory responses of TLR4 signaling that have such devastating consequences in the premature host.

  14. Role of angiogenesis in the pathogenesis of oral lichen planus

    Nitasha Mittal


    Full Text Available Background: The etiology of oral lichen planus (OLP is not fully understood. It is generally considered to be a T-cell mediated chronic inflammatory oral mucosal disease. There is increasing evidence that chronic inflammation is linked to the diseases associated with endothelial dysfunction and is involved in the induction of aberrant angiogenesis. Aim: Our aim was to evaluate the role of angiogenesis in the pathogenesis of OLP by immunohistochemistry, using the CD34 antibody. Materials and Methods: Forty tissue sections (7 of erosive lichen planus, 18 of reticular oral lichen planus, and 15 of normal oral mucosa, were assessed for microvessel density (MVD in five selected areas of high inflammatory infiltrate by immunohistochemistry for the expression of CD34 antibody. Results and Conclusion: The mean MVD was 44.47 in the control group (normal oral mucosa and 97.24 in the OLP group, showing that there is increased angiogenesis in the latter. Reticular OLP had mean MVD of 84.61 and erosive OLP had mean MVD of 129.71, showing relatively greater angiogenesis in erosive OLP as compared to reticular OLP. Thus, angiogenesis can be considered to play a role in both the etiopathogenesis and the progression of OLP.


    Kaur Amandeep


    Full Text Available A peptic ulcer is a sore on the lining of the stomach or duodenum. The two most common types of peptic ulcer are called “gastric ulcers” and “duodenal ulcers”. Peptic ulcers are found to be due to an imbalance between aggressive factors such as hydrochloric acid (HCL, pepsin, refluxed bile, leukotrienes (LTs, reactive oxygen species (ROS and defensive factors, which include the function of the mucus-bicarbonate barrier, prostaglandins (PGs, mucosal blood flow, cell renewal and migration, nonenzymatic and enzymatic antioxidants and some growth factors. H. pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs are the predominant causes of peptic ulcer disease. Also, a numbers of factors are implicated in the pathogenesis of gastric ulcer, among which major factors involved are bacterial infection (Helicobacter pylori, certain medications (NSAID, chemicals (Hcl/ethanol ,gastric cancer and minor factors are stress, smoking, spicy food and nutritional deficiencies. The idea behind treating ulcers is to lower the amount of acid that your stomach makes, to neutralize the acid that is made and to protect the injured area so it can have time to heal. The main aim of this review article has to summarize the ulcerogenic mechanisms of various mediators involved in Peptic ulcer disease.

  16. Clotrimazole nanoparticle gel for mucosal administration

    Esposito, Elisabetta, E-mail: [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Ravani, Laura [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Contado, Catia [Department of Chemistry, University of Ferrara, Ferrara (Italy); Costenaro, Andrea [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Drechsler, Markus [Macromolecular Chemistry II, University of Bayreuth (Germany); Rossi, Damiano [Department of Biology and Evolution, LT Terra and Acqua Tech UR7, University of Ferrara, Ferrara (Italy); Menegatti, Enea [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Grandini, Alessandro [Department of Biology and Evolution, LT Terra and Acqua Tech UR7, University of Ferrara, Ferrara (Italy); Cortesi, Rita [Department of Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy)


    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{sup Registered-Sign }. An anticandidal activity study demonstrated that both CLO-MAD and CLO-NLC were more active against Candida albicans with respect to the pure drug. Highlights: Black-Right-Pointing-Pointer Comparison between monoolein aqueous dispersion (MAD) and nanostructured lipid carrier (NLC). Black-Right-Pointing-Pointer Clotrimazole (CLO) encapsulated with high entrapment efficiency both in MAD and in NLC. Black-Right-Pointing-Pointer The solid matrix of NLC controls CLO degradation better than MAD. Black-Right-Pointing-Pointer CLO containing MAD and NLC exhibits a higher anticandidal activity than the free drug. Black-Right-Pointing-Pointer Simple production of CLO-NLC based poloxamer gel, suitable for industry scaling up.

  17. Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by IL-23.

    Muyiwa Awoniyi

    Full Text Available IL-12 and IL-23 regulate innate and adaptive immunity to microbial pathogens through influencing the expression of IFN-γ, IL-17, and IL-22. Herein we define the roles of IL-12 and IL-23 in regulating host resistance and intestinal inflammation during acute Salmonella infection. We find that IL-23 alone is dispensable for protection against systemic spread of bacteria, but synergizes with IL-12 for optimal protection. IL-12 promotes the production of IFN-γ by NK cells, which is required for resistance against Salmonella and also for induction of intestinal inflammation and epithelial injury. In contrast, IL-23 controls the severity of inflammation by inhibiting IL-12A expression, reducing IFN-γ and preventing excessive mucosal injury. Our studies demonstrate that IL-23 is a homeostatic regulator of IL-12-dependent, IFN-γ-mediated intestinal inflammation.

  18. Acute pancreatitis

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  19. Cystitis - acute

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  20. Pathogenesis of Painful Diabetic Neuropathy

    Amir Aslam


    Full Text Available The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person’s daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin of pain could be in the peripheral nerves of the central nervous system. In this review, we discuss various possible mechanisms of the pathogenesis of pain in PDN. We discuss the role of hyperglycaemia in altering the physiology of peripheral nerves. We also describe central mechanisms of pain.

  1. Raynaud's phenomenon: pathogenesis and management.

    Bakst, Richard; Merola, Joseph F; Franks, Andrew G; Sanchez, Miguel


    Raynaud's phenomenon is a common clinical disorder for which patients frequently seek the expertise and care of dermatologists. It is manifested by recurrent vasospasm of the fingers and toes, often associated with exposure to cold temperature or emotional stress. The phenomenon is named after Maurice Raynaud, who, as a medical student, defined the first case in 1862 as episodic, symmetric, acral vasospasm characterized by pallor, cyanosis, suffusion, and a sense of fullness or tautness, which may be painful. Despite more than 140 years of research, the pathophysiology of Raynaud's phenomenon continues to elude investigators. Accordingly, although many pharmacologic treatments have been reported, there is still no cure or gold standard therapy. Further, response to treatment varies and is difficult to predict. Recently, there has been renewed interest in finding the pathogenetic mechanisms of Raynaud's phenomenon, an effort that has led to more potential targeted therapeutics. The purpose of this review is to discuss recent breakthroughs in the pathogenesis and treatment of Raynaud's phenomenon.

  2. IFN-γ Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection.

    Dolowschiak, Tamas; Mueller, Anna Angelika; Pisan, Lynn Joanna; Feigelman, Rounak; Felmy, Boas; Sellin, Mikael Erik; Namineni, Sukumar; Nguyen, Bidong Dinh; Wotzka, Sandra Yvonne; Heikenwalder, Mathias; von Mering, Christian; Mueller, Christoph; Hardt, Wolf-Dietrich


    Salmonella Typhimurium (S.Tm) causes acute enteropathy resolving after 4-7 days. Strikingly, antibiotic therapy does not accelerate disease resolution. We screened for factors blocking remission using a S.Tm enterocolitis model. The antibiotic ciprofloxacin clears pathogen stool loads within 3-24 hr, while gut pathology resolves more slowly (ψ50: ∼48 hr, remission: 6-9 days). This delayed resolution is mediated by an interferon-γ (IFN-γ)-dependent response that is triggered during acute infection and continues throughout therapy. Specifically, IFN-γ production by mucosal T and NK cells retards disease resolution by maintaining signaling through the transcriptional regulator STAT1 and boosting expression of inflammatory mediators like IL-1β, TNF, and iNOS. Additionally, sustained IFN-γ fosters phagocyte accumulation and hampers antimicrobial defense mediated by IL-22 and the lectin REGIIIβ. These findings reveal a role for IFN-γ in delaying resolution of intestinal inflammation and may inform therapies for acute Salmonella enteropathy, chronic inflammatory bowel diseases, or disease resolution during antibiotic treatment.

  3. Differential Gene Expression and Infection Profiles of Cutaneous and Mucosal Leishmania braziliensis Isolates from the Same Patient

    Alves-Ferreira, Eliza V. C.; Toledo, Juliano S.; De Oliveira, Arthur H. C.; Ferreira, Tiago R.; Ruy, Patricia C.; Pinzan, Camila F.; Santos, Ramon F.; Boaventura, Viviane; Rojo, David; López-Gonzálvez, Ángelez; Rosa, Jose C.; Barbas, Coral; Barral-Netto, Manoel; Barral, Aldina; Cruz, Angela K.


    Background Leishmaniasis is a complex disease in which clinical outcome depends on factors such as parasite species, host genetics and immunity and vector species. In Brazil, Leishmania (Viannia) braziliensis is a major etiological agent of cutaneous (CL) and mucosal leishmaniasis (MCL), a disfiguring form of the disease, which occurs in ~10% of L. braziliensis-infected patients. Thus, clinical isolates from patients with CL and MCL may be a relevant source of information to uncover parasite factors contributing to pathogenesis. In this study, we investigated two pairs of L. (V.) braziliensis isolates from mucosal (LbrM) and cutaneous (LbrC) sites of the same patient to identify factors distinguishing parasites that migrate from those that remain at the primary site of infection. Methodology/Principal Findings We observed no major genomic divergences among the clinical isolates by molecular karyotype and genomic sequencing. RT-PCR revealed that the isolates lacked Leishmania RNA virus (LRV). However, the isolates exhibited distinct in vivo pathogenesis in BALB/c mice; the LbrC isolates were more virulent than the LbrM isolates. Metabolomic analysis revealed significantly increased levels of 14 metabolites in LbrC parasites and 31 metabolites in LbrM parasites that were mainly related to inflammation and chemotaxis. A proteome comparative analysis revealed the overexpression of LbrPGF2S (prostaglandin f2-alpha synthase) and HSP70 in both LbrC isolates. Overexpression of LbrPGF2S in LbrC and LbrM promastigotes led to an increase in infected macrophages and the number of amastigotes per cell at 24–48 h post-infection (p.i.). Conclusions/Significance Despite sharing high similarity at the genome structure and ploidy levels, the parasites exhibited divergent expressed genomes. The proteome and metabolome results indicated differential profiles between the cutaneous and mucosal isolates, primarily related to inflammation and chemotaxis. BALB/c infection revealed that

  4. Pathogenesis and Prediction of Future Rheumatoid Arthritis


    AWARD NUMBER: W81XWH-13-1-0408 TITLE: Pathogenesis and Prediction of Future Rheumatoid Arthritis...5a. CONTRACT NUMBER Pathogenesis and Prediction of Future Rheumatoid Arthritis 5b. GRANT NUMBER W81XWH-13-1-0408 5c... pathogenesis of RA that can ultimately be targeted to prevent RA. This project has proposed to use a unique set of serum samples and clinical data

  5. Pulmonary edema in acute carbon monoxide poisoning

    Kim, Kun Sang; Chang, Kee Hyun; Lee, Myung Uk [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    Acute carbon monoxide poisoning has frequently occurred in Korean, because of the coal briquette being widely used as fuel in Korean residences. Carbon monoxide poisoning has been extensively studied, but it has been sparsely reported that pulmonary edema may develop in acute CO poisoning. We have noticed nine cases of pulmonary edema in acute CO poisoning last year. Other possible causes of pulmonary edema could be exclude in all cases but one. The purpose of this paper is to describe nine cases of pulmonary edema complicated in acute CO poisoning and discuss the pathogenesis and the prognosis.

  6. Intestinal colonization with Candida albicans and mucosal immunity

    Xiao-Dong Bai; Xian-Hua Liu; Qing-Ying Tong


    AIM: To observe the relationship between intestinal lumen colonization with Candida albicans and mucosal secretory IgA (sIgA).METHODS: A total of 82 specific-pathogen-free mice were divided randomly into control and colonization groups. After Candida albicans were inoculated into specific-pathogenfree mice, the number of Candida albicans adhering to cecum and mucosal membrane was counted. The lymphocyte proliferation in Peyer's patch and in lamina propria was shown by BrdU incorporation, while mucosal sIgA (surface membrane) isotype switch in Peyer's patch was investigated. IgA plasma cells in lamina propria were observed by immunohistochemical staining. Specific IgA antibodies to Candida albicans were measured with ELISA.RESULTS: From d 3 to d 14 after Candida albicans gavaging to mice, the number of Candida albicans colonizing in lumen and adhering to mucosal membrane was sharply reduced.Candida albicans translocation to mesenteric lymph nodes occurred at early time points following gavage administration and disappeared at later time points. Meanwhile, the content of specific IgA was increased obviously. Proliferation and differentiation of lymphocytes in lamina propria were also increased.CONCLUSION: Lymphocytes in lamina propria play an important role in intestinal mucosal immunity of specificpathogen-free mice when they are first inoculated with Candida albicans. The decreasing number of Candida albicans in intestine is related to the increased level of specific IgA antibodies in the intestinal mucus.

  7. Type 1 diabetes pathogenesis - Prevention???

    C S Muralidhara Krishna


    Full Text Available Pathogenesis of type 1 diabetes is multi-faceted, including, autoimmunity, genetics and environment. Autoimmunity directed against pancreatic islet cells results in slowly progressive selective beta-cell destruction ("Primary autoimmune insulitis", culminating over years in clinically manifested insulin-dependent diabetes mellitus (IDDM. Circulating serum autoantibodies directed against the endocrine cells of the islets of Langerhans (Islet cell autoantibodies - ICAb are an important hallmark of this disease. Assays for islet cell autoantibodies have facilitated the investigation and understanding of several facets in the pathogenesis of autoimmune diabetes. Their applications have extended into clinical practice and have opened new avenues for early preclinical prediction and preventive prophylaxis in IDDM/type 1 DM. Recently, surprisingly, differences in insulin content between T1DM islets, as well as, ′patchy′ or ′lobular′ destruction of islets have been described. These unique pathobiological phenomena, suggest that beta cell destruction may not always be inexorable and inevitably complete/total, and thus raise hopes for possible therapeutic interruption of beta cell autoimmunity - destruction and cure of type 1 diabetes. "Recurrent or secondary autoimmune insulitis" refers to the rapid reappearance of islet cell autoantibodies post pancreas transplant, and selective islet beta cell destruction in the grafted pancreas [never forgetting or "anamnestic" beta cell destructive memory], in the absence of any graft pancreas rejection [monozygotic twin to twin transplantation]. The one definite environmental factor is congenital rubella, because of which a subset of children subsequently develop type 1 diabetes. The putative predisposing factors are viruses, gluten and cow′s milk. The putative protective factors include gut flora, helminths, viral infections, and Vitamin D. Prevention of T1DM can include: Primary prevention strategies

  8. Oral mucosal alterations among the institutionalized elderly in Brazil

    Raquel Conceição Ferreira


    Full Text Available This study determined the prevalence of oral mucosal alterations and associated factors among the institutionalized elderly in Brazil. Data were collected through a structured questionnaire, a review of their medical records and an intra-oral examination. A sample of 335 individuals over 60 years of age was randomly selected. In total, 646 alterations were diagnosed; 59.1% were variations of the normal oral mucosa. The most frequent variation consisted of sublingual varicosities (51.6%. Denture stomatitis (15.2% and denture hyperplasia (12.8% were the most frequent lesions. Elderly patients who wore dentures had a significantly higher prevalence of oral mucosal lesions (p = 0.00 than those that didn't wear dentures. There was a high prevalence of variations of the normal oral mucosa and of mucosal lesions, especially denture-induced lesions, among the institutionalized elderly.

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

    Wodzinski, Amelia


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

  10. Mucosal immunity in the gut: the non-vertebrate perspective.

    Garcia-Garcia, Erick; Galindo-Villegas, Jorge; Mulero, Victor


    Much is now known about the vertebrate mechanisms involved in mucosal immunity, and the requirement of commensal microbiota at mucosal surfaces for the proper functioning of the immune system. In comparison, very little is known about the mechanisms of immunity at the barrier epithelia of non-vertebrate organisms. The purpose of this review is to summarize key experimental evidence illustrating how non-vertebrate immune mechanisms at barrier epithelia compare to those of higher vertebrates, using the gut as a model organ. Not only effector mechanisms of gut immunity are similar between vertebrates and non-vertebrates, but it also seems that the proper functioning of non-vertebrate gut defense mechanisms requires the presence of a resident microbiota. As more information becomes available, it will be possible to obtain a more accurate picture of how mucosal immunity has evolved, and how it adapts to the organisms' life styles.

  11. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

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


    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.

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

    Spivakovsky, Sylvia


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

  13. The pathogenesis of Charcot neuroarthropathy: current concepts

    Shelly A. M. Larson


    Full Text Available The pathogenesis of Charcot neuroarthropathy (CN has been poorly understood by clinicians and scientists alike. Current researchers have made progress toward understanding the cause of CN and possible treatment options. The authors review the current literature on the pathogenesis of this debilitating disorder and attempt to explain the roles of inflammation, bone metabolism, and advanced glycation end products.

  14. Local Renin-Angiotensin System in the Pancreas: The Significance in Acute Pancreatitis

    Lai PBS


    Full Text Available Acute pancreatitis is a complex disease entity of which the pathogenesis is still not completely known. Research into the initiation and propagation of the diseases would hopefully help to design new treatment strategies for patients, especially those with severe acute pancreatitis. The novel observation of the activation of the local pancreatic renin-angiotensin system in experimental pancreatitis opens up new horizons for research regarding the pathogenesis of acute pancreatitis.

  15. Acute Bronchitis

    ... Smoking also slows down the healing process. Acute bronchitis treatment Most cases of acute bronchitis can be treated at home.Drink fluids, but ... bronchial tree. Your doctor will decide if this treatment is right for you. Living with acute bronchitis Most cases of acute bronchitis go away on ...

  16. Molecular pathogenesis of multiple myeloma.

    Furukawa, Yusuke; Kikuchi, Jiro


    Multiple myeloma (MM), one of the most intractable malignancies, is characterized by the infiltration and growth of plasma cells, the most differentiated cells in the B-cell lineage, in the bone marrow. Despite the introduction of novel therapeutic agents, including proteasome inhibitors and immunomodulatory drugs, the prognosis of patients with MM is still worse than that of most hematological malignancies. A better understanding of the molecular pathogenesis of the disease is essential to achieve any improvement of treatment outcome of MM patients. All MM cases pass through the phase of asymptomatic expansion of clonal plasma cells, referred to as monoclonal gammopathy of undetermined significance (MGUS). It has long been believed that MM evolves linearly from MGUS to terminal phases, such as extramedullary tumors and plasma cell leukemia via the accumulation of novel mutations. However, recent studies using next-generation sequencing have disclosed the complex genomic architecture of the disease. At each step of progression, the acquisition of novel mutations is accompanied by subclonal evolution from reservoir clones with branching patterns. Each subclone may carry novel mutations and distinct phenotypes, including drug sensitivity. In addition, minor clones already exist at the MGUS stage, which could expand later in the clinical course, resulting in relapse and/or leukemic conversion. The ultimate goal of treatment is to eradicate all clones, including subclonal populations with distinct biological characteristics. This goal could be achieved by further improving treatment strategies that reflect the genomic landscape of the disease.

  17. Molecular Pathogenesis of MALT Lymphoma

    Katharina Troppan


    Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

  18. Intestinal dendritic cells in the regulation of mucosal immunity

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


    The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which....... The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality...

  19. Oral mucosal diseases in the office setting--part I: Aphthous stomatitis and herpes simplex infections.

    Sciubba, James J


    This article is an update and review of the most common nontraumatic ulcerative and vesicular lesions of the oral cavity. Details concerning their etiology, pathogenesis, clinical presentation, differential diagnosis, and management are included. Comparisons are made between the various forms of aphthous ulcerations and their viral counterparts. Lesions of herpes simplex origin are described for both primary and recurrent or secondary forms and differentiation from aphthous ulcerations is made. Treatment options for both the chronic and more acute forms of this condition are discussed.

  20. Pathophysiology of pulmonary complications of acute pancreatitis

    George W Browne; CS Pitchurnoni


    Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia,acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids,chemoattractants such as tumor necrsosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, IL-8, fMet-leu-phe (a bacterial wall product), nitric oxide, substance P, and macrophage inhibitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines.

  1. Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain

    Shim Byoung-Shik


    Full Text Available Abstract Background Sublingual (s.l. administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S (rADV-S of severe acute respiratory syndrome-associated coronavirus (SARS-CoV induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. Results Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n. administration. In addition, s.l. immunization induced antigen-specific CD8+ T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. Conclusion Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.

  2. Preventing and Therapeutic Effect of Propolis in Radiotherapy Induced Mucositis of Head and Neck Cancers: A Triple-Blind, Randomized, Placebo-Controlled Trial

    Javadzadeh Bolouri, Abbas; Pakfetrat, Atessa; Tonkaboni, Arghavan; Aledavood, Seyed Amir; Fathi Najafi, Mohsen; Delavarian, Zahra; Shakeri, Mohammad Taghi; Mohtashami, Azade


    Background: Mucositis is one of the acute complications of radiotherapy which can ulcerate oral mucosa and cause severe pain and discomfort which can affect oral normal function. Propolis is a natural source of flavenoid which has antiulcer, antibacterial, antifungal, healing and anti-inflammatory effects. Using such an affordable compound without any bad smell or taste that has reasonable price can help the radiotherapy undergoing patients. Objectives: Our goal is assessing the preventing and therapeutic effect of propolis in radiotherapy induced mucositis in patients with head and neck cancer. Patients and Methods: In a randomized triple blind clinical trial, 20 patient were selected randomly to swish and swallow 15 ml of water based extract of propolis mouth wash 3 times a day in the case group (n = 10) and 15 ml placebo mouth wash in control group (n = 10). we use NIC-CTC scale for determining mucositis grading. Results: We use T-test, Man-Whitney, Chi-square, and Friedman as analyzing tests. Case group had significantly (P 0.05). Conclusions: This is a pilot study which shows water based extract of propolis efficiently prevents and heals radiotherapy induced mucositis. PMID:26634113

  3. Mucosal delivery routes for optimal immunization: targeting immunity to the right tissues.

    Czerkinsky, C; Holmgren, J


    The mucosal immune system exhibits a high degree of anatomic compartmentalization related to the migratory patterns of lymphocytes activated at different mucosal sites. The selective localization of mucosal lymphocytes to specific tissues is governed by cellular "homing" and chemokine receptors in conjunction with tissue-specific addressins and epithelial cell-derived chemokines that are differentially expressed in "effector" tissues. The compartmentalization of mucosal immune responses imposes constraints on the selection of vaccine administration route. Traditional routes of mucosal immunization include oral and nasal routes. Other routes for inducing mucosal immunity include the rectal, vaginal, sublingual, and transcutaneous routes. Sublingual administration is a new approach that results in induction of mucosal and systemic T cell and antibody responses with an exceptionally broad dissemination to different mucosae, including the gastrointestinal and respiratory tracts, and the genital mucosa. Here, we discuss how sublingual and different routes of immunization can be used to generate immune responses in the desired mucosal tissue(s).

  4. Polymer nanomicelles for efficient mucus delivery and antigen-specific high mucosal immunity.

    Noh, Young-Woock; Hong, Ji Hyun; Shim, Sang-Mu; Park, Hye Sun; Bae, Hee Ho; Ryu, Eun Kyoung; Hwang, Jung Hwan; Lee, Chul-Ho; Cho, Seong Hun; Sung, Moon-Hee; Poo, Haryoung; Lim, Yong Taik


    Micelles for mucosal immunity: A mucosal vaccine system based on γ-PGA nanomicelles and viral antigens was synthesized. The intranasal administration of the vaccine system induces a high immune response both in the humoral and cellular immunity (see picture).

  5. The optimal use of granulocyte macrophage colony stimulating factor in radiation induced mucositis in head and neck squamous cell carcinoma.

    Patni Nidhi


    Full Text Available Objective: Evaluation of response of granulocyte macrophage colony stimulating factor (GM-CSF on acute radiation toxicity profile in head and neck squamous cell carcinoma. Methods and Materials: Thirty three patients with proven stage I or II head & neck carcinoma received conventional external beam radiation therapy. Out of these, six patients received postoperative adjuvant therapy while remaining 27 received definitive RT. Patients were given 100 mcg GM-CSF subcutaneously per day along with radiation after they developed grade 2 mucositis and /or grade 2 dysphagia and / or complained of moderate pain. GM-CSF was administered till there was a subjective relief or objective response. Patients were evaluated for oral ulceration, swallowing status, pain and weight loss. Response to the treatment and patient outcome was assessed. Results: There was a decreased severity of mucositis and dysphagia in the evaluated patients. None of the patients suffered severe pain or required opioids. The mean weight loss was only 1.94%. Minimal side effects were experienced with GM-CSF. Conclusions: GM-CSF reduces the severity of acute side effects of radiation therapy thereby allowing completion of the treatment without interruption. Its remarkable response needs to be evaluated further in large randomized trials. The time of initiation and cessation of GM-CSF during radiation therapy and the required dose needs to be established.

  6. The pleiotropic role of vitamin A in regulating mucosal immunity.

    Sirisinha, Stitaya


    The effect of vitamin A on mucosal immunity has never been subjected to extensive studies until recently. We started to work in this area in the early 1970s when we observed that children with protein-calorie malnutrition (PCM) often had defective mucosal immunity, judging from the incidence of respiratory tract infections and diarrhea. We reported that these children had depressed secretory IgA (sIgA) levels in their nasal wash fluids. The IgA level in specimens collected from those superimposed with some degrees of vitamin A deficiency state appeared to be more severely affected. In order to better understand the underlying mechanism associated with this condition, we started to study more detail the deficiency state using experimental vitamin A-deficient rats. From a series of experiments using this animal model, we proposed that vitamin A was needed for transport and/or secretion of sIgA across the mucosa. This conclusion was based on the observation that the secretory component of sIgA synthesized by the epithelial cells of these vitamin A deficient animals was adversely affected as compared to the control animals. From that time onward, much progress has been made by several other groups showing that other mechanisms could also influence the integrity and immune function of the mucosa. For instance, recent studies demonstrated that retinoic acid which is a biologically active form of vitamin A has an essential role in mucosal homeostasis, controlling tolerance and immunity in these non-lymphoid tissues. Such a conclusion was made possible by the availability of sophisticated new molecular biology and genetic engineering techniques together with advances in the field of immunoregulation, e.g., the discovery of dendritic cells (DCs) and T helper cell subsets in 1980s, and the role of Toll-like receptors (TLRs) together with other innate immune regulators in controlling adaptive immune response in the early 1990s. These advances provided considerable new

  7. Acute fatty liver of pregnancy

    Ko, Hin Hin; Yoshida, Eric


    Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. Although the exact pathogenesis is unknown, this disease has been linked to an abnormality in fetal fatty acid metabolism. Early diagnosis of AFLP sometimes can be difficult because it shares features with other common conditions such as pre-eclampsia, viral hepatitis and cholestasis of pregnancy. However, a careful history and physical examination, in...


    Eduardo Magalhães Rego


    Full Text Available Differentiation syndrome (DS represents a life-threatening complication in patients with acute promyelocytic leukemia (APL undergoing induction therapy with all-trans retinoic acid (ATRA or arsenic trioxide (ATO. It affects about 20-25% of all patients and there are no definitive diagnostic criteria. Clinically, DS is characterized by weight gain, fever not attributable to infection, respiratory distress, cardiac involvement, hypotension, and/or acute renal failure. At the histological point of view, there is an extensive interstitial and intra-alveolar pulmonary infiltration by maturing myeloid cells, endothelial cell damage, intra-alveolar edema, inter-alveolar hemorrhage, and fibrinous exsudates. DS pathogenesis is not completely understood, but it is believed that an excessive inflammatory response is the main phenomenon involved, which results in increased production of chemokines and expression of adhesion molecules on APL cells. Due to the high morbidity and mortality associated with DS, its recognition and the prompt initiation of the treatment is of utmost importance. Dexamethasone is considered the mainstay of treatment of DS, and the recommended dose is 10 mg twice daily by intravenous route until resolution of DS. In severe cases (respiratory or acute renal failure it is recommended the discontinuation of ATRA or ATO until recovery.

  9. Porcine epidemic diarrhea virus infection: Etiology, epidemiology, pathogenesis and immunoprophylaxis.

    Jung, Kwonil; Saif, Linda J


    Porcine epidemic diarrhea virus (PEDV), a member of the genera Alphacoronavirus in the family Coronaviridae, causes acute diarrhea/vomiting, dehydration and high mortality in seronegative neonatal piglets. For the last three decades, PEDV infection has resulted in significant economic losses in the European and Asian pig industries, but in 2013-2014 the disease was also reported in the US, Canada and Mexico. The PED epidemic in the US, from April 2013 to the present, has led to the loss of more than 10% of the US pig population. The disappearance and re-emergence of epidemic PED indicates that the virus is able to escape from current vaccination protocols, biosecurity and control systems. Endemic PED is a significant problem, which is exacerbated by the emergence (or potential importation) of multiple PEDV variants. Epidemic PEDV strains spread rapidly and cause a high number of pig deaths. These strains are highly enteropathogenic and acutely infect villous epithelial cells of the entire small and large intestines although the jejunum and ileum are the primary sites. PEDV infections cause acute, severe atrophic enteritis accompanied by viremia that leads to profound diarrhea and vomiting, followed by extensive dehydration, which is the major cause of death in nursing piglets. A comprehensive understanding of the pathogenic characteristics of epidemic or endemic PEDV strains is needed to prevent and control the disease in affected regions and to develop an effective vaccine. This review focuses on the etiology, epidemiology, disease mechanisms and pathogenesis as well as immunoprophylaxis against PEDV infection.

  10. Screening of key genes and inflammatory signalling pathway involved in the pathogenesis of HLA-B27-associated acute anterior uveitis by gene expression microarray%人类白细胞抗原-B27相关性前葡萄膜炎患者差异基因的表达特征

    胡小凤; 卢弘; 王婧; 张孝生; 张晓龙; 刘旭辉; 许卓再; 胡俊敏; 卢清君


    Objective To investigate the genes and signalling pathways located upstream of the inflammatory processes in human leukocyte antigen (HLA)-B27-associated acute anterior uveitis by gene expression microarray.Methods Experimental study.HLA-B27-positive and-negative monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS).Gene expression microarrays were used to identify the differentially expressed genes.Differentially expressed (DE) genes were testified by real-time PCR and analyzed by a series of bioinformatics-based techniques such as Gene Ontology,Kyoto Encyclopedia of Genes and Genomes.Results Gene expression microarray analysis revealed marked differences between HLA-B27-positive acute anterior uveitis(AAU) and HLA-B27-negative healthy control peripheral monocytes in the genes that were upregulated in response to LPS stimulation with 1105 genes and 25 genes respectively.Gene Ontology enrichment and pathway analysis indicated that genes participating in protein transport and folding were essential to the inflammatory process.The LPS receptorToll-like receptor(TLR)4 induced TLR signalling pathway and pathway related to Vibrio cholerae infection were located upstream of the network and contribute to the overall response.Among the DE genes,PIK3 CA,PIK3CB,AKT3,and MAPK1 might play critical roles in inflammation.Conclusions Equivalent LPS stimulation induces a different response in HLA-B27-positive peripheral monocytes compared to normal control,suggesting that the TLR pathway is involved in the pathogenesis of HLA-B27-associated AAU.%目的 研究人类白细胞抗原(HLA)-B27相关性前葡萄膜炎患者外周血单核细胞炎症通路差异基因的表达特征.方法 实验研究.抽取3例HLA-B27阳性前葡萄膜炎患者及2例健康对照者外周血,分离后获得的单核细胞经含霍乱弧菌的脂多糖刺激后提取RNA,使用基因表达谱芯片进行检测,实时荧光定

  11. Altered Th17/Treg Ratio in Nasal Polyps With Distinct Cytokine Profile: Association With Patterns of Inflammation and Mucosal Remodeling.

    Wu, Dawei; Wang, Jianting; Zhang, Min


    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease that can be classified as eosinophilic or noneosinophilic. Nasal polyps can exhibit different types of mucosal inflammation and responses to treatment. Imbalanced ratios of T-helper 17(Th17) and regulatory T (Treg) cells may contribute to the pathogenesis of nasal polyps.This study assessed the frequency of Th17 and Treg cells and related cytokines in patients with nasal polyps and tested for associations with mucosal remodeling.Surgical samples from 12 controls and 33 CRSwNP patients were analyzed histopathologically. The frequency of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) and tissues were determined using flow cytometry. Th17 and Treg cells-related cytokines in plasma were measured by Cytometric Bead Array (CBA) multiplex assays and enzyme-linked immunosorbent assays (ELISAs).Eosinophilic CRSwNP (ECRSwNP) patients exhibited robust eosinophilia, whereas non-ECRSwNP patients were characterized by neutrophilia. Compared with non-ECRSwNP, an increased Th17/Treg ratio in ECRSwNP was associated with a less increased frequency of Th17 cells and a more striking reduction of Treg cells. An altered Th17/Treg cell ratio was positively correlated with eosinophilic and neutrophilic infiltration, submucosal basement membrane thickness, and the degree of subepithelial collagen deposition. Compared with non-ECRSwNP, ECRSwNP had higher levels of IL-17A and IL-4, and lower levels of IL-10 and TGF-β1, whereas non-ECRSwNP showed higher levels of IFN-γ and IL-6.Th17/Treg cell imbalance in nasal polyps (both in tissues and PBMCs) with distinct cytokine profile may contribute to different inflammatory patterns (eosinophilic versus neutrophilic inflammation) and corresponding features of mucosal remodeling. Effective strategies can be designed to target a Th17/Treg imbalance to restore immune homeostasis in nasal polyps.

  12. Role of toll like receptors in irritable bowel syndrome: differential mucosal immune activation according to the disease subtype.

    Liliana Belmonte

    Full Text Available BACKGROUND: The irritable bowel syndrome (IBS is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown. METHODOLOGY AND FINDINGS: In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed. TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1β. CONCLUSIONS: Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits.

  13. Pathogenesis of Helicobacter pylori infection.

    Hofman, Paul; Waidner, Barbara; Hofman, Véronique; Bereswill, Stefan; Brest, Patrick; Kist, Manfred


    Research in the last year has provided new insights into the function of the the cag-associated type IV secretion system and the vacuolating toxin VacA. A quite new aspect was disclosed by the finding that Helicobacter pylori in Mongolian gerbils colonizes a very distinct topology in the gastric mucous layer, obviously providing optimal conditions for long-term survival. Further research activities focused on H. pylori ammonia and metal metabolism as well as on bacterial stress defence mechanisms. Differential expression of approximately 7% of the bacterial genome was found at low pH suggesting that H. pylori has evolved a multitude of acid-adaptive mechanisms. VacA was shown to interrupt phagosome maturation in macrophage cell lines as well as to modulate and interfere with T lymphocyte immunological functions. Gastric mucosa as well as the H. pylori-infected epithelial cell line AGS strongly express IL-8 receptor A and B, which might contribute to the augmentation of the inflammatory response. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. The chronic imbalance between apoptosis and cell proliferation is the first step of gastric carcinogenesis. In this regard, it was demonstrated that coexpression of two H. pylori proteins, CagA and HspB, in AGS cells, caused an increase in E2F transcription factor, cyclin D3, and phosphorylated retinoblastoma protein. Taken together, we now have a better understanding of the role of different virulence factors of H. pylori. There is still a lot to be learned, but the promising discoveries summarized here, demonstrate that the investigation of the bacterial survival strategies will give novel insights into pathogenesis and disease development.

  14. Human mucosal leishmaniasis: neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines.

    Boaventura, Viviane S; Santos, Claire S; Cardoso, Cristina R; de Andrade, José; Dos Santos, Washington L C; Clarêncio, Jorge; Silva, João S; Borges, Valeria M; Barral-Netto, Manoel; Brodskyn, Claudia I; Barral, Aldina


    Mucosal leishmaniasis (ML) is characterised by severe tissue destruction. Herein, we evaluated the involvement of the IL-17-type response in the inflammatory infiltrate of biopsy specimens from 17 ML patients. IL-17 and IL-17-inducing cytokines (IL-1β, IL-23, IL-6 and TGF-β) were detected by immunohistochemistry in ML patients. IL-17(+) cells exhibited CD4(+), CD8(+) or CD14(+) phenotypes, and numerous IL-17(+) cells co-expressed the CC chemokine receptor 6 (CCR6). Neutrophils, a hallmark of Th17-mediated inflammation, were regularly detected in necrotic and perinecrotic areas and stained positive for neutrophil elastase, myeloperoxidase and MMP-9. Taken together, these observations demonstrate the existence of Th17 cells in ML lesions associated with neutrophils in areas of tissue injury and suggest that IL-17 is involved in ML pathogenesis.

  15. Altered systemic bioavailability and organ distribution of azathioprine in methotrexate-induced intestinal mucositis in rats

    Sadaf A Karbelkar


    Conclusion: Study outcome has thrown light on altered fate of AZA when administered to individuals with mucositis which suggests modified drug therapy. These findings can further be investigated in different drug classes which might be administered concomitantly in mucositis and study outcome can be further confirmed in mucositis patients in clinical practice also.

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

    Jensen, Siri Beier; Peterson, Douglas E.


    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...

  17. The pathogenesis of foot-and-mouth disease in pigs

    Carolina eStenfeldt


    Full Text Available The greatest proportion of foot-and-mouth disease (FMD clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies specific to pigs. However, accumulated evidence from FMD outbreaks and experimental investigations suggest that critical components of FMD pathogenesis, immunology, and vaccinology cannot be extrapolated from investigations performed in cattle to explain or predict outcomes of infection or vaccination in pigs. Furthermore, it has been shown that failure to account for these differences may have substantial consequences when FMD outbreaks occur in areas with dense pig populations. Recent experimental studies have confirmed some aspects of conventional wisdom by demonstrating that pigs are more susceptible to FMD virus (FMDV infection via exposure of the upper gastrointestinal tract (oropharynx than through inhalation of virus. The infection spreads rapidly within groups of pigs that are housed together, although efficiency of transmission may vary depending on virus strain and exposure intensity. Multiple investigations have demonstrated that physical separation of pigs is sufficient to prevent virus transmission under experimental conditions. Detailed pathogenesis studies have recently demonstrated that specialized epithelium within porcine oropharyngeal tonsils constitute the primary infection sites following simulated-natural virus exposure. Furthermore, epithelium of the tonsil of the soft palate supports substantial virus replication during the clinical phase of infection, thus providing large amounts of virus that can be shed into the environment. Due to massive amplification and shedding of virus, acutely infected pigs constitute a considerable source of contagion. FMDV infection results in modulation of several components of the host immune response. The infection is ultimately cleared in association with a strong humoral response and, in

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

    Cotrim, Ana P. [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yoshikawa, Masanobu [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa (Japan); Sunshine, Abraham N.; Zheng Changyu [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Mitchell, James B. [Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Baum, Bruce J., E-mail: [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)


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

  19. Photobiomodulation reduces oral mucositis by modulating NF-kB

    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


    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.

  20. Peptic ulcer pathophysiology: acid, bicarbonate, and mucosal function

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


    . Bicarbonate secretion is inhibited by atropine, muscarinic antagonists, alpha-adrenoceptor agonists, indomethacin, bile acids, tobacco smoking, and probably also by infection by Helicobacter pylori. Apart from mucus and bicarbonate, the mucosal defence is supported by a hydrophobic epithelial lining, rapid...

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

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


    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).

  2. Neural fibrolipoma in pharyngeal mucosal space: A rare occurrence

    Nishith Kumar


    Full Text Available Neural fibrolipoma is a rare lesion presenting in early childhood, as a slow-growing fusiform swelling of a nerve, usually in the forearm or wrist (median nerve, associated with symptoms of compression neuropathy. There are only few case reports of neural fibrolipoma in neck and no such case has been reported in pharyngeal mucosal space.

  3. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

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


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

  4. Management of oral mucositis in patients with cancer.

    Stone, R.; Fliedner, M.C.; Smiet, A.C.M.


    Oral mucositis (OM) is a distressing toxic effect of chemotherapy and radiotherapy. It can increase the need for total parenteral nutrition and opioid analgesics, prolong hospital stays, increase the risk of infection, and greatly diminish a patient's quality of life. Nurses play a critical role in

  5. Conjunctiva-associated lymphoid tissue in avian mucosal immunity

    Ginkel, van F.W.; Gulley, S.L.; Lammers, A.; Hoerr, F.J.; Gurjar, R.; Toro, H.


    Conjunctiva-associated lymphoid tissue’s (CALT) role in generating avian mucosal adaptive immunity was measured by analyzing cellular composition, expression of the polymeric immunoglobulin receptor (pIgR), and production of cytokines and antibodies in chickens ocular exposed to a replication-defici

  6. Mucosal damage and neutropenia are required for Candida albicans dissemination.

    Andrew Y Koh


    Full Text Available Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections.

  7. The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation

    Yinghua Xu; Nicholas H Hunt; Shisan Bao


    An imbalance of mucosal pro- and anti-inflammatory cytokines is crucial in the pathogenesis of inflammatory bowel disease (IBD).GM-CSF influences the development of hemopoietic cells.The precise role of GM-CSF in IBD remains to be elucidated.GM-CSF gene knockout (GM-CSF-/-) and wild-type (Wt) mice were challenged with 2.5% dextran sulfate sodium (DSS) for 7 days.The ensued clinical and pathological changes,macrophage infiltration,colonic cytokine production,and bacterial counts were examined.DSS-treated GM-CSF-/- mice developed more severe acute colitis than DSS-treated Wt mice,reflected by a greater body weight loss,more rectal bleeding,and aggravated histopathological changes.More infiltrating macrophages were observed in GM-CSF-/-,compared with Wt mice following DSS challenge,correlating with monocyte chemoattractant protein-1 (MCP-1)production.The levels of colonic IL-17 and TNF-α were increased significantly in GM-CSF-/- mice,but not in Wt mice,following DSS administration.The level of IL-6 was increased by 1.5- and 2-fold in the colon of GM-CSF-/-and Wt mice,respectively,following DSS challenge.No significant changes in IL-4 and IFN-y were detected in Wt and GM-CSF-/-mice following DSS treatment.The bacteria recovery from colon was increased about 15- and 5-fold,respectively,in Wt mice and GM-CSF-/- mice following DSS challenge.These results suggest that GM-CSF-/- mice are more susceptible to acute DSS-induced colitis,possibly because of an impaired gut innate immune response as a result of diminished GM-CSF.

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

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


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

  9. Ethanol impairs mucosal immunity against Streptococcus pneumoniae infection by disrupting interleukin 17 gene expression.

    Trevejo-Nunez, Giraldina; Chen, Kong; Dufour, Jason P; Bagby, Gregory J; Horne, William T; Nelson, Steve; Kolls, Jay K


    Acute ethanol intoxication suppresses the host immune responses against Streptococcus pneumoniae. As interleukin 17 (IL-17) is a critical cytokine in host defense against extracellular pathogens, including S. pneumoniae, we hypothesized that ethanol impairs mucosal immunity against this pathogen by disrupting IL-17 production or IL-17 receptor (IL-17R) signaling. A chronic ethanol feeding model in simian immunodeficiency virus (SIV)-infected rhesus macaques and acute ethanol intoxication in a murine model were used. Transcriptome analysis of bronchial brushes in the nonhuman primate model showed downregulation of the expression of IL-17-regulated chemokines in ethanol-fed animals, a finding also replicated in the murine model. Surprisingly, recombinant CXCL1 and CXCL5 but not IL-17 or IL-23 plus IL-1β rescued bacterial burden in the ethanol group to control levels. Taken together, the results of this study suggest that ethanol impairs IL-17-mediated chemokine production in the lung. Thus, exogenous luminal restoration of IL-17-related chemokines, CXCL1 and CXCL5, improves host defenses against S. pneumoniae.

  10. Oral health as a predictive factor for oral mucositis

    Fabio Luiz Coracin


    Full Text Available OBJECTIVES: Oral mucositis is a complication frequently associated with hematopoietic stem cell transplantation, decreasing a patient's quality of life and increasing the occurrence of opportunistic infections. The purpose of this study was to determine the incidence and severity of oral mucositis and to assess the correlation of this disease with the oral health of an individual at the time of hematopoietic stem cell transplantation. METHODS: Before transplantation, patients' oral health and inflammatory conditions were determined using the gingival index and the plaque index, which are based on gingival bleeding and the presence of dental plaque, respectively. Additionally, the dental health status was determined using the decayed, missing, and filled teeth index. The monitoring of oral mucositis was based on the World Health Organization grading system and was performed for five periods: from Day 0 to D+5, from D+6 to D+10, from D+11 to D+15, from D+16 to D+20, and from D+21 to D+30. RESULTS: A total of 97 patients (56% male and 44% female who underwent hematopoietic stem cell transplantation at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo between January 2008 and July 2009 were prospectively examined. The incidence of ulcerative mucositis was highest from days +6 to +10 and from days +11 to +15 in the patients who underwent autologous and allogeneic hematopoietic stem cell transplantation, respectively. CONCLUSION: The data, including the dental plaque and periodontal status data, showed that these oral health factors were predictive of the incidence and severity of oral mucositis in a cohort of patients with similar conditioning regimens before hematopoietic stem cell transplantation.

  11. Ophthalmic lymphoma: epidemiology and pathogenesis.

    Sjö, Lene Dissing


    with relapse. Furthermore, we found that the frequency of translocations involving the MALT1- and IGH-gene loci is low in ocular region MALT lymphoma (2 of 42, 5%), but may predict increased risk of relapse (Sjo et al. 2008b). In conclusion the incidence of ophthalmic lymphoma is increasing at a high rate in Denmark. Ophthalmic lymphoma consists primarily of MALT lymphoma. The molecular pathogenesis of MALT lymphoma arising in the ocular region rarely involves translocations in the MALT1- and IGH-gene loci.

  12. An Odyssey to Viral Pathogenesis.

    Oldstone, Michael B A


    polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

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

    Elsadek, Hany M; Radwan, Mamdouh M


    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.

  14. 47,XYY karyotype in acute myeloid leukemia.

    Palanduz, S; Aktan, M; Ozturk, S; Tutkan, G; Cefle, K; Pekcelen, Y


    A case of acute myelomonocytic leukemia (AMMoL; M4) with a 47,XYY karyotype is reported. This chromosome aneuploidy was found in both bone marrow cells and mitogen-stimulated lymphocytes. The contribution of XYY chromosomal constitution in the pathogenesis of AMMoL is controversial.

  15. Acute pulmonary edema after near strangulation

    Shumaker, D.; Kottamasu, S.; Preston, G.; Treloar, D.


    We report a case of acute, noncardiogenic pulmonary edema in an 11 year old boy who suffered strangulation during an altercation. The clinical presentation was characterized by moderate respiratory distress and hemoptysis. Both the radiographic and clinical findings resolved during the three day admission which followed. A review of the literature is presented, and possible pathogenesis is discussed.

  16. Ossicular bone modeling in acute otitis media

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per


    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

  17. Could MicroRNAs be Regulators of Gout Pathogenesis?

    Yangang Wang


    Full Text Available MicroRNAs (miRNAs are a class of noncoding RNAs that mainly negatively regulate gene expression. miRNAs have important roles in many diseases, including inflammatory diseases. Gout is a common arthritis caused by deposition of monosodium urate crystals within joints. Recent studies suggested that miRNAs may be involved in the development of inflammatory arthritis, including acute gouty arthritis. In the present review, we systemically discuss relevant publications in order to provide a better understanding on the possible role of miRNAs in gout. miRNAs may act as regulators of gout pathogenesis via several pathways. Targeting miRNAs may be a promisingstrategy in the treatment of gout.

  18. Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance.

    Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa; Massoudi, Dawiyat; Kernien, John F; Vignali, Dario A; Sullivan, Jeremy A; Wilkes, David S; Burlingham, William J; Greenspan, Daniel S


    We have shown previously that collagen V (col(V)) autoimmunity is a consistent feature of atherosclerosis in human coronary artery disease and in the Apoe(-/-) mouse model. We have also shown sensitization of Apoe(-/-) mice with col(V) to markedly increase the atherosclerotic burden, providing evidence of a causative role for col(V) autoimmunity in atherosclerotic pathogenesis. Here we sought to determine whether induction of immune tolerance to col(V) might ameliorate atherosclerosis, providing further evidence for a causal role for col(V) autoimmunity in atherogenesis and providing insights into the potential for immunomodulatory therapeutic interventions. Mucosal inoculation successfully induced immune tolerance to col(V) with an accompanying reduction in plaque burden in Ldlr(-/-) mice on a high-cholesterol diet. The results therefore demonstrate that inoculation with col(V) can successfully ameliorate the atherosclerotic burden, suggesting novel approaches for therapeutic interventions. Surprisingly, tolerance and reduced atherosclerotic burden were both dependent on the recently described IL-35 and not on IL-10, the immunosuppressive cytokine usually studied in the context of induced tolerance and amelioration of atherosclerotic symptoms. In addition to the above, using recombinant protein fragments, we were able to localize two epitopes of the α1(V) chain involved in col(V) autoimmunity in atherosclerotic Ldlr(-/-) mice, suggesting future courses of experimentation for the characterization of such epitopes.




    Full Text Available Head and neck cancer is the commonest cancer in India and consists of about one-third of all cancers. Among viral infections, Epstein Barr virus (EBV has been implicated in the association of many head and neck cancers. Role of EBV as etiological factor in our population remains unknown. AIMS & OBJECTIVES: To determine the EBV related etiology of mucosal Head and Neck Squamous Cell Carcinoma (HNSCC in Kashmir Valley and if positive to define sub-typing of EBV and to find a correlation between the burden of EBV and disease status. MATERIAL METHODS: Observational single centre retrospective –prospective study. The study included 53 tissue samples from patients with Squamous Cell carcinoma of Head and Neck region. An equal number of blood samples were taken from healthy volunteers as a control for the reaction process. Sample collection and storage was done as per standard protocol. DNA amplification was done by Polymerase chain reaction. RESULTS: We did not observe any sample which tested positive for EBV. All samples were negative for EBV DNA. CONCLUSION: EBV has no role in the pathogenesis of Head and Neck Cancers in Kashmiri ethnic population of India. Different Genetic makeup of our population may be responsible for it. Further studies are needed to elucidate the etiology of head and neck Carcinoma in our population.

  20. Invariant natural killer T cells and mucosal-associated invariant T cells in multiple sclerosis.

    Bianchini, Elena; De Biasi, Sara; Simone, Anna Maria; Ferraro, Diana; Sola, Patrizia; Cossarizza, Andrea; Pinti, Marcello


    Multiple sclerosis (MS) is a chronic progressive inflammatory demyelinating disorder of the central nervous system, and in several countries is a leading cause of permanent neurological disability in young adults, particularly women. MS is considered an autoimmune disease, caused by an aberrant immune response to environmental triggers in genetically susceptible subjects. However, the contribution of the innate or of the adaptive immune system to the development and progression of the disease has not yet been fully elucidated. Innate-like T lymphocytes are unconventional T cells that bridge the innate and adaptive arms of the immune system, because they use a T cell receptor to sense external ligands, but behave like innate cells when they rapidly respond to stimuli. These cells could play an important role in the pathogenesis of MS. Here, we focus on invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells, and we review the current knowledge on their biology and possible involvement in MS. Although several studies have evaluated the frequency and functions of iNKT and MAIT cells both in MS patients and in experimental mouse models, contradictory observations have been reported, and it is not clear whether they exert a protective or a pro-inflammatory and harmful role. A better understanding of how immune cells are involved in MS, and of their interactions could be of great interest for the development of new therapeutic strategies.

  1. Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

    Semyachkina-Glushkovskaya, O. V.; Pavlov, A. N.; Semyachkin-Glushkovskiy, I. A.; Gekalyuk, A. S.; Ulanova, M. V.; Lychagov, V. V.; Tuchin, V. V.


    The adrenergic system plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhage. Because the impaired gastric mucosal blood flow (GMBF) is the major cause of gastroduodenal lesions, including ulcer bleeding (UB), we studied the adrenergic mechanism responsible for regulation of GMBF in rats with a model of stress-induced UB (SUB) using the laser Doppler flowmetry (LDF). First, we examined the effect of adrenaline on GMBF in rats under normal state and during UB. In all healthy animals the submucosal adrenaline injection caused a decrease in local GMBF. During UB the submucosal injection of adrenaline was accompanied by less pronounced GMBF suppression in 30,3% rats with SUB vs. healthy ones. In 69,7% rats with SUB we observed the increase in local GMBF after submucosal injection of adrenaline. Second, we studied the sensitivity of gastric β2-adrenoreceptors and the activity of two factors which are involved in β2-adrenomediated vasorelaxation-KATP -channels and NO. The effects of submucosal injection of isoproterenol, ICI118551 and glybenclamide on GMBF as well as NO levels in gastric tissue were significantly elevated in rats with SUB vs. healthy rats. Thus, our results indicate that high activation of gastric β2-adrenoreceptors associated with the increased vascular KATP -channels activity and elevated NO production is the important adrenergic mechanism implicated in the pathogenesis of UB.

  2. Staphylococcal enterotoxins in the Etiopathogenesis of Mucosal Autoimmunity within the Gastrointestinal Tract

    MaryAnn Principato


    Full Text Available The staphylococcal enterotoxins (SEs are the products of Staphylococcus aureus and are recognized as the causative agents of classical food poisoning in humans following the consumption of contaminated food. While illness evoked by ingestion of the SE or its producer organism in tainted food are often self-limited, our current understanding regarding the evolution of S. aureus provokes the utmost concern. The organism and its associated toxins, has been implicated in a wide variety of disease states including infections of the skin, heart, sinuses, inflammatory gastrointestinal disease, toxic shock, and Sudden Infant Death Syndrome. The intricate relationship between the various subsets of immunocompetent T cells and accessory cells and the ingested material found within the gastrointestinal tract present daunting challenges to the maintenance of immunologic homeostasis. Dysregulation of the intricate balances within this environment has the potential for extreme consequences within the host, some of which are long-lived. The focus of this review is to evaluate the relevance of staphylococcal enterotoxin in the context of mucosal immunity, and the underlying mechanisms that contribute to the pathogenesis of gastrointestinal autoimmune disease.

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

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


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

  4. Vulnerability of gastric mucosa in diabetic rats, its pathogenesis and amelioration by Cuminum cyminum

    N Vador


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

  5. Current understanding in pathogenesis of atopic dermatitis

    Tess McPherson


    Full Text Available There have been advances in our understanding of the complex pathogenesis of atopic eczema over the past few decades. This article examines the multiple factors which are implicated in this process.

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

    Aghamohamamdi, Azar; Hosseinimehr, Seyed Jalal


    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.

  7. Pivotal Role of Carbohydrate Sulfotransferase 15 in Fibrosis and Mucosal Healing in Mouse Colitis.

    Kenji Suzuki

    Full Text Available Induction of mucosal healing (MH is an important treatment goal in inflammatory bowel disease (IBD. Although the molecular mechanisms underlying MH in IBD is not fully explored, local fibrosis would contribute to interfere mucosal repair. Carbohydrate sulfotransferase 15 (CHST15, which catalyzes sulfation of chondroitin sulfate to produce rare E-disaccharide units, is a novel mediator to create local fibrosis. Here we have used siRNA-based approach of silencing CHST15 in dextran sulfate sodium (DSS induced colitis in mice, human colon fibroblasts and cancer cell lines. In a DSS-induced acute colitis model, CHST15 siRNA reduced CHST15 mRNA in the colon, serum IL-6, disease activity index (DAI and accumulation of F4/80+ macrophages and ER-TR7+ fibroblasts, while increased Ki-67+ epithelial cells. In DSS-induced chronic colitis models, CHST15 siRNA reduced CHST15 mRNA in the colon, DAI, alpha-smooth muscle actin+ fibroblasts and collagen deposition, while enhanced MH as evidenced by reduced histological and endoscopic scores. We also found that endoscopic submucosal injection achieved effective pancolonic delivery of CHST15 siRNA in mice. In human CCD-18 Co cells, CHST15 siRNA inhibited the expression of CHST15 mRNA and selectively reduced E-units, a specific product biosynthesized by CHST15, in the culture supernatant. CHST15 siRNA significantly suppressed vimentin in both TGF-ß-stimulated CCD18-Co cells and HCT116 cells while up-regulated BMP7 and E-cadherin in HCT116 cells. The present study demonstrated that blockade CHST15 represses colonic fibrosis and enhances MH partly though reversing EMT pathway, illustrating a novel therapeutic opportunity to refractory and fibrotic lesions in IBD.

  8. Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats

    Vink Carolien


    Full Text Available Abstract Background Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation. Rats were fed a control diet or the same diet supplemented with buthionine sulfoximine (BSO; glutathione depletion or cystine (glutathione maintenance. Inert chromium ethylenediamine-tetraacetic acid (CrEDTA was added to the diets to quantify intestinal permeability. At day 4 after oral gavage with Salmonella enteritidis (or saline for non-infected controls, Salmonella translocation was determined by culturing extra-intestinal organs. Liver and ileal mucosa were collected for analyses of glutathione, inflammation markers and oxidative damage. Faeces was collected to quantify diarrhoea. Results Glutathione depletion aggravated ileal inflammation after infection as indicated by increased levels of mucosal myeloperoxidase and interleukin-1β. Remarkably, intestinal permeability and Salmonella translocation were not increased. Cystine supplementation maintained glutathione in the intestinal mucosa but inflammation and oxidative damage were not diminished. Nevertheless, cystine reduced intestinal permeability and Salmonella translocation. Conclusion Despite increased infection-induced mucosal inflammation upon glutathione depletion, this tripeptide does not play a role in intestinal permeability, bacterial translocation and diarrhoea. On the other hand, cystine enhances gut barrier function by a mechanism unlikely to be related to glutathione.

  9. Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection

    Françoise Stoll-Keller


    Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection.

  10. Effect of electroacupunture on gastric mucosal intestinal trefoil factor gene expression of stress-induced gastric mucosal injury in rats

    Xi-Ping Li; Jie Yan; Shou-Xiang Yi; Xiao-Rong Chang; Ya-Ping Lin; Zong-Bao Yang; Ai Huang; Rong Hu


    AIM: To investigate electroacupunture(EA) at the acupoints of Stomach Meridian of Foot-Yangming(SMFY),Gallbladder Meridian of Foot-Yangming(SMFY) on gastric mucosal intestinal trefoil factor (ITF) gene expression detection in stress-induced rats with gastric mucosal lesion, and to explore the regulatory mechanism and significance of EA-related gastric mucosal protective effect.METHODS: Forty rats were randomly divided into 4 groups: Blank group, Model group, Model group+EA at acupoints of SMFY group("SMFY group"), and Model group+EA at acupoints of GMFY group(GMFY group).All rats (except blank group) were made model by water immersion and restraint stress (WRS). Then the gastric mucosa tissue in each rat was taken off after assessment of gastric mucosal lesion index(GUI), and the expression of ITF mRNA of the tissues was detected by reverse transcription-polymerase chain reaction(RT-PCR) method.RESULTS: Compared with Model group(54.3 ± 1.34),the GUI value in SMFY group (31±2.21) decreased significantly(P 0.05), in SMFY group(0.76± 0.01)with an extremely obvious difference (P<0.01), furthermore the expression in SMFY group was significantly higher than in GMFY group (P< 0.01).CONCLUSION: The gastric mucosal protective effect by EA at the acupoints of SMFY and GMFY was related to the expression variance of ITF, indicating certain meridian specificity exists. It could be one proof for the TCM theory "Relative particularity between SMFY and stomach".

  11. An Unusual Case of Colon Perforation Complicating Acute Pancreatitis

    Anthony A. Aghenta


    Full Text Available Colonic complications of severe acute pancreatitis occur rarely. Although there have been several theories on how pancreatic pseudocysts rupture into the colon, the exact pathogenesis remains unknown. We report an unusual case of pseudocysts complicating severe acute pancreatitis presenting with colonic perforation in a 71-year-old man with a history of chronic mesenteric ischemia. Pressure effects from a giant pseudocyst and intravascular volume depletion with acute insult on chronic mesenteric ischemia are highlighted as possible etiologic factors.

  12. Autophagy in lung disease pathogenesis and therapeutics

    Stefan W. Ryter


    Full Text Available Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics.

  13. Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats.

    S. Christensen; Kusano, E; Yusufi, A N; Murayama, N; Dousa, T P


    A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study...

  14. Mucosal versus muscle pain sensitivity in provoked vestibulodynia

    Witzeman K


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

  15. Anisodamine augments mucosal blood flow during gut ischemia/reperfusion

    Hu Sen; Sheng Zhiyong


    Objective: To determine if anisodamine is able to augment mucosal perfusion during gut ischemia-reperfusion (I/R). Methods: A jejunal sac was formed in Sprague Dawley rat. A Laser Doppler probe and a tonometer were inserted into the sac which was filled with saline. The superior mesenteric artery was occluded (SMAO) for 60minutes followed by 90 minutes of reperfusion. At the end of 60 minutes of SMAO, either 0.2mg/kg of anisodmine or dobutamine was injected into the jejunal sac. Laser Doppler mucosal blood flow and regional PCO2 (PrCO2) measurements were made. Results: Mucosal blood flow was significantly increased at 30,60 and 90 minutes of reperfusion (R30, R60, R90 ) when intraluminal anisodamine or dobutamine was introduced compared to intraluminal saline only (44±3.3)% or (48±4.1)% vs. (37±2.6) % at R30, (57±5.0)% or (56±4.7)% vs. (45±2.7)% at R60, (64±3.3) % or (56 ± 4.2) % vs. (48 ± 3.4) % at R90 , respectively P<0.05). Blood flow changes were also reflected by lowering of jejunal PrCO2 measurements after intraluminal anisodamine or dobutamine compared with that of the saline controls (41±3. 1)mmHg or (44±3.0)mmHg vs. (49±3.7) mmHg at R30 , (38±3.7)mmHg or (40±2. 1)mmHg vs. (47±3.8) mmHgat R60, (34±2.1) mmHg or (39± 3.0) mmHg vs. (46±3.4) mmHg at R90, respectively,P<0. 05). The most interesting finding was that there were significantly higher mucosal blood flow and lower jejunal PrCO2 in anisodamine group than those in dobutamine group at 90 minutes of reperfusion (64± 3.3) %vs. (56±4.2)% for blood flow or (34 ± 2.1)mmHg vs. (39 ± 3.0)mmHg for PrCO2, respectively, P<0.05),suggesting that anisodamine had more lasting effect on mucosal perfusion than dobutamine. Conclusions:Intraluminal anisodamine can augment mucosal blood flow during gut I/R, and it may provide the protective effect on gut from ischemia and reperfusion injury.

  16. Acute pancreatitis

    Bo-Guang Fan


    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  17. Acute pancreatitis

    Bo-Guang Fan


    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  18. [Physiological importance of calpains in gastric mucosal defense].

    Hata, Shoji; Sorimachi, Hiroyuki


    The continuous and/or improper ingestion of irritants, including alcohol, NSAIDs, and Helicobacter pylori, often leads to serious gastropathies, affecting a wide range of people. A complex gastric defense system works to protect against these threats, for example by secreting mucus. Recently, by analysis of gene targeting mice for two gastrointestinal-tract-specific calpains, calpain-8 and calpain-9, we have demonstrated that they are cooperatively involved in the mucosal defense against stress-induced gastropathies. Calpains-8 and -9 are members of Ca2+ -dependent intracellular proteases comprising a superfamily in almost all eukaryotes, and form a functional complex, "G-calpain", expressed specifically in the mucus-producing cells. In this review, we show our recent results on calpains -8 and -9, and discuss gastric mucosal defense mechanisms involving them.

  19. Induction of allergen-specific tolerance via mucosal routes.

    Mascarell, Laurent; Zimmer, Aline; Van Overtvelt, Laurence; Tourdot, Sophie; Moingeon, Philippe


    Allergen-specific immunotherapy is the only curative treatment of allergies against insect venom, house dust mites, tree/grass pollens, or cat dander. Subcutaneous immunotherapy is successful to reorient the immune system and re-establish long-term tolerance. However, major drawbacks for using this route include: repeated injections, as well as the risk of anaphylaxis. In this context, alternative mucosal routes of administration are being considered together with the combined use of adjuvants/vector systems and recombinant allergens or peptide fragments. Herein, we review the current status in the use of mucosal routes (i.e., sublingual, oral, intranasal) for allergen-specific immunotherapy, as well as the latest understanding with respect to underlying mechanisms of action.

  20. Novel ways for immune intervention in immunotherapy: mucosal allergy vaccines.

    Mascarell, Laurent; Van Overtvelt, Laurence; Moingeon, Philippe


    Allergen-specific immunotherapy is currently the only curative treatment for allergy. Subcutaneous immunotherapy (SCIT) has been successfully used to treat patients who are allergic to insect venom, house dust mites, or tree or grass pollens. In the context of potentially severe, albeit infrequent, side effects associated with SCIT, mucosal routes of administration are being investigated to conduct allergenic desensitization. This article reviews recent developments in the field of nasal, oral, and sublingual immunotherapy as they relate to safety, clinical efficacy, and immune mechanisms of action. Implications for the design and development of improved allergy vaccines that could be used through such nonparenteral routes are discussed. Specifically, allergen presentation platforms and adjuvants facilitating the targeting of immune cells at mucosal surfaces to promote tolerance induction are reviewed.

  1. Development of Mucosal Vaccines Based on Lactic Acid Bacteria

    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.

  2. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng


    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

  3. Effects of zinc acexamate on gastric mucosal resistance factors.

    Esplugues, J V; Bulbena, O; Escolar, G; Martí-Bonmatí, E; Esplugues, J


    The effects of zinc acexamate on gastric defensive systems were evaluated in the rat. Gastric ulcers induced by oral administration of three necrotic agents (0.6 N HCl, 25% NaCl, 100% ethanol) were markedly reduced by different pretreatments with zinc acexamate. This cytoprotective effect was not modified by previous treatment with indomethacin (30 mg/kg orally). Zinc acexamate pretreatment also prevents the disruption of the gastric mucosal barrier induced by aspirin (40 mM) and increases mucus production in the gastric glands and tracheal walls. These observations suggest that the antiulcer effects described for zinc salts could be the result, at least partly, of an action increasing gastric mucosal defensive systems.

  4. Mucosal immunity in the female genital tract, HIV/AIDS.

    Reis Machado, Juliana; da Silva, Marcos Vinícius; Cavellani, Camila Lourencini; dos Reis, Marlene Antônia; Monteiro, Maria Luiza Gonçalves dos Reis; Teixeira, Vicente de Paula Antunes; Miranda Corrêa, Rosana Rosa


    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.

  5. Mucosal Immunity in the Female Genital Tract, HIV/AIDS

    Juliana Reis Machado


    Full Text Available 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.

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

    Koshio, Shunsuke


    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.

  7. Isoniazid Induced Lupus Presenting as Oral Mucosal Ulcers with Pancytopenia

    Shah, Ria; Ankale, Padmaraj; Sinha, Kanishk; Iyer, Aparna; Jayalakshmi, T. K.


    Drug Induced Lupus Erythematous (DILE) is a rare adverse reaction to a large variety of drugs including Isoniazid (INH), with features resembling idiopathic Systemic Lupus Erythematosus (SLE). Diagnosis require identification of a temporal relationship between drug administered and symptom. It is an idiosyncratic reaction, with no pre-existing lupus. Our case highlights a rare presentation of isoniazid induced lupus with profound pancytopenia and mucosal ulcers, thus posing a diagnostic chall...

  8. Intestinal epithelial cells and their role in innate mucosal immunity

    Maldonado-Contreras, A. L.; McCormick, Beth A


    The mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts are covered by a layer of epithelial cells that are responsible for sensing and promoting a host immune response in order to establish the limits not only for commensal microorganisms but also for foreign organisms or particles. This is a remarkable task as the human body represents a composite of about 10 trillion human-self cells plus non-self cells from autochthonous or indigenous microbes that outnumber human ...

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

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


    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate...

  10. [Changes of rat gastric mucosal barrier under stress conditions].

    Zhan, Xianbao; Li, Zhaoshen; Cui, Zhongmin; Duan, Yimin; Nie, Shinan; Liu, Jing; Xu, Guoming


    OBJECTIVE To explore the changes of rat gastric mucosal barrier under conditions of water immersion restraint stress. METHODS Eighty rats were randomly divided into Group A (20 rats), B (40 rats) and C (20 rats) after being fasted for 24 hours. And then Group A was divided into two subgroups with ten rats in each. The two subgroups in Group A were given normal saline or omeprazole respectively while under the stress condition. The changes of gastric acid or bicarbonate secretion were determined. Group B (40 rats) were randomly divided into four subgroups,which were subgroup control, 1h, 2h and 4h after beginning of the stress. The quantity of glandular mucosal adherent mucus, the thickness of mucus gel layer and ulcer index were measured after stress in Group B. The glandular mucosal samples were labeled by Lanthanum and observed by transmission electromicroscopy. Group C was randomly divided into two subgroups in the same way with Group A. And each subgroup received normal saline or omeprazole respectively H(+) loss in gastric lumen was calculated by determining the difference of acidity between lavage and drainage fluid H(+) concentration. RESULTS It was found that gastric alkaline secretion decreased progressively (P omeprazole subgroup, the amount of H(+) loss (micromol) was 7.46 +/- 1.22, 4.56 +/- 0.35, 3.11 +/- 0.81, 2.32 +/- 1.42 and 2.13 +/- 1.60, which decreased progressively, however still higher than those in normal saline subgroup (P "bicarbonate secretion is inhibited; gastric barrier is damaged; and hydrogen permeability through gastric mucosal barrier increases under stress conditions.

  11. What interactions drive the salivary mucosal pellicle formation?

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


    The bound salivary pellicle is essential for protection of both the enamel and mucosa in the oral cavity. The enamel pellicle formation is well characterised, however the mucosal pellicle proteins have only recently been clarified and what drives their formation is still unclear. The aim of this study was to examine the salivary pellicle on particles with different surface properties (hydrophobic or hydrophilic with a positive or negative charge), to determine a suitable model to mimic the mu...

  12. NRAS and BRAF mutation frequency in primary oral mucosal melanoma

    Buery, R. R.; Siar, C. H.; Katase, N; Gunduz, M; Lefeuvre, M.; Fujii, M.; Inoue, M.; Setsu, K.; Nagatsuka, H


    Oral mucosal melanoma (OMM) is a fatal sarcoma of unknown etiology. Histological morphology and genetic events are distinct from those of its cutaneous counterpart. Mutation and up-regulation of c-kit has been identified in OMM which may activate downstream molecules such as RAS and RAF. These molecules are involved in the mitogen-activated protein kinase (MAPK) pathway leading to tremendous cell proliferation and survival. NRAS and BRAF mutation and protein expression have been studied in ot...

  13. Mucosal Kaposi sarcoma, a Rare Cancer Network study

    Robert C. Miller


    Full Text Available Kaposi’s sarcoma (KS most often affect the skin but occasionally affect the mucosa of different anatomic sites. The management of mucosal KS is seldom described in the literature. Data from 15 eligible patients with mucosal KS treated between 1994 and 2008 in five institutions within three countries of the Rare Cancer Network group were collected. The inclusion criteria were as follows: age >16 years, confirmed pathological diagnosis, mucosal stages I and II, and a minimum of 6 months’ follow-up after treatment. Head and neck sites were the most common (66%. Eleven cases were HIV-positive. CD4 counts correlated with disease stage. Twelve patients had biopsy only while three patients underwent local resection. Radiotherapy (RT was delivered whatever their CD4 status was. Median total radiation dose was 16.2 Gy (0-45 delivered in median 17 days (0-40 with four patients receiving no RT. Six patients underwent chemotherapy and received from 1 to 11 cycles of various regimens namely vinblastin, caelyx, bleomycine, or interferon, whatever their CD4 counts was. Five-year disease free survival were 81.6% and 75.0% in patients undergoing RT or not, respectively. Median survival was 66.9 months. Radiation-induced toxicity was at worse grade 1-2 and was manageable whatever patients’ HIV status. This small series of mucosal KSs revealed that relatively low-dose RT is overall safe and efficient in HIV-positive and negative patients. Since there are distant relapses either in multicentric cutaneous or visceral forms in head and neck cases, the role of systemic treatments may be worth investigations in addition to RT of localized disease. Surgery may be used for symptomatic lesions, with caution given the risk of bleeding.

  14. Smoking and the pathogenesis of gastroduodenal ulcer--recent mechanistic update.

    Maity, Pallab; Biswas, Kaushik; Roy, Somenath; Banerjee, Ranajit K; Bandyopadhyay, Uday


    Peptic ulcer is a common disorder of gastrointestinal system and its pathogenesis is multifactorial, where smoking and nicotine have significant adverse effects. Smoking and chronic nicotine treatment stimulate basal acid output which is more pronounced in the smokers having duodenal ulcer. This increased gastric acid secretion is mediated through the stimulation of H2-receptor by histamine released after mast cell degranulation and due to the increase of the functional parietal cell volume or secretory capacity in smokers. Smoking and nicotine stimulate pepsinogen secretion also by increasing chief cell number or with an enhancement of their secretory capacity. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking also increases bile salt reflux rate and gastric bile salt concentration thereby increasing duodenogastric reflux that raises the risk of gastric ulcer in smokers. Smoking and nicotine not only induce ulceration, but they also potentiate ulceration caused by H. pylori, alcohol, nonsteroidal anti-inflammatory drugs or cold restrain stress. Polymorphonuclear neutrophils (PMN) play an important role in ulcerogenesis through oxidative damage of the mucosa by increasing the generation of reactive oxygen intermediates (ROI), which is potentiated by nicotine and smoking. Nicotine by a cAMP-protein kinase A signaling system elevates the endogenous vasopressin level, which plays an aggressive role in the development of gastroduodenal lesions. Smoking increases production of platelet activating factor (PAF) and endothelin, which are potent gastric ulcerogens. Cigarette smoking and nicotine reduce the level of circulating epidermal growth factor (EGF) and decrease the secretion of EGF from the salivary gland, which are necessary for gastric mucosal cell renewal. Nicotine also decreases prostaglandin generation in the gastric mucosa of smokers, thereby making the mucosa susceptible to

  15. JAM-related proteins in mucosal homeostasis and inflammation.

    Luissint, Anny-Claude; Nusrat, Asma; Parkos, Charles A


    Mucosal surfaces are lined by epithelial cells that form a physical barrier protecting the body against external noxious substances and pathogens. At a molecular level, the mucosal barrier is regulated by tight junctions (TJs) that seal the paracellular space between adjacent epithelial cells. Transmembrane proteins within TJs include junctional adhesion molecules (JAMs) that belong to the cortical thymocyte marker for Xenopus family of proteins. JAM family encompasses three classical members (JAM-A, JAM-B, and JAM-C) and related molecules including JAM4, JAM-like protein, Coxsackie and adenovirus receptor (CAR), CAR-like membrane protein and endothelial cell-selective adhesion molecule. JAMs have multiple functions that include regulation of endothelial and epithelial paracellular permeability, leukocyte recruitment during inflammation, angiogenesis, cell migration, and proliferation. In this review, we summarize the current knowledge regarding the roles of the JAM family members in the regulation of mucosal homeostasis and leukocyte trafficking with a particular emphasis on barrier function and its perturbation during pathological inflammation.

  16. Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

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


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

  17. Cancer patients with oral mucositis: challenges for nursing care

    Sarah Nilkece Mesquita Araújo


    Full Text Available 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.

  18. Subversion of mucosal barrier polarity by Pseudomonas aeruginosa

    Joanne eEngel


    Full Text Available The lumenal surfaces of human body are lined by a monolayer of epithelia that together with mucus secreting cells and specialized immune cells form the mucosal barrier. This barrier is one of the most fundamental components of the innate immune system, protecting organisms from the vast environmental microbiota. The mucosal epithelium is comprised of polarized epithelial cells with distinct apical and basolateral surfaces that are defined by unique set of protein and lipid composition and are separated by tight junctions. The apical surface serves as a barrier to the outside world and is specialized for the exchange of materials with the lumen. The basolateral surface is adapted for interaction with other cells and for exchange with the bloodstream. A wide network of proteins and lipids regulates the formation and maintenance of the epithelium polarity. Many human pathogens have evolved virulence mechanisms that target this network and interfere with epithelial polarity to enhance binding to the apical surface, enter into cells, and/or cross the mucosal barrier. This review highlights recent advances in our understanding of how Pseudomonas aeruginosa, an important opportunistic human pathogen that preferentially infects damaged epithelial tissues, exploits the epithelial cell polarization machinery to enhance infection.

  19. Cell-associated HIV mucosal transmission: the neglected pathway.

    Anderson, Deborah J; Le Grand, Roger


    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.

  20. Role of mucosal dendritic cells in inflammatory bowel disease

    Jan Hendrik Niess


    The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents.These local immune responses require a tight control,the outcome of which is in most cases the induction of tolerance.Local T cell immunity is an important compartment of the specific intestinal immune system.T cell reactivity is programmed during the initial stage of its activation by professional presenting cells.Mucosal dendritic cells(DCs)are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment.Mucosal DCs are a heterogeneous population that can either initiate(innate and adaptive)immune responses,or control intestinal inflammation and maintain tolerance.Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease(IBD),Crohn's disease(CD)and ulcerative colitis(UC).This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.(C)2008 The WJG Press.All rights reserved.

  1. Altered faecal and mucosal microbial composition in post-infectious irritable bowel syndrome patients correlates with mucosal lymphocyte phenotypes and psychological distress

    Sundin, J.; Rangel, I.; Fuentes Enriquez de Salamanca, Susana; Heikamp-De Jong, I.; Hultgren-Hörnquist, E.; Vos, De W.M.; Brummer, R.J.


    Background A subset of irritable bowel syndrome (IBS) patients, denoted post-infectious IBS (PI-IBS), develop symptoms after an enteric infection. Bacterial dysbiosis and mucosal inflammation have been proposed to be involved in the pathophysiology of this entity. Aim To characterise the mucosal

  2. Acute radiation proctitis. A clinical, histopathological and histochemical study

    Hovdenak, Nils


    The aim of the study is: 1) A sequential description of the clinical course of acute radiation proctitis during pelvic RT. 2) A sequential description of the rectal mucosal histopathology during pelvic RT as a possible substrate for clinical toxicity. 3) To assess the mucosal protease activity during RT as a possible explanation of the observed tissue changes. 4) To assess the efficacy of prophylactic sucralfate in acute radiation proctitis a randomised study was initiated and carried out together with a meta-analysis of previously available data. 5) Most studies on clinical acute toxicity in pelvic RT use either the RTOG/EORTC score system or focus on diarrhoea/stool frequency. A more differentiated and sensitive recording was developed and tested to pick up symptoms escaping the commonly used scores. 6) Study the relation between histopathological findings and the clinical picture. 4 papers presenting various studies are included. The titles are: 1) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. 2) Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer. 3) Profiles and time course of acute radiation toxicity symptoms during conformal radiotherapy for cancer of the prostate. 4) Sucralfate does not ameliorate acute radiation proctitis. Some future prospects are discussed.

  3. An overview of challenges limiting the design of protective mucosal vaccines for finfish

    Hetron Mweemba Munang'andu


    Full Text Available 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.

  4. Salivary MUC5B-mediated adherence (ex vivo) of Heliocobacter pylori during acute stress.

    J.A. Bosch; E.J.C. de Geus; T.J.M. Ligtenberg; K. Nazmi; E.C.I. Veerman; J. Hoogstraten; A.V. Amerongen Nieuwland


    Biochemical host defenses at mucosal sites, such as the oral cavity, play a key role in the regulation of microbial ecology and the prevention of infectious disease. This study investigated the effects of acute stress on the salivary levels of the carbohydrate structure sulfo-Lewis-super(a ) (SL), w

  5. Advances in research of mucosal immunity and mucosal vaccines%黏膜免疫和黏膜疫苗研究进展



    Mucosal immunity covers a variety of mucosal surfaces susceptible to different pathogens.This review explores the basic principles of mucosal immunity in light of the diversity of mucosal surfaces and their unique tissue environments,and offers some thoughts on approaches for developing vaccines to induce mucosal immunity,predominantly based on experiments studying immune responses to infection and vaccination in large animals.%黏膜免疫包括各种对不同病原体易感的黏膜表面.此文根据黏膜表面的多样性及其独特的组织环境探索黏膜免疫的基本原理,并基于大动物对感染和疫苗接种的免疫应答的实验研究,为研制诱导黏膜免疫的疫苗提供一些思路.

  6. Contemporary Management of Acute Biliary Pancreatitis

    Orhan Ozkan


    Full Text Available Acute biliary pancreatitis is one of the major causes of acute pancreatitis.Gallstones, biliary sludge and microlithiasis, especially in pancreatitis without detectable reason, can be the cause of acute pancreatitis. Acute biliary pancreatitis has many controversions in the literature, and its classification and guidelines are being updated very frequently. Atlanta classifications which determine the definitions and guidelines about acute pancreatitis were renewed and published in 2013. It has various clinical aspects, ranging from a mild form which is easily treated, to a severe form that causes complications leading to mortality. The pathogenesis of this disease has not been fully elucidated and several theories have been suggested. New scoring systems and laboratory methods such as proteomics have been suggested for both diagnosis and to predict disease severity, and research on these topics is still in progress. Novel therapeutic approaches with technological developments such as ERCP, ES, MRCP, and EUS are also suggested.

  7. 儿茶素对重症急性胰腺炎大鼠肠黏膜屏障功能的保护作用%Protective effect of epigallocatechin-3-gallate in the intestinal mucosal barrier injury of severe acute pancreatitis in rats

    林英卓; 黄文青; 杜荣国


    Objective The study was designed to investigate the intestinal mucosa barrier function changes in rats with severe acute pancreatitis (SAP),and the intervention effect of epigallocatechin-3-gallate(EGCG) injection and its mechanisms of protection on intestinal mucosa barrier function injury of SAP with the purpose of providing evidence for preventing and curing intestinal mucosa barrier function injury of SAP in clinical practice.Methods A total of 80 healthy male Sprauge-Dawley (SD) rats were randomly divided into a normal group (Normal),a sham-operation group (Sham),a SAP model group (Model),and a EGCG treated group (EGCG),with 24 rats (except 8 rats in the normal group) in each group.The latter three groups each had three subgroups at three time points:6,12,24hours.Rats with SAP were prepared with retrograde cholangiopancreatic duct infusion in 5% sodium taurocholate.The dynamic changes of the indexes of intestinal mucosa barrier function injury and Pancreas injury were observed at various time points in each group,including the levels of Plasma diamine oxidase (DAO) and serum amylase and malondialdehyde (MDA),nitric oxide(NO),inducible nitric oxide synthase(iNOS)in gut.Results 1.The levels of serum amylase [(3158.64 ± 218.25)μ/L,(4277.24 ± 231.35)μ/L,(5842.76 ± 248.18)μ/L] and plasma DAO concentration [(4.23 ± 0.51) μ/L,(5.13 ± 0.32)μ/L,(7.83 ± 0.76) μ/L] in the Model group were significantly higher at 6 h,12 h,24 h postoperation than the Normal group[serum amylase:(2074.11 ± 101.56)μ/L,DAO:(2.32 ± 0.48) μ/L] and Sham group [serum amylase:(1885.27 ± 103.89) μ/L,(1778.57 ± 98.94) μ/L,(1935.24 ± 105.87) μ/L].The levels of serum amylase [(2576.70 ± 123.43) μ/L,(2783.77 ± 155.53) μ/L,(2902.32 ±176.25) μ/L] and plasma DAO concentration (3.59 ± 0.57) μ/L,(3.98 ± 0.67) μ/L,(6.44 ± 0.71) μ/L in the EGCG group were lower than the Model group,but higher than the Normal group and the Sham group.Compared with the Normal group and the

  8. Trichomonas vaginalis Pathogenesis: a Narrative Review

    Zahra Arab-Mazar


    Full Text Available In the latest articles which were published during 2013-2014, Trichomonas vaginalis (T. vaginalis was mentioned as a neglected sexual transmission disease (STD, while the exact mechanism of its pathogenesis has not been cleared yet. Although trichomonasiasis is easy curable, there is concern that resistance to drug are increasing. This common infection as concerning the important public health implications needs more research to be done for understanding the diagnosis, treatment, immunology and pathogenesis. In this review we searched all valuable and relevant information considering the pathogenesis of T. vaginalis. We referred to the information databases of Medline, PubMed, Scopus and Google scholar. The used keywords were the combinations of T. vaginalis and words associated with pathogenicity. This review discusses the host-parasite interaction and pathogenicity of this parasite.

  9. Pathogenesis of Alzheimer′s disease

    Russell H Swerdlow


    Full Text Available Russell H SwerdlowDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USAAbstract: Alzheimer’s disease (AD is incredibly common. Increasing longevity ensures its prevalence will rise even further. Ongoing efforts to understand AD pathogenesis reveal numerous tantalizing leads. Formulating a comprehensive AD pathogenesis theory capable of incorporating these disparate leads, though, has proven difficult. This review discusses current attempts to formulate a comprehensive AD pathogenesis theory. In doing so, it focuses on clinical and molecular relationships between AD and aging. A better understanding of these relationships could inform and impact future development of AD-directed treatment strategies.Keywords: Alzheimer’s disease, aging, amyloid, cascade, mitochondria

  10. Role of Thr399Ile and Asp299Gly polymorphisms of toll-like receptor-4 gene in acute dental abscess

    Miri-Moghaddam, Ebrahim; Baghaee, Elnaz; Bazi, Ali; Garme, Yasaman


    Background Apical Periodontitis (AP) is an inflammatory disease that affects the tissues surrounding the root end of a tooth. The disease which is caused by endodontic infections presents in different clinical ways including development of an acute abscess. Recent studies have provided information suggesting role of a multitude of factors in pathogenesis of acute apical abscess (AAA). In this case-control study, our goal was to evaluate the frequency and potential role of two common polymorphisms of toll like receptor-4 (TLR-4) gene; Thr399Ile (1196 C>T) and Asp299Gly (+896 A>G), in 50 patients with AAA as cases and 50 patients with asymptomatic apical periodontitis (AAP) as controls. Material and Methods Saliva sample containing mucosal epithelial cells was used for DNA extraction. Polymorphisms were detected by Tetra-ARMS (Amplification Refractory Mutation System) PCR method. Statistical analyses were carried out in SPSS 21 software. Results Homozygous wild type (CC) and heterozygous (CT) genotypes of Thr399Ile polymorphism were detected in 84% and 16% of AAA patients respectively. In controls, respective ratios were 94% (CC) and 6% (CT). Observed difference was not statistically significant (P>0.05) for distribution of these genotypes. The mutant homozygous (TT) genotype of this polymorphism was identified in neither of the participants. Overall, T allele frequency was obtained 8% in AAA and 3% in AAP (OR=2.6, 95% CI; 0. 6-10.6, p>0.05). For Asp299Gly polymorphism, no individual was detected with the mutant allele in case or control groups. Conclusions Our results indicated a possible role for Thr399Ile polymorphism in acute presentations of abscess in AAA. However, the impact of this polymorphism needs to be more assessed in future studies. Key words:Genetic polymorphism, periapical abscess, periapical periodontitis, toll-like receptor 4. PMID:28210435

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

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


    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

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

    Iza Farhana Ismail


    Full Text Available 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.

  13. Evidence for the involvement of infectious agents in the pathogenesis of Crohn's disease


    Many advances have been made in the understanding of Crohn's disease (CD) pathogenesis during the last decade.CD is currently seen as a predominantly T-lymphocyte-driven disease characterized by the presence of a complex cocktail of interacting cytokines,chemokines and other mediators produced by a variety of cell types.Prevailing theories of CD pathogenesis suggest that patients' T-lymphocytes are inappropriately activated in the setting of an immune imbalance,which is itself caused by an unfortunate confluence of genetic and environmental factors.The T-cell response then leads to the chronic inflammation characteristic for the disease.Various environmental factors may play a role in the development of CD,but microbes are most consistently implied.This theory is based on epidemiological,clinicopathological,genetic and experimental evidence.Despite the abundance of arguments for the implication of bacteria in the aetiopathogenesis of CD,the precise role of bacteria in this disease still remains elusive.Three not necessarily mutually exclusive theories have been proposed:(1) an unidentified persistent pathogen;(2) an abnormally permeable mucosal barrier leading to excessive bacterial translocation;and (3) a breakdown in the balance between putative "protective" versus "harmful" intestinal bacteria ("dysbiosis").At present,one cannot exclude with certainty any of these three proposed hypotheses;they may all apply to CD to a certain extent.2008 WIG.All rights reserved.

  14. Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease.

    Tawfik, Ahmed; Flanagan, Paul K; Campbell, Barry J


    Multiple studies have demonstrated alterations in the intestinal microbial community (termed the microbiome) in Crohn's disease (CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosa-associated adherent, invasive Escherichia coli (E. coli) (AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili (FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold (M)-cells of the follicle-associated epithelium. Resistance to stress genes (htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn's pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.

  15. Progress in the pathogenesis of pterygium.

    Liu, Ting; Liu, Yangwuyue; Xie, Lin; He, Xiangge; Bai, Ji


    Pterygium is a type of benign uncontrolled growth of the conjunctive tissue that lays over the sclera. It can significantly alter visual function in advanced cases and become inflamed, leading to redness and irritation in the area. Although the exact etiology of pterygium remains uncertain, recent advances have provided important insight into the pathogenesis of pterygium. These studies indicate that tumor suppressor gene p53 and other genes associated with DNA repair, cell proliferation, migration and angiogenesis are critical for the development of pterygium. In addition, Human papillomavirus infection has been shown to be a risk factor in some populations. In this article, the current understanding of the pathogenesis of pterygium is reviewed.

  16. Protein misfolding disorders: pathogenesis and intervention

    Gregersen, Niels


    proteins, the living cell contains a large number of intracellular proteases, e.g. the proteasome, which together with the chaperones comprise the cellular protein quality control systems. Many inherited disorders due to amino acid substitutions exhibit loss-of-function pathogenesis because the aberrant...... be accompanied by a gain-of-function pathogenesis, which in many cases determines the pathological and clinical features. Examples are Parkinson and Huntington diseases. Although a number of strategies have been tried to decrease the amounts of accumulated and aggregated proteins, a likely future strategy seems...

  17. Hepatic encephalopathy: etiology, pathogenesis, and clinical signs.

    Salgado, Melissa; Cortes, Yonaira


    Hepatic encephalopathy (HE) is a manifestation of clinical signs that may result from a variety of liver diseases. In small animals, HE is most commonly a result of portosystemic shunting. The pathogenesis is not completely understood, although it is likely multifactorial. Theories of pathogenesis include altered ammonia metabolism and glutamine and glutamate transmission, an increase in gamma-aminobutyric acid agonists and benzodiazepine-like substances, alterations of the serotonergic system and amino acid metabolism, elevated taurine levels, contributions from inflammatory mediators, and toxic effects of manganese. An understanding of the underlying mechanisms that result in HE may lead to new treatments in the future.

  18. The role of EBV in MS pathogenesis

    Christensen, Tove


    Environmental factors operate on a background of genetic susceptibility in the pathogenesis of MS. Human herpesviruses, notably Epstein-Barr virus (EBV), and human endogenous retroviruses are factors associated with MS. EBV association is found in epidemiological surveys where late EBV infection ....... EBV cannot stand alone as a causal factor of MS, but is likely to play an indirect role as an activator of the underlying disease process.......Environmental factors operate on a background of genetic susceptibility in the pathogenesis of MS. Human herpesviruses, notably Epstein-Barr virus (EBV), and human endogenous retroviruses are factors associated with MS. EBV association is found in epidemiological surveys where late EBV infection...

  19. Oral manifestations of acute leukaemia

    Ivanović Mirjana


    Full Text Available Acute leukaemia is the most common form of chilhood cancer. The aim of this paper was to underline the importance of oral manifestations in children with acute leukaemia. The disease and its treatment can directly or indirectly affect oral health. Oral manifestations are gingival inflammation and enlargement. Leukaemic cells are capable of infiltrating the gingiva and the deeper periodontal tissues which leads to ulceration and infection of oral tissues. Gingival bleeding is a common sign in patients with leukaemia. Symptoms include local lymphadenopathy, mucous membrane Petechiae and ecchymoses. Cytotoxic drugs have direct effects like mucositis, involving atrophy, desquamation and ulceration of the mucosa, with increasing the risk for local and systemic infections. Leukaemia can directly influence dental care and dental treatment, while oral lesions may have life-threatening consequences. Knowledge and skills among dentists may also not be adequate to treat children with acute leukaemia. It is therefore imperative that all stomatologists be aware of dental problems that occur in leukaemia in order to be able to effectively carry out appropriate measures to mitigate these problems.

  20. Acute cholecystitis

    Halpin, Valerie


    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the cystic duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  1. Acute intermittent porphyria.

    Herrick, Ariane L; McColl, Kenneth E L


    Acute intermittent porphyria (AIP) is characterised by neurovisceral crises the most common clinical presentation of which is abdominal pain. It is an autosomal dominant condition with incomplete penetrance and is potentially life-threatening. The key point in management is to suspect and confirm the diagnosis as early as possible in order to treat the attack and to avoid inappropriate treatments which may exacerbate the crisis. In this chapter we briefly outline the haem biosynthetic pathway and how deficiencies in individual enzymes give rise to the different porphyrias. We then describe the clinical features and diagnosis of AIP, followed by a discussion of pathogenesis, highlighting advances in the molecular biology of AIP and introducing the debate as to whether neurovisceral crises might result from porphyrin precursor neurotoxicity or from haem deficiency. Finally we discuss management, including family screening, avoidance of triggering factors, analgesia, maintenance of a high calorie intake, and administration of haem derivatives.

  2. Profiles and Time Course of Acute Radiation Toxicity Symptoms during Conformal Radiotherapy for Cancer of the Prostate

    Hovdenak, Nils; Karlsdottir, Aasa; Soerbye, Halfdan; Dahl, Olav [Univ. of Bergen (Norway). Div. of Gastroenterology


    Symptoms of gastrointestinal toxicity are dose-limiting for pelvic radiotherapy (RT). Existing toxicity registrations (RTOG/EORTC) are helpful in defining maximal tolerated doses, but tend to underestimate the total toxicity burden by excluding several minor complaints. We have applied a more detailed and quantitative recording of symptoms and related these scores to RT-induced endoscopic and histopathologic changes. Prevalence and severity of specific toxicity symptoms were recorded before, during (weeks 2 and 6) and 2 and 8 weeks after RT in 96 patients undergoing external beam RT for localized prostate cancer. RTOG/EORTC acute toxicity and ad hoc total toxicity scores (TTS) were recorded. TTS scores were calculated by adding scores based on visual analog scale (VAS) grading of individual symptoms. Fifty of the patients also underwent sequential proctoscopy with mucosal biopsy. Individual symptoms increased, but differed in prevalence and intensity during and after RT. TTS increased during the entire treatment course in spite of normalizing histopathologic and endoscopic changes from week 2 onwards. Twenty-seven patients had no RTOG/EORTC toxicity, four had grade 3 and none had grade 4 toxicity. All patients with grade 0 had increased TTS. Thus, TTS appeared more sensitive than RTOG/EORTC scoring. The study demonstrates that multiple toxicity symptoms contribute to total toxicity in response to pelvic RT. TTS is a feasible and sensitive method for detecting and quantifying acute toxicity and unveils morbidity which remains hidden with the RTOG/EORTC score system. The development and timing of symptoms may give clues to pathogenesis, treatment, and prophylaxis.

  3. Clinical features of the head and neck mucosal melanoma. А review

    A. V. Ignatova


    Full Text Available Melanoma is an aggressive and rare neoplasm of melanocytic origin. Mucosal melanomas of the head and neck account for 1 % of neoplasms, 0,2–8,0 4 % of all melanomas and over 50 % of all mucosal melanomas. To date, in Russian and foreign literature only few retrospective series and case reports have been reported on mucosal melanoma. Despite melanoma’s common histological origin, head and neck mucosal melanoma presentation has some specific features due to its anatomical localization and poor clinical outcomes compared with those of cutaneous melanomas. Mucosal melanoma has a high metastatic potential. Five-year overall survival does not exceed 30 %. Advances in understanding of the clinical presentation can be used for prediction of behaviour and prognosis of this disease. We considered and analised articles devoted to clinical features of head and neck mucosal melanoma according to its localization.

  4. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P


    of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus......-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral...

  5. Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model

    Chun-Yan Yeung; Wai-Tao Chan; Chun-Bin Jiang; Mei-Lien Cheng; Chia-Yuan Liu; Szu-Wen Chang; Jen-Shiu Chiang Chiau; Hung-Chang Lee


    Background and Aims Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model. Methods Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orall...

  6. Osteonecrosis. Part 1. Risk factors and pathogenesis

    Ekaterina Valeriyevna Ilyinykh


    Full Text Available The paper considers different risk factors for osteonecrosis (ON and some aspects of its pathogenesis: impairments in the differentiation of stromal cells, the vascular provision of intraand extravasal genesis, the quality of proper bone tissue due to generalized or local osteoporosis, intravascular coagulation factors contributing to microthrombogenesis. The basic types of ON are identified.

  7. Catamenial migraine: epidemiology, pathogenesis, diagnosis, clinical features

    S A Gromova


    Full Text Available Based on a review of the literature, the authors consider the pathogenesis, diagnosis, epidemiology, and clinical features of catamenial migraine. The view that catamenial migraine attacks are severest receives more and more support. The criteria that may be used to predict a severer course of catamenial migraine attacks in a specific patient are to be further defined.

  8. Insights in the pathogenesis of Dobermann hepatitis

    Mandigers, Paulus Justinus Johannes


    The pathogenesis of Dobermann hepatitis has been under debate for several years. In this thesis two hypotheses were formulated and discussed. Hypothesis 1: In Dobermann dogs exists an autosomal genetic error in metabolism that leads to an abnormal copper metabolism which results in an increased he

  9. [Purulent corneal ulcers: etiology, pathogenesis, classification].

    Kasparova, Evg A


    Advanced purulent corneal ulcer, as well as abscess, is a serious vision-threatening condition notable for its fulminant course and possible loss of the eye due to endophthalmitis. Its leading causes, pathogenesis, and classifications are described and analyzed in this paper.

  10. Infantile Haemangioma: Pathogenesis, Evaluation, and Therapy

    S.R. Janmohamed (Sherief)


    markdownabstract__Abstract__ This thesis contains of: 1) Studies describing the pathogenesis of infantile haemangioma 2) The development of a novel scoring system for infantile haemangioma activity 3) Studies evaluating different therapy options for infantile haemangioma Hypoxia is important in th

  11. Frontoethmoidal encephaloceles, a study of their pathogenesis

    Hoving, Eelco; Vermeij-Keers, C


    A prospective clinical study of 30 patients with frontoethmoidal encephaloceles was performed in order to find support for a proposed theory concerning its pathogenesis, based on a previously performed embryological study and relevant findings in the literature. According to this proposed theory the

  12. Psoriasis: Pathogenesis, Assessment, and Therapeutic Update.

    Schleicher, Stephen M


    Psoriasis is a chronic condition that affects more than 7 million Americans. This article explores the pathogenesis and physical signs of psoriasis. Over the past 2 decades enhanced understanding of the immunologic basis of psoriasis has led to the development of new systemic agents that have revolutionized the management of this disease, and these modalities, along with traditional therapies, are described.

  13. Etiology and pathogenesis of adolescent idiopathic scoliosis

    Schlösser, Tom P C; Colo, Dino; Castelein, RM


    Despite many years of dedicated research into the etio-pathogenesis, not one single cause for adolescent idiopathic scoliosis has been identified. The purpose of this review is to give a comprehensive overview of the current evidence and main etiological theories. Intrinsic causal mechanisms are fou

  14. Pathogenesis of bovine spongiform encephalopathy in sheep

    Keulen, van L.J.M.; Vromans, M.E.W.; Dolstra, C.H.; Bossers, A.; Zijderveld, van F.G.


    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was dete

  15. Treatment modalities of oral mucositis after radiation of head and neck cancers; Prise en charge des mucites apres radiotherapie des cancers des voies aerodigestives superieures

    Lapeyre, M.; Charra-Brunaud, C.; Kaminsky, M.C.; Geoffrois, L.; Dolivet, G.; Pourel, N.; Marchal, C.; Bey, P.; Maire, F.; Simon, M. [Centre Alexis-Vautrin, 54 - Vandoeuvre-les-Nancy (France); Toussaint, B. [Hopital Central, Service de Chirurgie ORL, 54 - Nancy (France)


    Acute mucositis is common after radiotherapy for head and neck cancers. During the past 3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. At the present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxidants, Benzydamine hydrochloride), while others seem promising (Povidone-iodine, nonabsorbable antibiotic lozenges and anti-fungal, local GM-CSF, Glutamide, Low-energy laser, corticosteroids). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or anti-fungal topical (bicarbonates, Amphotericine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal sparing block, conformal radiotherapy and intensity modulated radiation therapy). (authors)

  16. [Lymphotropic therapy for acute purulent odontogenic jaw periostitis].

    Maĭborodin, I V; Lĭubarskiĭ, M S; Loĭko, E R; Sheplev, B V


    The structure of the gingival mucosa was studied by optic microscopy in patients with acute purulent odontogenic maxillary periostitis treated traditionally and receiving lymphotropic therapy. Lymphotropic administration of the antibiotic during 2 days resulted in less pronounced dilatation of the interstitial spaces and lymph vessels adjacent to the molars and higher counts of lymphocytes, monocytes, and macrophages. This indicated high efficiency of lymphotropic therapy of acute purulent maxillary periostitis for molars. Microcirculation parameters and tissue leukocyte cytogram in gingival mucosal tissue adjacent to the canines and premolars differed negligibly in patients treated by different methods.

  17. Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis.

    Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano


    Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5(-/-) mice or adoptive transfer of splenic naïve CD4(+) T-cells from wild type or CCR5(-/-) mice into RAG-1(-/-). CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4(+) and CD11b(+) leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs.

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

    Sujatha S Reddy


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

  19. Chemokines and chemokine receptors in HIV infection: Role in pathogenesis and therapeutics

    Suresh P


    Full Text Available Chemokines are known to function as regulatory molecules in leukocyte maturation, traffic, homing of lymphocytes and in the development of lymphoid tissues. Besides these functions in the immune system, certain chemokines and their receptors are involved in HIV pathogenesis. In order to infect a target cell, the HIV envelope glycoprotein gp120 has to interact with the cellular receptor CD-4 and co-receptor, CC or CXC chemokine receptors. Genetic findings have yielded major insights into the in vivo roles of individual co-receptors and their ligands in providing resistance to HIV infection. Mutations in chemokine receptor genes are associated with protection against HIV infections and also involved in delayed progression to AIDS in infected individuals. Blocking of chemokine receptors interrupts HIV infection in vitro and this offers new options for therapeutic strategies. Approaches have been made to study the CCR-5 inhibitors as antiviral therapies and possibly as components of a topical microbicide to prevent HIV-1 sexual transmission. Immune strategies aimed at generating anti-CCR-5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV- protective immunity. It also remains to be seen how these types of agents will act in synergy with existing HIV-1 targeted anti viral, or those currently in developments. Beyond providing new perspectives in fundamental aspects of the HIV-1 transmission and pathogenesis, chemokines and their receptors suggest new areas for developing novel therapeutic and preventive strategies against HIV infections. Studies in this review were identified through a search for relevant literature in the pubmed database of the national library of medicine. In this review, some developments in chemokine research with particular focus on their roles in HIV pathogenesis, resistance and therapeutic applications have been discussed.

  20. Contribution of Panton-Valentine leukocidin in community-associated methicillin-resistant Staphylococcus aureus pathogenesis.

    Binh An Diep

    Full Text Available Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA strains typically carry genes encoding Panton-Valentine leukocidin (PVL. We used wild-type parental and isogenic PVL-deletion (Delta pvl strains of USA300 (LAC and SF8300 and USA400 (MW2 to test whether PVL alters global gene regulatory networks and contributes to pathogenesis of bacteremia, a hallmark feature of invasive staphylococcal disease. Microarray and proteomic analyses revealed that PVL does not alter gene or protein expression, thereby demonstrating that any contribution of PVL to CA-MRSA pathogenesis is not mediated through interference of global gene regulatory networks. Inasmuch as a direct role for PVL in CA-MRSA pathogenesis remains to be determined, we developed a rabbit bacteremia model of CA-MRSA infection to evaluate the effects of PVL. Following experimental infection of rabbits, an animal species whose granulocytes are more sensitive to the effects of PVL compared with the mouse, we found a contribution of PVL to pathogenesis over the time course of bacteremia. At 24 and 48 hours post infection, PVL appears to play a modest, but measurable role in pathogenesis during the early stages of bacteremic seeding of the kidney, the target organ from which bacteria were not cleared. However, the early survival advantage of this USA300 strain conferred by PVL was lost by 72 hours post infection. These data are consistent with the clinical presentation of rapid-onset, fulminant infection that has been associated with PVL-positive CA-MRSA strains. Taken together, our data indicate a modest and transient positive effect of PVL in the acute phase of bacteremia, thereby providing evidence that PVL contributes to CA-MRSA pathogenesis.