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Sample records for acute mucosal pathogenesis

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

    Directory of Open Access Journals (Sweden)

    Egan Erin A

    2010-01-01

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

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

    OpenAIRE

    Kanter, Mehmet; Demir, Halit; Karakaya, Cengiz; Ozbek, Hanefi

    2005-01-01

    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 exper-imental model.

  3. Acute pancreatitis: Etiology and common pathogenesis

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

    Science.gov (United States)

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

    2013-02-01

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

  5. Pathogenesis of acute lung injury in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

    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.

  6. Pathogenesis of severe acute respiratory syndrome

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

    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.

  7. Oral mucositis in children suffering from acute lymphoblastic leukaemia

    OpenAIRE

    Pels, Elżbieta

    2012-01-01

    Aim of the study Oral mucositis is the most commonly reported side effect observed in neoplastic patients treated with chemotherapy and radiotherapy of the head and neck region as well as in patients who have received a haematopoietic stem cell transplant. The aim of the study was to assess the oral mucosa status in children with acute lymphoblastic leukaemia (ALL) during antineoplastic therapy. Material and methods The clinical examination included 78 children aged 2-18 with ALL. The clinica...

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

    Institute of Scientific and Technical Information of China (English)

    Zhao-chun Chi; Quan-jiang Dong; Chang-xin Geng

    2014-01-01

    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.

  9. MOLECULAR PATHOGENESIS OF SECONDARY ACUTE PROMYELOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Neil Osheroff

    2011-01-01

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    Balanced chromosomal translocations that generate chimeric oncoproteins are considered to be initiating lesions in the pathogenesis of acute myeloid leukemia. The most frequent is the t(15;17(q22;q21, which fuses the PML and RARA genes, giving rise to acute promyelocytic leukemia (APL. An increasing proportion of APL cases are therapy-related (t-APL, which develop following exposure to radiotherapy and/or chemotherapeutic agents that target DNA topoisomerase II (topoII, particularly mitoxantrone and epirubicin. To gain insights into molecular mechanisms underlying the formation of the t(15;17 we mapped the translocation breakpoints in a series of t-APLs, which revealed significant clustering according the nature of the drug exposure. Remarkably, in approximately half of t-APL cases arising following mitoxantrone treatment for breast carcinoma or multiple sclerosis, the chromosome 15 breakpoint fell within an 8-bp “hotspot” region in PML intron 6, which was confirmed to be a preferential site of topoII-mediated DNA cleavage induced by mitoxantrone.  Chromosome 15 breakpoints falling outside the “hotspot”, and the corresponding RARA breakpoints were also shown to be functional topoII cleavage sites. The observation that particular regions of the PML and RARA loci are susceptible to topoII-mediated DNA damage induced by epirubicin and mitoxantrone may underlie the propensity of these agents to cause APL.

     

  10. Depletion of mucosal substance P in acute otitis media

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Schmidt, Peter Thelin; Hermansson, Ann; Holst, Jens Juul; Thomsen, Jens

    2004-01-01

    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...... fiber release of SP. MATERIAL AND METHODS: To investigate possible release of SP in the middle ear mucosa during AOM, we used a well-established rat model of AOM caused by Streptococcus pneumoniae. Following tissue extraction on Days 1, 3 and 6 post-inoculation, the mucosal concentration of SP was...... measured using a radioimmunoassay. RESULTS: Compared to sham-inoculated control ears, the concentration of SP was significantly reduced on Day 1 and even further reduced on Day 3, whereas partial replenishment was found on Day 6. CONCLUSION: SP seems to be depleted in the rat middle ear mucosa in the...

  11. Pathogenesis and prognostication in acute lymphoblastic leukemia

    OpenAIRE

    Zuckerman, Tsila; Rowe, Jacob M.

    2014-01-01

    The process of lymphoid maturation is tightly controlled by the hierarchical activation of transcription factors and selection through functional signal transduction. Acute lymphoblastic leukemia (ALL) represents a group of B/T-precursor-stage lymphoid cell malignancies arising from genetic alterations that block lymphoid differentiation and drive aberrant cell proliferation and survival. With recent advances in next-generation sequencing, we are discovering new mutations affecting normal lym...

  12. Current concept of pathogenesis of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Xie Ning Wu

    2000-01-01

    @@ 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.

  13. Pathogenesis of pancreatic encephalopathy in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Xi-Ping Zhang; Hua Tian

    2007-01-01

    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.

  14. Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease.

    Science.gov (United States)

    Tugizov, Sharof

    2016-01-01

    Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

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

    DEFF Research Database (Denmark)

    Lindell, G; Bukhave, Klaus; Lilja, I; Madsen, J. Rask; Graffner, H

    1997-01-01

    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...

  16. Acute mucosal reactions in patients with advanced head and neck cancer treated with concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    We conducted a clinical study to analyze the acute reactions in the oral cavity and the oropharyngeal (OCOPH) mucosa in patients with advanced head and neck cancer (HNC) undergoing a definitive treatment consisted of 3-D conformal radiotherapy combined with concomitant chemotherapy. Twenty nine patients with HNC who were treated between February 2008 and October 2009 were included in the study. The median age was 55 years (range 29-70). The site distribution was as follows: oropharynx, 20.7%; hypopharynx, 41.4%; larynx, 37.9%. The radiation technique used for 3-D conformal radiotherapy was named 'oblique photon fields' technique. The OCOPH mucosa as a critical normal tissue was delineated in every patient. Extraction of planning target volume (PTV50) from the volume of OCOPH mucosa led to formation of an OCOPH mucosa with extracted PTV50 (OCOPHEx mucosa). Acute mucosal reactions were recorded using Radiation Therapy Oncology Group (RTOG) grading system. The duration of a maximum grade of reaction was also recorded. A time intensity parameter, so-called Severity-Time Units (STU), quantifying the area under the acute reaction curve, was used to express the intensity of mucositis over time in every patient. Grade 3 acute mucosal reaction was manifested in 19 patients (65.5%). The median duration of confluent mucositis was 21 days (range 14-35). The STU less than 1000 mm2 and the STU more than 1500 mm2 was calculated in equal number of patients (9 patients, or 31.0%). Statistically significant difference in the distribution of the grade 3 reaction was found among patients with different site of the primary tumor (p = 0.003). Statistically significant difference was found between the grade of the acute mucositis and the volume of OCOPHEx mucosa, the dose in 50% of the volume of OCOPHEx (D50%, OCOPHEx) mucosa, and the mean dose to OCOPHEx mucosa (p = 0.02, p = 0.0002, p = 0.00001, respectively). The tested relation between STU and delineated volumes (PTV50 and OCOPHEx

  17. Mucosal Immunity and acute viral gastroenteritis: The example rotavirus

    OpenAIRE

    Rose, Markus A

    2014-01-01

    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 2...

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

    International Nuclear Information System (INIS)

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

  19. Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease

    OpenAIRE

    Xu, Xiao-rong; Liu, Chang-Qin; Feng, Bai-Sui; Liu, Zhan-Ju

    2014-01-01

    Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals. Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD, involving a wide range of molecules including cytokines. On the other hand, besides...

  20. EFFECT OF HELICOBACTER PYLORI INFECTION ON ACUTE STRESS-RELATED GASTRIC MUCOSAL DAMAGE OF SERIOUSLY ILL PATIENTS

    Institute of Scientific and Technical Information of China (English)

    赵超; 肖文; 叶光福; 周建平; 周其璋

    2002-01-01

    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

  1. Treatment of radiation-induced acute oral mucositis in a rat model

    International Nuclear Information System (INIS)

    The stem cells of the epithelial lining of the oral mucosa are non-specifically affected by many anti-cancer agents including radiation. Radiation-induced mucositis of upper aerodigestive tract is a major dose-limiting factor in the treatment of head and neck tumours. A new non-toxic drug (Compound A) consisting of Curcumin, -tocopherol and sun flower oil (SFO) was developed and its efficacy was tested in the treatment of radiation-induced normal tissue lesions. Mature (12 weeks old; 200-225g) female Sprague-Dawley rats were used in compliance with the Animal (Scientific Procedures) Act 1986. While under anaesthesia the animals tongue was slightly extended outside and a region of the underside of the tongue was irradiated in-situ with single doses of 2.27 MeV -rays from a 5mm diameter 90Sr/90Y plaque. The dose-rate of the source was ∼10Gy/min at the surface of the mucus membrane. Irradiations and subsequent assessment of the lesion were carried out under general anesthesia maintained by a 1.5% Halothane, oxygen mixture. Four groups of 36 animals were irradiated with single doses of either 13.5, 15, 16.5 or 18 Gy. Following irradiation the animals in each dose group were subdivided into four treatment subgroups of 9 rats to receive 0.5 ml per day of either Compound A, SFO, -tocopherol or water by oral gavage until the end of experiments. Nine animals were used at each dose point in each treatment group. Mucosal ulceration (erosion of mucosal epithelium) was considered as an end-point and this is referred by radiation-induced mucositis in the context of present experiments. From the day after irradiation until any acute radiation-induced oral mucosal lesion had healed the animals tongue were assessed daily for the presence of radiation-induced mucositis (mucosal ulceration). Quantal data for the incidence of radiation-induced mucositis were analysed using logit analysis and dose modification factor (DMF) was obtained. There was a modest increase in the ED50 values

  2. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Anna Falanga

    2011-12-01

    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.

  3. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Laura Russo

    2011-01-01

    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.

  4. Protective Effects of the Traditional Herbal Formula Oryeongsan Water Extract on Ethanol-Induced Acute Gastric Mucosal Injury in Rats

    OpenAIRE

    Jeon, Woo-Young; Lee, Mee-Young; Shin, In-Sik; Lim, Hye-Sun; Shin, Hyeun-Kyoo

    2012-01-01

    This study was performed to evaluate the protective effect and safety of Oryeongsan water extract (OSWE) on ethanol-induced acute gastric mucosal injury and an acute toxicity study in rats. Acute gastric lesions were induced via intragastric oral administration of absolute ethanol at a dose of 5 mL/kg. OSWE (100 and 200 mg/kg) was administered to rats 2 h prior to the oral administration of absolute ethanol. The stomach of animal models was opened and gastric mucosal lesions were examined. Ga...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-15

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

  6. Influence of plasma GSH level on acute radiation mucositis of the oral cavity

    International Nuclear Information System (INIS)

    The purpose of the study was to see how pretreatment plasma GSH level influences the severity of acute radiation mucositis of the oral cavity during therapeutic irradiation in patients with oral cancer. Thirteen patients with squamous cell circinoma of the oral cavity form the subject material. Radical radiotherapy (60 Gy in 25 fractions over 5 weeks) was given using telecobalt. Pretreatment plasma GSH level was measured by Beutler's method. The normal tissue reaction during radiotherapy was monitored and graded. The GSH levels ranged from 10.6-90.5 μM/L (mean 30.6 μM/L). Those who had higher GSH levels developed less severe mucositis. The mean GSH levels in the groups with different severity of reactions were: Grade 2 (four patients) = 50.7 μM/L; Grade 3 (five patients) = 26.1 μM/L; Grade 4 (two patients) = 20.4 μM/L and Grade 5 (two patients) = 26.1 μM/L; Grade 4 (two patients) = 20.4 μM/L and Grade 5 (two patients) = 13.6 μM/L. Plasma GSH estimation has the potential to predict individual sensitivity to acute radiation mucositis and may particularly be useful in hyperfractionated regimes. The study also affirms the radioprotective role of GSH and suggests that this effect is either due to protection against membrane lipid perodixation (since GSH does not enter the cell freely) or DNA damage (fractionated radiotherapy may permit freer entry of GSH into cell). 26 refs., 1 fig., 2 tabs

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

    International Nuclear Information System (INIS)

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

  8. A randomized controlled multicenter trial of actovegin against acute oral mucositis induced by chemo-radiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the efficacy and safety of actovegin against acute oral mucositis through a randomized controlled multicenter trial for nasopharyngeal carcinoma (NPC) patients treated by chemo-radiotherapy. Methods: From February 2006 to May 2007, a total of 161 patients with newly diagnosed stage II-IVA(1992 Fuzhou Stage) NPC were randomly assigned to the prevention group, the treatment group and the control group. All patients received current chemo-radiotherapy ± neoadjuvant chemotherapy. Radiation technique and dose were similar among the three groups. Intravenous infusion of actovegin was started when radiation started in the prevention group and when grade 2 mucositis occurred in the treatment group, which was given 30 ml daily, 5 times per week until the end of radiotherapy. Criteria of NCI CTC 2.0 and VRS were used to evaluate acute oral mucositis and pain degree, respectively. Results: 154 patients were eligible for the efficacy analysis, including 49 in the prevention group, 53 in the treatment group and 52 in the control group. In the prevention group and the control group, the incidence was 31% and 56% (P= 0.011) for grade 3-4 mucositis, 59% and 83% (P=0.009) for grade 2-3 pain. In the treatment group and the control group, the corresponding number was 38% and 60% (P=0.023), 70% and 90%, (P=0.014). The prevention group had a lower incidence (P=0.021) and longer average interval (P=0.009) of grade 2 mucositis when comparing with the control group. No drug-related adverse event was observed. Conclusions: Prophylactic or therapeutic use of actovegin by intravenous infusion can significantly reduce the severity of chemo-radiotherapy induced oral mucositis and pain. The prophylactic use may also postpone and decrease the incidence of grade 2 mucositis, which deserves clinic application. (authors)

  9. Role of Chemokines in the Pathogenesis of Acute Lung Injury

    OpenAIRE

    Bhatia, Madhav; Zemans, Rachel L.; Jeyaseelan, Samithamby

    2012-01-01

    Acute lung injury (ALI) is due to an uncontrolled systemic inflammatory response resulting from direct injury to the lung or indirect injury in the setting of a systemic process. Such insults lead to the systemic inflammatory response syndrome (SIRS), which includes activation of leukocytes—alveolar macrophages and sequestered neutrophils—in the lung. Although systemic inflammatory response syndrome is a physiologic response to an insult, systemic leukocyte activation, if excessive, can lead ...

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

    Science.gov (United States)

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

    2015-03-01

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

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

    International Nuclear Information System (INIS)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-09-01

    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)

  13. The acute lymphoblastic leukemia of Down Syndrome - Genetics and pathogenesis.

    Science.gov (United States)

    Izraeli, Shai

    2016-03-01

    Children with Down Syndrome (DS) are at markedly increased risk for acute lymphoblastic leukemia (ALL). The ALL is of B cell precursor (BCP) phenotype. T-ALL is only rarely diagnosed as well as infant leukemia. Gene expression profiling and cytogenetics suggest that DS-ALL is an heterogeneous disease. More than half of the leukemias are characterized by aberrant expression of the thymic stromal lymphopoietin (TSLP) receptor CRLF2 caused by genomic rearrangements. These rearrangements are often associated with somatic activating mutations in the receptors or in the downstream components of the JAK-STAT pathway. The activation of JAK-STAT pathway suggests that targeted therapy with JAK or downstream inhibitors may be effective for children with DS-ALL. The basis of the increased risk of BCP-ALL and in particular of the CRLF2 aberrations is presently unknown. Neither is it known which genes on the trisomic chromosome 21 are involved. PMID:26631987

  14. A Hypothetical-Mathematical Model of Acute Myeloid Leukaemia Pathogenesis

    Directory of Open Access Journals (Sweden)

    Andrei Cucuianu

    2010-01-01

    Full Text Available Acute myeloid leukaemia is defined by the expansion of a mutated haematopoietic stem cell clone, with the inhibition of surrounding normal clones. Haematopoiesis can be seen as an evolutionary tree, starting with one cell that undergoes several divisions during the expansion phase, afterwards losing functional cells during the aging-related contraction phase. During divisions, offspring cells acquire ‘variations’, which can be either normal or abnormal. If an abnormal variation is present in more than 25% of the final cells, a monoclonal, leukemic pattern occurs. Such a pattern develops if: (A1 The abnormal variation occurs early, during the first or second divisions; (A2 The variation confers exceptional proliferative capacity; (B A sizable proportion of the normal clones are destroyed and a previously non-significant abnormal clone gains relative dominance over a depleted environment; (C The abnormal variation confers relative ‘immortality’, rendering it significant during the contraction phase. Combinations of these pathways further enhance the leukemic risk of the system. A simple mathematical model is used in order to characterize normal and leukemic states and to explain the above cellular processes generating monoclonal leukemic patterns.

  15. Pathogenesis of acute hepatopancreatic necrosis disease (AHPND) in shrimp.

    Science.gov (United States)

    Lai, Hung-Chiao; Ng, Tze Hann; Ando, Masahiro; Lee, Chung-Te; Chen, I-Tung; Chuang, Jie-Cheng; Mavichak, Rapeepat; Chang, Sheng-Hsiung; Yeh, Mi-De; Chiang, Yi-An; Takeyama, Haruko; Hamaguchi, Hiro-o; Lo, Chu-Fang; Aoki, Takashi; Wang, Han-Ching

    2015-12-01

    Acute hepatopancreatic necrosis disease (AHPND), also called early mortality syndrome (EMS), is a recently emergent shrimp bacterial disease that has resulted in substantial economic losses since 2009. AHPND is known to be caused by strains of Vibrio parahaemolyticus that contain a unique virulence plasmid, but the pathology of the disease is still unclear. In this study, we show that AHPND-causing strains of V. parahaemolyticus secrete the plasmid-encoded binary toxin PirAB(vp) into the culture medium. We further determined that, after shrimp were challenged with AHPND-causing bacteria, the bacteria initially colonized the stomach, where they started to produce PirAB(vp) toxin. At the same early time point (6 hpi), PirB(vp) toxin, but not PirA(vp) toxin, was detected in the hepatopancreas, and the characteristic histopathological signs of AHPND, including sloughing of the epithelial cells of the hepatopancreatic tubules, were also seen. Although some previous studies have found that both components of the binary PirAB(vp) toxin are necessary to induce a toxic effect, our present results are consistent with other studies which have suggested that PirB(vp) alone may be sufficient to cause cellular damage. At later time points, the bacteria and PirA(vp) and PirB(vp) toxins were all detected in the hepatopancreas. We also show that Raman spectroscopy "Whole organism fingerprints" were unable to distinguish between AHPND-causing and non-AHPND causing strains. Lastly, by using minimum inhibitory concentrations, we found that both virulent and non-virulent V. parahaemolyticus strains were resistant to several antibiotics, suggesting that the use of antibiotics in shrimp culture should be more strictly regulated. PMID:26549178

  16. Assessment of the effect of local application of amifostine on acute radiation-induced oral mucositis in guinea pigs

    OpenAIRE

    Li, Chang Jiang; Wang, Sheng Zi; Wang, Shu Yi; Zhang, Yan Ping

    2014-01-01

    The aim of present study was to assess the radioprotective effects of the local application of amifostine to treat acute buccal mucositis in guinea pigs. A total of 32 guinea pigs were randomized into four groups: (Group A) topically administered 50 mg of amifostine plus radiotherapy (RT); (Group B) 100 mg amifostine plus RT; (Group C) normal saline plus RT; and (Group D) normal saline plus sham RT. The opportunity for administration was 15 min before irradiation. When administered, the cotto...

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

    Institute of Scientific and Technical Information of China (English)

    Mehmet Kanter; Halit Demir; Cengiz Karakaya; Hanefi Ozbek

    2005-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Verhoeven, D; Pichichero, M E

    2014-10-01

    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. PMID:24889648

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

    Science.gov (United States)

    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

    2016-06-01

    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. PMID:26729813

  1. The Role of Neutrophils in the Pathogenesis of Transfusion-Related Acute Lung Injury (TRALI)

    OpenAIRE

    Fung, Y.L.; Silliman, C. C.

    2009-01-01

    Transfusion-related acute lung injury (TRALI) is the major cause of transfusion related morbidity and mortality, world wide. Efforts to reduce or eliminate this serious complication of blood transfusion are hampered by an incomplete understanding of its pathogenesis. Currently, TRALI is thought to be mediated by donor alloantibodies directed against host leukocytes or the result of two distinct clinical events. For both proposed mechanisms the neutrophil (PMN) is the key effector cell. This p...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Spatiotemporal interplay of severe acute respiratory syndrome coronavirus and respiratory mucosal cells drives viral dissemination in rhesus macaques.

    Science.gov (United States)

    Liu, L; Wei, Q; Nishiura, K; Peng, J; Wang, H; Midkiff, C; Alvarez, X; Qin, C; Lackner, A; Chen, Z

    2016-07-01

    Innate immune responses have a critical role in the control of early virus replication and dissemination. It remains unknown, however, how severe acute respiratory syndrome coronavirus (SARS-CoV) evades respiratory innate immunity to establish a systemic infection. Here we show in Chinese macaques that SARS-CoV traversed the mucosa through the respiratory tract within 2 days, resulting in extensive mucosal infiltration by T cells, MAC387(+), and CD163(+) monocytes/macrophages followed by limited viral replication in the lung but persistent viral shedding into the upper airway. Mucosal monocytes/macrophages sequestered virions in intracellular vesicles together with infected Langerhans cells and migrated into the tonsils and/or draining lymph nodes within 2 days. In lymphoid tissues, viral RNA and proteins were detected in infected monocytes upon differentiation into dendritic cells (DCs) within 3 days. Systemic viral dissemination was observed within 7 days. This study provides a comprehensive overview of the spatiotemporal interactions of SARS-CoV, monocytes/macrophages, and the DC network in mucosal tissues and highlights the fact that, while these innate cells contribute to viral clearance, they probably also serve as shelters and vehicles to provide a mechanism for the virus to escape host mucosal innate immunity and disseminate systemically. PMID:26647718

  4. Assessment of the effect of local application of amifostine on acute radiation-induced oral mucositis in guinea pigs.

    Science.gov (United States)

    Li, Chang Jiang; Wang, Sheng Zi; Wang, Shu Yi; Zhang, Yan Ping

    2014-09-01

    The aim of present study was to assess the radioprotective effects of the local application of amifostine to treat acute buccal mucositis in guinea pigs. A total of 32 guinea pigs were randomized into four groups: (Group A) topically administered 50 mg of amifostine plus radiotherapy (RT); (Group B) 100 mg amifostine plus RT; (Group C) normal saline plus RT; and (Group D) normal saline plus sham RT. The opportunity for administration was 15 min before irradiation. When administered, the cotton pieces that had been soaked with 0.5 ml amifostine solution or saline were applied gently on the buccal mucosa of each guinea pig for 30 min. The animals in Groups A, B and C were irradiated individually with a single dose of 30 Gy to the bilateral buccal mucosa. Eight days after irradiation, the animals were scored macroscopically; they were then euthanized, and the buccal mucosal tissues were processed for hematoxylin-eosin staining and ICAM-1 immunohistochemical analysis. In Groups A and B, the mean macroscopic scores were 2.9 ± 0.6 and 2.4 ± 1.1, respectively. There was no significant difference between the two groups (P > 0.05). However, when they were separately compared with Group C (4.4 ± 0.7), a noticeable difference was obtained (P amifostine-treated groups were better than in Group C. The results demonstrated that topical administration of amifostine to the oral mucosa is effective treatment of acute radiation-induced mucositis. PMID:24706999

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

    Directory of Open Access Journals (Sweden)

    Izadi Sh

    2009-02-01

    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

  6. Assessment of the effect of local application of amifostine on acute radiation-induced oral mucositis in guinea pigs

    International Nuclear Information System (INIS)

    The aim of present study was to assess the radioprotective effects of the local application of amifostine to treat acute buccal mucositis in guinea pigs. A total of 32 guinea pigs were randomized into four groups: (Group A) topically administered 50 mg of amifostine plus radiotherapy (RT); (Group B) 100 mg amifostine plus RT; (Group C) normal saline plus RT; and (Group D) normal saline plus sham RT. The opportunity for administration was 15 min before irradiation. When administered, the cotton pieces that had been soaked with 0.5 ml amifostine solution or saline were applied gently on the buccal mucosa of each guinea pig for 30 min. The animals in Groups A, B and C were irradiated individually with a single dose of 30 Gy to the bilateral buccal mucosa. Eight days after irradiation, the animals were scored macroscopically; they were then euthanized, and the buccal mucosal tissues were processed for hematoxylin-eosin staining and ICAM-1 immunohistochemical analysis. In Groups A and B, the mean macroscopic scores were 2.9 ± 0.6 and 2.4 ± 1.1, respectively. There was no significant difference between the two groups (P > 0.05). However, when they were separately compared with Group C (4.4 ± 0.7), a noticeable difference was obtained (P < 0.05). No mucositis was observed in Group D. Comparisons of the expression of ICAM-1 were in agreement with the macroscopic data. Histologically, superficial erosion, exudate and ulcer formation were all observed in the RT groups; only the severity and extent were different. The microscopic observations in the amifostine-treated groups were better than in Group C. The results demonstrated that topical administration of amifostine to the oral mucosa is effective treatment of acute radiation-induced mucositis. (author)

  7. Mucosa-adhesive water-soluble polymer film for treatment of acute radiation-induced oral mucositis

    International Nuclear Information System (INIS)

    Purpose: To examine the usefulness and safety of a mucosa-adhesive water-soluble polymer film (AD film) containing anesthetics and antibiotics for the treatment of acute radiation-induced oral mucositis. Materials and Methods: To prepare AD films, 600 mg of hydroxy-propyl-cellulose was dissolved in ethyl alcohol, and mixed with a solution containing tetracaine, ofloxacine, miconazole, guaiazulene, and triacetin. The gel obtained was dried to form 30 translucent round sheets (20 mg per sheet) of 7.5 cm in diameter and 0.2 mm in thickness. The AD film showed excellent adhesive and coating properties when placed on wet oral mucosa. From 1993 to 1994, we used the AD film in 25 patients with acute radiation-induced oral mucositis, in an attempt to alleviate their pain and prevent secondary oral infection. All patients had received definitive radiotherapy for oral carcinoma. Intensity and duration of oral pain from mucositis, relief rates at rest and while eating, and presence of bacterial and/or fungal infection were compared with those of 27 patients treated with topical anesthetics (viscous lidocaine, XylocaineTM) and/or general systemic analgesics from 1990 to 1992 (NonAD Group). Results: The intensity of oral pain was the same in the two groups. The mean duration of pain of the AD film Group (10 days) was significantly shortened compared with the NonAD Group (15 days). The rates of complete pain relief at rest and while eating of the AD film Group were statistically higher than those of the NonAD Group: 82% vs. 44%, and 68% vs. 22%, respectively. No secondary bacterial or fungal infections were observed in the AD film Group, whereas 4 cases of documented infections were found in the NonAD Group. No acute or chronic adverse effects of AD film were observed during the 3-year follow-up period. The rates for local control of oral carcinoma and overall survival, at the end of the follow-up period, were 96% and 87% for the AD film Group vs. 92% and 85% for the NonAD Group

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    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

  10. Acute Hendra virus infection: Analysis of the pathogenesis and passive antibody protection in the hamster model

    International Nuclear Information System (INIS)

    Hendra virus (HeV) and Nipah virus (NiV) are recently-emerged, closely related and highly pathogenic paramyxoviruses. We have analysed here the pathogenesis of the acute HeV infection using the new animal model, golden hamster (Mesocricetus auratus), which is highly susceptible to HeV infection. HeV-specific RNA and viral antigens were found in multiple organs and virus was isolated from different tissues. Dual pathogenic mechanism was observed: parenchymal infection in various organs, including the brain, with vasculitis and multinucleated syncytia in many blood vessels. Furthermore, monoclonal antibodies specific for the NiV fusion protein neutralized HeV in vitro and efficiently protected hamsters from HeV if given before infection. These results reveal the similarities between HeV and NiV pathogenesis, particularly in affecting both respiratory and neuronal system. They demonstrate that hamster presents a convenient novel animal model to study HeV infection, opening new perspectives to evaluate vaccine and therapeutic approaches against this emergent infectious disease.

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

    Institute of Scientific and Technical Information of China (English)

    Li-Rong Liu; Shi-Hai Xia

    2006-01-01

    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.

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

    Science.gov (United States)

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

    2009-01-01

    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.

  13. A prospective, randomized, multi-center trial to investigate Actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Purpose: A multi-center prospective randomized trial was conducted to evaluate the efficacy and safety of Actovegin in the prevention and treatment of chemoradiotherapy-induced acute oral mucositis. Methods and materials: Between February 2006 and May 2007, 156 evaluable patients with nasopharyngeal carcinoma were randomized to Group 1 (n = 53) for prevention, Group 2 (n = 51) for treatment, and Group 3 (n = 52) for control. All patients received concomitant chemoradiotherapy ± induction chemotherapy. Radiation technique and dose were similar among 3 groups. Intravenous Actovegin of 30 ml daily (5 days/week) was administrated from day 1 of the radiotherapy for Group 1 and from the onset of grade 2 mucositis for Group 2, until the end of the radiotherapy. Results: The incidence of grade 3 mucositis was lower in Group 1 compared with Group 3 (26.4% vs. 55.8%, P = 0.002). Group 2 had a lower progression rate of mucositis from grade 2 to 3 compared with Group 3 (39.2% vs. 60.4%, P = 0.035). There was no difference in the onset time of grade 3 mucositis among 3 groups. Actovegin was well tolerated and no treatment-related adverse events were observed. Conclusions: Actovegin is effective in the prevention and treatment of chemoradiotherapy-induced oral mucositis.

  14. Relevance of keratinocyte growth factor administration protocol for amelioration of acute radiation-induced oral mucositis

    International Nuclear Information System (INIS)

    Keratinocyte growth factor (rHuKGF) significantly reduces oral mucositis in the mouse tongue model. The present study was initiated to optimise the KGF treatment protocol, using mucosal ulceration as the endpoint. Fractionated irradiation with 5x3 Gy/week was followed by test irradiation on day 7 or 14. In the first experiment, 1 or 3 injections (5 mg/kg/day) were applied either before the onset of fractionation (day -3, day -2, days -3 to -1) or over the first weekend (day +4. day +5, days +4 to +6), followed by one further injection at the subsequent weekend (day +4/day +11). In a second experiment, graded doses of KGF (1-30 mg/kg) were administered on days -3, +4 +11. After 5 or 10 fractions of 3 Gy, the ED50 for test irradiation was 5.1±1.9 Gy or 5.7±1.5 Gy, respectively, compared to 10.7±1.0 Gy for test irradiation alone. This indicates effective repopulation in week 2. KGF administration over the weekend before irradiation plus on day +4 increased the ED50 to 12.1-12.3 Gy, independent of the number of injections. Injections over the first weekend plus on day +11 resulted in ED50 values of 12.8-14.3 Gy, again independent of KGF injection number. In the dose optimisation study, KGF doses as low as 1 mg/kg resulted in a significant increase in ED50s for all days studied. Maximum efficacy was found with doses of 15-22.5 mg/kg, with ED50 values of 12.1±1.3 Gy (day -3), 14.4±1.3 Gy (day +4), and 13.7 Gy (day +11) Higher KGF doses did not result in a further increase in ED50. In conclusion, a marked increase in oral mucosal radiation tolerance by KGF was observed in all protocols tested. Repeated injections on consecutive days did not increase the effect. A significant effect of dose per injection was demonstrated, with optimum doses (mouse tongue mucosa) of 15-22.5 mg/kg

  15. Frequency and pathogenesis of silent subcortical brain infarction in acute first-ever ischemic stroke

    International Nuclear Information System (INIS)

    We have often observed silent subcortical brain lesions on CT or MRI in first-ever ischemic stroke, but there is little published information on the relationship of these lesions to stroke subtypes. Here, we describe the incidence of MRI-detected silent subcortical brain lesions, including infarctions and white matter lesions, in a series of patients with first-ever ischemic stroke classified according to stroke subtypes. We also discuss the pathogenesis of these silent subcortical lesions. We evaluated 171 patients with acute first-ever ischemic stroke. The subjects were divided into three groups: lacunar, atherothrombotic and cardioembolic infarction groups. We evaluated silent subcortical brain infarction (SSBI), enlargement of perivascular space (EPS), and other white-matter lesions using MRI. Hypertension was observed in 67.6% of lacunar infarction, 57.1% of atherosclerotic infarction, and 54.1% of cardioembolic infarction. SSBI was more frequently observed in lacunar infarction than the others (lacunar vs. atherothrombotic vs. cardiogenic infarction, 81.5% vs. 44.4% vs. 42.1%, p=0.006). High-grade EPS (grade 2 or higher) was also observed more frequently in lacunar infarction than in the others (lacunar vs. atherothrombotic vs. cardiogenic infarction, 63.3% vs. 24.2% vs. 0%, p<0.001). Scheltens' score of silent subcortical lesions was significantly higher in lacunar infarction than in the others. The frequency of silent subcortical ischemic brain lesions was significantly higher in lacunar infarction than in atherosclerotic or cardioembolic infarction. We suggest that the pathogenesis of silent subcortical ischemic brain lesions is common to that of lacunar infarction, that is, small-vessel vasculopathy. (author)

  16. A rare aggravation of severe mucositis post chemotherapy in a child with acute lymphoblastic leukemia [v1; ref status: indexed, http://f1000r.es/1tf

    OpenAIRE

    Adlette Inati; Grace Akouri; Abbas, Hussein A.

    2013-01-01

    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 rec...

  17. Efficacy and effects of palifermin for the treatment of oral mucositis in patients affected by acute lymphoblastic leukemia.

    Science.gov (United States)

    Lucchese, Alessandra; Matarese, Giovanni; Ghislanzoni, Luis Huanca; Gastaldi, Giorgio; Manuelli, Maurizio; Gherlone, Enrico

    2016-04-01

    This randomized-controlled trial studied the efficacy of palifermin, administered as a dose during hematopoietic stem cell transplant (HSCT) therapy, as primary prophylaxis on pediatric patients with acute lymphoblastic leukemia in order to reduce oral mucositis (OM). Patients in the palifermin group were randomly assigned to receive palifermin, 60 μg/kg, intravenously as a single dose 3 days before and 0, +1, and +2 post autologous HSCT infusion. The patients in the control group received only a placebo treatment. OM-related assessments were the WHO oral-toxicity scale and the patient-reported outcomes. There was a statistically significant reduction in the incidence of OM grade 3 and 4 in the palifermin group compared to the control group. There was also a reduction in the degree of severity of OM in the palifermin group (1.65 grade respect to 2.33 in the control group). Palifermin could prevent the recurrence of severe OM and improve the quality of life in patients with acute lymphoblastic leukemia (ALL). PMID:26428409

  18. Grade 4 oral mucositis and prolonged pancytopenia with high dose intravenous methotrexate in a patient of philadelphia positive acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Vidisha M. Shah

    2012-02-01

    Full Text Available Antimetabolite drugs are rarely associated with grade 3 or 4 mucositis. However specific side effects such as bone marrow suppression, pancytopenia, hospitalization, high cost limit the use of intravenous methotrexate. Here we report a case of 25-year-old girl patient with Acute Lymphoblastic Leukemia (ALL treated with 24 hour methotrexate in her continuous phase of chemotherapy. After 12 hours of completing the treatment she developed oral mucosal pain & she was not able to speak. After a week, her White Blood Cell (WBC count was 600/cumm with fever and she could not speak and eat or drink. So she was hospitalized for few days till she can drink something. We report high grade mucositis with methotrexate. Hematologists should be aware of this possible side effect to undertake early intervention. [Int J Basic Clin Pharmacol 2012; 1(1.000: 36-38

  19. Pathogenesis of the mucosal hyperplasia in self-filling blind loops of rat jejunum: a morphometric study in germ free animals.

    OpenAIRE

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

    1987-01-01

    Bacterial overgrowth and high intraluminal concentrations of deconjugated bile acids are thought to be responsible for mucosal hyperplasia in self-filling blind loops of rat jejunum. To investigate this hypothesis further we have assessed the three dimensional architecture of these loops created in germ free animals without or with di- or mono-association of different bacterial species. It was found that mucosal hyperplasia develops in the absence of any bacterial contamination and that bacte...

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

    Directory of Open Access Journals (Sweden)

    Alexander Swidsinski

    2012-01-01

    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.

  1. Amelioration of acute oral mucositis by Keratinocyte growth factor: fractionated irradiation

    International Nuclear Information System (INIS)

    Purpose: The aim of the present study was to quantify the protective efficacy of recombinant human keratinocyte growth factor (rHuKGF) in oral mucosa. Methods and Materials: Mouse tongue mucosal ulceration was analyzed as the clinically relevant end point. Fractionated irradiation of the snout with 5 daily fractions of 3 Gy was followed by graded test doses, given to a test area of the lower tongue, on Day 7. rHuKGF was injected s.c. in daily doses of 5 mg/kg before radiotherapy, during radiotherapy, over the weekend break, or a combination. Moreover, single rHuKGF injections (5 or 15 mg/kg) were given on Day -1 or on Day 4. Results: In a single-dose control experiment, the ED50, i.e., the dose after which ulcer induction is expected in 50% of the mice, was 10.9 ± 0.7 Gy. Fractionated irradiation without keratinocyte growth factor rendered an ED50 for test irradiation of 5.6 ± 3.7 Gy. Keratinocyte growth factor increased the ED50 values to 7.8 ± 3.3 Gy (Days -3 to -1, p=0.01), 8.3 ± 1.6 Gy (Days -4 to -2, p=0.0008), 10.5 ± 1.4 Gy (Days 0 to +2, p=0.0002), 11.0 ± 0.5 Gy (Days 0 to +4, p=0.002), 10.6 ± 1.4 Gy (Days +4 to +6, p=0.0021), 10 ± 0.07 (Days -3 to +1, p=0.0001) or 11.0 ± 0.02 (Days +4 to +8, p=0.0001). This is equivalent to compensation of approximately 1.5 fractions of 3 Gy when rHuKGF is given before radiotherapy and 3-4 fractions in all other protocols by rHuKGF treatment. Single rHuKGF injections were similarly (5 mg/kg) or more (15 mg/kg) effective. Conclusions: In conclusion, these results indicate a marked increase in oral mucosal radiation tolerance by rHuKGF, which is most pronounced if the growth factor is applied during fractionated radiotherapy. The effect seems to be based on complex mechanisms, predominantly changes in both epithelial proliferation and differentiation processes

  2. Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, M. A. H.; Lopez-Lopez, E.; te Winkel, M. L.; Tissing, W.; de Rooij, J. D. E.; Gutierrez-Camino, A.; Garcia-Orad, A.; den Boer, E.; Pieters, R.; Pluijm, S. M. F.; de Jonge, R.; van den Heuvel-Eibrink, M. M.

    2015-01-01

    Methotrexate (MTX) is an effective and toxic chemotherapeutic drug in the treatment of pediatric acute lymphoblastic leukemia (ALL). In this prospective study, we aimed to identify metabolic and genetic determinants of MTX toxicity. One hundred and thirty-four Dutch pediatric ALL patients were treat

  3. Disparate Requirement for T Cells in Resistance to Mucosal and Acute Systemic Candidiasis

    OpenAIRE

    Jones-Carson, Jessica; Vazquez-Torres, Andres; Warner, Thomas; Balish, Edward

    2000-01-01

    Although highly susceptible to orogastric candidiasis, T-cell receptor δ- and α-chain knockout mice, deficient in γδ and αβ T cells, respectively, were found to be resistant to disseminated candidiasis of endogenous origin and to acute systemic candidiasis (resulting from intravenous injection).

  4. 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

    Institute of Scientific and Technical Information of China (English)

    王春芳; 李真; 徐立然

    2012-01-01

    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.

  5. MicroRNA signature of intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.

    Science.gov (United States)

    Asaoka, T; Sotolongo, B; Island, E R; Tryphonopoulos, P; Selvaggi, G; Moon, J; Tekin, A; Amador, A; Levi, D M; Garcia, J; Smith, L; Nishida, S; Weppler, D; Tzakis, A G; Ruiz, P

    2012-02-01

    Despite continuous improvement of immunosuppression, small bowel transplantation (SBT) is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need to uncover novel insights that will lead to strategies to achieve better control of ACR. We hypothesized that particular miRNAs provide critical regulation of the intragraft immune response. The aim of our study was to identify miRNAs involved in intestinal ACR. We examined 26 small intestinal mucosal biopsies (AR/NR group; 15/11) obtained from recipients after SBT or multivisceral transplantation. We investigated the expression of 384 mature human miRNAs and 280 mRNAs associated with immune, inflammation and apoptosis processes. We identified differentially expressed 28 miRNAs and 58 mRNAs that characterized intestinal ACR. We found a strong positive correlation between the intragraft expression levels of three miRNAs (miR-142-3p, miR-886-3p and miR-132) and 17 mRNAs including CTLA4 and GZMB. We visualized these miRNAs within cells expressing CD3 and CD14 proteins in explanted intestinal allografts with severe ACR. Our data suggested that miRNAs have a critical role in the activation of infiltrating cells during intestinal ACR. These differences in miRNA expression patterns can be used to identify novel biomarkers and therapeutic targets for immunosuppressive agents. PMID:22026534

  6. A New Model for Predicting Acute Mucosal Toxicity in Head-and-Neck Cancer Patients Undergoing Radiotherapy With Altered Schedules

    Energy Technology Data Exchange (ETDEWEB)

    Strigari, Lidia, E-mail: strigari@ifo.it [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Pedicini, Piernicola [Department of Medical Physics, Regional Cancer Hospital C.R.O.B, Rionero in Vulture (Italy); D' Andrea, Marco [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Pinnaro, Paola; Marucci, Laura; Giordano, Carolina [Department of Radiotherapy, Regina Elena National Cancer Institute, Rome (Italy); Benassi, Marcello [Department of Medical Physics, Istituto Scientifico Romagnolo per lo Studio e la Cura dei tumori, Meldola (Italy)

    2012-08-01

    Purpose: One of the worst radiation-induced acute effects in treating head-and-neck (HN) cancer is grade 3 or higher acute (oral and pharyngeal) mucosal toxicity (AMT), caused by the killing/depletion of mucosa cells. Here we aim to testing a predictive model of the AMT in HN cancer patients receiving different radiotherapy schedules. Methods and Materials: Various radiotherapeutic schedules have been reviewed and classified as tolerable or intolerable based on AMT severity. A modified normal tissue complication probability (NTCP) model has been investigated to describe AMT data in radiotherapy regimens, both conventional and altered in dose and overall treatment time (OTT). We tested the hypothesis that such a model could also be applied to identify intolerable treatment and to predict AMT. This AMT NTCP model has been compared with other published predictive models to identify schedules that are either tolerable or intolerable. The area under the curve (AUC) was calculated for all models, assuming treatment tolerance as the gold standard. The correlation between AMT and the predicted toxicity rate was assessed by a Pearson correlation test. Results: The AMT NTCP model was able to distinguish between acceptable and intolerable schedules among the data available for the study (AUC = 0.84, 95% confidence interval = 0.75-0.92). In the equivalent dose at 2 Gy/fraction (EQD2) vs OTT space, the proposed model shows a trend similar to that of models proposed by other authors, but was superior in detecting some intolerable schedules. Moreover, it was able to predict the incidence of {>=}G3 AMT. Conclusion: The proposed model is able to predict {>=}G3 AMT after HN cancer radiotherapy, and could be useful for designing altered/hypofractionated schedules to reduce the incidence of AMT.

  7. Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia

    Science.gov (United States)

    Duque-Afonso, Jesús; Feng, Jue; Scherer, Florian; Lin, Chiou-Hong; Wong, Stephen H.K.; Wang, Zhong; Iwasaki, Masayuki; Cleary, Michael L.

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; however, its genetic diversity limits investigation into the molecular pathogenesis of disease and development of therapeutic strategies. Here, we engineered mice that conditionally express the E2A-PBX1 fusion oncogene, which results from chromosomal translocation t(1;19) and is present in 5% to 7% of pediatric ALL cases. The incidence of leukemia in these mice varied from 5% to 50%, dependent on the Cre-driving promoter (Cd19, Mb1, or Mx1) used to induce E2A-PBX1 expression. Two distinct but highly similar subtypes of B cell precursor ALLs that differed by their pre–B cell receptor (pre-BCR) status were induced and displayed maturation arrest at the pro-B/large pre–B II stages of differentiation, similar to human E2A-PBX1 ALL. Somatic activation of E2A-PBX1 in B cell progenitors enhanced self-renewal and led to acquisition of multiple secondary genomic aberrations, including prominent spontaneous loss of Pax5. In preleukemic mice, conditional Pax5 deletion cooperated with E2A-PBX1 to expand progenitor B cell subpopulations, increasing penetrance and shortening leukemia latency. Recurrent secondary activating mutations were detected in key signaling pathways, most notably JAK/STAT, that leukemia cells require for proliferation. These data support conditional E2A-PBX1 mice as a model of human ALL and suggest targeting pre-BCR signaling and JAK kinases as potential therapeutic strategies. PMID:26301816

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

    Science.gov (United States)

    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

    2006-10-01

    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. PMID:16926041

  9. Study of Qingre Liyan Decoction(清热利咽汤)in Treating and Preventing Acute Radioactive Oral Mucositis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To study the effect of Qingre Liyan Decoction(清热利咽汤,QRLYD)in the prevention and treatment of acute radiative oral mucositis(AROM),and to explore the mechanism of QRLYD by detecting epidermal growth factor(EGF)and T lymphocytes(CD3,CD4,and CD8).Methods:Sixty patients conforming with the standard were randomly assigned to two groups,30patients in each group.Patients in the trial group were treated with QRLYD,and those in the control group were treated with Dobell's solution,both groups receiving conventional radiation treatment.The treatment course for both groups was 6 weeks on average.Blood routine test,CD3,CD4,and CD8in the peripheral blood and EGF in the saliva were detected one day before and on the 14th and 28th day of radio-therapy.Results:Patients in the trial group were in good condition with normal spirits and intake of food and drinks.The incidence of AROM is lower and the effect in preventing AROM is higher in the trial group than those in the control group(P<0.05).The EGF in saliva,and CD4 and CD8 in the blood of patients in the trial group were higher than those in the control group(P<0.05).Conclusion:QRLYD can cure and prevent AROM.The mechanism may be related with its effects in enhancing body immunity and promoting salivary EGF.

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

    Science.gov (United States)

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

    2000-02-01

    AIM:To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS:A rat model with 30% TBSA full thickness burn injury was employed and the gastric acid production,together with gastric mucosal blood flow (GMBF) and energy charge (EC) were measured serially within 48h postburn.RESULTS:The gastric acid production in the acute shock period was markedly inhibited after severe burn injury.At the 3rd h postburn,the gastric juice volume, total acidity and acid output were already significantly decreased (P anti-acid drugs during burn shock period was unreasonable in some respects. Therefore, taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment. PMID:11819529

  11. Innate Lymphoid Cells are the Predominant Source of Interleukin-17A During the Early Pathogenesis of Acute Respiratory Distress Syndrome

    OpenAIRE

    Muir, Roshell; Osbourn, Megan; Dubois, Alice V.; Doran, Emma; Small, Donna M; Monahan, Avril; O'Kane, Cecilia M.; McAllister, Katherine; Fitzgerald, Denise C; Kissenpfennig, Adrien; McAuley, Daniel F; Ingram, Rebecca J.

    2015-01-01

    Rationale: IL-17A is purported to help drive early pathogenesis in acute respiratory distress syndrome (ARDS) by enhancing neutrophil recruitment. Whilst IL-17A is the archetypal cytokine of T helper (Th)17 cells, it is produced by a number of lymphocytes, the source during ARDS being unknown. Objectives: To identify the cellular source and the role of IL17A in the early phase of lung injuryMethods: Lung injury was induced in WT (C57BL/6) and IL-17 KO mice with aerosolised LPS (100 µg) or Pse...

  12. Pancytopenic Prodrome (pre-ALL) of Acute Lymphoblastic Leukemia in Adults: Possible Pathogenesis

    OpenAIRE

    Sohn, Sang Kyun; Suh, Jang Soo; Lee, Jaetae; Lee, Kyu Bo

    1998-01-01

    We report two cases of adult acute lymphoblastic leukemia presenting with preleukemic phase of pancytopenia with a few abnormal lymphoid cells in bone marrow aspirates. The initial diagnosis of each case was suspicious aplastic anemia and hypoplastic anemia. Both cases progressed to overt acute lymphoblastic leukemia within 1 year. We suggest that initial pancytopenic phase (pre-ALL) may precede the diagnosis of acute lymphoblastic leukemia in adults and differential diagnosis from myelodyspl...

  13. Effects of near-infrared laser radiation on the survival and inflammatory potential of Candida spp. involved in the pathogenesis of chemotherapy-induced oral mucositis.

    Science.gov (United States)

    Clemente, A M; Rizzetto, L; Castronovo, G; Perissi, E; Tanturli, M; Cozzolino, F; Cavalieri, D; Fusi, F; Cialdai, F; Vignali, L; Torcia, M G; Monici, M

    2015-10-01

    Candida spp. usually colonize ulcerative lesions of atrophic mucosa in patients with chemotherapy-induced oral mucositis inducing severe inflammation. The spread of antifungal-resistant strains strongly encouraged the search of complementary or alternative therapeutic strategies to cure inflamed mucosa. In this paper, we studied the effects of a near-infrared (NIR) laser system with dual-wavelength emission (808 nm + 904 nm) on the survival and inflammatory potential of C. albicans, C. glabrata, and C. parapsilosis. Laser treatment was performed with a Multiwave Locked System laser. Survival and apoptosis of fungal strains were evaluated by colony-forming units (CFU) counting and annexin V staining. Cytokine production was evaluated by ImmunoPlex array. Laser treatment significantly affected the survival of Candida spp. by inducing apoptosis and induced a lower production of inflammatory cytokines by dendritic cells compared to untreated fungi. No differences in the survival and inflammatory potential were recorded in treated or untreated Saccharomyces cerevisiae cells, used as the control non-pathogenic microorganism. Laser treatment altered the survival and inflammatory potential of pathogenic Candida spp. These data provide experimental support to the use of NIR laser radiation as a co-adjuvant of antifungal therapy in patients with oral mucositis (OM) complicated by Candida infections. PMID:26173694

  14. Dose–response analysis of acute oral mucositis and pharyngeal dysphagia in patients receiving induction chemotherapy followed by concomitant chemo-IMRT for head and neck cancer

    International Nuclear Information System (INIS)

    Dose–response curves (DRCs) and the quantitative parameters describing these curves were generated for grade 3 oral mucositis and dysphagia in 144 patients using individual patient DVHs. Curve fits to the oral mucositis clinical data yielded parameter values of mean dose in 2 Gy equivalent, MD50 = 51 Gy (95% CI 40–61), slope of the curve, k = 1(95% CI 0.6–1.5). R2 value for the goodness of fit was 0.80. Fits to the grade 3 dysphagia clinical data yielded parameter values of MD50 = 44.5 Gy (95% CI 36–53), k = 2.6 (95% CI 0.8–4.5). R2 value for the goodness of fit was 0.65. This is the first study to derive DRCs in patients receiving induction chemotherapy followed by chemo-radiation (IC-C-IMRT) for head and neck cancer. The dose–response model described in this study could be useful for comparing acute mucositis rates for different dose–fractionation schedules when using IMRT for head and neck cancer.

  15. A C-type lectin receptor pathway is responsible for the pathogenesis of acute cyclophosphamide-induced cystitis in mice.

    Science.gov (United States)

    Dejima, Takashi; Shibata, Kensuke; Yamada, Hisakata; Takeuchi, Ario; Hara, Hiromitsu; Eto, Masatoshi; Naito, Seiji; Yoshikai, Yasunobu

    2013-12-01

    Hemorrhagic cystitis often arises after cyclophosphamide (CYP) administration. As yet, however, the mechanism involved in its pathogenesis is unknown. In this study, it was found that the Fc receptor γ chain (FcRγ)- caspase recruitment domain-containing protein 9 (CARD9)-dependent pathway rather than the myeloid differentiation primary response gene 88 (MyD88)-dependent pathway is involved in the pathogenesis of acute CYP-induced cystitis in mice. Rapid and transient production of interleukin (IL)-6 and IL-1β was detected in the bladder at 4 hr, preceding IL-23 and IL-17A production and an influx of neutrophils, which reached a peak at 24 hr after injection. As assessed by weight, edema and neutrophil infiltration, cystitis was significantly attenuated in CARD9 knockout (KO) and FcRγKO mice, this attenuation being accompanied by impaired production of IL-1β, IL-6, IL-23 and IL-17A. The major source of IL-17A is the vesical γδ T cell population: IL-17AKO, CδKO and Tyk2KO mice showed little IL-17A production and reduced neutrophil infiltration in the bladder after CYP injection. These results suggest that FcRγ-CARD9-dependent production of proinflammatory cytokines such as IL-1β, IL-6, and IL-23 and the subsequent activation of IL-17A-producing γδ T cells are at least partly involved in the pathogenesis of acute CYP-induced cystitis in mice. PMID:24102807

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    Golbabapour, Shahram; Hajrezaie, Maryam; Hassandarvish, Pouya; Abdul Majid, Nazia; Hadi, A Hamid A; Nordin, Noraziah; Abdulla, Mahmood A

    2013-01-01

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

  18. Role of ET and ANF in the pathogenesis of early acute pancreatitis

    International Nuclear Information System (INIS)

    Objective: To investigate the role played by endothelin (ET) and atrial natriuretic factor (ANF) in the development of acute pancreatitis. Methods: Plasma ET and ANF levels were measured with RIA in 35 patients with mild acute pancreatitis (MAP) and 17 patients with severe acute pancreatitis (SAP) within 24-48h after onset of disease as well as in 30 controls. Patients with Imrie score>3, APACHE II score ≥8 were classified as severe. Results: Plasma ET levels in patients with SAP (59.20 + 10. 69pg/ml) were significantly higher than those in controls (P0.05. Conclusion: Increased Et levels in Sap patients might aggravate the ischemia and impairment of microcirculation, leading to endogenous injury of pancreatic tissue. Administration of ET/ET receptor antagonists early in the course might be therapeutically helpful. Effect of ANF seemed to be negligible. (authors)

  19. Serum amyloid A: An acute-phase protein involved in tumour pathogenesis

    Science.gov (United States)

    Sodin-Semrl, S.; Kovacevic, A.

    2016-01-01

    The synthesis of acute-phase protein serum amyloid A (SAA) is largely regulated by inflammation-associated cytokines and a high concentration of circulating SAA may represent an ideal marker for acute and chronic inflammatory diseases. However, SAA is also synthesized in extrahepatic tissues, e.g. human carcinoma metastases and cancer cell lines. An increasing body of in vitro data supports the concept of involvement of SAA in carcinogenesis and neoplastic diseases. Accumulating evidence suggests that SAA might be included in a group of biomarkers to detect a pattern of physiological events that reflect the growth of malignancy and host response. This review is meant to provide a broad overview of the many ways that SAA could contribute to tumour development, and accelerate tumour progression and metastasis, and to gain a better understanding of this acute-phase reactant as a possible link between chronic inflammation and neoplasia. PMID:18726069

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

    Directory of Open Access Journals (Sweden)

    Tudor Thomas

    2012-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Naoyoshi; Maeda; Toshimitsu; Uede

    2010-01-01

    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.

  2. Elevation of S100A4 expression in buccal mucosal fibroblasts by arecoline: involvement in the pathogenesis of oral submucous fibrosis.

    Directory of Open Access Journals (Sweden)

    Cheng-Chia Yu

    Full Text Available BACKGROUND: S100A4, a member of the calcium-binding proteins, is dramatically elevated in a variety of fibrotic diseases. Areca quid chewing is the most important etiological factor in the pathogenesis of oral submucous fibrosis (OSF. OSF has been considered as a pre-cancerous condition of oral mucosa. The aim of this study was to determine the critical role of S100A4 expression in the pathogenesis of OSF both in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDING: Thirty OSF tissues from areca quid chewers and ten normal buccal mucosa samples without areca quid chewing were analyzed by using immunohistochemistry for S100A4 expression in vivo. Collagen gel contraction capability and expression of tissue inhibitor of metalloproteinases 1 (TIMP1/MMP9 in arecoline-stimulated BMFs with S100A4 knockdown was presented in vitro. Initially, S100A4 expression was higher in areca quid chewing-associated OSF specimens than normal buccal mucosa specimens (p = 0.001. Arecoline, a major areca nut alkaloid, led to dose- and time-dependent elevation of S100A4 expression in normal buccal mucosa fibroblasts BMFs (p<0.05. The additions of pharmacological agents rapamycin (mTOR inhibitor, PD98059 (ERK inhibitor, and Bay117082 (NF-κB inhibitor were found to inhibit arecoline-induced S100A4 expression (p<0.05 in BMFs. Down-regulation of S100A4 by lentiviral infection significantly reversed arecoline-induced collagen gel contraction and TIMP1/MMP9 expression. CONCLUSION/SIGNIFICANCE: These results suggest that S100A4 expression is significantly up-regulated in OSF specimens. Arecoline-induced S100A4 expression was down-regulated by rapamycin, PD98059, and Bay117082. Targeting S100A4 might be a potential therapeutic target for OSF through TIMP1/MMP9 down-regulation.

  3. Molecular pathogenesis of plasminogen Hakodate: the second Japanese family case of severe type I plasminogen deficiency manifested late-onset multi-organic chronic pseudomembranous mucositis.

    Science.gov (United States)

    Osaki, Tsukasa; Souri, Masayoshi; Song, Young-Seok; Izumi, Naohiro; Law, Ruby; Ichinose, Akitada

    2016-08-01

    A 64-year-old man first developed ligneous conjunctivitis at the age of 58 years after right pulmonary resection because of suspected cancer; otherwise, he had been healthy. Since then, he began to suffer from various forms of chronic pseudomembranous mucositis. Laboratory tests demonstrated that he had 7.8 % of plasminogen activity and 5.9 % of the normal antigen level. Thus, he was diagnosed as having severe type I plasminogen deficiency, making him the third case in Japan. DNA sequencing and PCR-restriction fragment length polymorphism analyses revealed that this patient was a compound heterozygote of a G-to-A missense mutation (G266E) in exon VIII and a g-to-a mutation at the obligatory splicing acceptor site in intron 12 (IVS12-1g>a). These two mutations were confirmed to be novel. Molecular modeling and splice site strength calculation predicted conformational disorder(s) for the Glu266 mutant and a drastic decrease in splicing efficiency for intron 12, respectively. Western blot analysis demonstrated that the patient contained a small amount of the normal-sized plasminogen protein. Mass spectrometric analysis of the patient's plasminogen revealed a peptide containing the wild-type Gly266 residue and no peptides with mutations at Glu266. However, he had never suffered from thrombosis. Low levels of fibrinogen/fibrin degradation products (FDP), D-dimer, and plasmin-α2-plasmin inhibitor complex clearly indicated a hypo-fibrinolytic condition. However, his plasma concentration of elastase-digested crosslinked FDPs was 4.8 U/mL, suggesting the presence of an on-going plasmin(ogen)-independent "alternative" fibrinolytic system, which may protect the patient from thrombosis. The patient has been free from recurrence of ligneous conjunctivitis for approximately 2.5 years. PMID:27193180

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

    OpenAIRE

    Shahram Golbabapour; Maryam Hajrezaie; Pouya Hassandarvish; Nazia Abdul Majid; A. Hamid A. Hadi; Noraziah Nordin; Mahmood A. Abdulla

    2013-01-01

    The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The e...

  5. Central role of neutrophil in the pathogenesis of severe acute pancreatitis.

    Science.gov (United States)

    Yang, Zhi-Wen; Meng, Xiao-Xiao; Xu, Ping

    2015-11-01

    Severe acute pancreatitis (SAP) is an acute abdominal disease with the strong systemic inflammatory response, and rapidly progresses from a local pancreatic damage into multiple organ dysfunction. For many decades, the contributions of neutrophils to the pathology of SAP were traditionally thought to be the chemokine and cytokine cascades that accompany inflammation. In this review, we focus mainly on those recently recognized aspects of neutrophils in SAP processes. First, emerging evidence suggests that therapeutic interventions targeting neutrophils significantly lower tissue damage and protect against the occurrence of pancreatitis. Second, trypsin activation promotes the initial neutrophils recruitment into local pancreas, and subsequently neutrophils infiltration in turn triggers trypsin production. Finally, neutrophils have the unique ability to release neutrophil extracellular traps even in the absence of pathogens. PMID:26249268

  6. Role of free radicals in the pathogenesis of acute chest syndrome in sickle cell disease

    OpenAIRE

    Farber Harrison W; Klings Elizabeth S

    2001-01-01

    Abstract Acute chest syndrome (ACS) of sickle cell disease (SCD) is characterized pathologically by vaso-occlusive processes that result from abnormal interactions between sickle red blood cells (RBCs), white blood cells (WBCs) and/or platelets, and the vascular endothelium. One potential mechanism of vascular damage in ACS is by generation of oxygen-related molecules, such as superoxide (O2-), hydrogen peroxide (H2O2), peroxynitrite (ONOO-), and the hydroxyl (•OH) radical. The present review...

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

    OpenAIRE

    Tuñón, María Jesús; Alvarez, Marcelino; Jesús M. Culebras; González-Gallego, Javier

    2009-01-01

    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 de...

  8. The Role of Leucoyte-Derived Free Oxygen Radicals in the Pathogenesis of Experimental Acute Pancreatitis

    OpenAIRE

    Akpinar, E; Özden, I.; N. Savci; A. Emre

    1995-01-01

    The role of free oxygen radicals in experimental acute pancreatitis induced by common bile duct ligation was investigated by measuring malondialdehyde levels in the rat pancreas. Also, the potential role of leucocytes as the source of free oxygen radicals was tested by inducing leukopenia with methotrexate. The malondialdehyde levels in the control, pancreatitis and pancreatitis + methotrexate groups were 9.6 ± 2.0, 44.8 ± 11.4, and 25.6 ± 5.0 nmol malondialdehyde/ g pancreas tissue respectiv...

  9. Role of free radicals in the pathogenesis of acute chest syndrome in sickle cell disease

    Directory of Open Access Journals (Sweden)

    Farber Harrison W

    2001-07-01

    Full Text Available Abstract Acute chest syndrome (ACS of sickle cell disease (SCD is characterized pathologically by vaso-occlusive processes that result from abnormal interactions between sickle red blood cells (RBCs, white blood cells (WBCs and/or platelets, and the vascular endothelium. One potential mechanism of vascular damage in ACS is by generation of oxygen-related molecules, such as superoxide (O2-, hydrogen peroxide (H2O2, peroxynitrite (ONOO-, and the hydroxyl (•OH radical. The present review summarizes the evidence for alterations in oxidant stress during ACS of SCD, and the potential contributions of RBCs, WBCs and the vascular endothelium to this process.

  10. Cannabinoid HU210 Protects Isolated Rat Stomach against Impairment Caused by Serum of Rats with Experimental Acute Pancreatitis

    OpenAIRE

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

    2012-01-01

    Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alte...

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

    Science.gov (United States)

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

    2016-04-01

    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 (respectivePvalues: 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

  12. A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis.

    Science.gov (United States)

    Zyromski, Nicholas J; Mathur, Abhishek; Pitt, Henry A; Lu, Debao; Gripe, John T; Walker, Julia J; Yancey, Kyle; Wade, Terence E; Swartz-Basile, Deborah A

    2008-09-01

    Obesity is clearly an independent risk factor for increased severity of acute pancreatitis (AP), although the mechanisms underlying this association are unknown. Adipokines (including leptin and adiponectin) are pleiotropic molecules produced by adipocytes that are important regulators of the inflammatory response. We hypothesized that the altered adipokine milieu observed in obesity contributes to the increased severity of pancreatitis. Lean (C57BL/6J), obese leptin-deficient (LepOb), and obese hyperleptinemic (LepDb) mice were subjected to AP by six hourly intraperitoneal injections of cerulein (50 microg/kg). Severity of AP was assessed by histology and by measuring pancreatic concentration of the proinflammatory cytokines IL-1beta and IL-6, the chemokine MCP-1, and the marker of neutrophil activation MPO. Both congenitally obese strains of mice developed significantly more severe AP than wild-type lean animals. Severity of AP was not solely related to adipose tissue volume: LepOb mice were heaviest; however, LepDb mice developed the most severe AP both histologically and biochemically. Circulating adiponectin concentrations inversely mirrored the severity of pancreatitis. These data demonstrate that congenitally obese mice develop more severe AP than lean animals when challenged by cerulein hyperstimulation and suggest that alteration of the adipokine milieu exacerbates the severity of AP in obesity. PMID:18583460

  13. Pathogenesis of non-antibody mediated transfusion-related acute lung injury from bench to bedside.

    Science.gov (United States)

    Peters, Anna L; van Hezel, Maike E; Juffermans, Nicole P; Vlaar, Alexander P J

    2015-01-01

    Transfusion-related acute lung injury (TRALI) is a major cause of transfusion-related mortality. Causative factors are divided in antibody mediated TRALI and non-antibody mediated TRALI. Antibody mediated TRALI is caused by passive transfusion of cognate antibodies and non-antibody mediated TRALI is caused by transfusion of aged cellular blood products. This review focuses on mechanisms in non-antibody mediated TRALI which includes soluble mediators accumulating during storage of red blood cells (RBCs) and platelets (PLTs), as well as changes in morphology and function of aged PLTs and RBCs. These mediators cause TRALI in two-hit animal models and have been implicated in TRALI onset in clinical studies. Pre-clinical studies show a clear relation between TRALI and increased storage time of cellular blood products. Observational clinical studies however report conflicting data. Knowledge of pathophysiological mechanisms of TRALI is necessary to improve storage conditions of blood products, develop prevention strategies and develop a therapy for TRALI. PMID:25277811

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

    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.

  15. Israeli Acute Paralysis Virus: Epidemiology, Pathogenesis and Implications for Honey Bee Health

    Science.gov (United States)

    Chen, Yan Ping; Pettis, Jeffery S.; Corona, Miguel; Chen, Wei Ping; Li, Cong Jun; Spivak, Marla; Visscher, P. Kirk; DeGrandi-Hoffman, Gloria; Boncristiani, Humberto; Zhao, Yan; vanEngelsdorp, Dennis; Delaplane, Keith; Solter, Leellen; Drummond, Francis; Kramer, Matthew; Lipkin, W. Ian; Palacios, Gustavo; Hamilton, Michele C.; Smith, Barton; Huang, Shao Kang; Zheng, Huo Qing; Li, Ji Lian; Zhang, Xuan; Zhou, Ai Fen; Wu, Li You; Zhou, Ji Zhong; Lee, Myeong-L.; Teixeira, Erica W.; Li, Zhi Guo; Evans, Jay D.

    2014-01-01

    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. PMID:25079600

  16. Mucosal immunoglobulins.

    Science.gov (United States)

    Woof, Jenny M; Mestecky, Jiri

    2005-08-01

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

  17. Mechanism of the preventive effect of breviscapus on pathogenesis of acute kidney injury in rats with sepsis

    Directory of Open Access Journals (Sweden)

    Mei YANG

    2015-01-01

    Full Text Available Objective To investigate the inhibitory effect and its related mechanism of Erigeron breviscapus on pathogenesis of acute kidney injury (AKI in rats with sepsis. Methods Thirty-six male Wistar rats were randomly assigned into control group, sepsis model group (CLP group, and breviscapine treatment group (treatment group, n=12 each. The sepsis model was reproduced by cecal ligation and puncture (CLP. The rats were sacrificed 24 h after operation. The levels of blood urea nitrogen (BUN and serum creatinine (Scr were assayed with enzymatic assays, endothelin 1 (ET-1 and inducible nitric oxide synthase (iNOS with ELISA, renal malondialdehyde (MDA and superoxide dismutase (SOD activities with xanthine oxide method, and the degree of renal tissue injury by micros copic examination after HE staining. Results Compared with the control group, the levels of Scr, BUN, ET-1, iNOS, MDA and iNOS in CLP groups significantly increased, while the SOD activities significantly decreased (P<0.05. Compared with the CLP group, the levels of Scr, BUN, ET-1, iNOS, MDA and iNOS were lower markedly in treatment group, while the SOD activity elevated markedly (P<0.05. Conclusions Breviscapine may reduce AKI in rats with sepsis, and the effect may be related to the improvement of renal microcirculation, reduction of antioxidant enzyme activity, and decrease in oxidation products. DOI: 10.11855/j.issn.0577-7402.2014.11.01

  18. Protective role of 1,25(OH2vitamin D3 in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice

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    Zhao Hongwei

    2012-05-01

    Full Text Available Abstract Background Intestinal hyper-permeability plays a critical role in the etiopathogenesis of inflammatory bowel disease (IBD by affecting the penetration of pathogens, toxic compounds and macromolecules. 1,25-dihydroxyvitamin D3 [1,25(OH2D3], the active form of vitamin D, has been shown to be an important regulator of IBD and recent epidemiology suggests that patients with IBD have an impaired vitamin D status. The purpose of this study is to investigate the possible protective effects of 1,25(OH2D3 on mucosal injury and epithelial barrier disruption on dextran sulfate sodium (DSS-induced acute colitis model. Methods We used DSS-induced acute colitis model to investigate the protective effects of 1,25(OH2D3 on mucosal injury and epithelial barrier integrity. Severity of colitis was evaluated by disease activity index (DAI, body weight (BW change, colon length, histology, myeloperoxidase (MPO activity, and proinflammatory cytokine production including tumor necrosis factor-α (TNF-α and interferon-γ (IFN-γ. In vitro the protective role of 1,25(OH2D3 was assessed by incubating Caco-2 cells with or without DSS and measuring transepithelial electrical resistance (TEER and fluorescein isothiocyanate dextran (FITC-D. The intestinal permeability was analyzed by FITC-D, bacterial translocation and measurement of lipopolysaccharide (LPS. Ultrastructural features of the colon tissue and Caco-2 cell monolayer were observed by electron microscopy. Expressions of tight junction (TJ proteins in the colon mucosa and Caco-2 cells were detected by immunohistochemistry, immunofluorescence, Western blot and real-time fluorescent quantitative PCR, respectively. Results DSS-induced acute colitis model was characterized by a reduced BW, AUC of BW, serum calcium, higher DAI, AUC of DAI, shortened colon length, elevated MPO activity, worsened histologic inflammation, increased mononuclear cell numbers in mesenteric lymph nodes (MLNs and colonic lamina propria

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

    NARCIS (Netherlands)

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

    2005-01-01

    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

  20. Antioxidant Properties and Gastroprotective Effects of 2-(EthylthioBenzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats.

    Directory of Open Access Journals (Sweden)

    Nafal Nazarbahjat

    Full Text Available A series of new 2-(ethylthiobenzohydrazone derivatives (1-6 were prepared and characterised by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly prepared compounds were screened for their in vitro antioxidant activities using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH and ferric reducing antioxidant power (FRAP assays. Among them, most powerful antioxidant, compound 1 has been selected in order to illustrate anti-ulcer effect on ethanol-induced gastric mucosal lesions in rats. Four groups of Sprague Dawley rats were respectively treated with 10% Tween 20 as ulcer control group, 20 mg/kg omeprazole as reference group, 50 mg/kg and 100 mg/kg compound 1 as experimental animals. Macroscopically, ulcer control group showed extensive hemorrhagic lesions of gastric mucosa compared with omeprazole or compound 1. Rats pre-treated with compound 1 showed increased in gastric pH and gastric mucus. Histologically, ulcer control group showed severe damage to gastric mucosa with edema and leucocytes infiltration of submucosal layer. In immunohistochemical analysis, rats which were pre-treated with compound 1 showed up-regulation of HSP70 and down-regulation of Bax proteins. In conclusion, the gastroprotective effect of compound 1 may be due to its antioxidant activity, and/or due to up-regulation of HSP70 and down-regulation of Bax protein in stained tissue section.

  1. Study on the pathogenesis of gastric mucosal injury in rats with duodenogastric reflux%十二指肠胃反流对大鼠胃黏膜损伤机制的研究

    Institute of Scientific and Technical Information of China (English)

    张艳丽; 姚树坤; 刘俊宝

    2012-01-01

    successful .The expression index of TNF-a and IL-1? in group both A and B were significantly higher than those in control group (P0.05).The apoptosis cells could be seen intensively in mucosa in DGR model group.Apoptosis index in group both A and B were significantly higher than that of group C(P0.05).Conclusion (Different components in DGR induce gastric mucosa injury,over expression of TNF-a and IL-ip as well as cell apoptosis may play important roles in the pathogenesis of gastric mucosal injury with DGR.

  2. Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile

    OpenAIRE

    WANG Min; Yan, Jingjun; He, Xingxing; Zhong, Qiang; Zhan, Chengye; Li, Shusheng

    2016-01-01

    Background Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways asso...

  3. Pretherapeutic Plasma Pro- and Anti- Inflammatory Mediators Are Related to High Risk of Oral Mucositis in Pediatric Patients with Acute Leukemia: A Prospective Cohort Study

    OpenAIRE

    Ye, Ying; Carlsson, Göran; Agholme, Monica Barr; Karlsson-Sjöberg, Jenny; Yucel-Lindberg, Tülay; Pütsep, Katrin; Modéer, Thomas

    2013-01-01

    Objective This prospective study evaluated clinical risk indicators as well as pro- and anti- inflammatory mediators at the time of malignancy diagnosis in relation to chemotherapy-related oral mucositis in pediatric population. Methods Patients (n = 104) under 18 years of age with primary malignancies and undergoing chemotherapy were included. Potential risk indicators were analyzed using binary logistic regression with oral mucositis as the outcome. In a subgroup (n = 35), plasma samples at...

  4. Oral Mucositis: understanding the pathology and management

    OpenAIRE

    Georgiou, M; Patapatiou, G; S. Domoxoudis; Pistevou-Gompaki, K; A. Papanikolaou

    2012-01-01

    Oral Mucositis is a common complication of cancer therapy which may limit the completion of treatment and affect the quality of life of the patient. As we have come to understand its pathogenesis new developments in its management and prevention have allowed us minimize this side effect.

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

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    Yongsheng You

    2016-01-01

    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.

  6. Mucosal Immunization with Surface-Displayed Severe Acute Respiratory Syndrome Coronavirus Spike Protein on Lactobacillus casei Induces Neutralizing Antibodies in Mice

    OpenAIRE

    Lee, Jong-Soo; Poo, Haryoung; Han, Dong P.; Hong, Seung-Pyo; Kim, Kwang; Cho, Michael W.; Kim, Eun; Sung, Moon-Hee; Kim, Chul-Joong

    2006-01-01

    Induction of mucosal immunity may be important for preventing SARS-CoV infections. For safe and effective delivery of viral antigens to the mucosal immune system, we have developed a novel surface antigen display system for lactic acid bacteria using the poly-γ-glutamic acid synthetase A protein (PgsA) of Bacillus subtilis as an anchoring matrix. Recombinant fusion proteins comprised of PgsA and the Spike (S) protein segments SA (residues 2 to 114) and SB (residues 264 to 596) were stably exp...

  7. Cytokines levels, Severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer - a prospective pilot study

    International Nuclear Information System (INIS)

    The purpose of this pilot study was to detect a correlation between serum cytokine levels and severity of mucositis, necessitating installation of a percutaneous endoscopic gastrostomy tube (PEG) in head and neck (H&N) cancer patients receiving combined chemo-radiation therapy. Fifteen patients with H&N epithelial cancer were recruited to this study. All patients received radiotherapy to the H&N region, with doses ranging from 50-70 Gy. Chemotherapy with cisplatin, carboplatin, 5-fluorouracil and taxanes was given to high-risk patients, using standard chemotherapy protocols. Patients were evaluated for mucositis according to WHO common toxicity criteria, and blood samples were drawn for inflammatory (IL-1, IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10) cytokine levels before and during treatment. A positive correlation was found between IL-6 serum levels and severity of mucositis and dysphagia; specifically, high IL-6 levels at week 2 were correlated with a need for PEG tube installation. A seemingly contradictory correlation was found between low IL-8 serum levels and a need for a PEG tube. These preliminary results, indicating a correlation between IL-6 and IL-8 serum levels and severity of mucositis and a need for a PEG tube installation, justify a large scale study

  8. 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

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    Wang QS

    2015-11-01

    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

  9. Infectious agents in coronary atheromas: a possible role in the pathogenesis of plaque rupture and acute myocardial infarction

    OpenAIRE

    Maria de Lourdes HIGUCHI; Jose A. F. RAMIRES

    2002-01-01

    In this review we report our recent findings of histopathological features of plaque instability and the association with Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) infection, studying thrombosed coronary artery segments (CAS) of patients who died due to acute myocardial infarction. Vulnerable plaques are known to be associated with fat atheromas and inflammation of the plaque. Here we demonstrated that vulnerability is also related with focal positive vessel remodeling that mai...

  10. Histopathology and pathogenesis of caerulein-, duct ligation-, and arginine-induced acute pancreatitis in Sprague-Dawley rats and C57BL6 mice.

    Science.gov (United States)

    Zhang, Jun; Rouse, Rodney L

    2014-09-01

    Three classical rodent models of acute pancreatitis were created in an effort to identify potential pre-clinical models of drug-induced pancreatitis (DIP) and candidate non-invasive biomarkers for improved detection of DIP. Study objectives included designing a lexicon to minimize bias by capturing normal variation and spontaneous and injury-induced changes while maintaining the ability to statistically differentiate degrees of change, defining morphologic anchors for novel pancreatic injury biomarkers, and improved understanding of mechanisms responsible for pancreatitis. Models were created in male Sprague-Dawley rats and C57BL6 mice through: 1) administration of the cholecystokinin analog, caerulein; 2) administration of arginine; 3) surgical ligation of the pancreatic duct. Nine morphologically detectable processes were used in the lexicon; acinar cell hypertrophy; acinar cell autophagy; acinar cell apoptosis; acinar cell necrosis; vascular injury; interstitial edema, inflammation and hemorrhage; fat necrosis; ductal changes; acinar cell atrophy. Criteria were defined for scoring levels (0 = absent, 1 = mild, 2 = moderate, 3 = severe) for each lexicon component. Consistent with previous studies, histopathology scores were significant greater in rats compared to mice at baseline and after treatment. The histopathology scores in caerulein and ligation-treated rats and mice were significantly greater than those of arginine-treated rats and mice. The present study supports a multifaceted pathogenesis for acute pancreatitis in which intra-acinar trypsinogen activation, damage to acinar cells, fat cells, and vascular cells as well as activation/degranulation of mast cells and activated macrophages all contribute to the initiation and/or progression of acute inflammation of the exocrine pancreas. PMID:24585404

  11. 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

    Energy Technology Data Exchange (ETDEWEB)

    Macann, Andrew, E-mail: amacann@adhb.govt.nz [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)

    2014-03-01

    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.

  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

    International Nuclear Information System (INIS)

    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. Infectious agents in coronary atheromas: a possible role in the pathogenesis of plaque rupture and acute myocardial infarction.

    Science.gov (United States)

    Higuchi, Maria de Lourdes; Ramires, Jose A F

    2002-01-01

    In this review we report our recent findings of histopathological features of plaque instability and the association with Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) infection, studying thrombosed coronary artery segments (CAS) of patients who died due to acute myocardial infarction. Vulnerable plaques are known to be associated with fat atheromas and inflammation of the plaque. Here we demonstrated that vulnerability is also related with focal positive vessel remodeling that maintains relatively well preserved lumen even in the presence of large atheromatous plaques. This phenomena may explain why the cinecoronariography may not detect large and dangerous vulnerable plaques. Greater amount of these bacteria in vulnerable plaques is associated with adventitial inflammation and positive vessel remodeling: the mean numbers of lymphocytes were significantly higher in adventitia than in the plaque, good direct correlation was obtained between numbers of CD20 B cells and numbers of CP infected cells in adventitia, and between % area of MP-DNA in the plaque and cross sectional area of the vessel, suggesting a cause-effect relationship. Mycoplasma is a bacterium that needs cholesterol for proliferation and may increase virulence of other infectious agents. In conclusion, co-infection by Mycoplasma pneumoniae and Chlamydia pneumoniae may represent an important co-factor for plaque instability, leading to coronary plaque thrombosis and acute myocardial infarction, since larger amount of these bacteria strongly correlated with histological signs of more vulnerability of the plaque. The search of CMV and Helicobacter pilori in these tissues resulted negative. PMID:12219114

  14. Infectious agents in coronary atheromas: a possible role in the pathogenesis of plaque rupture and acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    HIGUCHI Maria de Lourdes

    2002-01-01

    Full Text Available In this review we report our recent findings of histopathological features of plaque instability and the association with Mycoplasma pneumoniae (MP and Chlamydia pneumoniae (CP infection, studying thrombosed coronary artery segments (CAS of patients who died due to acute myocardial infarction. Vulnerable plaques are known to be associated with fat atheromas and inflammation of the plaque. Here we demonstrated that vulnerability is also related with focal positive vessel remodeling that maintains relatively well preserved lumen even in the presence of large atheromatous plaques. This phenomena may explain why the cinecoronariography may not detect large and dangerous vulnerable plaques. Greater amount of these bacteria in vulnerable plaques is associated with adventitial inflammation and positive vessel remodeling: the mean numbers of lymphocytes were significantly higher in adventitia than in the plaque, good direct correlation was obtained between numbers of CD20 B cells and numbers of CP infected cells in adventitia, and between % area of MP-DNA in the plaque and cross sectional area of the vessel, suggesting a cause-effect relationship. Mycoplasma is a bacterium that needs cholesterol for proliferation and may increase virulence of other infectious agents. In conclusion, co-infection by Mycoplasma pneumoniae and Chlamydia pneumoniae may represent an important co-factor for plaque instability, leading to coronary plaque thrombosis and acute myocardial infarction, since larger amount of these bacteria strongly correlated with histological signs of more vulnerability of the plaque. The search of CMV and Helicobacter pilori in these tissues resulted negative.

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

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    J. L. Pérez-Arellano

    1995-01-01

    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.

  16. Pathogenesis of Hepatic Encephalopathy

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    Irena Ciećko-Michalska

    2012-01-01

    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.

  17. Mucosal and Peripheral Lin− HLA-DR+ CD11c/123− CD13+ CD14− Mononuclear Cells Are Preferentially Infected during Acute Simian Immunodeficiency Virus Infection

    OpenAIRE

    Moore, Andrew C.; Bixler, Sandra L.; Mark. G. Lewis; Verthelyi, Daniela; Mattapallil, Joseph J.

    2012-01-01

    Massive infection of memory CD4 T cells is a hallmark of early simian immunodeficiency virus (SIV) infection, with viral infection peaking at day 10 postinfection (p.i.), when a majority of memory CD4 T cells in mucosal and peripheral tissues are infected. It is not clear if mononuclear cells from the monocyte and macrophage lineages are similarly infected during this early phase of explosive HIV and SIV infections. Here we show that, at day 10 p.i., Lin− HLA-DR+ CD11c/123− CD13+ CD14− macrop...

  18. INTERRELATIONS BETWEEN NEUTRO PHIL ENZYMES AND THEIR INHIBITORS IN PATHOGENESIS OF ACUTE RESPIRATORY DISTRESS SYNDROME ASSOCIATED WITH INFLUENZA PNEUMONIA

    Directory of Open Access Journals (Sweden)

    E. V. Prutkina

    2012-01-01

    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.

  19. Radiation induced oral mucositis

    OpenAIRE

    P S Satheesh Kumar; Anita Balan; Arun Sankar; Tinky Bose

    2009-01-01

    Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concer...

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

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    Paolo Nardi

    2015-12-01

    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

  1. Isolated mucosal Leishmaniasis

    OpenAIRE

    Deepak Sundriyal; Naveen Kumar; Raj Kumar; Brijesh Sharma

    2013-01-01

    Leishmaniasis is a term used to define a group of clinical syndrome caused by various species of parasite Leishmania. Three main clinical types of leishmaniasis are visceral leishmaniasis, cutaneous leishmaniasis and mucocutaneous leishmaniasis. However, isolated presentation as mucosal disease is rare. We report a case of primarily mucosal leishmaniasis.

  2. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

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

  3. Endothelial microparticles carrying hedgehog-interacting protein induce continuous endothelial damage in the pathogenesis of acute graft-versus-host disease.

    Science.gov (United States)

    Nie, Di-Min; Wu, Qiu-Ling; Zheng, Peng; Chen, Ping; Zhang, Ran; Li, Bei-Bei; Fang, Jun; Xia, Ling-Hui; Hong, Mei

    2016-05-15

    Accumulating evidence suggests that endothelial microparticles (EMPs), a marker of endothelial damage, are elevated in acute graft-versus-host disease (aGVHD), and that endothelial damage is implicated in the pathogenesis of aGVHD, but the mechanisms remain elusive. In this study, we detected the plasma EMP levels and endothelial damage in patients and mice with aGVHD in vivo and then examined the effects of EMPs derived from injured endothelial cells (ECs) on endothelial damage and the role of hedgehog-interacting protein (HHIP) carried by EMPs in these effects in vitro. Our results showed that EMPs were persistently increased in the early posttransplantation phase in patients and mice with aGVHD. Meanwhile, endothelial damage was continuous in aGVHD mice, but was temporary in non-aGVHD mice after transplantation. In vitro, EMPs induced endothelial damage, including increased EC apoptosis, enhanced reactive oxygen species, decreased nitric oxide production and impaired angiogenic activity. Enhanced expression of HHIP, an antagonist for the Sonic hedgehog (SHH) signaling pathway, was observed in patients and mice with aGVHD and EMPs from injured ECs. The endothelial damage induced by EMPs was reversed when the HHIP incorporated into EMPs was silenced with an HHIP small interfering RNA or inhibited with the SHH pathway agonist, Smoothened agonist. This work supports a feasible vicious cycle in which EMPs generated during endothelial injury, in turn, aggravate endothelial damage by carrying HHIP into target ECs, contributing to the continuously deteriorating endothelial damage in the development of aGVHD. EMPs harboring HHIP would represent a potential therapeutic target for aGVHD. PMID:27009877

  4. Migraine Pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Nabih M. M.D. Ramadan

    2000-01-01

    @@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

  5. Multiple Mucosal Neuroma Syndrome

    Directory of Open Access Journals (Sweden)

    Thami Gurvinder P

    1997-01-01

    Full Text Available A case of multiple mucosal neuroma syndrome recently classified as Multiple Endocrinal Neoplasia (MEN, type 2b, is reported for its rarity and importance of diagnosis at an early age.

  6. Nasal mucosal biopsy

    Science.gov (United States)

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

  7. Live bacterial delivery systems for development of mucosal vaccines

    NARCIS (Netherlands)

    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.

    2000-01-01

    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

  8. Oral mucositis in myelosuppressive cancer therapy.

    Science.gov (United States)

    Epstein, J B; Schubert, M M

    1999-09-01

    -inflammatory medications. These approaches to management have undergone initial study, but additional investigation is needed to determine their effectiveness with respect to the prevention of mucositis and symptom management and to determine appropriate doses and frequencies of intervention. Current studies and our increasing understanding of the pathogenesis of oral mucositis will lead to new approaches to management and improved quality of life for these patients. PMID:10503852

  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

    Directory of Open Access Journals (Sweden)

    Mohammed A. Alshawsh

    2011-11-01

    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. Pathogenesis of Candida vulvovaginitis.

    Science.gov (United States)

    Sobel, J D

    1989-01-01

    The occurrence of candida vulvovaginitis (CVV) has been estimated based on statistical data from Great Britain to be an increase to 200/100,000 over 10 years to 1984. CVV in the US is the 2nd commonest cause of vaginal infection, with bacterial vaginosis occurring twice as often. 85-90% of the yeasts isolated from the vagina are candida albicans, based on biotyping rather that the newer methods of DNA hybridization. The pathogenesis of CVV is discussed in terms of the microbiology (virulence factors, adherence, germ tube and mycelium formation, proteinase secretion, and switching colonies), asymptomatic vaginal colonization, transformation to symptomatic vaginitis, host predisposing factors (pregnancy, oral contraceptives, diabetes mellitus, antimicrobes, and other), vaginal defense mechanisms (humoral system, phagocytic system, cell mediated immunity, vaginal flora, other), and pathogenesis of recurrent and chronic CVV (internal reservoir, sexual transmission, vaginal relapse, and experimental models) The discussion of the development of virulent symptoms is capsuled in the following comments. Vaginal cell receptivity varies among individuals, but all strains of C. Albicans adhere to both exfoliated vaginal and buccal epithelial cells, or mucosal surfaces, through the yeast surface mannoprotein. It is suggested from in vitro studies that germ tube and mycelium formation facilitates vaginal mucosal invasion. Exogenous and endogenous factors may enhance germination and precipitate symptomatic vaginitis, or inhibit germination. Increased proteinase secretion may be a result of the transformation from the blastoconidium/colonization phase to the germinated invasive vaginitis stage or an independent virulence factor. It is reported that hereditable spontaneous switching may occur spontaneously in vivo also. Colonizing yeasts with a change in environment can transform to a more virulent phase. Colonization rates vary from 10-25%, and the critical issue is understanding

  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

    Institute of Scientific and Technical Information of China (English)

    张波; 刘燕燕; 刘丛丛; 武华

    2011-01-01

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

    Science.gov (United States)

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

    2016-09-01

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

  13. Mucosal biofilms of Candida albicans

    OpenAIRE

    Ganguly, Shantanu; Mitchell, Aaron P.

    2011-01-01

    Biofilms are microbial communities that form on surfaces and are embedded in an extracellular matrix. C. albicans forms pathogenic mucosal biofilms that are evoked by changes in host immunity or mucosal ecology. Mucosal surfaces are inhabited by many microbial species; hence these biofilms are polymicrobial. Several recent studies have applied paradigms of biofilm analysis to study mucosal C. albicans infections. These studies reveal that the Bcr1 transcription factor is a master regulator of...

  14. Alteration of the Redox State with Reactive Oxygen Species for 5-Fluorouracil-Induced Oral Mucositis in Hamsters

    OpenAIRE

    Yoshino, Fumihiko; Yoshida, Ayaka; Nakajima, Atsushi; Wada-Takahashi, Satoko; Takahashi, Shun-suke; Lee, Masaichi Chang-il

    2013-01-01

    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 muc...

  15. 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

    Institute of Scientific and Technical Information of China (English)

    刘补报; 李得溪

    2015-01-01

    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.

  16. Mucosal immunity in invertebrates

    Czech Academy of Sciences Publication Activity Database

    Bilej, Martin

    Vol. 1. Elsevier: Academic Press, 2015 - (Městecký, J.; Strober, W.; Russell, M.; Kelsall, B.; Cheroutre, H.; Lambrecht, B.), s. 135-144. (Fourth Edition). ISBN 978-0-12-415847-4 Institutional support: RVO:61388971 Keywords : mucosal immunity * invertebrates Subject RIV: EC - Immunology

  17. Oral mucosal manifestations of autoimmune skin diseases.

    Science.gov (United States)

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

    2015-10-01

    A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches. PMID:26117595

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

    Science.gov (United States)

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

    2005-10-01

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

  19. Allopurinol gel mitigates radiation-induced mucositis and dermatitis

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  1. Oral mucositis: recent perspectives on prevention and treatment

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio da Silva Santos

    2009-10-01

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

  2. Mucosal regeneration during radiotherapy

    International Nuclear Information System (INIS)

    Background and purpose: Regeneration of the aerodigestive mucosa is known to occur during conventionally fractionated radiotherapy. The circumstances surrounding its time of onset and magnitude are not well understood, however. Material and methods: Mucosal reactions were observed in 100 patients undergoing conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving accelerated treatment at 1.8 Gy twice daily over 3(1(2)) weeks on the Trans Tasman Radiation Oncology Group head and neck cancer trials. Similar observations in 61 patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten 3.0-4.2 Gy fractions over 2 weeks are compared. Results: Several findings emerged from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater rates of dose accumulation. 3. The timing of reactions suggested the presence of a strong regenerative mucosal response that started before the manifestation of 'patchy' (grade II) mucosal reactions. 4. The regenerative response was strong enough to 'make good' damage accumulated at a rate of 2 Gy/day in over a third of cases. 5. The linear quadratic model without time correction failed to provide an adequate prediction of the frequency or intensity of mucosal reactions produced by any of the regimes. A simple model of the regenerative response is presented. Conclusions: This study suggests that the timing and magnitude of the regenerative response vary between sites and individuals but are linked to the amount of epithelial cellular depletion occurring during treatment

  3. Small intestinal mucosal toxicity of cis-platinum--comparison of toxicity with platinum analogues and dexamethasone.

    OpenAIRE

    Allan, S G; Smyth, J. F.

    1986-01-01

    Cis-platinum causes profound gastrointestinal symptoms in patients and these may persist for many days after drug administration. Gut mucosal toxicity may be a factor in the pathogenesis of such prolonged nausea, vomiting and anorexia. The effects of cis-platinum on mouse ileal mucosal architecture, villus epithelial cell influx and disaccharidase activity are described in comparison with dhe effects of two platinum analogues, CBDCA and CHIP. In addition the effect of dexamethasone, a useful ...

  4. Collaborative studies in mucosal immunology in Goroka.

    Science.gov (United States)

    Clancy, Robert

    2010-01-01

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

  5. New Pathways for Alimentary Mucositis

    OpenAIRE

    Keefe, Dorothy M. K.; Joanne M. Bowen

    2008-01-01

    Alimentary mucositis is a major dose-limiting toxicity associated with anticancer treatment. It is responsible for reducing patient quality of life and represents a significant economic burden in oncology. The pathobiology of alimentary mucositis is extremely complex, and an increased understanding of mechanisms and pathway interactions is required to rationally design improved therapies. This review describes the latest advances in defining mechanisms of alimentary mucositis pathobiology in ...

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

    Science.gov (United States)

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

    2008-03-01

    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. PMID:17693944

  7. NOX1 is responsible for cell death through STAT3 activation in hyperoxia and is associated with the pathogenesis of Acute Respiratory Distress Syndrome

    OpenAIRE

    Carnesecchi, Stephanie; Dunand-Sauthier, Isabelle; Zanetti, Filippo; Singovski, Grigory; Deffert, Christine; Donati, Yves; Cagarelli, Thomas; Pache, Jean-Claude; Krause, Karl-Heinz; Reith, Walter; Barazzone-Argiroffo, Constance

    2014-01-01

    Reactive oxygen species (ROS) contribute to alveolar cell death in Acute Respiratory Distress Syndrome (ARDS) and we previously demonstrated that NOX1-derived ROS contributed to hyperoxia-induced alveolar cell death in mice. The study investigates whether NOX1 expression is modulated in epithelial cells concomitantly to cell death and associated to STAT3 signaling in the exudative phase of ARDS. In addition, the role of STAT3 activation in NOX1-dependent epithelial cell death was confirmed by...

  8. Motor response to acute dopaminergic challenge with apomorphine and levodopa in Parkinson's disease: implications for the pathogenesis of the on-off phenomenon.

    OpenAIRE

    Colosimo, C.; MERELLO, M; Hughes, A J; Sieradzan, K; A. J. Lees

    1996-01-01

    OBJECTIVES--To evaluate the contribution of postsynaptic changes to motor fluctuations, three groups of parkinsonian patients with differing responses to treatment were acutely challenged with two dopaminergic drugs-apomorphine and levodopa-having different mechanisms of action. METHODS--Forty two patients with Parkinson's disease (14 untreated, eight with a stable response to levodopa, and 20 with levodopa induced motor fluctuations) were challenged on two consecutive days with apomorphine a...

  9. New Concepts in the Pathogenesis, Diagnosis and Control of Diseases Caused by the Bovine Viral Diarrhea Virus

    OpenAIRE

    1988-01-01

    The new information on the pathogenesis and epidemiology of mucosal disease of cattle is reviewed. It is now known that clinical mucosal disease occurs only in cattle which were infected with a pestivirus in early gestation and were born with persistent viral infection and specific immunotolerance. These animals may be clinically normal at birth but may develop fatal mucosal disease, perhaps following superinfection with another pestivirus, usually between 6 and 24 months of age. They may als...

  10. Mucosal healing in ulcerative colitis

    DEFF Research Database (Denmark)

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

    2013-01-01

    . With the introduction of the tumor necrosis factor-alpha inhibitors for the treatment of UC, it has become increasingly evident that the disease course is influenced by whether or not the patient achieves mucosal healing. Thus, patients with mucosal healing have fewer flare-ups, a decreased risk of...

  11. Experience with registered mucosal vaccines.

    Science.gov (United States)

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

    2003-01-30

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

  12. 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.

    Science.gov (United States)

    Kawagishi, Takahiro; Kanai, Yuta; Tani, Hideki; Shimojima, Masayuki; Saijo, Masayuki; Matsuura, Yoshiharu; Kobayashi, Takeshi

    2016-02-01

    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. PMID:26901882

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

    Science.gov (United States)

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

    2012-01-01

    Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis. PMID:23285225

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Mucositis Grades and Yeast Species

    OpenAIRE

    Ognjenović, Marina; Milatić, Katja; Parat, Katica; Kovačić, Ivan; Ježina Bušelić, Marina A.; Božić, Joško

    2013-01-01

    Surgically treated patients with oral, head and neck cancer commonly develop mucositis during additional irradiation therapy. Oral mucosa inflammation other than irradiation is mostly caused by Candida albicans, yeast of Candida genus. This study evaluated possible connection between grades of oral mucositis and oral yeast profile in irradiated patients before, during and after irradiation. In 25 examined patients mucosits grades »0« to »2« before irradiation with 20% positive smears and o...

  16. Cutaneous and mucosal pain syndromes

    Directory of Open Access Journals (Sweden)

    Siddappa K

    2002-01-01

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

  17. Irradiation mucositis and oral flora

    International Nuclear Information System (INIS)

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

  18. Pathogenesis of cerebral malaria

    International Nuclear Information System (INIS)

    Full text: Cerebral Malaria (CM) is the most severe complication of malaria and a major cause of death. The mechanisms underlying human CM pathogenesis might be due to mechanical cause, as demonstrated by cytoadherence of parasitised erythrocytes pRB, or to excessive cytokine production by the host in response to Plasmodium falciparum, or a combination of the two together with neuronal injury by malaria toxins. Antibody response, genetic traits and other factors have been proposed to explain why only some episodes have life-threatening complications. The microvascular endothelial cell is a major target of inflammatory cytokines overproduced in infectious diseases. Fatal CM is associated with widespread induction of endothelial activation markers, with significant higher levels of ICAM, VCAM and E-selectin expression on vessels in the brain. 199 patients were admitted at the hospital and were classified with malaria-based neurological disfunctions, such as acute psychosis, ataxia, hallucinations, fever and convulsions, prostration or coma. On a flow chart, 65 of those patients with the most acute syndromes mentioned above, were found to have negative BSN (blood slide), compared to 124 where the BSN showed to be positive. Identically to the 10 other patients from the severe form group, also presented positive BSN. The condition of some of these two subgroup patients (15), will later evolve into a more severe form with acute neurological disfunctions attributed to the cerebral malaria. The interesting aspect in regards to the 65 patients considered as having CM, upon severe manifestations of the disease, show no or little peripheral parasitemia. This fact confirms our experimental conclusion that, in the process of pRB adhesion to the microvessels of the brain, they are sequestered by monocytes and platelets, leading to vessel rupture. This fact could be an explanation of the lower % of circulating pRB and low peripheral parasitemia. There is a relationship between

  19. Pathogenesis of Alcoholic Liver Disease.

    Science.gov (United States)

    Dunn, Winston; Shah, Vijay H

    2016-08-01

    Alcoholic liver disease includes a broad clinical-histological spectrum from simple steatosis, cirrhosis, acute alcoholic hepatitis with or without cirrhosis to hepatocellular carcinoma as a complication of cirrhosis. The pathogenesis of alcoholic liver disease can be conceptually divided into (1) ethanol-mediated liver injury, (2) inflammatory immune response to injury, (3) intestinal permeability and microbiome changes. Corticosteroids may improve outcomes, but this is controversial and probably only impacts short-term survival. New pathophysiology-based therapies are under study, including antibiotics, caspase inhibition, interleukin-22, anakinra, FXR agonist and others. These studies provide hope for better future outcomes for this difficult disease. PMID:27373608

  20. A case of fatal acute intermittent porphyria: laboratory diagnosis and pathogenesis considerations / Un caz fatal de porfirie acută intermitentă: diagnostic de laborator şi consideraţii patogenice

    Directory of Open Access Journals (Sweden)

    Bălaşa Rodica

    2014-09-01

    Full Text Available Porfiria acută intermitentă (PAI este o boală metabolică, cu transmitere autosomal dominantă, cu alterarea căii de biosinteză a hemului prin deficitul enzimei porphobilinogen (PBG dezaminaza. Acest diagnostic trebuie să fie evocate în toate cazurile de adultii care prezintă simptome inexplicabile, dar cu unele caracteristici clinice sugestive: femei cu vârstă reproductivă, dureri abdominale, slăbiciune musculară, hiponatremie prelungită şi severă, urină închisă la culoare sau roşie.

  1. Mucosal Leishmaniasis: An Underestimated Presentation of a Neglected Disease

    Directory of Open Access Journals (Sweden)

    Alessio Strazzulla

    2013-01-01

    Full Text Available We present a review of current knowledge about mucosal leishmaniasis (ML. Although involvement of mucous membranes is classically admitted in New World leishmaniasis, particularly occurring in infection by Leishmania (L. braziliensis species complex, ML is also a possible presentation of Old World leishmaniasis, in either L. donovani or L. major species complex infections. Thus, ML has to be considered not only as a Latin American disease but as an Old and New World disease. We describe ML epidemiology, pathogenesis, clinics, diagnosis, and therapy. Considering both its highly disfiguring lesions and its possible lethal outcome, ML should not be underestimated by physicians. Moreover, leishmaniasis is expected to increase its burden in many countries as sandfly vector distribution is widespreading towards non-endemic areas. Finally, the lack of clear understanding of ML pathogenesis and the absence of effective human vaccines strongly claim for more research.

  2. Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy: a double-blind randomised clinical trial

    OpenAIRE

    Stokman, MA; Spijkervet, FKL; Burlage, FR; Dijkstra, PU; Manson, WL; de Vries, EGE; Roodenburg, JLN

    2003-01-01

    Mucositis is an acute inflammation of the oral mucosa because of radiotherapy and/or chemotherapy. All patients receiving radiotherapy in the head and neck region develop oral mucositis. The aim of this study was to analyse the effects of selective oral flora elimination on radiotherapy-induced oral mucositis, in a double-blind, randomised, placebo-controlled trial. Sixty-five patients with a malignant tumour in the head and neck regions to be treated with primary curative or postoperative ra...

  3. High dose rate interstitial radiotherapy for tongue cancer with special reference to mucosal reaction

    International Nuclear Information System (INIS)

    To decide the most suitable dose schedule of high dose rate interstitial radiotherapy (HDRISR) for the tongue cancer, we paid attention to the acute mucosal reaction after radiation therapy. There is the European Organization for Research on Treatment of Cancer/Radiotherapy Oncology Group (EORTC/RTOG) scoring system for the intraoral mucosal reaction after radiation therapy, but this scoring system does not assess the degree of the mucosal reaction adequately at the disapprearing phase. So we modify the scoring system at the disappearing phase of mucosal reaction. When the mucositis turns to disappear phase, the score is 3.5 and when the coating area reduces less than 50% area at the peak mucosal reaction, the score is 2.5. When the coating becomes transparent, the score is further reduced by 1 degree. When there is only erythema, the score is 1, and when reaction disappears completely, the score is 0. We observed 10 cases of tongue cancer treated with interstitital brachytherapy; 5 cases were treated with HDRISR and 5 cases were low dose rate interstitital radiotherapy (LDRISR). During the appearing phase, we used the EORTC/RTOG scoring system and during the disappearing phase, the new scoring system. This system reflected the mucosal healing course very well. (author)

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

    International Nuclear Information System (INIS)

    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.)

  5. Pathogenesis of Parkinson's disease

    OpenAIRE

    Riederer, Peter; Lange, Klaus W.

    1992-01-01

    The importance of genetic aspects, ageing, environmental factors, head trauma, defective mitochondrial respiration, altered iron metabolism, oxidative stress and glutamatergic overactivity of the basal ganglia in the pathogenesis of Parkinson's disease (PD) are considered in this review.

  6. Arterivirus molecular biology and pathogenesis.

    Science.gov (United States)

    Snijder, Eric J; Kikkert, Marjolein; Fang, Ying

    2013-10-01

    Arteriviruses are positive-stranded RNA viruses that infect mammals. They can cause persistent or asymptomatic infections, but also acute disease associated with a respiratory syndrome, abortion or lethal haemorrhagic fever. During the past two decades, porcine reproductive and respiratory syndrome virus (PRRSV) and, to a lesser extent, equine arteritis virus (EAV) have attracted attention as veterinary pathogens with significant economic impact. Particularly noteworthy were the 'porcine high fever disease' outbreaks in South-East Asia and the emergence of new virulent PRRSV strains in the USA. Recently, the family was expanded with several previously unknown arteriviruses isolated from different African monkey species. At the molecular level, arteriviruses share an intriguing but distant evolutionary relationship with coronaviruses and other members of the order Nidovirales. Nevertheless, several of their characteristics are unique, including virion composition and structure, and the conservation of only a subset of the replicase domains encountered in nidoviruses with larger genomes. During the past 15 years, the advent of reverse genetics systems for EAV and PRRSV has changed and accelerated the structure-function analysis of arterivirus RNA and protein sequences. These systems now also facilitate studies into host immune responses and arterivirus immune evasion and pathogenesis. In this review, we have summarized recent advances in the areas of arterivirus genome expression, RNA and protein functions, virion architecture, virus-host interactions, immunity, and pathogenesis. We have also briefly reviewed the impact of these advances on disease management, the engineering of novel candidate live vaccines and the diagnosis of arterivirus infection. PMID:23939974

  7. Search for compounds for prevention and treatment of oral mucositis induced by radiotherapy

    International Nuclear Information System (INIS)

    In the clinical setting, the frequency of adverse effects is directly linked to the results of treatment. However, in the case of head and neck radiotherapy for cancer, adverse effects are unavoidable and among them, oral mucositis is considered to be the most significant and debilitating acute complication associated with such radiation therapy. In patients receiving head and neck radiotherapy, the prevalence of mucositis is 85-100% and mucositis-associated pain is the main type of cancer treatment-related pain. A mouthwash or iceball containing sodium alginate, sodium azulene sulfonate and fibrinolysin deoxyribonuclease is widely used for the prevention and treatment of mucositis. In the USA, many strategies for the prevention of oral mucositis have been evaluated, but conflicting data has made the results inconclusive. Keratinocyte Growth Factor 1 (KGF1) has achieved promising results in therapy and is the only medication currently approved by the Food and Drug Administration (FDA), though in Japan, it is not covered by the National Health Insurance scheme. Therefore, we feel it is important to establish useful strategies for the prevention and treatment of radiotherapy-induced mucositis based on significant scientific evidence. As oxidative stress is associated with radiation-induced mucositis, in this study, we used 60Co-γray-induced HO-1-N-1 cell injury to studying the characteristics of mucositis in this regard and found that two well-known antioxidants, N-Acetyl-L-cysteine and catechins, had preventive effects against γray-induced cytotoxicity. N-Acetyl-L-cysteine and catechins would therefore be good materials for the prevention of mucositis in patients undergoing cancer radiotherapy. (author)

  8. Poliovirus, pathogenesis of poliomyelitis, and apoptosis.

    OpenAIRE

    Blondel, B.; Colbère-Garapin, F.; Couderc, T.; Wirotius, A.; Guivel-Benhassine, F.

    2005-01-01

    Poliovirus (PV) is the causal agent of paralytic poliomyelitis, an acute disease of the central nervous system (CNS) resulting in flaccid paralysis. The development of new animal and cell models has allowed the key steps of the pathogenesis of poliomyelitis to be investigated at the molecular level. In particular, it has been shown that PV-induced apoptosis is an important component of the tissue injury in the CNS of infected mice, which leads to paralysis. In this review the molecular biolog...

  9. Gastric mucosal blood flow measurement

    International Nuclear Information System (INIS)

    Pertechnetate clearance (C/sub Tc/) by the stomach before and after betazole stimulation was compared to regional measurements of gastric blood flow utilizing nuclide (Chromium-51 and Cerium-141)-labeled microspheres in five piglets. Pertechnetate clearance closely correlated (correlation coefficient 0.926) with mucosal blood flow in the gastric corpus measured by the microsphere technique. Betazole increased blood flow in the corpus region by 100 percent but did not alter this relationship. Except in one experiment, microsphere blood flow valves in the antrum and fundus were unchanged by betazole and did not significantly correlate with pertechnetate clearance. Pertechnetate clearance appears to be a reliable method of determining gastric mucosal blood flow in experimental animals and may be considered as a noninvasive method for measuring such flow in humans. (U.S.)

  10. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Al Mofleh Ibrahim

    1997-01-01

    Full Text Available The past few years have witnessed a tremendous progress in our knowledge regarding the pathogenesis, diagnosis, prognostic evaluation and classification of acute pancreatitis. The role of ischemia, lysosomal enzymes, oxygen free radicals, polymorphnuclear cells-byproducts and inflammatory mediators in the pathogenesis of pancreatic necrosis and multiple organ failure has been emphasized. Furthermore, the recent knowledge about agents infecting pancreatic necrosis, routes of infection, bacteriological examination of fine needle aspirate and appropriate antibiotics have changed the concept of acute pancreatitis. New diagnostic tests such as rapid urinary trypsinogen-2 test and inflammatory mediators including polymorphnuclear elastase, C-reactive protein and interleukin-6 contribute to early diagnosis, prognostic evaluation and initiation of an appropriate therapy.

  11. Therapeutic management of radiation-induced oral mucositis

    International Nuclear Information System (INIS)

    Background: Acute reactions of oral mucosa are a frequent side effect of radiotherapy, which often necessitates interruption of the treatment. Marked proliferation of tumor stem cells during treatment interruptions may occur in squamous cell carcinomata, which represent the majority of tumors in the head and neck area. Hence a fatal consequence of treatment breaks may be a significant decrease in tumor cure rates. Furthermore, marked acute responses frequently result in increased late sequelae ('consequential damage'). Therefore, amelioration of the mucosal response aiming at avoiding treatment breaks and at reduction of late reactions coul definitely increase the therapeutic success of radiation treatment. Results: A variety of prophylactic and therapeutic methods have been proposed for the management of acute radiation reactions of the oral mucosa. Frequently, their efficiacy has been established for chemotherapy or in combination with other immunosuppressive treatments. Hence, systemical rather than local effects have to be considered. Conclusions: In general, prophylaxis of oral mucositis is mainly based on dental restoration or edentation, in combination with frequent oral hygienic measures after the meals and with antiseptic mouthwashes. Intensive personal care is recommended. The necessity of a percutaneous endoscopic gastrostoma is dependent on the status of the patient and on size and localization of the treatment area, i.e. the impairment of food uptake which is to be expected. Therapeutic intervention is restricted to local or systemic treatment of pain and local application of antimycotics and antibiotics. (orig./VHE)

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

    NARCIS (Netherlands)

    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.

    2009-01-01

    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

  13. Ethanol Impairs Mucosal Immunity against Streptococcus pneumoniae Infection by Disrupting Interleukin 17 Gene Expression

    OpenAIRE

    Trevejo-Nunez, Giraldina; Chen, Kong; Dufour, Jason P.; Bagby, Gregory J.; Horne, William T.; Nelson, Steve; Kolls, Jay K.

    2015-01-01

    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...

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

    OpenAIRE

    Mehdipour, M.; A Taghavi Zenoz; I Asvadi Kermani; Hosseinpour, A.

    2011-01-01

    "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...

  15. Enteral nutrition and mucosal immunity: implications for feeding strategies in surgery and trauma

    OpenAIRE

    Sigalet, David L.; Mackenzie, Shannon L.; Hameed, S Morad

    2004-01-01

    Systemic inflammatory responses to severe trauma and surgical illnesses may be partly responsible for numerous complications, including sepsis, multiple organ failure and unregulated hypermetabolism leading to protein-calorie malnutrition. The integrity of the gastrointestinal tract appears to be an important factor in the pathogenesis of the systemic inflammatory response and sepsis. Resuscitation and nutrition support strategies for preserving gut mucosal integrity have therefore been stron...

  16. Mucosal Immune Regulation in Intestinal Disease. The role of bacterial products, food components and drugs

    OpenAIRE

    Bol-Schoenmakers, M

    2009-01-01

    The challenge of the mucosal gut associated immune system is to remain unresponsive to food products and commensal microbiota, while mounting an appropriate immune response towards pathogens. This implicates the necessity of tight immune regulation within the gut associated lymphoid tissue (GALT). Imbalance between tolerance and immunity (e.g. intestinal homeostasis) contributes to the pathogenesis of intestinal diseases like inflammatory bowel disease (IBD) and food allergies. The first part...

  17. Protective mucosal immunity mediated by epithelial CD1d and IL-10

    OpenAIRE

    Olszak, Torsten; Neves, Joana F.; Dowds, C. Marie; Baker, Kristi; Glickman, Jonathan; Davidson, Nicholas O; Lin, Chyuan-Sheng; Jobin, Christian; Brand, Stephan; Sotlar, Karl; Wada, Koichiro; Katayama, Kazufumi; Nakajima, Atsushi; Mizuguchi, Hiroyuki; Kawasaki, Kunito

    2014-01-01

    The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host1,2. CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease3–8. As CD1d crosslinking on ...

  18. Oral Mucositis Induced By Anticancer Therapies

    OpenAIRE

    Al-Ansari, S.; Zecha, J.A.E.M.; Barasch, A.; Lange, de, J.; Rozema, F.R.; Raber-Durlacher, J. E.

    2015-01-01

    Oral mucositis induced by conventional cytotoxic cancer therapies is a common and significant clinical problem in oncology. Mucositis symptoms, which include severe pain, may lead to dose reductions and unplanned interruptions of chemotherapy and/or radiotherapy, and often affect patients' quality of life. In addition, ulcerative mucositis represents a risk factor for local or systemic infectious complications that may be life-threatening in immunosuppressed patients. The development of biolo...

  19. Management of chemo/radiation-induced oral mucositis in patients with head and neck cancer: A review of the current literature.

    Science.gov (United States)

    Moslemi, Dariush; Nokhandani, Akram Mohammadi; Otaghsaraei, Mahsa Taheri; Moghadamnia, Yasaman; Kazemi, Sohrab; Moghadamnia, Ali Akbar

    2016-07-01

    Oropharyngeal mucositis is an important complication in non-surgical cancer treatments. It represents the major complication in radiotherapy of tumors located in head and neck areas. Many results have been published in order to define the best clinical protocol for prophylaxis or treatment of mucositis, but a consensus has not been attained yet. In this review, some recent topics in prophylaxis and treatment of mucositis related to radiation therapy are reconsidered using PUBMED and GOOGLE SCHOOLAR search engines from 2000 to 2015. In this review, more than 100 clinical studies have been selected and divided into the prophylactic or therapeutic uses of the evaluated treatment agents. The number of patients and kind of study design, the clinical features, prevalence, risk factors, pathogenesis, diagnosis, complication, prophylaxis and the treatment of mucositis were also specified. Nevertheless, it has not been truly achieved a consensus protocol of prophylaxis and treatment of oral mucositis. PMID:27113797

  20. Study of reduction methods for irradiation on oral mucositis. The examination of reduction methods for mucosal failure

    International Nuclear Information System (INIS)

    Reduction methods for irradiation on oral mucosa examined concerning in acute phase of the carbon ion radiotherapy for head and neck malignancies. We enforced a mechanical teeth and gingival cleaning as an Oral hearth care and gargled a polaprezinc with sodium alginate, and azulene- lidocaine with glycerin sodium as a oral linces before radiation. The response of the mucosal failure was reduced compare with no care group. In this Result, we considered that oral hearth care for prevention of infection, and mucosa protection by the drug was important factor. (author)

  1. Pelvis dilatation and mucosal thickening of transplanted kidney: comparative study of resistive index and ultrasonographic finding

    International Nuclear Information System (INIS)

    Diagnostic ability of duplex Doppler ultrasonography relying on resistive index is limited when clinical symptoms and signs of rejection are subtle or renal dysfunction is caused by other conditions such as urinary tract infection. To investigate the significance in the changes of renal pelvis, a combined analysis of resistive index and ultrasonographic findings in cases of renal pelvis dilatation and mucosal thickening was undertaken. A mean resistive index was calculated from Doppler measurements of the main, segmental and interlobar arteries. The cause of mucosal thickening was retrospectively analysed using the clinical and laboratory findings. Twenty three cases of renal pelvis dilatation and 17 cases of mucosal thickening were found in a total of 159 renal transplantation cases. In 14 of the 23 cases with renal pelvis dilatation, renal function was normal and their mean resistive index was 0.64 ± 0.04. Pelvis and ureter dilatation caused by ureteral stenosis or compression was demonstrated in 6 cases and their mean resistive index (0.72 ± 0.05) was increased. Mucosal thickening of renal pelvis was found in 7 of 32 cases with acute injection and in 2 of 13 cases with chronic rejection, but their mean resistive index was not different from that of the cases without pelvic mucosal changes. Three cases of acute rejection associated with urinary tract infection and 2 cases of chronic rejection in whom resistive indices were indeterminate, but mucosal thickening of the renal pelvis was prominent at ultrasonography. In renal transplant patients having indeterminate resistive index and mucosal thickening of the renal pelvis, ultrasonographic features must be correlated with the clinical and laboratory findings for an accurate diagnosis and treatment of renal dysfunction

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Voice disorders in mucosal leishmaniasis.

    Directory of Open Access Journals (Sweden)

    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

  4. Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: a placebo-controlled double-blind randomized study

    International Nuclear Information System (INIS)

    Purpose: The aim of the study was to test the hypothesis that aerobic Gram-negative bacteria (AGNB) play a crucial role in the pathogenesis of radiation-induced mucositis; consequently, selective elimination of these bacteria from the oral flora should result in a reduction of the mucositis. Methods and Materials: Head-and-neck cancer patients, when scheduled for treatment by external beam radiation therapy (EBRT), were randomized for prophylactic treatment with an oral paste containing either a placebo or a combination of the antibiotics polymyxin E, tobramycin, and amphotericin B (PTA group). Weekly, the objective and subjective mucositis scores and microbiologic counts of the oral flora were noted. The primary study endpoint was the mucositis grade after 3 weeks of EBRT. Results: Seventy-seven patients were evaluable. No statistically significant difference for the objective and subjective mucositis scores was observed between the two study arms (p=0.33). The percentage of patients with positive cultures of AGNB was significantly reduced in the PTA group (p=0.01). However, complete eradication of AGNB was not achieved. Conclusions: Selective elimination of AGNB of the oral flora did not result in a reduction of radiation-induced mucositis and therefore does not support the hypothesis that these bacteria play a crucial role in the pathogenesis of mucositis

  5. Imaging of acute pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Merkle, Elmar M.; Goerich, Johannes [Department of Radiology, University Hospitals of Ulm, Steinhoevel Strasse 9, 89075 Ulm (Germany)

    2002-08-01

    Acute pancreatitis is defined as an acute inflammatory process of the pancreas with variable involvement of peripancreatic tissues or remote organ systems. This article reports the current classification, definition and terminology, epidemiology and etiology, pathogenesis and pathological findings, clinical and laboratory findings, and finally imaging findings of acute pancreatitis with emphasis on cross-sectional imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging. (orig.)

  6. Nutrition and Gut Mucositis in Pediatric Oncology

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko

    . Unfortunately, effective treatment strategies against mucositis are not in general available. The overall aim of the present PhD was to study interactions between mucositis, inflammation and nutrition. We hypothesized that toxic reactions in the alimentary tract, induced by chemotherapy, followed by release...

  7. Chronic rhinosinusitis pathogenesis.

    Science.gov (United States)

    Stevens, Whitney W; Lee, Robert J; Schleimer, Robert P; Cohen, Noam A

    2015-12-01

    There are a variety of medical conditions associated with chronic sinonasal inflammation, including chronic rhinosinusitis (CRS) and cystic fibrosis. In particular, CRS can be divided into 2 major subgroups based on whether nasal polyps are present or absent. Unfortunately, clinical treatment strategies for patients with chronic sinonasal inflammation are limited, in part because the underlying mechanisms contributing to disease pathology are heterogeneous and not entirely known. It is hypothesized that alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier, and tissue remodeling all contribute to the chronic inflammatory and tissue-deforming processes characteristic of CRS. Additionally, the host innate and adaptive immune responses are also significantly activated and might be involved in pathogenesis. Recent advancements in the understanding of CRS pathogenesis are highlighted in this review, with special focus placed on the roles of epithelial cells and the host immune response in patients with cystic fibrosis, CRS without nasal polyps, or CRS with nasal polyps. PMID:26654193

  8. Schwannomas and their pathogenesis.

    Science.gov (United States)

    Hilton, David A; Hanemann, Clemens Oliver

    2014-04-01

    Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney's complex. Schwannomas have a variety of morphological appearances, but they behave as World Health Organization (WHO) grade I tumors, and only very rarely undergo malignant transformation. Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation. The genetic pathways and morphological features of schwannomas associated with different genetic syndromes will be discussed. Merlin has multiple functions, including within the nucleus and at the cell membrane, and this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. PMID:24450866

  9. The pathogenesis of tendinopathy

    DEFF Research Database (Denmark)

    Magnusson, S Peter; Langberg, Henning; Kjær, Michael

    2010-01-01

    , such as tendinopathy, which is characterized by pain during activity, localized tenderness upon palpation, swelling and impaired performance. Tendon histological changes include reduced numbers and rounding of fibroblasts, increased content of proteoglycans, glycosaminoglycans and water...... injury mechanisms, thus implying that one or more 'weak links' are present in the structure. Understanding how tendon tissue adapts to mechanical loading will help to unravel the pathogenesis of tendinopathy....

  10. Pathogenesis of Lassa Fever

    OpenAIRE

    Walker, David H.; Yun, Nadezhda E.

    2012-01-01

    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 pathogenesi...

  11. Simian Varicella Virus Pathogenesis

    OpenAIRE

    Mahalingam, Ravi; Messaoudi, Ilhem; Gilden, Don

    2010-01-01

    Because varicella zoster virus (VZV) is an exclusively human pathogen, the development of an animal model is necessary to study pathogenesis, latency, and reactivation. The pathological, virological, and immunological features of simian varicella virus (SVV) infection in nonhuman primates are similar to those of VZV infection in humans. Both natural infection of cynomolgus and African green monkeys as well as intrabronchial inoculation of rhesus macaques with SVV provide the most useful model...

  12. Mucosal Antibodies Induced by Intranasal but Not Intramuscular Immunization Block Norovirus GII.4 Virus-Like Particle Receptor Binding.

    Science.gov (United States)

    Tamminen, Kirsi; Malm, Maria; Vesikari, Timo; Blazevic, Vesna

    2016-06-01

    Noroviruses (NoVs) account for the majority of diagnosed cases of viral acute gastroenteritis worldwide. Virus-like particle (VLP)-based vaccines against NoV are currently under development. Serum antibodies that block the binding of NoV VLPs to histo-blood group antigens, the putative receptors for NoV, correlate with protection against NoV infection. The role of functional mucosal antibodies in protection is largely unknown, even though the intestinal mucosa is the entry port for NoV. Balb/c mice were immunized intramuscularly (IM) or intranasally (IN) with NoV GII.4 VLPs, and systemic and mucosal blocking antibody responses were studied. IN immunization elicited NoV-specific serum and mucosal IgG and IgA antibodies, whereas IM immunized animals completely lacked IgA. Both immunization routes induced similar blocking activity in serum but only IN route generated blocking antibodies in mucosa. The level of IgA in the mucosal (nasal) lavages strongly correlated (r = 0.841) with the blocking activity, suggesting that IgA, but not IgG, is the major NoV blocking antibody on mucosal surfaces. The results indicate that only mucosal immunization route induces the development of functional anti-NoV IgA on mucosal surface. PMID:27135874

  13. Management of radiation therapy-induced mucositis in head and neck cancer patients. Part I: Clinical significance, pathophysiology and prevention

    Directory of Open Access Journals (Sweden)

    Wei Cheong Ngeow

    2011-12-01

    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 to provide instead an overview of all the possible remedies available, as well as highlighting to researchers the gaps that need to be filled. The first part of this review outlines the clinical significance and pathophysiology of radiation-induced mucositis, and looks into some of the preventive approaches available.

  14. Treatment of oral mucositis due to chemotherapy

    Science.gov (United States)

    Bagán-Sebastián, José V

    2016-01-01

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

  15. Oral mucositis. A complication of radiotherapy

    International Nuclear Information System (INIS)

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

  16. Molecular Pathogenesis of Spondyloarthritis

    DEFF Research Database (Denmark)

    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...... Associate Professor Allan Stensballe The output of this PhD programme, besides from this dissertation, includes 5 published papers, 30 ECTS PhD courses, oral presentations of posters in national and international research environment and a short-term scholarship at the La Jolla Institute for Allergy and...

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

    Directory of Open Access Journals (Sweden)

    Zhonghui Wen

    2004-01-01

    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.

  18. Lymphocyte Trafficking to Mucosal Tissues

    DEFF Research Database (Denmark)

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

    2015-01-01

    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 with...

  19. Pathogenesis of Arrhythmogenic Cardiomyopathy.

    Science.gov (United States)

    Asimaki, Angeliki; Kleber, Andre G; Saffitz, Jeffrey E

    2015-11-01

    Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease. It is characterized by frequent ventricular arrhythmias and increased risk of sudden cardiac death typically arising as an early manifestation before the onset of significant myocardial remodelling. Myocardial degeneration, often confined to the right ventricular free wall, with replacement by fibrofatty scar tissue, develops in many patients. ACM is a familial disease but genetic penetrance can be low and disease expression is highly variable. Inflammation might promote disease progression. It also appears that exercise increases disease penetrance and accelerates its development. More than 60% of probands harbour mutations in genes that encode desmosomal proteins, which has raised the possibility that defective cell-cell adhesion might play a role in disease pathogenesis. Recent advances have implicated changes in the canonical wingless-type mouse mammary tumour virus integration site (Wnt)/β-catenin and Hippo signalling pathways and defects in forwarding trafficking of ion channels and other proteins to the intercalated disk in cardiac myocytes. In this review we summarize the current understanding of the pathogenesis of ACM and highlight future research directions. PMID:26199027

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

    Science.gov (United States)

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

    2014-01-01

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

  1. Exploiting Mucosal Immunity for Antiviral Vaccines.

    Science.gov (United States)

    Iwasaki, Akiko

    2016-05-20

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

  2. Effect of ageing on colonic mucosal regeneration

    Institute of Scientific and Technical Information of China (English)

    Ferenc Sipos; Katalin Leiszter; Zsolt Tulassay

    2011-01-01

    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. Microbiota and mucosal immunity in amphibians

    Directory of Open Access Journals (Sweden)

    Bruno M Colombo

    2015-03-01

    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.

  4. Primary Mucosal Melanoma: Uncommonly Described Entity

    Directory of Open Access Journals (Sweden)

    Kaushal Yadav

    2015-12-01

    Full Text Available Because of rarity and clinical challenges arising from different anatomic location, our understanding of optimal management of mucosal melanoma remains limited. The most common sites for primary mucosal melanoma are head and neck followed by anorectal, and vulvovaginal regions. Data are limited but improved understanding has led to change in management from more radical excision to conservative surgery with negative margins. We try to summarize available evidences for management this uncommonly described entity.

  5. Irritable bowel syndrome: Diagnosis and pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Magdy El-Salhy

    2012-01-01

    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. Stress gastric ulcer after cardiac surgery: Pathogenesis risk factors and medical management

    OpenAIRE

    Mahdi Ait Houssa; Noureddine Atmani; Fouad Nya; Abdessamad Abdou; Younes Moutakiallah; Mehdi Bamous; Mohamed Drissi; Abdelatif Boulahya

    2013-01-01

    Stress ulcer lesions of upper gastrointestinal tract are well recognized in patients undergoing open cardiac surgery. Gastrointestinal bleeding following cardiac surgery is infrequent with significant morbidity and mortality. The pathogenesis of mucosal lesions and subsequent haemorrhage is complex and multifactorial. The diagnosis as well as the treatment of this complication remains a challenge for surgeons. Identifying the source of bleeding can be difficult. Despite of the successful con...

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

    OpenAIRE

    Liguori, Gennaro; Cortale, Maurizio; Cimino, Fabrizio; Sozzi, Michele

    2008-01-01

    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 perform...

  8. Pathogenesis of Lassa fever.

    Science.gov (United States)

    Yun, Nadezhda E; Walker, David H

    2012-10-01

    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. PMID:23202452

  9. Pathogenesis of Lassa Fever

    Directory of Open Access Journals (Sweden)

    David H. Walker

    2012-10-01

    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.

  10. Pathogenesis of Lassa Fever

    Science.gov (United States)

    Yun, Nadezhda E.; Walker, David H.

    2012-01-01

    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. PMID:23202452

  11. 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

    Institute of Scientific and Technical Information of China (English)

    段云; 张方信; 单体栋; 邵珂; 张盼

    2011-01-01

    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.

  12. Pathogenesis of nasal polyposis.

    Science.gov (United States)

    Hulse, K E; Stevens, W W; Tan, B K; Schleimer, R P

    2015-02-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition that affects a large proportion of the population world-wide and is associated with high cost of management and significant morbidity. Yet, there is a lack of population-based epidemiologic studies using current definitions of CRSwNP, and the mechanisms that drive pathogenesis in this disease remain unclear. In this review, we summarize the current evidence for the plethora of factors that likely contribute to CRSwNP pathogenesis. Defects in the innate function of the airway epithelial barrier, including diminished expression of antimicrobial products and loss of barrier integrity, combined with colonization by fungi and bacteria likely play a critical role in the development of chronic inflammation in CRSwNP. This chronic inflammation is characterized by elevated expression of many key inflammatory cytokines and chemokines, including IL-5, thymic stromal lymphopoietin and CCL11, that help to initiate and perpetuate this chronic inflammatory response. Together, these factors likely combine to drive the influx of a variety of immune cells, including eosinophils, mast cells, group 2 innate lymphoid cells and lymphocytes, which participate in the chronic inflammatory response within the nasal polyps. Importantly, however, future studies are needed to demonstrate the necessity and sufficiency of these potential drivers of disease in CRSwNP. In addition to the development of new tools and models to aid mechanistic studies, the field of CRSwNP research also needs the type of robust epidemiologic data that has served the asthma community so well. Given the high prevalence, costs and morbidity, there is a great need for continued research into CRS that could facilitate the development of novel therapeutic strategies to improve treatment for patients who suffer from this disease. PMID:25482020

  13. The Microbiological Context of HIV Resistance: Vaginal Microbiota and Mucosal Inflammation at the Viral Point of Entry

    OpenAIRE

    Schellenberg, John J.; Plummer, Francis A.

    2012-01-01

    Immune activation is increasingly recognized as a critical element of HIV infection and pathogenesis, causing expansion of virus founder populations at the mucosal port of entry and eventual exhaustion of cellular immune effectors. HIV susceptibility is well known to be influenced by concurrent sexually transmitted infections; however, the role of commensal vaginal microbiota is poorly characterized. Bacterial vaginosis (BV) is a risk factor for HIV acquisition in studies worldwide; however, ...

  14. Inside the mucosal immune system.

    Directory of Open Access Journals (Sweden)

    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.

  15. Gastric mucosal resistance to acute injury in experimental portal hypertension

    OpenAIRE

    Calatayud, Sara; Ramírez, M Carmen; Sanz, M Jesús; Moreno, Lucrecia; Hernández, Carlos; Bosch, Jaume; Piqué, Jose M; Esplugues, Juan V.

    2001-01-01

    The gastric mucosa of portal hypertensive rats exhibits important microvascular changes and a nitric oxide (NO)-dependent hyperemia. This study analyses whether portal hypertensive mucosa exhibits changes in its ability to withstand aggression.Portal hypertension was induced by partial portal vein ligation (PPVL) or common bile duct ligation (CBDL) and gastric damage was induced by oral administration of ethanol or aspirin. Experiments were performed in conscious or anaesthetized rats and som...

  16. [Immunoglobulin for prevention of radiogenic mucositis].

    Science.gov (United States)

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

    1995-07-01

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

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

    International Nuclear Information System (INIS)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

    2008-12-15

    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.

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

    Directory of Open Access Journals (Sweden)

    R. K. Rao

    2009-01-01

    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.

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

    International Nuclear Information System (INIS)

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

  1. Recent progress in melasma pathogenesis.

    Science.gov (United States)

    Lee, Ai-Young

    2015-11-01

    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. PMID:26230865

  2. Treatment of oral mucositis due to chemotherapy

    OpenAIRE

    Chaveli-López, Begonya; Bagán-Sebastián, José V.

    2016-01-01

    Introduction The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the management of oral mucositis caused by chemotherapy in cancer patients. Material and Methods An exhaustive search was made of the PubMed-Medline, Cochrane Library and Scopus databases, crossing the key words “oral mucositis”, “prevention” and “treatment” with the terms “chemotherapy” and “radiotherapy” by means of the bool...

  3. Acute genital ulcers

    OpenAIRE

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

    2014-01-01

    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...

  4. The role of Smad7 in oral mucositis

    OpenAIRE

    Bian, Li; Han, Gangwen; Zhao, Carolyn W.; Garl, Pamela J.; Wang, Xiao-Jing

    2015-01-01

    Oral mucositis, a severe oral ulceration, is a common toxic effect of radio- or chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at least 40% and up to 70%, of individuals treated with standard chemotherapy regimens or upper-body radiation, develop oral mucositis. To date, there is no FDA approved drug to treat oral mucositis in cancer patients. The key challenges for oral mucositis treatment are to repair a...

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

    OpenAIRE

    Mark Puvanendran; Anja Lieder; Wolfgang Issing

    2012-01-01

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

  6. 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

    Institute of Scientific and Technical Information of China (English)

    白春宏; 安洪; 王莎莉; 蒋电明; 范伟; 聂海

    2010-01-01

    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

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

    NARCIS (Netherlands)

    Wells, J.

    2011-01-01

    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

  8. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses.

    Science.gov (United States)

    Su, Shuo; Wong, Gary; Shi, Weifeng; Liu, Jun; Lai, Alexander C K; Zhou, Jiyong; Liu, Wenjun; Bi, Yuhai; Gao, George F

    2016-06-01

    Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015. In this review we aim to compare and contrast the different HCoVs with regard to epidemiology and pathogenesis, in addition to the virus evolution and recombination events which have, on occasion, resulted in outbreaks amongst humans. PMID:27012512

  9. Highlights in pathogenesis of vitiligo.

    Science.gov (United States)

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

    2015-03-16

    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. PMID:25789295

  10. Management of mucositis in oral irradiation

    International Nuclear Information System (INIS)

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

  11. Mucosal biofilm detection in chronic otitis media

    DEFF Research Database (Denmark)

    Wessman, Marcus; Bjarnsholt, Thomas; Eickhardt-Sørensen, Steffen Robert; Johansen, Helle Krogh; Homøe, Preben

    2014-01-01

    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 surg...

  12. Topical morphine for oral mucositis in children

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Fujiwara,Masachika

    1986-12-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Wei Cheong Ngeow

    2011-12-01

    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.

  15. Molecular mechanisms of rosacea pathogenesis

    Directory of Open Access Journals (Sweden)

    Davydova A.M.

    2013-09-01

    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.

  16. Inflammation in the Pathogenesis of Lyme Neuroborreliosis

    Science.gov (United States)

    Ramesh, Geeta; Didier, Peter J.; England, John D.; Santana-Gould, Lenay; Doyle-Meyers, Lara A.; Martin, Dale S.; Jacobs, Mary B.; Philipp, Mario T.

    2016-01-01

    Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis. PMID:25892509

  17. Induction of mucosal and systemic antibody responses against the HIV coreceptor CCR5 upon intramuscular immunization and aerosol delivery of a Virus-like Particle based vaccine

    Science.gov (United States)

    Hunter, Z; Smyth, HD; Durfee, P; Chackerian, B

    2009-01-01

    Virus-like particles (VLPs) can be exploited as platforms to increase the immunogenicity of poorly immunogenic antigens, including self-proteins. We have developed VLP-based vaccines that target two domains of the HIV coreceptor CCR5 that are involved in HIV binding. These vaccines induce anti-CCR5 antibodies that bind to native CCR5 and inhibit SIV infection in vitro. Given the role of mucosal surfaces in HIV transmission and replication, we also asked whether an aerosolized, VLP-based pulmonary vaccine targeting CCR5 could induce a robust mucosal response in addition to a systemic response. In rats, both intramuscular and pulmonary immunization induced high titer IgG and IgA against the vaccine in the serum, but only aerosol vaccination induced IgA antibodies at local mucosal sites. An intramuscular prime followed by an aerosol boost resulted in strong serum and mucosal antibody responses. These results show that VLP-based vaccines targeting CCR5 induce high-titer systemic antibodies, and can elicit both local and systemic mucosal response when administered via an aerosol. Vaccination against a self-molecule that is critically involved during HIV transmission and pathogenesis is an alternative to targeting the virus itself. More generally, our results provide a general method for inducing broad systemic and mucosal antibody responses using VLP-based immunogens. PMID:19849995

  18. Strategies of mucosal immunotherapy for allergic diseases

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    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.

  19. HVEM is a TNF Receptor with Multiple Regulatory Roles in the Mucosal Immune System.

    Science.gov (United States)

    Shui, Jr-Wen; Kronenberg, Mitchell

    2014-04-01

    The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or CD270 (1,2). In recent years, we have focused on understanding HVEM function in the mucosa of the intestine, particularly on the role of HVEM in colitis pathogenesis, host defense and regulation of the microbiota (2,3,4). HVEM is an unusual TNF receptor because of its high expression levels in the gut epithelium, its capacity to bind ligands that are not members of the TNF super family, including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi-directional functionality, acting as a signaling receptor or as a ligand for the receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel disease (IBD) risk gene as a result of genome wide association studies (5,6). This suggests HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense and the microbiota. Consistent with this, using mouse models, we have revealed how HVEM is involved in colitis pathogenesis, mucosal host defense and epithelial immunity (3,7). Although further studies are needed, our results provide the fundamental basis for understanding why Hvem is an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with multiple regulatory functions in the mucosa. PMID:24851095

  20. Pathogenesis of and unifying hypothesis for idiopathic pouchitis.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2009-04-01

    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.

  1. Pathogenesis of and unifying hypothesis for idiopathic pouchitis.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2012-02-01

    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. Current concepts of the pathogenesis of inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

    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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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. 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. 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. Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting

  5. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-24

    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.

  6. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    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

  7. Pathogenesis and new therapeutic targets

    OpenAIRE

    Mertens, Michael

    2010-01-01

    Acute lung injury and its pronounced form, acute respiratory distress syndrome, are life-threatening diseases with 190,000 patients and 74,500 deaths per year in the United States. Until now there have been no therapeutic approaches to lower morbidity and mortality, except for ventilation with small tidal volumes. This partially results from a lack of understanding of the underlying mechanism of ventilator induced acute lung injury on the alveolar and alveolar capillary level. In addition, ph...

  8. Probiotics as Antifungals in Mucosal Candidiasis.

    Science.gov (United States)

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

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. PMID:26826375

  9. Cough-induced Tracheobronchial Mucosal Bleeding.

    Science.gov (United States)

    Hira, Harmanjit Singh

    2011-01-01

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

  10. Oral presentation of an oesophageal mucosal tear

    OpenAIRE

    Uppal, S; De P, R

    1999-01-01

    Tears of the oesophageal wall following sudden forceful vomiting are well documented in literature. In Boerhaave's syndrome there is transmural rupture associated with complications including pneumothorax, pneumomediastinum, surgical emphysema and shock. In Mallory-Weiss syndrome mucosal tears are associated with haematemesis and shock. In neither of these conditions has intraluminal obstruction been described as an aetiological factor. We present a case with similar pathophysiology where oes...

  11. Mucosal immunity to the hookworm Ancylostoma ceylanicum

    OpenAIRE

    Alkazmi, Luay Mahmood M. A.

    2004-01-01

    The host-parasite relationship of the hookworm Ancylostoma ceylanicum was explored in a hamster model system, focusing on intestinal mucosal responses to infection. Primary infection induced a rapid reduction in villous height culminating in excess of 75% reduction by day 35. Crypts of Lieberkuhn increased in depth achieving maximum depth by day 35. Mitotic figures in crypts and mast cells increased until day 28. Goblet cells increased continuously from background levels of 50 cell/mm² to...

  12. Characterization of Mucosal Candida albicans Biofilms

    OpenAIRE

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

    2009-01-01

    C. albicans triggers recurrent infections of the alimentary tract mucosa that result from biofilm growth. Although the ability of C. albicans to form a biofilm on abiotic surfaces has been well documented in recent years, no information exists on biofilms that form directly on mucosal surfaces. The objectives of this study were to characterize the structure and composition of Candida biofilms forming on the oral mucosa. We found that oral Candida biofilms consist of yeast, hyphae, and commens...

  13. Frank hematuria as the presentation feature of acute leukemia

    Directory of Open Access Journals (Sweden)

    Suriya Owais

    2010-01-01

    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.

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

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

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

  15. Genes contributing to prion pathogenesis

    DEFF Research Database (Denmark)

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

    2008-01-01

    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), and...

  16. Supersaturated Calcium Phosphate Rinse in Preventing Oral Mucositis in Young Patients Undergoing Autologous or Donor Stem Cell Transplant

    Science.gov (United States)

    2016-03-21

    Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Juvenile Myelomonocytic Leukemia; Mucositis; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Childhood Rhabdomyosarcoma; Previously Treated Myelodysplastic Syndromes; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Unspecified Childhood Solid Tumor, Protocol Specific

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

    Science.gov (United States)

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

    2015-11-01

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

  18. Acute genital ulcers.

    Science.gov (United States)

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

    2014-01-01

    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. PMID:24473429

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

    Science.gov (United States)

    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...

  20. On the pathogenesis of IDDM

    DEFF Research Database (Denmark)

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

    1994-01-01

    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...

  1. Biology and pathogenesis of Acanthamoeba

    OpenAIRE

    Siddiqui Ruqaiyyah; Khan Naveed

    2012-01-01

    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...

  2. Pathogenesis of postoperative adhesion formation

    NARCIS (Netherlands)

    Hellebrekers, B.W.J.; Kooistra, T.

    2011-01-01

    Background: Current views on the pathogenesis of adhesion formation are based on the "classical concept of adhesion formation", namely that a reduction in peritoneal fibrinolytic activity following peritoneal trauma is of key importance in adhesion development. Methods: A non-systematic literature s

  3. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    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.

  4. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Andersen, Jesper Bøje

    2014-01-01

    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...

  5. Correlation Between Mucosal IL-6 mRNA Expression Level and Virulence Factors of Helicobacter pylori in Iranian Adult Patients With Chronic Gastritis

    OpenAIRE

    Azadegan-Dehkordi, Fatemeh; Bagheri, Nader; Shirzad, Mahsa; Sanei, Mohammad Hossein; Hashemzadeh-Chaleshtori, Morteza; Rafieian-Kopaei, Mahmoud; Tabatabaiefar, Mohammad Amin; Shirzad, Hedayatollah

    2015-01-01

    Background: Helicobacter pylori infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells that contribute to sustained local inflammation. In this study, we sought to examine IL-6 expression in H. pylori-infected and uninfected gastric mucosa and elucidate the implication in the pathogenesis of H. pylori-associated gastritis in human. Objectives: The current study aimed to determine mucosal IL-6 mRNA expression level...

  6. Melatonin is more effective than ascorbic acid and β-carotene in improvement of gastric mucosal damage induced by intensive stress

    OpenAIRE

    Akinci, Aysin; Esrefoglu, Mukaddes; Cetin, Asli; Ates, Burhan

    2015-01-01

    Introduction Oxidative stress has been considered to play a primary role in the pathogenesis of stress-induced gastric damage. The aim of this study was to investigate the effects of melatonin, ascorbic acid and β-carotene on stress-induced gastric mucosal damage. Material and methods Fifty-six male Wistar albino rats were divided into control, stress, stress + standard diet, stress + saline, stress + melatonin, stress + ascorbic acid and stress + β-carotene groups. The rats from stress group...

  7. A Clinicopathologic Study of 24 Cases of Systemic Mastocytosis Involving the Gastrointestinal Tract and Assessment of Mucosal Mast Cell Density in Irritable Bowel Syndrome and Asymptomatic Patients

    OpenAIRE

    Doyle, Leona A.; Sepehr, Golrokh J.; Hamilton, Matthew J; Akin, Cem; Castells, Mariana C.; Hornick, Jason L.

    2014-01-01

    Counting mast cells in gastrointestinal (GI) mucosal biopsies is becoming an increasingly common practice. The primary reason for this exercise is to evaluate for possible involvement by systemic mastocytosis (SM). However, the features of mastocytosis in GI biopsies are not well described. In addition, recent studies have suggested that increased mast cells may be involved in the pathogenesis of some cases of diarrhea-predominant irritable bowel syndrome (IBS); the term “mastocytic enterocol...

  8. Gut Mucosal FOXP3+ Regulatory CD4+ T Cells and Nonregulatory CD4+ T Cells Are Differentially Affected by Simian Immunodeficiency Virus Infection in Rhesus Macaques▿

    OpenAIRE

    Allers, Kristina; Loddenkemper, Christoph; Hofmann, Jörg; Unbehaun, Anett; Kunkel, Désirée; Moos, Verena; Kaup, Franz-Josef; Stahl-Hennig, Christiane; Sauermann, Ulrike; Epple, Hans-Jörg; Schneider, Thomas

    2010-01-01

    The gastrointestinal tract represents a major site for human and simian immunodeficiency virus (HIV and SIV) replication and CD4+ T-cell depletion. Despite severe depletion of mucosal CD4+ T cells, FOXP3+ regulatory CD4+ T cells (Treg) are highly increased in the gut mucosa of chronically HIV-infected individuals and may contribute to HIV pathogenesis, either by their immunosuppressive function or as a significant target cell population for virus production. Little is known about the suscepti...

  9. Some aspects of periodontitis pathogenesis in children

    Directory of Open Access Journals (Sweden)

    Shcherbina I.N.

    2013-12-01

    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.

  10. Enteroviruses in Acute Myocardial Infarction

    OpenAIRE

    A Gholoobi; MS Nabavinia; T Mohamadpoor; MS Alavi; Z Meshkat

    2012-01-01

    Background: Human enteroviruses (EVs) may have a role as a possible risk factor in the pathogenesis of MI. The aim of this study was to evaluate the presence of enterovirus genomic RNA in peripheral blood samples of patients with acute myocardial infarction (MI). Methods: We investigated the presence of enterovirus genomic RNA in the peripheral blood of 115 patients with acute MI hospitalized in the Coronary Care Unit of Imam Reza and Ghaem University Hospitals (Mashhad, Iran) by RT-PCR using...

  11. Acute pancreatitis complicating severe dengue

    OpenAIRE

    Vishakha Jain; O P Gupta; Tarun Rao; Siddharth Rao

    2014-01-01

    Dengue is an arthropod borne viral infection endemic in tropical and subtropical continent. Severe dengue is life threatening. Various atypical presentations of dengue have been documented. But we present a rare and fatal complication of severe dengue in form of acute pancreatitis. A 27-year-old male had presented with severe dengue in decompensated shock and with pain in abdomen due to pancreatitis. The pathogenesis of acute pancreatitis in dengue is not clearly understood, but various mecha...

  12. Treatment modalities of oral mucositis after radiation of head and neck cancers

    International Nuclear Information System (INIS)

    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)

  13. Low-Level Laser Therapy for Treatment of Oral Mucositis

    OpenAIRE

    Ravina Naomi Tarigan; Yuniardini Septorini Wimardhani

    2012-01-01

    Radiation and chemotherapy are the treatment options for head and neck cancer. Several side effects related to those treat-ment have been shown. Oral mucositis is a common side effect in patients undergoing those treatment. The presence of oral mucositis in these patients would influencing quality of life therefore compromising treatment outcome. The spec-trum of oral mucositis can be clinically seen as thinning of oral mucosa, oral discomfort to painful oral lesion causing mastication impair...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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....

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

    Directory of Open Access Journals (Sweden)

    Satoshi Iyama

    2014-10-01

    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.

  16. Scoring irradiation mucositis in head and neck cancer patients

    International Nuclear Information System (INIS)

    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)

  17. Scoring irradiation mucositis in head and neck cancer patients

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-01-01

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

  18. Acute Biliary Pancreatitis: Diagnosis and Treatment

    OpenAIRE

    Hazem Zakaria

    2009-01-01

    Gallstones are the commonest cause of acute pancreatitis (AP), a potentially life-threatening condition, worldwide. The pathogenesis of acute pancreatitis has not been fully understood. Laboratory and radiological investigations are critical for diagnosis as well prognosis prediction. Scoring systems based on radiological findings and serologic inflammatory markers have been proposed as better predictors of disease severity. Early endoscopic retrograde cholangiopancreatography (ERCP) is benef...

  19. Topical protection of human esophageal mucosal integrity.

    Science.gov (United States)

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

    2015-06-15

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

  20. Research controversies in management of oral mucositis.

    Science.gov (United States)

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

    2000-01-01

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

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

    OpenAIRE

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

    1994-01-01

    The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the eff...

  2. The role of mucosal microbiota in the development, maintenance, and pathologies of the mucosal immune system

    Czech Academy of Sciences Publication Activity Database

    Cebra, J. J.; Jiang, H. Q.; Boiko, N.; Tlaskalová, Helena

    Elsevier academic press, 2005, s. 335-368. ISBN 0-120491544-2 R&D Projects: GA ČR GA310/01/0933; GA AV ČR IAA5020205; GA AV ČR IBS5020203; GA MZd NK6742 Institutional research plan: CEZ:AV0Z50200510 Keywords : gnotobiological techniques * mucosal * commensal bacteria Subject RIV: EE - Microbiology, Virology

  3. Aegle Marmelos Enhances Gastric Mucosal Protection: Relevance for NSAIDS-Induced Gastric Mucosal Injury

    Directory of Open Access Journals (Sweden)

    P.Singh

    2012-07-01

    Full Text Available Objective: In order to study the gastroprotective effect of Aegle marmelos extract (AM, this study was undertaken on aspirin-induced ulcerogenesis in cannulated free-moving rats. Background: Most of the non-steroidal anti-inflammatory drugs (NSAIDs including aspirin (ASP cause gastric ulcer. The efficacy of several plants for the treatment of gastroduodenal disease is confirmed by clinical research, while basic scientific research helps us to uncover the mechanisms by which these plants exert their therapeutic effects. Method: To assess the possible antiulcer effect of AM, lesion index, gastric secretions glycoprotein levels and mucosal histopathology were determined in ASP induced gastric mucosal injury in cannulated free-moving rats. Results: Pretreatment with AM significantly prevented the development of gastric mucosal lesion and decreased the gastric toxicity produced by ulcerogen. In addition, ulcerated rats showed depletion of gastric wall mucus, glycoproteins and enhanced gastric acid secretion whereas treatment with AM prevented these ASP induced responses in cannulated free-moving rats. Histological studies confirmed the results. Conclusion: The present finding suggests that AM promotes ulcer protection by the decrease in ulcer index, gastric secretions and increase in the glycoprotein level, gastric mucin content and maintenance of mucosal epithelium. AM protects the gastric mucosa against ulceration by its antisecretory and cytoprotective property.

  4. Rotaviruses: from pathogenesis to vaccination

    OpenAIRE

    Greenberg, Harry B.; Estes, Mary K.

    2009-01-01

    Rotaviruses cause life-threatening gastroenteritis in children worldwide; the enormous disease burden has focused efforts to develop vaccines and led to the discovery of novel mechanisms of gastrointestinal virus pathogenesis and host responses to infection. Two live-attenuated vaccines for gastroenteritis (Rotateq and Rotarix) have been licensed in many countries. This review summarizes the latest data on these vaccines, their effectiveness and challenges to global vaccination. Recent insigh...

  5. Molecular biology and pathogenesis of hepatitis E virus

    Indian Academy of Sciences (India)

    Vivek Chandra; Shikha Taneja; Manjula Kalia; Shahid Jameel

    2008-11-01

    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.

  6. Epigenetics and Colorectal Cancer Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-06-05

    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.

  7. The Etiology and Pathogenesis of Chronic Rhinosinusitis: a Review of Current Hypotheses.

    Science.gov (United States)

    Lam, Kent; Schleimer, Robert; Kern, Robert C

    2015-07-01

    Chronic rhinosinusitis (CRS) is a broad clinical syndrome that is characterized by prolonged mucosal inflammation of the nose and paranasal sinuses, and is typically divided into two subtypes based on the presence or absence of nasal polyps. The etiology and pathogenesis of both forms remain areas of active research. Over the last 15 years, a number of hypotheses have been proposed to explain all or part of the clinical CRS spectrum. These hypotheses reflect the concept that CRS results from a dysfunctional interplay between individual host characteristics and factors exogenous to the host. Six broad theories on CRS etiology and pathogenesis are discussed as follows: (1) the "fungal hypothesis," (2) the "superantigen hypothesis," (3) the "biofilm hypothesis," and (4) the "microbiome hypothesis," all of which emphasize key environmental factors, and (5) the "eicosanoid hypothesis" and (6) the "immune barrier hypothesis," which describe specific host factors. These theories are reviewed, and the evidence supporting them is critically appraised. PMID:26143392

  8. Gastrointestinal mucosal barrier function and diseases.

    Science.gov (United States)

    Oshima, Tadayuki; Miwa, Hiroto

    2016-08-01

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

  9. Pharmacotherapy of Oral Mucositis with Palifermin

    Directory of Open Access Journals (Sweden)

    Piotr Rzepecki

    2009-01-01

    Full Text Available Oral mucositis (OM is one of the most debilitating and common side effects of intensive anti-cancer treatment. OM is associated with adverse clinical and economic outcomes. In addition to its symptomatic impact, OM increases the likelihood of unplanned breaks or delays in anti-cancer treatment, reduction in dose of chemotherapy, use of feeding tube placement or total parenteral nutrition, the need for an intravenous line, opioid use and hospitalization. Palifermin is a N-truncated recombinant human keratinocyte growth factor (KGF, a member of the fibroblast growth factor (FGF family, which binds specifically to the human KGF receptor and induces proliferation and differentiation of epithelial cells, including gastrointestinal epithelial cells, hepatocytes, type II pneumocytes, and transitional urothelial cells. It is the first agent approved by the U.S Food and Drug Administration and other regulatory authorities around the world for use in the prevention of oral mucositis caused by high-dose chemotherapy and stem cell transplantation. The following review aims to cover the recent peer-reviewed literature pertaining to the role of palifermin in the prevention of OM in different groups of patients treated with radiation therapy or chemotherapy against cancers.

  10. Dexmedetomidine decreases the oral mucosal blood flow.

    Science.gov (United States)

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

    2013-12-01

    There is an abundance of blood vessels in the oral cavity, and intraoperative bleeding can disrupt operations. There have been some interesting reports about constriction of vessels in the oral cavity, one of which reported that gingival blood flow in cats is controlled by sympathetic α-adrenergic fibres that are involved with vasoconstriction. Dexmedetomidine is a sedative and analgesic agent that acts through the α-2 adrenoceptor, and is expected to have a vasoconstrictive action in the oral cavity. We have focused on the relation between the effects of α-adrenoceptors by dexmedetomidine and vasoconstriction in oral tissues, and assessed the oral mucosal blood flow during sedation with dexmedetomidine. The subjects comprised 13 healthy male volunteers, sedated with dexmedetomidine in a loading dose of 6 μg/kg/h for 10 min and a continuous infusion of 0.7 μg/kg/h for 32 min. The mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and palatal mucosal blood flow (PMBF) were measured at 0, 5, 10, 12, 22, and 32 min after the start of the infusion. The HR, CO, and PBMF decreased significantly during the infusion even though there were no differences in the SV. The SVR increased significantly but the PMBF decreased significantly. In conclusion, PMBF was reduced by the mediating effect of dexmedetomidine on α-2 adrenoceptors. PMID:23958351

  11. Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy

    International Nuclear Information System (INIS)

    Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n=12) or single prophylaxis (n=5), or left untreated (n=7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature >38 deg C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy. (author)

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

    Directory of Open Access Journals (Sweden)

    M Mehdipour

    2011-03-01

    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.

  13. Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation

    Directory of Open Access Journals (Sweden)

    Titus A Reaves

    2005-03-01

    Full Text Available The symptomatic phases of many inflammatory diseases are characterized by migration of large numbers of neutrophils (PMN across a polarized epithelium and accumulation within a lumen. For example, acute PMN influx is common in diseases of the gastrointestinal system (ulcerative colitis, Crohn's disease, bacterial enterocolitis, gastritis, hepatobiliary system (cholangitis, acute cholecystitis, respiratory tract (bronchial pneumonia, bronchitis, cystic fibrosis, bronchiectasis, and urinary tract (pyelonephritis, cystitis. Despite these observations, the molecular basis of leukocyte interactions with epithelial cells is incompletely understood. In vitro models of PMN transepithelial migration typically use N-formylated bacterial peptides such as fMLP in isolation to drive human PMNs across epithelial monolayers. However, other microbial products such as lipopolysaccharide (LPS are major constituents of the intestinal lumen and have potent effects on the immune system. In the absence of LPS, we have shown that transepithelial migration requires sequential adhesive interactions between the PMN beta2 integrin CD11b/CD18 and JAM protein family members. Other epithelial ligands appear to be abundantly represented as fucosylated proteoglycans. Further studies indicate that the rate of PMN migration across mucosal surfaces can be regulated by the ubiquitously expressed transmembrane protein CD47 and microbial-derived factors, although many of the details remain unclear. Current data suggests that Toll-like receptors (TLR, which recognize specific pathogen-associated molecular patterns (PAMPs, are differentially expressed on both leukocytes and mucosal epithelial cells while serving to modulate leukocyte-epithelial interactions. Exposure of epithelial TLRs to microbial ligands has been shown to result in transcriptional upregulation of inflammatory mediators whereas ligation of leukocyte TLRs modulate specific antimicrobial responses. A better

  14. The hepatitis delta virus: Replication and pathogenesis.

    Science.gov (United States)

    Sureau, Camille; Negro, Francesco

    2016-04-01

    Hepatitis delta virus (HDV) is a defective virus and a satellite of the hepatitis B virus (HBV). Its RNA genome is unique among animal viruses, but it shares common features with some plant viroids, including a replication mechanism that uses a host RNA polymerase. In infected cells, HDV genome replication and formation of a nucleocapsid-like ribonucleoprotein (RNP) are independent of HBV. But the RNP cannot exit, and therefore propagate, in the absence of HBV, as the latter supplies the propagation mechanism, from coating the HDV RNP with the HBV envelope proteins for cell egress to delivery of the HDV virions to the human hepatocyte target. HDV is therefore an obligate satellite of HBV; it infects humans either concomitantly with HBV or after HBV infection. HDV affects an estimated 15 to 20million individuals worldwide, and the clinical significance of HDV infection is more severe forms of viral hepatitis - acute or chronic -, and a higher risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV monoinfection. This review covers molecular aspects of HDV replication cycle, including its interaction with the helper HBV and the pathogenesis of infection in humans. PMID:27084031

  15. Effects of mucosal loading on vocal fold vibration

    Science.gov (United States)

    Tao, Chao; Jiang, Jack J.

    2009-06-01

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

  16. Chemotherapy induced intestinal mucositis; from bench to bed

    NARCIS (Netherlands)

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

    2008-01-01

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

  17. Mucosal tolerance to food and environmental antigens in humans

    Czech Academy of Sciences Publication Activity Database

    Městecký, Jiří

    Praha: Carolinum, 2012. s. 50-50. ISBN 978-80-7395-456-7. [International Nutrition and Diagnostics Conference /12./. 27.08.2012-30.08.2012, Praha] Institutional research plan: CEZ:AV0Z50200510 Keywords : Mucosal barrier * immune system * mucosal tolerance Subject RIV: EC - Immunology

  18. Mucosal Immune Regulation in Early Infancy: Monitoring and Intervention

    NARCIS (Netherlands)

    J. Hol (Jeroen)

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-10-01

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

  20. [The role of defensins in the pathogenesis of chronic-inflammatory bowel disease].

    Science.gov (United States)

    Schmid, M; Fellermann, K; Wehkamp, J; Herrlinger, K; Stange, E F

    2004-04-01

    Defensins are endogenous antimicrobial peptides with a broad activity spectrum. Even at micromolar concentrations gramnegative and grampositive bacteria, but also mycobacteria, as well as fungi (candida), viruses (herpes) and protozoa (giardia lamblia) are destroyed. As part of the innate immune system defensins are expressed by the intestinal epithelium and contribute to the maintenance of the mucosal barrier. This barrier appears to be defective in inflammatory bowel diseases since on one hand, the immune response is directed against the "normal" luminal bacterial flora and on the other hand, mucosal adherent and invasive bacteria have been observed in these diseases. A defective defensin expression may well explain these phenomena. Indeed, Crohn's disease of the terminal ileum, especially if associated with a NOD2 mutation, is characterised by a diminished alpha-defensin (human defensin 5 and 6) expression, and in inflamed Crohn's colitis, in contrast to ulcerative colitis, the beta-defensin (human beta-defensins 2 and 3) response is reduced. Through a deficient chemical mucosal barrier this defect could lead to increased bacterial invasion into the intestinal mucosa and might well explain an adequate inflammatory response. Although the final proof that this deficient defensin response leads to a reduced antibacterial activity of the intestinal mucosa is still lacking, the most plausible concept of pathogenesis of Crohn's disease is a defensin deficiency syndrome. PMID:15095125

  1. The pathogenesis of hyaline arteriolosclerosis.

    OpenAIRE

    Gamble, C. N.

    1986-01-01

    Although hyaline arteriolosclerosis is very common and has been of interest to pathologists for well over 100 years, its pathogenesis has never been determined. This study demonstrates that iC3b bound via an ester linkage to hydroxyl groups on the repeating disaccharide units of hyaluronic acid is a major component of arteriolar hyaline. The deposition of iC3b within the walls of arterioles appears to be due to slow spontaneous activation of the alternative complement pathway and random bindi...

  2. Biology and pathogenesis of Acanthamoeba

    Directory of Open Access Journals (Sweden)

    Siddiqui Ruqaiyyah

    2012-01-01

    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.

  3. Molecular pathogenesis of hereditary hemochromatosis.

    Science.gov (United States)

    Liu, Jingqi; Pu, Chunwen; Lang, Lang; Qiao, Liang; Abdullahi, Mohanud Abukar Haji; Jiang, Chunmeng

    2016-08-01

    Hereditary hemochromatosis (HH) is an inherited iron overload disorder characterized by normal iron-driven erythropoiesis and abnormal iron metabolism, leading to excess iron deposited in parenchymal cells of liver, heart, and endocrine glands. Iron hormone, hepcidin, plays a critical role in iron homeostasis through interaction with ferroportin (FPN), a major cellular iron exporter. Hepcidin is encoded by hepcidin antimicrobial peptide (HAMP). Mutations in hepcidin and any genes that regulate the biology of hepcidin, including hemochromatosis genes (HFE), Hemojuvelin (HJV), transferring receptor 2 (TFR2) and FPN, result in hemochromatosis. The identification of hepcidin and its role will provide a better understanding for pathogenesis of HH. PMID:27031690

  4. Acute abdomen

    International Nuclear Information System (INIS)

    The book first presents the anatomy and physiology of the abdomen and continues with chapters discussing clinical and laboratory aspects and a suitable order of diagnostic examinations with reference to the acute processes, explaining the diagnostic tools: ultrasonography, radiography including angiography and CT, tapping techniques and endoscopy together with their basic principles, examination techniques, and diagnosis. One chapter presents a complete survey of the processes involving the entire abdomen - as e.g. peritonitis, ileus, abdominal trauma, intraperitoneal hemorrage. This chapter profoundly discusses the diagnostics and therapies including emergency measures and surgery. Problems requiring consultation among varous specialists, in internal medicine, gynecology, urology, or pediatrics, are discussed in great detail. Information for the anesthetist is given for cases of emergency. More than one third of the book is devoted to organ-specific information, dicussing the pathogenesis, diagnostics, and therapy of the oesophagus, stomach, large and small intestine, bile ducts, pankreas, liver, spleen, and the abdominal vessels and the abdominal wall. (orig.) With 153 figs., 90 tabs

  5. Oral mucosal involvement in visceral leishmaniasis

    Institute of Scientific and Technical Information of China (English)

    Sunny Garg; Richik Tripathi; Kamlakar Tripathi

    2013-01-01

    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.

  6. Topical and mucosal liposomes for vaccine delivery.

    Science.gov (United States)

    Romero, Eder Lilia; Morilla, Maria Jose

    2011-01-01

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

  7. [Pathogenesis of large vessel vasculitis].

    Science.gov (United States)

    Samson, M; Bonnotte, B

    2016-04-01

    Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are two granulomatous vasculitis affecting large arteries that present specific epidemiological and clinical features. Their pathogenesis is not fully understood but major advances have been obtained during the last years, thus allowing the emergence of new therapeutic strategies. GCA and TA develop on a specific genetic background but share some similarities regarding the immunological pathways involved in their pathogenesis. The trigger of these diseases is not clearly identified but it is thought that an infectious agent could activate and lead to the maturation of dendritic cells that are localized in the adventitia of arteries. Then, the cells of the adaptative immune response are recruited and activated: CD4 T cells that polarize into Th1 and Th17 cells, cytotoxic CD8 T cells and Natural Killer cells. Furthermore, the T regulatory cells (Treg) are decreased both in GCA and TA. Humoral immune response seems also to be involved, especially in TA. Then, the cytokines produced by T lymphocytes (especially IL-17 and IFN-γ) trigger the recruitment and activation of monocytes and their differentiation into macrophages and multinuclear giant cells that produce IL-1β and IL-6 that are responsible for general symptoms of GCA and TA, and cytotoxic mediators and growth factors that trigger the remodeling of the arterial wall leading to aneurysms and ischemic manifestations of GCA an TA. PMID:26620872

  8. Pathogenesis of chronic rhinosinusitis: inflammation.

    Science.gov (United States)

    Van Crombruggen, Koen; Zhang, Nan; Gevaert, Philippe; Tomassen, Peter; Bachert, Claus

    2011-10-01

    Chronic rhinosinusitis (CRS) is a heterogeneous group of inflammatory diseases of the nasal and paranasal cavities either accompanied by polyp formation (CRSwNP) or without polyps (CRSsNP). CRSsNP and CRSwNP are prevalent medical conditions associated with substantial impaired quality of life, reduced workplace productivity, and serious medical treatment costs. Despite recent research evidence that contributes to further unveiling the pathophysiology of these chronic airway conditions, the cause remains poorly understood and appears to be multifactorial. A diverse spectrum of alterations involving histopathology, inflammatory cell and T-cell patterns, remodeling parameters (eg, TGF-β), eicosanoid and IgE production, microorganisms, and epithelial barrier malfunctions is reported in the search to describe the pathogenesis of this heterogeneous group of upper airway diseases. Furthermore, novel evidence indicates considerable heterogeneity within the CRSwNP subgroup determining the risk of comorbid asthma. The characterization of specific disease subgroups is a challenging scientific and clinical task of utmost importance in the development of diagnostic tools and application of individualized treatments. This review focuses on recent evidence that sheds new light on our current knowledge regarding the inflammatory process of CRS to further unravel its pathogenesis. PMID:21868076

  9. Molecular Pathogenesis of Neuromyelitis Optica

    Directory of Open Access Journals (Sweden)

    Simon A Broadley

    2012-10-01

    Full Text Available Neuromyelitis optica (NMO is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG against aquaporin-4 (AQP4, a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6 have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies.

  10. Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Wu Li

    2012-01-01

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

  11. Role of oxygen free radicals in patients with acute pancreatitis

    OpenAIRE

    Park, Byung Kyu; Chung, Jae Bock; Lee, Jin Heon; Suh, Jeong Hun; Park, Seung Woo; Song, Si Young; Kim, Hyeyoung; Kim, Kyung Hwan; Kang, Jin Kyung

    2003-01-01

    AIM: The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis. The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreatitis.

  12. Caspase-11 Modulates Inflammation and Attenuates Toxoplasma gondii Pathogenesis.

    Science.gov (United States)

    Coutermarsh-Ott, Sheryl L; Doran, John T; Campbell, Caroline; Williams, Tere M; Lindsay, David S; Allen, Irving C

    2016-01-01

    Toxoplasma gondii is an obligate intracellular parasite that is the etiologic agent responsible for toxoplasmosis. Infection with T. gondii results in activation of nucleotide binding domain and leucine rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Recently, a noncanonical inflammasome has been characterized which functions through caspase-11 and appears to augment many biological functions previously considered to be dependent upon the canonical inflammasome. To better elucidate the function of this noncanonical inflammasome in toxoplasmosis, we utilized Asc (-/-) and Casp11 (-/-) mice and infected these animals with T. gondii. Our data indicates that caspase-11 modulates the innate immune response to T. gondii through a mechanism which is distinct from that currently described for the canonical inflammasome. Asc (-/-) mice demonstrated increased disease pathogenesis during the acute phase of T. gondii infection, whereas Casp11 (-/-) mice demonstrated significantly attenuated disease pathogenesis and reduced inflammation. This attenuated host response was associated with reduced local and systemic cytokine production, including diminished IL-1β. During the chronic phase of infection, caspase-11 deficiency resulted in increased neuroinflammation and tissue cyst burden in the brain. Together, our data suggest that caspase-11 functions to protect the host by enhancing inflammation during the early phase of infection in an effort to minimize disease pathogenesis during later stages of toxoplasmosis. PMID:27378827

  13. Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - a new mechanism of gastric mucosal protection.

    Science.gov (United States)

    Ueda, Kazuki; Ueyama, Takashi; Oka, Masashi; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

    2009-07-01

    Heme oxygenase (HO)-1 is implicated in cytoprotection in various organs. We tested a possibility that polaprezinc (PZ), an anti-ulcer drug, could induce HO-1 in the gastric mucosa. Male 6-week-old Wistar rats were intragastrically administered PZ. Gastric expression of HO-1 was assessed by real time RT-PCR and western blotting, and localization of HO-1 was observed by in situ hybridization and immunohistochemistry. The levels of HO-1 mRNA were increased in a dose-dependent manner. The levels of HO-1 mRNA were increased 4-fold by PZ at the dose of 200 mg/kg at 3 h as compared with control levels. The levels of immunoreactive HO-1 were increased 3-fold at 6 h. Signals for HO-1 mRNA and immunoreactivity were detected strongly in the surface gastric mucosal cells and moderately in the gastric macrophages. Treatment with an HO-1 inhibitor, stannous mesoporphyrin (SnMP) significantly worsened the HCl-induced acute gastric mucosal lesions and increased the apoptosis of mucosal cells. Mucosal lesions were decreased by pretreatment with PZ, while they were increased by co-administration with SnMP. These data indicate for the first time that PZ is an effective inducer of HO-1 in the stomach. PZ-induced HO-1 functions as a part of the mucosal protective effects of PZ. PMID:19542683

  14. The Secretion of IL-22 from Mucosal NKp44+ NK Cells Is Associated with Microbial Translocation and Virus Infection in SIV/SHIV-Infected Chinese Macaques

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2014-01-01

    Full Text Available Microbial translocation (MT causes systemic immune activation in chronic human immunodeficiency virus (HIV infection. The role of a novel subtype of innate lymphoid cells, the NKp44+ NK cells, in HIV/simian immunodeficiency virus- (SIV- induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV- infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44+ NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44+ NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44+ NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44+ NK cells and interleukin-22 (IL-22 secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44+ NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

  15. Tolerance of gastric mucosal flap to postoperative irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Devineni, V.R.; Hayden, R.; Fredrickson, J.; Sicard, G. (Washington Univ. Medical Center, St. Louis, MO (USA))

    1991-05-01

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

  16. Tolerance of gastric mucosal flap to postoperative irradiation

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Radio-induced oral and pharyngeal mucositis: Management updates

    International Nuclear Information System (INIS)

    Mucositis is a major side effect induced by radiotherapy and/or chemotherapy of head and neck cancer. This toxicity impacts patient's quality of life and may compromise optimal treatments. Pathophysiology, risk factors, incidence and consequences of mucositis will be discussed in this review. Its management remains principally supportive (pain medication and nutritional support); however, in recent years several studies have revealed that the use of low level energy laser is particularly useful in the prevention and treatment of chemo- and radio-induced mucositis. (authors)

  19. Epidemiological, clinical anf pathogenetic studies of acute intermittent porphyria

    OpenAIRE

    Bylesjö, Ingemar

    2008-01-01

    Porphyrias are inherited metabolic disorders characterised by an impairment of heme biosynthesis. Acute intermittent porphyria (AIP) is the most common of the acute porphyrias in Sweden. Acute attacks of AIP are characterised by neuro-psychiatric symptoms, including epileptic seizures. Environmental and acquired factors are related to the induction of symptoms. Acute attacks of AIP are treated with high doses of glucose and/or hematin infusions. The pathogenesis of the neuro-psychiatric sympt...

  20. Local and systemic pathogenesis and consequences of regimen-induced inflammatory responses in patients with head and neck cancer receiving chemoradiation

    OpenAIRE

    Elvio G. Russi; Raber-Durlacher, Judith E.; Sonis, Stephen T.

    2014-01-01

    Treatment-related toxicities are common among patients with head and neck cancer, leading to poor clinical outcomes, reduced quality of life, and increased use of healthcare resources. Over the last decade, much has been learned about the pathogenesis of cancer regimen-related toxicities. Historically, toxicities were separated into those associated with tissue injury and those with behavioural or systemic changes. However, it is now clear that tissue-specific damage such as mucositis, derma...

  1. PEPTIC ULCER: A REVIEW ON ETIOLOGY AND PATHOGENESIS

    Directory of Open Access Journals (Sweden)

    Kaur Amandeep

    2012-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Nitasha Mittal

    2012-01-01

    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.

  3. Pathogenesis of recurrent aphthous stomatitis: a review of literature

    International Nuclear Information System (INIS)

    Recurrent aphthous stomatitis represents a very common chronic but poorly understood mucosal disorder, affecting 10% to 20% of the world population. They occur in men and women of all ages, races and geographic regions. It is estimated that at least 1 in 5 individuals has at least once been afflicted with aphthous ulcers. There are 3 clinical subtypes that is minor, major and herpetiform on the basis of their size and number. Minor aphthous ulcers are the most common subtype, representing 80% to 90% of all recurrent aphthous ulcers. There are four stages of the lesion, these includes premonitory, preulcerative, ulcerative, and healing stage. Clinically, RAS present as extremely painful, shallow ulcerations with an erythematous halo on unattached oral mucosa. Attacks may be precipitated by local trauma, stress, food intake, drugs, hormonal changes and vitamin and trace element deficiencies. Local and systemic conditions and genetic, immunological and microbial factors all may playa role in the pathogenesis of recurrent aphthous stomatitis. The primary differential diagnosis is herpes simplex. (author)

  4. Pathogenesis of Takayasu's arteritis: a 2011 update.

    Science.gov (United States)

    Arnaud, Laurent; Haroche, Julien; Mathian, Alexis; Gorochov, Guy; Amoura, Zahir

    2011-11-01

    While our knowledge of the pathogenesis of Takayasu's arteritis (TA) has considerably improved during the last decade, the exact pathogenic sequence remains to be elucidated. It is now hypothesised that an unknown stimulus triggers the expression of the 65kDa Heat-shock protein in the aortic tissue which, in turn, induces the Major Histocompatibility Class I Chain-Related A (MICA) on vascular cells. The γδ T cells and NK cells expressing NKG2D receptors recognize MICA on vascular smooth muscle cells and release perforin, resulting in acute vascular inflammation. Pro-inflammatory cytokines are released and increase the recruitment of mononuclear cells within the vascular wall. T cells infiltrate and recognize one or a few antigens presented by a shared epitope, which is associated with specific major Histocompatibility Complex alleles on the dendritic cells, these latter being activated through Toll-like receptors. Th1 lymphocytes drive the formation of giant cells through the production of interferon-γ, and activate macrophages with release of VEGF resulting in increased neovascularisation and PDGF, resulting in smooth muscle migration and intimal proliferation. Th17 cells induced by the IL-23 microenvironnement also contribute to vascular lesions through activation of infiltrating neutrophils. Although still controversial, dendritic cells may cooperate with B lymphocytes and trigger the production of anti-endothelial cell auto-antibodies resulting in complement-dependent cytotoxicity against endothelial cells. In a near future, novel drugs specifically designed to target some of the pathogenic mechanisms described above could be expanding the physician's therapeutic arsenal in Takayasu's arteritis. PMID:21855656

  5. The Correlation Analysis between Spleen Deficiency and Gastric Mucosal Injury%脾虚与胃黏膜损伤相关性的理论探讨

    Institute of Scientific and Technical Information of China (English)

    施甜; 朱方石; 徐婷婷

    2011-01-01

    This research studies the correlation between spleen asthenia and gastric mucosal injury from 4 aspects of pathogenesis, pathology, syndrome, and therapy. The results indicated that the pathological condition of spleen asthenia supply objective bases for the gastric mucosal injury, meanwhile, the gastric mucosal injury is easy to aggravate spleen asthenia. There is a correlativity of mutual causes and effects between the two diseases. The standpoint may supply the rationale for therapeutic principles of "Treat from spleen asthenia" treating the gastric mucosal diseases.%本文就脾虚与胃黏膜损伤的相关性从中医发病学、痛机关联现、证型归纳属性及治法归类等4个方面,进行了理论探讨.认为中医脾虚的病理状态为胃黏膜损伤提供了客观条件,而胃黏膜损伤因素则又易加重脾虚证侯,二者间存在着互为因果的相关关系.其观点为构建“从脾虚论治”胃黏膜损伤性疾病的治则观提供了理论基础.

  6. Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer

    International Nuclear Information System (INIS)

    Purpose: To determine the prophylactic properties of amifostine against acute and late toxicities from radiochemotherapy in patients with head-and-neck cancer. Methods and Materials: Fifty patients were randomized to receive conventional radiotherapy (RT) (2-Gy fractions, 5 days weekly, to a total of 60-74 Gy, depending on the tumor localization and TNM classification) and carboplatin (90 mg/m2 infusion once per week before RT). Amifostine (300 mg/m2) was administered in the study group only 15-30 min before RT for 6-7.5 weeks. The primary study end point was the grading of acute and late nonhematologic toxicities (mucositis, dysphagia, xerostomia) induced by radiochemotherapy. Secondary end points included treatment duration, hematologic toxicity, and clinical outcome. Results: The treatment duration was significantly shorter in the amifostine-treated group (p=0.013), because treatment interruptions were more frequent in the control group. Acute toxicities (mucositis and dysphagia) were less severe in the amifostine-treated group. By Week 3, all in the control group experienced Grade 2 mucositis compared with only 9% in the amifostine-treated group (p<0.0001). By Week 5, 52.2% of the patients in the control group experienced Grade 4 mucositis compared with 4.5% in the amifostine-treated group (p=0.0006). Similar results were obtained for dysphagia. At 3 months of follow-up, only 27% of patients in the study group experienced Grade 2 xerostomia compared with 73.9% in the control group (p=0.0001). Eighteen months after cessation of therapy, the proportion of patients with Grade 2 xerostomia was 4.5% vs. 30.4% for each respective treatment group (p=0.047). Cytoprotection with amifostine did not affect treatment outcome, with 90.9% complete responses in the amifostine-treated group compared with 78.3% in the control group (p=0.414). Conclusion: Amifostine was effective in reducing mucositis and dysphagia resulting from radiochemotherapy in patients with head

  7. Mucosal tissue transglutaminase expression in celiac disease

    OpenAIRE

    Villanacci, Vincenzo; Not, Tarcisio; Sblattero, Daniele; Gaiotto, Tiziano; Chirdo, Fernando; Galletti, Anna; Bassotti, Gabrio

    2008-01-01

    Abstract Tissue transglutaminase (tTG) plays an important role in celiac disease pathogenesis and antibodies to tTG are a diagnostic marker of gluten-sensitive enteropathy. The aim of this study was to investigate the localization of tTG in the duodenal mucosa in control tissues and in different histological stages of celiac disease by using a commercial and a novel set of anti-tTG monoclonal antibodies, to see whether this assessment can be useful for diagnostic purpose. The distribution of ...

  8. Acute Bronchitis

    Science.gov (United States)

    ... of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your cough ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when people ...

  9. Chamomile Mouth Rinse Effects on Mucositis Reduction After Radiotherapy

    Directory of Open Access Journals (Sweden)

    Talaipour AR

    2000-05-01

    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,

  10. Indomethacin decreases gastroduodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

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

    1995-01-01

    BACKGROUND: Cyclooxygenase inhibitors reduce mucosal bicarbonate secretion in the duodenum, but the evidence for their effect on bicarbonate secretion in the stomach remains controversial. We have, therefore, studied how indomethacin influences gastroduodenal bicarbonate secretion and luminal rel...

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

    Science.gov (United States)

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

  12. Radiation-induced mucositis pain in mesopharyngeal and hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Radiation therapy in head and neck malignancy often triggers painful mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). To better understand how radiation-induced pain develops over time, we studied numerical rating scale (NRS 0-5) pain scores in 27 subjects undergoing 60-72 Gy radiation therapy for newly diagnosed cancer- 13 with mesopharynx and 14 with hypopharynx. Mucositis severity was evaluated using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) based on mucositis pain, analgesic administration, and oral feedings of our subjects, with 8 mesopharyngeal and 10 with hypopharyngeal cancer had been pain-free before radiation therapy. The mucositis and pain course was severer in mesopharyngeal than in hypopharyngeal cancer. NSAIDs and opioid use was similar in both cancer types, which also required tube feeding in 7 subjects (38.9%). (author)

  13. Sevelamer crystals in the gastrointestinal tract (GIT): a new entity associated with mucosal injury.

    Science.gov (United States)

    Swanson, Benjamin J; Limketkai, Berkeley N; Liu, Ta-Chiang; Montgomery, Elizabeth; Nazari, Kamran; Park, Jason Y; Santangelo, William C; Torbenson, Michael S; Voltaggio, Lysandra; Yearsley, Martha M; Arnold, Christina A

    2013-11-01

    We report the first description of sevelamer crystals (Renagel and Renvela, Genzyme; phosphate-lowering agents) in the gastrointestinal tract. We prospectively collected cases with novel, histologically identical crystals from 4 major academic centers over a 1-year period and studied pertinent clinicopathologic features. Sevelamer usage in the setting of chronic kidney disease was demonstrated in all cases (n=15 total cases, 7 patients). Sites of involvement included the esophagus (n=2), small bowel (n=2), and colon (n=11). The background mucosa was normal in only 1 case. Notable mucosal abnormality included chronic mucosal damage (n=5), acute inflammation (n=4), inflammatory polyp (n=2), extensive ulceration (n=2), ischemia (n=1), and necrosis (n=1). In general, sevelamer crystals displayed broad, curved, and irregularly spaced "fish scales" with a variably eosinophilic to rusty brown color on hematoxylin and eosin (H&E) staining and violet color on periodic acid-Schiff-alcian special staining with diastase (PAS/D). To validate these findings, sevelamer tablets (Renvela) were crushed and submitted for histologic processing; the findings were identical to those in the patient specimens. The possibility of Kayexalate (sodium polystyrene sulfonate) and cholestyramine had been raised in error. However, Kayexalate has narrow, rectangular "fish scales" and is violet on H&E and magenta on PAS/D; cholestyramine lacks internal "fish scales," is bright orange on H&E, variably gray or hot pink on PAS/D, and is unassociated with mucosal injury. Further study is required to determine whether sevelamer plays a causal role in these injuries; however, its crystal is an important mimic of both Kayexalate and choleystyramine. As the history of sevelamer administration was not documented in any pathology requisition, awareness of sevelamer's characteristic morphology is crucial to avoid the diagnostic pitfalls of its mimics. PMID:24061514

  14. In vivo mucosal delivery of bioactive human interleukin 1 receptor antagonist produced by Streptococcus gordonii

    Directory of Open Access Journals (Sweden)

    Tagliabue Aldo

    2003-09-01

    Full Text Available Abstract Background Interleukin-1 (IL-1 is a cytokine involved in the initiation and amplification of the defence response in infectious and inflammatory diseases. IL-1 receptor antagonist (IL-1ra is an inactive member of the IL-1 family and represents one of the most potent mechanisms for controlling IL-1-dependent inflammation. IL-1ra has proven effective in the therapy of acute and chronic inflammatory diseases in experimental animal models and also in preliminary clinical trials. However, optimisation of therapeutic schedules is still needed. For instance, the use of drug delivery systems targeting specific mucosal sites may be useful to improve topical bioavailability and avoid side effects associated with systemic administration. Results In order to develop systems for the delivery of IL-1ra to mucosal target sites, a Streptococcus gordonii strain secreting human IL-1ra was constructed. The recombinant IL-1ra produced by S. gordonii was composed of the four amino acid residues RVFP of the fusion partner at the N-terminus, followed by the mature human IL-1ra protein. RFVP/IL-1ra displayed full biological activity in vitro in assays of inhibition of IL-1β-induced lymphocyte proliferation and was released by recombinant S. gordonii in vivo both at the vaginal and the gastrointestinal mucosa of mice. RFVP/IL-1ra appeared beneficial in the model of ulcerative colitis represented by IL-2-/- mice (knock-out for the interleukin-2 gene, as shown by the body weight increase of IL-2-/- mice locally treated with S. gordonii producing RFVP/IL-1ra. Conclusions These results indicate that recombinant S. gordonii can be successfully used as a delivery system for the selective targeting of mucosal surfaces with therapeutic proteins.

  15. Mucosal melanoma of nasal cavity and paranasal sinus

    Directory of Open Access Journals (Sweden)

    Dwivedi Raghav

    2008-01-01

    Full Text Available Mucosal melanoma of the nasal cavity and paranasal sinuses is seldom encountered in routine ENT practice. These tumors have poor prognosis owing to higher rates of locoregional recurrence and distant metastasis. Various treatment modalities have been employed over time but the ideal treatment approach still remains an open issue. This article presents some commonly accepted guidelines in treating these rare mucosal neoplasms.

  16. Prevention and treatment of oral mucositis in patients receiving chemotherapy

    OpenAIRE

    Alvariño Martín, Carlos; Sarrión, Gracia

    2014-01-01

    Oral mucositis is one of the most common side effects of cancer treatment (chemotherapy and/or radiotherapy). It is an inflammatory process that affects the mucosa of the oral cavity, giving rise to erythematous areas in combination with ulcers that can reach a large size. The true importance of oral mucositis is the complications it causes – fundamentally intense pain associated to the oral ulcers, and the risk of overinfection. This in turn may require reduction or even suspension of the an...

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

    OpenAIRE

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

    2012-01-01

    Oral mucositis affects more than three-fourths of patients undergoing chemotherapy and represents a significant burden to patients and caregivers. Lesions develop as a result of chemotherapeutic agents attacking the rapidly dividing cells of the gastrointestinal tract. Severity can range from mild, painless tissue changes to bleeding ulcerations that prevent oral intake and require narcotic pain relievers. Oral mucositis also leads to an increased risk of infection and can often delay further...

  18. Oral mucositis induced by anticancer treatments: physiopathology and treatments

    OpenAIRE

    Lionel, D'Hondt; Christophe, Lonchay; Marc, André; Jean-Luc, Canon

    2006-01-01

    Oral mucositis is a frequent and devastating side effect of anticancer treatments. It impairs the patient's quality of life and also can be life threatening because severe infections and delayed or incomplete anticancer treatments may result. This problem has been largely overlooked and underestimated in the past. However, recently studies have been performed to precisely identify the epidemiology, cost, consequences, physiopathology, and treatments of oral mucositis. Clinical guidelines have...

  19. Oral health as a predictive factor for oral mucositis

    OpenAIRE

    Fabio Luiz Coracin; Paulo Sergio da Silva Santos; Gallottini, Marina H. C.; Rosaura Saboya; Priscila Tavares Musqueira; Alessandra Barban; Dalton de Alencar Fischer Chamone; Frederico Luiz Dulley; Fabio Daumas Nunes

    2013-01-01

    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 a...

  20. Mucosal Immune Regulation in Early Infancy: Monitoring and Intervention

    OpenAIRE

    Hol, Jeroen

    2011-01-01

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

  1. Extrathymically generated regulatory T cells control mucosal Th2 inflammation

    OpenAIRE

    Josefowicz, Steven Z.; Niec, Rachel E.; Kim, Hye Young; Treuting, Piper; Chinen, Takatoshi; Zheng, Ye; Umetsu, Dale T.; Rudensky, Alexander Y.

    2012-01-01

    A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma, and intestinal inflammation1. Regulatory T (Treg) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tTreg cells) an...

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

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2010-01-01

    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...

  3. Effect of cysteamine on gastroduodenal mucosal histamine in rat.

    OpenAIRE

    Boesby, S; Man, W K; Mendez-Diaz, R; Spencer, J

    1983-01-01

    Cysteamine administration to rats is followed by a high incidence of peptic ulceration. The aim of the present study was to investigate the effect of cysteamine on gastric and duodenal mucosal histamine and gastric mucosal histamine formation capacity. After a four hour fast, cysteamine in doses of 50, 100, 200, 300, 400, and 500 mg/kg bodyweight was injected subcutaneously to male Wistar rats; saline injection was used as control. After 24 hours the animals were killed; the stomach and duode...

  4. Review of Preclinical Studies on Treatment of Mucositis and Associated Pain

    OpenAIRE

    Viet, C.T.; Corby, P.M.; Akinwande, A.; Schmidt, B L

    2014-01-01

    Oral mucositis is a significant problem in cancer patients treated with radiation or chemotherapy, often hindering definitive cancer treatment. For patients with oral mucositis, pain is the most distressing symptom, leading to loss of orofacial function and poor quality of life. While oral mucositis has been well-described, its pathophysiology is poorly understood. Oral health professionals treating patients with mucositis have almost no effective therapies to treat or prevent oral mucositis....

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

    OpenAIRE

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

    2010-01-01

    Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, th...

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

    OpenAIRE

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

    2010-01-01

    Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, th...

  7. Pulmonary edema in acute carbon monoxide poisoning

    International Nuclear Information System (INIS)

    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

  8. Using Light to Treat Mucositis and Help Wounds Heal

    Science.gov (United States)

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

    2008-01-01

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

  9. Low-Level Laser Therapy for Treatment of Oral Mucositis

    Directory of Open Access Journals (Sweden)

    Ravina Naomi Tarigan

    2012-12-01

    Full Text Available Radiation and chemotherapy are the treatment options for head and neck cancer. Several side effects related to those treat-ment have been shown. Oral mucositis is a common side effect in patients undergoing those treatment. The presence of oral mucositis in these patients would influencing quality of life therefore compromising treatment outcome. The spec-trum of oral mucositis can be clinically seen as thinning of oral mucosa, oral discomfort to painful oral lesion causing mastication impairment with increasing risk of infection. The Multinational Association for Supportive Care in Cancer (MASCC/International Society for Oral Oncology (ISOO has recommended some means that have important role in the management oral mucositis. The low-level laser therapy (LLLT is a relatively new way of reducing the severity of oral mucositis, although the true mechanism of action is still under study. This review aimed in exploring update about the usage of LLLT for oral mucositis treatment.DOI: 10.14693/jdi.v17i3.42

  10. Inside the brachycephalic nose: intranasal mucosal contact points.

    Science.gov (United States)

    Schuenemann, Riccarda; Oechtering, Gerhard U

    2014-01-01

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

  11. Radiation-induced mucositis pain in laryngeal cancer

    International Nuclear Information System (INIS)

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

  12. Endoscopic Mucosal Resection of Mucosal Neoplasm Located on the Duodenal Bulb through Endoscope Retroflexion

    Institute of Scientific and Technical Information of China (English)

    Hua LI; Qiang LI; De-jun ZHOU; Jian-zhang HU; Guo-qing ZHANG; Feng-ling LI

    2010-01-01

    OBJECTIVE To assess the results of endoscopic mucosalresection (EMR) of benign mucosal neoplasms located on theduodenal bulb using endoscope retrofl exion.METHODS This study involved 14 patients with 16 mucosal neoplasms located on the duodenal bulb. The diameter of each neoplasm was less than 15 mm. After endoscope retroflexion within the duodenum for evaluation of the size, extent and depth of the tumor, EMR was a empted with endoscope retrofl exion for removing the lesion in the duodenal bulb. The rate of endoscope retrofl exion, the time required for endoscope retrofl exion, median operation time, curative resection rate, en bloc resection rate,complication, and median follow-up period were evaluated.RESULTS Sixteen lesions in 14 patents (median age of 56 years, 5 female, 9 male) were removed through EMR. The mean size of the lesions resected was 6.9 mm (median size of 5.5 mm, range of 3-15 mm). Post-EMR histologic examination revealed Brunner's gland hyperplasia in 6, gastric mucosal metaplasia in 5, adenoma in 1,chronic inflammation in 3, and benign lymphocytic hyperplasia in 1. The curative resection rate was 100% (16/16), and the en bloc resection rate was 94% (15/16), with EMR. One of the lesions was piecemeal removed through EMR for its large size (15 mm) and for its involving the area from the duodenal bulb to the pyloric ring.The success rate of endoscope retrofl exion within the duodenum was 94% (15/16). The time required for endoscope retrofl exion was longer for the fi rst 10 lesions (median time of 2 min, range of 1-2.5 min) than that for the last 5 lesions (median time of 1.5 min, range of 1-2 min). The median follow-up period was 22 months (range of 4-48 months). During the follow-up, no residual, no pyloric or duodenal stenosis was found in any of the patients after EMR.There was no severe hemorrhage, or perforations occurring. CONCLUSION EMR of mucosal neoplasm located on the duodenal bulb through endoscope retrofl exion, which is a feasible and

  13. Mucosal effects of tenofovir 1% gel.

    Science.gov (United States)

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

    2015-01-01

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

  14. Type 1 diabetes pathogenesis - Prevention???

    Directory of Open Access Journals (Sweden)

    C S Muralidhara Krishna

    2015-01-01

    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

  15. Assessment of Cancer Therapy-Induced Oral Mucositis Using a Patient-Reported Oral Mucositis Experience Questionnaire

    OpenAIRE

    Gussgard, Anne Margrete; Hope, Andrew; Jokstad, Asbjørn; Tenenbaum, Howard; Wood, Robert

    2014-01-01

    Objectives Treatment of oral mucositis (OM) is challenging. In order to develop and test useful treatment approaches, the development of reliable, reproducible and simpler methods than are currently available for assessment of OM is important. A Patient-Reported Oral Mucositis Symptom (PROMS) scale was assessed in patients with head and neck cancer to determine if the patient-reported OM experience, as determined by using the PROMS scale, correlate with OM assessed by clinician-based scori...

  16. Autologous transplantation of oral mucosal epithelial cell sheets cultured on an amniotic membrane substrate for intraoral mucosal defects.

    Directory of Open Access Journals (Sweden)

    Takeshi Amemiya

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

  17. Intranasal Delivery of Group B Meningococcal Native Outer Membrane Vesicle Vaccine Induces Local Mucosal and Serum Bactericidal Antibody Responses in Rabbits

    OpenAIRE

    Shoemaker, David R.; Saunders, Nancy B.; Brandt, Brenda L.; Moran, E. Ellen; LaClair, Andrew D.; Zollinger, Wendell D.

    2005-01-01

    We have previously shown that intranasal immunization of mice with meningococcal native outer membrane vesicles (NOMV) induces both a good local mucosal antibody response and a good systemic bactericidal antibody response. However, in the intranasal mouse model, some of the NOMV entered the lung and caused an acute granulocytic response. We therefore developed an alternate animal model using the rabbit. This model reduces the probability of lung involvement and more closely mimics intranasal ...

  18. Low-level laser therapy: a standard of supportive care for cancer therapy-induced oral mucositis in head and neck cancer patients?

    OpenAIRE

    Jadaud, E.; Bensadoun, RJ

    2012-01-01

    Background and aims: Oral mucositis (OM) is still a common and severe acute side-effect of many oncologic treatments, especially in patients treated for head and neck cancer. It may affect quality of life, require supportive care and impact treatment planning and its efficacy. Low-level laser therapy (LLLT) seems to promote pain relief and reduces OM incidence and its severity. It has been recommended for these patients as a treatment option but without any consensus in the LLLT procedure. Ne...

  19. Molecular Pathogenesis of MALT Lymphoma

    Directory of Open Access Journals (Sweden)

    Katharina Troppan

    2015-01-01

    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.

  20. Inflammation and Atherosclerosis: Current Pathogenesis

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2012-08-01

    Full Text Available BACKGROUND: The inflammatory nature of atherosclerosis is well established but the agent(s that incite inflammation in the artery wall remain largely unknown. CONTENT: Chronic inflammation is recognized as a major driving force in atherogenesis. The sites of atherosclerotic plaque development in the arterial wall are characterized by cholesterol accumulation and infiltration of peripheral blood monocytes, which gradually differentiate into macrophages. Cholesterol crystals, the common constituents of atherosclerotic lesions, include NLRP3 inflammasome activation and IL-1β secretion in human macrophages, promote an inflammatory milieu and thus drive lesion progression. Consequently, the cholesterol crystal-induced inflammasome activation may represent an important link between cholesterol metabolism and inflammation in atherosclerotic lesions. SUMMARY: The crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. The cholesterol crystal-induced inflammasome activation in macrophages may represent an important link between cholesterol metabolism and inflammation in atherosclerotic lesions. This finding provides new insights into the pathogenesis of atherosclerosis and indicates new potential molecular targets for the therapy of this disease. KEYWORDS: atherosclerosis, inflammation, neutrophil, macrophages, inflammasome, cholesterol crystal.

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

    Science.gov (United States)

    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.

    2015-01-01

    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

  2. Physiopathology, prevention and treatment of the oral mucositis induced by chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    The oral mucositis is a frequent and potentially severe complication of the antineoplasic therapy; it is considered that approximately 400.000 new patients per year in United States will develop acute or chronic complications in oral cavity after the beginning of its treatment. Some of the basic manifestations that are inside the clinical descriptions understand the erythema, the desquamation, formation of ulcers, the bled, and exudation. The epithelial oropharynge surface has a quick replication rate, and for this reason it is highly exposed to the direct insult due to the cytotoxic effects of the chemotherapy, the radiotherapy, and indirectly the infectious agents. The paper includes topics like physiopathology, risk factors, chemotherapy, radiotherapy, the patient's evaluation and conclusions

  3. Clotrimazole nanoparticle gel for mucosal administration

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Elisabetta, E-mail: ese@unife.it [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)

    2013-01-01

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

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

    Science.gov (United States)

    Jung, Kwonil; Saif, Linda J

    2015-05-01

    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. PMID:25841898

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

    Directory of Open Access Journals (Sweden)

    Sya N Ukena

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

  6. SERUM MAGNESIUM IN ACUTE MYOCARDIAL INFARCTION

    OpenAIRE

    Nambakam Tanuja; Girish P

    2015-01-01

    BACKGROUND: In myocardial infarction, there occurs functional deficit of available magnesium due to trapping of free magnesium in adipocytes. Magnesium has been implicated in the pathogenesis of acute myocardial infarction and its complications. Magnesium ions are considered essential for the maintenance of functional integrity of myocardium. The serum magnesium concentration was found to have g reat significance in acute myocardial infarction. The present study was un...

  7. Simultaneous acute appendicitis and ectopic pregnancy

    OpenAIRE

    Ankouz Amal; Ousadden Abdelmalek; Majdoub Karim; Chouaib Ali; Maazaz Khalid; Taleb Khalid

    2009-01-01

    The acute abdomen in pregnancy is a surgical emergency. Ectopic pregnancy and appendicitis are two causes of acute abdomen in pregnancy. Difficulties in correctly identifying the cause of the pain can be hazardous to the patient and care needs to be taken in obtaining a prompt and accurate diagnosis enabling the most appropriate management. The case presented here underlies the pathogenesis of the simultaneous existence of these two conditions in a patient.

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

    Directory of Open Access Journals (Sweden)

    Carolina eStenfeldt

    2016-05-01

    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

  9. The Pathogenesis of Foot-and-Mouth Disease in Pigs.

    Science.gov (United States)

    Stenfeldt, Carolina; Diaz-San Segundo, Fayna; de Los Santos, Teresa; Rodriguez, Luis L; Arzt, Jonathan

    2016-01-01

    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 to 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 contrast to

  10. The Pathogenesis of Foot-and-Mouth Disease in Pigs

    Science.gov (United States)

    Stenfeldt, Carolina; Diaz-San Segundo, Fayna; de los Santos, Teresa; Rodriguez, Luis L.; Arzt, Jonathan

    2016-01-01

    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 to 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 contrast to

  11. Protective mucosal immunity mediated by epithelial CD1d and IL-10.

    Science.gov (United States)

    Olszak, Torsten; Neves, Joana F; Dowds, C Marie; Baker, Kristi; Glickman, Jonathan; Davidson, Nicholas O; Lin, Chyuan-Sheng; Jobin, Christian; Brand, Stephan; Sotlar, Karl; Wada, Koichiro; Katayama, Kazufumi; Nakajima, Atsushi; Mizuguchi, Hiroyuki; Kawasaki, Kunito; Nagata, Kazuhiro; Müller, Werner; Snapper, Scott B; Schreiber, Stefan; Kaser, Arthur; Zeissig, Sebastian; Blumberg, Richard S

    2014-05-22

    The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host. CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease. As CD1d crosslinking on model IECs results in the production of the important regulatory cytokine interleukin (IL)-10 (ref. 9), decreased epithelial CD1d expression--as observed in inflammatory bowel disease--may contribute substantially to intestinal inflammation. Here we show in mice that whereas bone-marrow-derived CD1d signals contribute to NKT-cell-mediated intestinal inflammation, engagement of epithelial CD1d elicits protective effects through the activation of STAT3 and STAT3-dependent transcription of IL-10, heat shock protein 110 (HSP110; also known as HSP105), and CD1d itself. All of these epithelial elements are critically involved in controlling CD1d-mediated intestinal inflammation. This is demonstrated by severe NKT-cell-mediated colitis upon IEC-specific deletion of IL-10, CD1d, and its critical regulator microsomal triglyceride transfer protein (MTP), as well as deletion of HSP110 in the radioresistant compartment. Our studies thus uncover a novel pathway of IEC-dependent regulation of mucosal homeostasis and highlight a critical role of IL-10 in the intestinal epithelium, with broad implications for diseases such as inflammatory bowel disease. PMID:24717441

  12. Effect of Radiotherapy and Chemotherapy on the Risk of Mucositis During Intensity-Modulated Radiation Therapy for Oropharyngeal Cancer

    International Nuclear Information System (INIS)

    Purpose: To define the roles of radiotherapy and chemotherapy on the risk of Grade 3+ mucositis during intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer. Methods and Materials: 164 consecutive patients treated with IMRT at two institutions in nonoverlapping treatment eras were selected. All patients were treated with a dose painting approach, three dose levels, and comprehensive bilateral neck treatment under the supervision of the same radiation oncologist. Ninety-three patients received concomitant chemotherapy (cCHT) and 14 received induction chemotherapy (iCHT). Individual information of the dose received by the oral mucosa (OM) was extracted as absolute cumulative dose–volume histogram (DVH), corrected for the elapsed treatment days and reported as weekly (w) DVH. Patients were seen weekly during treatment, and peak acute toxicity equal to or greater than confluent mucositis at any point during the course of IMRT was considered the endpoint. Results: Overall, 129 patients (78.7%) reached the endpoint. The regions that best discriminated between patients with/without Grade 3+ mucositis were found at 10.1 Gy/w (V10.1) and 21 cc (D21), along the x-axis and y-axis of the OM-wDVH, respectively. On multivariate analysis, D21 (odds ratio [OR] = 1.016, 95% confidence interval [CI], 1.009–1.023, p < 0.001) and cCHT (OR = 4.118, 95% CI, 1.659–10.217, p = 0.002) were the only independent predictors. However, V10.1 and D21 were highly correlated (rho = 0.954, p < 0.001) and mutually interchangeable. cCHT would correspond to 88.4 cGy/w to at least 21 cc of OM. Conclusions: Radiotherapy and chemotherapy act independently in determining acute mucosal toxicity; cCHT increases the risk of mucosal Grade 3 toxicity ≈4 times over radiation therapy alone, and it is equivalent to an extra ≈6.2 Gy to 21 cc of OM over a 7-week course.

  13. Effect of Radiotherapy and Chemotherapy on the Risk of Mucositis During Intensity-Modulated Radiation Therapy for Oropharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sanguineti, Giuseppe, E-mail: gsangui1@jhmi.edu [Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX (United States); Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD (United States); Sormani, Maria Pia [Department of Biostatistics, University of Genoa (Italy); Marur, Shanthi [Department of Oncology, Johns Hopkins University, Baltimore, MD (United States); Gunn, G. Brandon; Rao, Nikhil; Cianchetti, Marco [Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX (United States); Ricchetti, Francesco; McNutt, Todd; Wu Binbin [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD (United States); Forastiere, Arlene [Department of Oncology, Johns Hopkins University, Baltimore, MD (United States)

    2012-05-01

    Purpose: To define the roles of radiotherapy and chemotherapy on the risk of Grade 3+ mucositis during intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer. Methods and Materials: 164 consecutive patients treated with IMRT at two institutions in nonoverlapping treatment eras were selected. All patients were treated with a dose painting approach, three dose levels, and comprehensive bilateral neck treatment under the supervision of the same radiation oncologist. Ninety-three patients received concomitant chemotherapy (cCHT) and 14 received induction chemotherapy (iCHT). Individual information of the dose received by the oral mucosa (OM) was extracted as absolute cumulative dose-volume histogram (DVH), corrected for the elapsed treatment days and reported as weekly (w) DVH. Patients were seen weekly during treatment, and peak acute toxicity equal to or greater than confluent mucositis at any point during the course of IMRT was considered the endpoint. Results: Overall, 129 patients (78.7%) reached the endpoint. The regions that best discriminated between patients with/without Grade 3+ mucositis were found at 10.1 Gy/w (V10.1) and 21 cc (D21), along the x-axis and y-axis of the OM-wDVH, respectively. On multivariate analysis, D21 (odds ratio [OR] = 1.016, 95% confidence interval [CI], 1.009-1.023, p < 0.001) and cCHT (OR = 4.118, 95% CI, 1.659-10.217, p = 0.002) were the only independent predictors. However, V10.1 and D21 were highly correlated (rho = 0.954, p < 0.001) and mutually interchangeable. cCHT would correspond to 88.4 cGy/w to at least 21 cc of OM. Conclusions: Radiotherapy and chemotherapy act independently in determining acute mucosal toxicity; cCHT increases the risk of mucosal Grade 3 toxicity Almost-Equal-To 4 times over radiation therapy alone, and it is equivalent to an extra Almost-Equal-To 6.2 Gy to 21 cc of OM over a 7-week course.

  14. 8-prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis. Cell culture and murine model

    International Nuclear Information System (INIS)

    The major component in the pathogenesis of oral radiation-induced mucositis is progressive epithelial hypoplasia and eventual ulceration. Irradiation inhibits cell proliferation, while cell loss at the surface continues. We conceived to slow down this desquamation by increasing intercellular adhesion, regulated by the E-cadherin/catenin complex. We investigated if 8-prenylnaringenin (8-PN) or tamoxifen (TAM) decrease the shedding of irradiated human buccal epithelial cells in vitro and thus delay the ulcerative phase of radiation-induced mucositis in vivo. In vitro, aggregates of buccal epithelial cells were irradiated and cultured in suspension for 11 days. 8-PN or TAM were investigated regarding their effect on cell shedding. In vivo, the lower tongue surface of mice was irradiated with graded single doses of 25 kV X-rays. The incidence, latency, and duration of the resulting mucosal ulcerations were analyzed after topical treatment with 8-PN, TAM or solvent. 8-PN or TAM prevented the volume reduction of the irradiated cell aggregates during the incubation period. This was the result of a higher residual cell number in the treated versus the untreated irradiated aggregates. In vivo, topical treatment with 8-PN or TAM significantly increased the latency of mucositis from 10.9 to 12.1 and 12.4 days respectively, while the ulcer incidence was unchanged. 8-PN and TAM prevent volume reduction of irradiated cell aggregates in suspension culture. In the tongues of mice, these compounds increase the latency period. This suggests a role for these compounds for the amelioration of radiation-induced mucositis in the treatment of head and neck tumors. (orig.)

  15. Pathophysiological aspects of acute hepatic encephalopathy in the rat

    International Nuclear Information System (INIS)

    The aim of the present thesis is to elucidate the pathogenesis of acute hepatic encephalopathy (HE). In order to study acute HE, plasma and brain concentrations were measured of ammonia, aminoacids, lactate and polyamines as well as brain energy rich phosphates. In addition new techniques of brain research were developed and applied. 277 refs.; 29 figs.; 18 tabs

  16. Bacterial chemotactic oligopeptides and the intestinal mucosal barrier

    International Nuclear Information System (INIS)

    Intestinal absorption and enterohepatic circulation of N-formyl-methionyl-leucyl-125I-tyrosine, a bioactive synthetic analog of the bacterial chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine has been investigated in the rat. In ileum and proximal and distal colon, dithiothreitol, which increases mucosal permeability, increased peptide absorption and biliary recovery fourfold, 70-fold, and 20-fold over control values, respectively. When dithiothreitol was combined with d-l-benzyl succinate, a potent inhibitor of intestinal carboxypeptidase, absorption and biliary recovery from ileal loops increased markedly to 40-fold over control, whereas there was no further increase in absorption from colon loops. There was a strong correlation between biliary N-formyl-methionyl-leucyl-125I-tyrosine recovery and intestinal absorption of 51Cr-ethylenediaminetetraacetate, a marker of passive mucosal permeability (r = 0.97). We conclude that in the ileum both enzymic degradation and restricted mucosal permeability contribute to the intestinal barrier to luminal bacterial formyl oligopeptides. In the colon, however, enzymic mechanisms are less active and restricted mucosal permeability is the major factor. Abnormalities of the intestinal mucosal barrier to proinflammatory bacterial peptides could play a role in inflammatory disorders of the gut

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Intestinal colonization with Candida albicans and mucosal immunity

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    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.

  19. Acute acalculous cholecystitis.

    Science.gov (United States)

    Barie, Philip S; Eachempati, Soumitra R

    2003-08-01

    Acute cholecystitis can develop without gallstones in critically ill or injured patients. However, the development of acute acalculous cholecystitis is not limited to surgical or injured patients, or even to the intensive care unit. Diabetes, malignant disease, abdominal vasculitis, congestive heart failure, cholesterol embolization, and shock or cardiac arrest have been associated with acute acalculous cholecystitis. Children may also be affected, especially after a viral illness. The pathogenesis of acute acalculous cholecystitis is a paradigm of complexity. Ischemia and reperfusion injury, or the effects of eicosanoid proinflammatory mediators, appear to be the central mechanisms, but bile stasis, opioid therapy, positive-pressure ventilation, and total parenteral nutrition have all been implicated. Ultrasound of the gallbladder is the most accurate diagnostic modality in the critically ill patient, with gallbladder wall thickness of 3.5 mm or greater and pericholecystic fluid being the two most reliable criteria. The historical treatment of choice for acute acalculous cholecystitis has been cholecystectomy, but percutaneous cholecystostomy is now the mainstay of therapy, controlling the disease in about 85% of patients. Rapid improvement can be expected when the procedure is performed properly. The mortality rates (historically about 30%) for percutaneous and open cholecystostomy appear to be similar, reflecting the severity of illness, but improved resuscitation and critical care may portend a decreased risk of death. Interval cholecystectomy is usually not indicated after acute acalculous cholecystitis in survivors; if the absence of gallstones is confirmed and the precipitating disorder has been controlled, the cholecystostomy tube can be pulled out after the patient has recovered. PMID:12864960

  20. An Odyssey to Viral Pathogenesis.

    Science.gov (United States)

    Oldstone, Michael B A

    2016-05-23

    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. PMID:26514062

  1. Oral mucosal alterations among the institutionalized elderly in Brazil

    Directory of Open Access Journals (Sweden)

    Raquel Conceição Ferreira

    2010-09-01

    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.

  2. EFFECT OF EDTA ON GASTRIC MUCOSAL LESION INDUCED BY ASPIRIN

    Directory of Open Access Journals (Sweden)

    M.A FESHARAKI M.A

    2002-06-01

    Full Text Available Introduction. Gastric ulcer is a multifactorial disease, which its pathophysioligy has not been clear yet. The aim of this study was to obtain the prophylactic effects of EDTA on Aspirin induced gastric mucosal lesions. Methods. In fasted male rats the effect of a single oral dose of the EDTA was evaluated in the following test systems: combination of 1 ml EDTA 1.5% + 300 mg/kg aspirin and 1 ml EDTA 1.5%, 2.5%, 5% and 7.5% 30 minutes before 300 mg/kg aspirin. Then the gastric mucosal lesions were assessed microscopically and marcroscopically. Results. EDTA at different doses reduced macroscopic and microscpic gastric mucosal lesion induced by aspirin. Discussion. Combination therapy of EDTA and aspirin has distinct advantages regard to both low gastrointestinal toxicity and restored therapeutic activity.

  3. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  4. The pathogenesis of obstructive sleep apnea

    OpenAIRE

    Pham, Luu V.; Schwartz, Alan R.

    2015-01-01

    Obstructive sleep apnea (OSA) is a major source of cardiovascular morbidity and mortality, and represents an increasing burden on health care resources. Understanding underlying pathogenic mechanisms of OSA will ultimately allow for the development of rational therapeutic strategies. In this article, we review current concepts about the pathogenesis of OSA. Specifically, we consider the evidence that the upper airway plays a primary role in OSA pathogenesis and provide a framework for modelli...

  5. On the pathogenesis of shoulder impingement syndrome

    OpenAIRE

    Hyvönen, P. (Pirkko)

    2003-01-01

    Abstract The pathomechanism of the shoulder impingement syndrome has been under debat. Two main theories of the pathogenesis of the disease exists; mechanical (extrinsic) and degenerative (intrinsic) theory. The purpose of this work was to evaluate the pathogenesis of impingement syndrome with five studies that consentrate to aspects related to ethiopathology as outcome and recovery after surgery, radiological diagnosis, immunohisto- and histopathology of subacromial bursa, and subacr...

  6. Acute cognitive dysfunction after hip fracture

    DEFF Research Database (Denmark)

    Bitsch, M S; Foss, N B; Kristensen, B B;

    2006-01-01

    Patients undergoing hip fracture surgery often experience acute post-operative cognitive dysfunction (APOCD). The pathogenesis of APOCD is probably multifactorial, and no single intervention has been successful in its prevention. No studies have investigated the incidence of APOCD after hip...... fracture surgery in an optimized, multimodal, peri-operative rehabilitation regimen....

  7. Acute Brucellosis Presenting as Gastroenteritis: Case Report

    OpenAIRE

    Salih Bin Salih; Adel Alothman

    2013-01-01

    Brucellosis is a systemic infection with multiple presentations. In spite of its oral mode of transmission and gastrointestinal pathogenesis, systemic symptoms are usually more prominent than gastrointestinal ones. Acute brucellosis presenting as gastroenteritis is rare in adults and could be the only manifestation of the disease. We report a case of gastroenteritis caused by Brucella species.

  8. Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Françoise Stoll-Keller

    2012-10-01

    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.

  9. STARVATION INDUCED PROXIMAL GUT MUCOSAL ATROPHY DIMINISHED WITH AGING

    Science.gov (United States)

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

    2013-01-01

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

  10. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    International Nuclear Information System (INIS)

    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

  11. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-09-01

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

  12. Pathogenesis of salivary gland disease and xerostomia. The conception of Mikulicz's disease based on new knowledge

    International Nuclear Information System (INIS)

    This review focuses on two topics of salivary gland diseases regarding xerostomia. First, the pathogenesis and treatment of xerostomia after radiotherapy against head and neck cancer is discussed. It is well known that the extent of radiation-induced salivary dysfunction and mucositis depends on the radiation dose and field. Moreover, the balance in the defense system of oropharyngeal cavity alters after radiotherapy. This altered balance may impair the ability to maintain the stable immunological control mechanism. Second, the newly established concept about Mikulicz's disease is discussed. Recently, elevated IgG4 concentration in serum and prominent infiltrating by plasmacytes expressing IgG4 in the salivary glands in Mikulicz's disease were revealed. Mikulicz's disease is different from Sjoegren's syndrome, and may be a systemic IgG4-related plasmacytic disease. (author)

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

    Directory of Open Access Journals (Sweden)

    Abbas Javadzadeh Bolouri

    2015-10-01

    Full Text Available 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.

  14. The Significance of Interferon-γ in HIV-1 Pathogenesis, Therapy, and Prophylaxis

    OpenAIRE

    Roff, Shannon R.; Noon-Song, Ezra N.; Yamamoto, Janet K.

    2014-01-01

    Interferon-γ (IFNγ) plays various roles in the pathogenesis of HIV/AIDS. In an HIV-1 infected individual, the production of IFNγ is detected as early as the acute phase and continually detected throughout the course of infection. Initially produced to clear the primary infection, IFNγ together with other inflammatory cytokines are involved in establishing a chronic immune activation that exacerbates clinical diseases associated with AIDS. Unlike Type 1 IFNs, IFNγ has no direct antiviral activ...

  15. Investigation of how to prevent mucositis induced by chemoradiotherapy

    International Nuclear Information System (INIS)

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

  16. EFFECT OF EDTA ON GASTRIC MUCOSAL LESION INDUCED BY ASPIRIN

    OpenAIRE

    M.A FESHARAKI M.A; A SHARAITI KAMALABADI; R MOKHTARI

    2002-01-01

    Introduction. Gastric ulcer is a multifactorial disease, which its pathophysioligy has not been clear yet. The aim of this study was to obtain the prophylactic effects of EDTA on Aspirin induced gastric mucosal lesions. Methods. In fasted male rats the effect of a single oral dose of the EDTA was evaluated in the following test systems: combination of 1 ml EDTA 1.5% + 300 mg/kg aspirin and 1 ml EDTA 1.5%, 2.5%, 5% and 7.5% 30 minutes before 300 mg/kg aspirin. Then the gastric mucosal les...

  17. The presence of bacteria within tissue provides insights into the pathogenesis of oral lichen planus.

    Science.gov (United States)

    Choi, Yun Sik; Kim, Yunji; Yoon, Hye-Jung; Baek, Keum Jin; Alam, Jehan; Park, Hee Kyung; Choi, Youngnim

    2016-01-01

    Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease of unknown etiopathogenesis. Although various antigens have been considered, what actually triggers the inflammatory response of T cells is unknown. In the present study, we propose that intracellular bacteria present within tissues trigger T cell infiltration and provide target antigens. Sections of OLP (n = 36) and normal (n = 10) oral mucosal tissues were subjected to in situ hybridization using a universal probe targeting the bacterial 16S rRNA gene and immunohistochemistry with anti-CD3, anti-CD4, anti-CD8, and anti-macrophage-specific antibodies. Bacteria were abundant throughout the epithelium and the lamina propria of OLP tissues, which exhibited positive correlations with the levels of infiltrated CD3(+), CD4(+), and CD8(+) cells. Furthermore, bacteria were detected within the infiltrated T cells. Pyrosequencing analysis of the mucosal microbiota from OLP patients (n = 13) and control subjects (n = 11) revealed a decrease in Streptococcus and increases in gingivitis/periodontitis-associated bacteria in OLP lesions. Using the selected bacterial species, we demonstrated that certain oral bacteria damage the epithelial physical barrier, are internalized into epithelial cells or T cells, and induce production of T cell chemokines CXCL10 and CCL5. Our findings provide insights into the pathogenesis of OLP. PMID:27383402

  18. Mucosal MicroRNAs Expression Profiles before and after Exclusive Enteral Nutrition Therapy in Adult Patients with Crohn's Disease.

    Science.gov (United States)

    Guo, Zhen; Gong, Jianfeng; Li, Yi; Gu, Lili; Cao, Lei; Wang, Zhiming; Zhu, Weiming; Li, Jieshou

    2016-01-01

    MicroRNAs (miRNAs) have been shown to be important for the pathogenesis of Crohn's disease (CD). Exclusive enteral nutrition (EEN) is an effective therapy for inducing remission in CD. We aimed to investigate the alteration of miRNAs expression profile in the terminal ileal mucosa of CD patients before and after EEN. Twenty-five patients and ten healthy individuals were included. MiRNAs expression profile was firstly assessed using microarray technology and then validation was performed by qRT-PCR. The correlations between miRNAs and CD activity index (CDAI) score and serum C-reactive protein (CRP) level were also evaluated. Microarray analysis showed that mucosal miRNAs expression profile after EEN therapy was significantly changed compared with inflamed mucosa before treatment, and was most similar to the healthy one among all CD groups. Altered expressions of hsa-miR-192-5p, hsa-miR-423-3p, hsa-miR-99a-5p, hsa-miR-124-3p, hsa-miR-301a-5p, hsa-miR-495-5p, and hsa-let-7b-5p were confirmed by qRT-PCR. hsa-let-7b-5p was significantly correlated with serum CRP levels before and after EEN treatment (r = -0.518, p = 0.008, and r = -0.569, p = 0.003). Our study showed EEN induction therapy was associated with a trend for normalizing of the mucosal miRNAs expression profile, and expression of mucosal hsa-let-7b-5p was correlated with serum CRP level in patients with CD. PMID:27556489

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

    Directory of Open Access Journals (Sweden)

    Patni Nidhi

    2005-01-01

    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.

  20. The innate immune response in ischemic acute kidney injury

    OpenAIRE

    Jang, Hye Ryoun; Rabb, Hamid

    2008-01-01

    Kidney ischemia reperfusion injury is a major cause of morbidity in both allograft and native kidneys. Ischemia reperfusion-induced acute kidney injury is characterized by early, allo-antigen independent inflammation. Major components of the innate immune system are activated and participate in the pathogenesis of acute kidney injury, plus prime the allograft kidney for rejection. Soluble members of innate immunity implicated in acute kidney injury include the complement system, cytokines, an...

  1. The role of neutrophilic mediators in acute inflammation of the gut

    International Nuclear Information System (INIS)

    Activation of granulocytes within the lamina propria by luminally derived bacterial products may represent an important mechanism in the pathogenesis of inflammatory bowel disease. One objective of this thesis was to determine the effects of luminal perfusion with N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial product that attracts and activates granulocytes, on mucosal permeability in different regions of the rat small intestine and colon. Mucosal permeability was measured using the blood-to-lumen clearance of 51Cr-EDTA during luminal perfusion with FMLP dissolved in Tyrode's solution. Of the bowel segments studied, mucosal permeability was significantly increased only in the distal 10 cm of the ileum. In order to define the role of neutrophilic oxidants in FMLP-induced ileitis, we evaluated the protective effect of several free radical scavengers and antioxidant enzymes. Pretreatment with the either superoxide dismutase or catalase had no effect on the FMLP-induced increase in mucosal permeability. However, treatment with either Mn-desferrioxamine, PZ51, desferrioxamine, or dimethylsulfoxide significantly attenuated FMLP-induced mucosal damage. Non-oxidative toxins released from activated neutrophil may be another mechanism by which FMLP increases mucosal permeability. In order to investigate the role of neutrophilic proteases in FMLP-induced ileitis, the effects of the nonspecific protease inhibitor soybean trypsin inhibitor, and the elastase inhibitors MeOSuc-Ala-Ala-Pro-Val-CH2Cl(MAAPV) and Eglin C on the FMLP-induced increases in 51Cr-EDTA clearance were determined

  2. Bronchitis - acute

    Science.gov (United States)

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflammation in the main passages ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  3. Bronchitis - acute

    Science.gov (United States)

    Acute bronchitis is swelling and inflammation in the main passages that carry air to the lungs. The swelling narrows ... makes it harder to breathe. Another symptom of bronchitis is a cough. Acute means the symptoms have ...

  4. Acute Bronchitis

    Science.gov (United States)

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  5. Acute pancreatitis

    OpenAIRE

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    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 ingest...

  6. Acute pancreatitis

    OpenAIRE

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    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....

  7. Interactions Between Bacteria and the Gut Mucosa: Do Enteric Neurotransmitters Acting on the Mucosal Epithelium Influence Intestinal Colonization or Infection?

    Science.gov (United States)

    Green, Benedict T; Brown, David R

    2016-01-01

    The intestinal epithelium is a critical barrier between the internal and external milieux of the mammalian host. Epithelial interactions between these two host environments have been shown to be modulated by several different, cross-communicating cell types residing in the gut mucosa. These include enteric neurons, whose activity is influenced by bacterial pathogens, and their secreted products. Neurotransmitters appear to influence epithelial associations with bacteria in the intestinal lumen. For example, internalization of Salmonella enterica and Escherichia coli O157:H7 into the Peyer's patch mucosa of the small intestine is altered after the inhibition of neural activity with saxitoxin, a neuronal sodium channel blocker. Catecholamine neurotransmitters, such as dopamine and norepinephrine, also alter bacterial internalization in Peyer's patches. In the large intestine, norepinephrine increases the mucosal adherence of E. coli. These neurotransmitter actions are mediated by well-defined catecholamine receptors situated on the basolateral membranes of epithelial cells rather than through direct interactions with luminal bacteria. Investigations of the involvement of neuroepithelial communication in the regulation of interactions between the intestinal mucosa and luminal bacteria will provide novel insights into the mechanisms underlying bacterial colonization and pathogenesis at mucosal surfaces. PMID:26589216

  8. The Microbiological Context of HIV Resistance: Vaginal Microbiota and Mucosal Inflammation at the Viral Point of Entry

    Directory of Open Access Journals (Sweden)

    John J. Schellenberg

    2012-01-01

    Full Text Available Immune activation is increasingly recognized as a critical element of HIV infection and pathogenesis, causing expansion of virus founder populations at the mucosal port of entry and eventual exhaustion of cellular immune effectors. HIV susceptibility is well known to be influenced by concurrent sexually transmitted infections; however, the role of commensal vaginal microbiota is poorly characterized. Bacterial vaginosis (BV is a risk factor for HIV acquisition in studies worldwide; however, the etiology of BV remains enigmatic, and the mechanisms by which BV increases HIV susceptibility are not fully defined. A model of how vaginal microbiota influences HIV transmission is considered in the context of a well-established cohort of HIV-exposed seronegative (HESN commercial sex workers (CSW in Nairobi, Kenya, many of whom have increased levels of anti-inflammatory factors in vaginal secretions and reduced peripheral immune activation (immune quiescence. Elucidation of the relationship between complex microbial communities and inflammatory mucosal responses underlying HIV infection should be a priority for future prevention-focussed research.

  9. Acute biliary pancreatitis: Diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Hazem Zakaria

    2009-01-01

    Full Text Available Gallstones are the commonest cause of acute pancreatitis (AP, a potentially life-threatening condition, worldwide. The pathogenesis of acute pancreatitis has not been fully understood. Laboratory and radiological investigations are critical for diagnosis as well prognosis prediction. Scoring systems based on radiological findings and serologic inflammatory markers have been proposed as better predictors of disease severity. Early endoscopic retrograde cholangiopancreatography (ERCP is beneficial in a group of patients with gallstone pancreatitis. Laparoscopic cholecystectomy with preoperative endoscopic common bile duct clearance is recommended as a treatment of choice for acute biliary pancreatitis. The timing of cholecystectomy, following ERCP, for biliary pancreatitis can vary markedly depending on the severity of pancreatitis

  10. Intestinal mucosal barrier dysfunction participates in the progress of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Mao, Jing-Wei; Tang, Hai-Ying; Zhao, Ting; Tan, Xiao-Yan; Bi, Jian; Wang, Bing-Yuan; Wang, Ying-De

    2015-01-01

    Intestinal mucosal barrier dysfunction is closely related to liver diseases, which implies impaired gut-liver axis may play a role in the pathogenesis of NAFLD. In our study, rats were divided into three groups: normal chow diet (NCD) group, high-fat diet (HFD) group and TNBS-induced colitis with high-fat diet (C-HFD) group. Liver tissues were obtained for histological observation and TNF-α, IL-6 mRNA determination and blood samples were collected for liver enzymes and LPS analysis. Ultrastructural changes of jejuna epithelium, SIBO and amounts of CD103(+)MHCII(+)DCs and CD4(+)CD25(+)FoxP3(+)T-regs in terms of percentage in mesenteric lymph nodes (MLN) were observed by electron microscope, bacterial cultivation and flow cytometry, respectively. The results demonstrated the pathological characteristics accorded with nonalcoholic simple fatty liver (NAFL) and NASH in HFD group by week 8 and 12, respectively. Besides, the degree of hepatic steatosis and steatohepatitis was more severe in C-HFD group compared with HFD-group at the same time point. NAFLD activity score (NAS), liver enzymes, concentration of LPS and mRNA expressions of TNF-α, IL-6 were higher significantly in C-HFD group compared with HFD and NCD group at week 4, 8 and 12, respectively. In HFD group, epithelium microvilli atrophy, disruptive tight junctions and SIBO were present, and these changes were more severe in NASH compared with NAFL. The percentage of CD103+MHCII+DCs and CD4+CD25+FoxP3+T-regs decreased significantly in NAFL and NASH compared with NCD group. Our conclusion was that gut-liver axis was impaired in NAFLD, which played crucial role in the pathogenesis of NAFLD. PMID:26097546

  11. Effect of Chewing Gum on Oral Mucositis in Children Undergoing Chemotherapy: A Randomized Controlled Study

    OpenAIRE

    Eghbali, A.; Taherkhanchi, B; Bagheri, B; Sadeghi Sedeh, B

    2016-01-01

    Background Oral mucositis is an adverse effect of chemotherapy. Type of chemotherapy regimen is the most important factor causing mucositis. Oral mucositis is usually associated with transient decrease in saliva production. The goal was to study effects of gum consumption on oral mucositis in children undergoing chemotherapy. Materials and Method This randomized controlled trial was done in Amir Kabir Hospital, Arak, Iran. 130 children 5 to 15 years of age were studied. Control group was comp...

  12. Cancer Treatment-Induced Mucositis Pain: Strategies for Assessment and Management

    OpenAIRE

    Harris, Debra J

    2006-01-01

    Mucositis pain is a major clinical problem associated with cancer treatment. Mucosal tissue injury is a dose-limiting side effect and also limits nutritional intake and oral function, resulting in weight loss and nutritional deficits for many patients. The pathophysiology of mucositis is thought to be a complex array of cytokine-mediated events, which begins with mucosal atrophy and eventually leads to the painful ulceration of the mucosa. This article reviews current research related to pain...

  13. Mucosal Immunization with Helicobacter, CpG DNA, and Cholera Toxin Is Protective

    OpenAIRE

    Jiang, Weiwen; Baker, Henry J.; Smith, Bruce F.

    2003-01-01

    The mucosal delivery of antigens requires an effective adjuvant to induce mucosal immunity. Current mucosal adjuvants include cholera toxin (CT) and Escherichia coli heat-labile toxin. Unmethylated CpG immunostimulatory oligodeoxynucleotides (ODNs) have been proposed as novel mucosal adjuvants. In this study, mice were immunized with sonicated Helicobacter felis with CT and/or CpG ODN adjuvants. All groups receiving either adjuvant singly or in combination developed increased serum anti-H. fe...

  14. Current Trends in the Management of Oral Mucositis Related to Cancer Treatment

    OpenAIRE

    Biswal, Biswa Mohan

    2008-01-01

    Oral mucositis is one of the most common toxicities observed during radiotherapy and chemotherapy treatment for cancers. Mucositis results in sore mouth, altered taste sensation, pain and dysphagia leading to malnutrition. Left untreated, oral mucositis leads to ulceration, orodental infection, bleeding and discontinuation of effective radiotherapy or chemotherapy. Frequent hospitalization, enteral or parenteral nutrition, increased demand for analgesics ultimately account for increased cost ...

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

    Directory of Open Access Journals (Sweden)

    Sadaf A Karbelkar

    2016-01-01

    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. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-15

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

  17. Oral mucositis frequency in head and neck chemoradiotherapy

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-06-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma). PMID:27004972

  19. Mucosal neuroma syndrome--a phenotype for malignancy.

    OpenAIRE

    White, M P; Goel, K M; Connor, J M; Coutts, N A

    1985-01-01

    The mucosal neuroma syndrome is characterised by a typical physical appearance, neuromata on tongue and buccal mucosa, and a high risk of developing medullary thyroid carcinoma and phaeochromocytoma. A case is described and the importance of early recognition for prevention of malignancy is stressed.

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

    Energy Technology Data Exchange (ETDEWEB)

    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: bbaum@dir.nidcr.nih.gov [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2012-07-15

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

  1. Photobiomodulation reduces oral mucositis by modulating NF-kB

    Science.gov (United States)

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

    2015-12-01

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

  2. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    International Nuclear Information System (INIS)

    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

  3. Management of oral mucositis in patients with cancer.

    NARCIS (Netherlands)

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

    2005-01-01

    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

  4. Metagenomics of the Mucosal Microbiota of European Eels

    OpenAIRE

    Carda Diéguez, Miguel; Ghai, Rohit; Rodriguez Valera, Francisco; Amaro González, Carmen

    2014-01-01

    European eels are an economically important and threatened species that are prone to rapid collapse in farm conditions. Using metagenomics, we show that the eel mucosal microbiota has specific features distinguishing it from the surrounding aquatic community. This is a first step in dissecting the resident microbiota of this critical barrier that may have implications for maintenance of healthy eel populations.

  5. Mucosal barrier injury and stem cell transplant recipients

    NARCIS (Netherlands)

    Blijlevens, Nicolina Maria Anna

    2005-01-01

    The intensive chemotherapy with or without radiation therapy used to prepare for a haematopoietic stem cell transplant (HSCT) is unfortunately complicated by damage to the mucosa of the digestive tract. The resultant, mucosal barrier injury (MBI) causes painful ulcerations, which are readily apparen

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nishith Kumar

    2012-01-01

    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.

  8. Pharmacological Protection From Radiation ± Cisplatin-Induced Oral Mucositis

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Campbell, Eric L; Bruyninckx, Walter J; Kelly, Caleb J; Glover, Louise E; 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; Nemenoff, Raphael; Jedlicka, Paul; Taylor, Cormac T; Kominsky, Douglas J; Colgan, Sean P

    2014-01-16

    Acute intestinal inflammation involves early accumulation of neutrophils (PMNs) followed by either resolution or progression to chronic inflammation. Based on recent evidence that mucosal metabolism influences disease outcomes, we hypothesized that transmigrating PMNs influence the transcriptional profile of the surrounding mucosa. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by PMN-epithelial crosstalk. Transmigrating PMNs rapidly depleted microenvironmental O2 sufficiently to stabilize intestinal epithelial cell hypoxia-inducible factor (HIF). By utilizing HIF reporter mice in an acute colitis model, we investigated the relative contribution of PMNs and the respiratory burst to "inflammatory hypoxia" in vivo. CGD mice, lacking a respiratory burst, developed accentuated colitis compared to control, with exaggerated PMN infiltration and diminished inflammatory hypoxia. Finally, pharmacological HIF stabilization within the mucosa protected CGD mice from severe colitis. In conclusion, transcriptional imprinting by infiltrating neutrophils modulates the host response to inflammation, via localized O2 depletion, resulting in microenvironmental hypoxia and effective inflammatory resolution. PMID:24412613

  10. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-05-01

    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.

  11. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-01-01

    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.

  12. Staphylococcal enterotoxins in the Etiopathogenesis of Mucosal Autoimmunity within the Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    MaryAnn Principato

    2014-04-01

    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.

  13. Chemokines and chemokine receptors in mucosal homeostasis at the intestinal epithelial barrier in inflammatory bowel disease.

    Science.gov (United States)

    Zimmerman, Noah P; Vongsa, Rebecca A; Wendt, Michael K; Dwinell, Michael B

    2008-07-01

    Chemokines, a large family of small chemoattractive cytokines, and their receptors play an integral role in the regulation of the immune response and homeostasis. The ability of chemokines to attract specific populations of immune cells sets them apart from other chemoattractants. Chemokines produced within the gastrointestinal mucosa are critical players in directing the balance between physiological and pathophysiological inflammation in health, inflammatory bowel disease (IBD), and the progression to colon cancer. In addition to the well-characterized role of chemokines in directed trafficking of immune cells to the gut mucosa, the expression of chemokine receptors on the cells of the epithelium makes them active participants in the chemokine signaling network. Recent findings demonstrate an important role for chemokines and chemokine receptors in epithelial barrier repair and maintenance as well as an intricate involvement in limiting metastasis of colonic carcinoma. Increased recognition of the association between barrier defects and inflammation and the subsequent progression to cancer in IBD thus implicates chemokines as key regulators of mucosal homeostasis and disease pathogenesis. PMID:18452220

  14. Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O. V.; Pavlov, A. N.; Semyachkin-Glushkovskiy, I. A.; Gekalyuk, A. S.; Ulanova, M. V.; Lychagov, V. V.; Tuchin, V. V.

    2014-09-01

    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.

  15. Oral health as a predictive factor for oral mucositis

    Directory of Open Access Journals (Sweden)

    Fabio Luiz Coracin

    2013-06-01

    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.

  16. Developments in the production of mucosal antibodies in plants.

    Science.gov (United States)

    Vasilev, Nikolay; Smales, C Mark; Schillberg, Stefan; Fischer, Rainer; Schiermeyer, Andreas

    2016-01-01

    Recombinant mucosal antibodies represent attractive target molecules for the development of next generation biopharmaceuticals for passive immunization against various infectious diseases and treatment of patients suffering from mucosal antibody deficiencies. As these polymeric antibodies require complex post-translational modifications and correct subunit assembly, they are considered as difficult-to-produce recombinant proteins. Beside the traditional, mammalian-based production platforms, plants are emerging as alternative expression hosts for this type of complex macromolecule. Plant cells are able to produce high-quality mucosal antibodies as shown by the successful expression of the secretory immunoglobulins A (IgA) and M (IgM) in various antibody formats in different plant species including tobacco and its close relative Nicotiana benthamiana, maize, tomato and Arabidopsis thaliana. Importantly for biotherapeutic application, transgenic plants are capable of synthesizing functional IgA and IgM molecules with biological activity and safety profiles comparable with their native mammalian counterparts. This article reviews the structure and function of mucosal IgA and IgM antibodies and summarizes the current knowledge of their production and processing in plant host systems. Specific emphasis is given to consideration of intracellular transport processes as these affect assembly of the mature immunoglobulins, their secretion rates, proteolysis/degradation and glycosylation patterns. Furthermore, this review provides an outline of glycoengineering efforts that have been undertaken so far to produce antibodies with homogenous human-like glycan decoration. We believe that the continued development of our understanding of the plant cellular machinery related to the heterologous expression of immunoglobulins will further improve the production levels, quality and control of post-translational modifications that are 'human-like' from plant systems and enhance the

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

    Science.gov (United States)

    Elsadek, Hany M; Radwan, Mamdouh M

    2015-01-01

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

  18. Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats

    Directory of Open Access Journals (Sweden)

    Vink Carolien

    2009-04-01

    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.

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

    Science.gov (United States)

    Aghamohamamdi, Azar; Hosseinimehr, Seyed Jalal

    2016-03-01

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

  20. Contemporary Management of Acute Biliary Pancreatitis

    Directory of Open Access Journals (Sweden)

    Orhan Ozkan

    2014-03-01

    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.

  1. Acute exercise does not induce an acute phase response (APR) in Standardbred trotters

    DEFF Research Database (Denmark)

    Kristensen, Lena; Buhl, Rikke; Nostell, Katarina; Bak, Lars; Petersen, Ellen; Lindholm, Maria; Jacobsen, Stine

    2014-01-01

    have been caused by exercise-induced hemolysis, which indicates that horses might experience a condition similar to athlete’s anemia in humans. The pathogenesis and clinical implications of the hematological and blood-biochemical changes elicited by acute exercise in Standardbred trotters in the...

  2. Effect of electroacupunture on gastric mucosal intestinal trefoil factor gene expression of stress-induced gastric mucosal injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xi-Ping Li; Jie Yan; Shou-Xiang Yi; Xiao-Rong Chang; Ya-Ping Lin; Zong-Bao Yang; Ai Huang; Rong Hu

    2006-01-01

    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".

  3. Radio and chemioinduced oral mucositis treatment: comparison between conventional drug protocol and treatments with low intensity lasers; Tratamento da mucosite oral e quimioinduzida: comparacao entre protocolo medicamentoso convencional e tratamentos com lasers em baixa intensidade

    Energy Technology Data Exchange (ETDEWEB)

    Alencar, Anelise Ribeiro Peixoto

    2011-07-01

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

  4. Stem Cells in the Intestine: Possible Roles in Pathogenesis of Irritable Bowel Syndrome.

    Science.gov (United States)

    Ratanasirintrawoot, Sutheera; Israsena, Nipan

    2016-07-30

    Irritable bowel syndrome is one of the most common functional gastrointestinal (GI) disorders that significantly impair quality of life in patients. Current available treatments are still not effective and the pathophysiology of this condition remains unclearly defined. Recently, research on intestinal stem cells has greatly advanced our understanding of various GI disorders. Alterations in conserved stem cell regulatory pathways such as Notch, Wnt, and bone morphogenic protein/TGF- β have been well documented in diseases such as inflammatory bowel diseases and cancer. Interaction between intestinal stem cells and various signals from their environment is important for the control of stem cell self-renewal, regulation of number and function of specific intestinal cell types, and maintenance of the mucosal barrier. Besides their roles in stem cell regulation, these signals are also known to have potent effects on immune cells, enteric nervous system and secretory cells in the gut, and may be responsible for various aspects of pathogenesis of functional GI disorders, including visceral hypersensitivity, altered gut motility and low grade gut inflammation. In this article, we briefly summarize the components of these signaling pathways, how they can be modified by extrinsic factors and novel treatments, and provide evidenced support of their roles in the inflammation processes. Furthermore, we propose how changes in these signals may contribute to the symptom development and pathogenesis of irritable bowel syndrome. PMID:27184041

  5. Evidence for the involvement of infectious agents in the pathogenesis of Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    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.

  6. Mycoplasma gallisepticum modifies the pathogenesis of influenza A virus in the avian tracheal epithelium.

    Science.gov (United States)

    Sid, Hicham; Hartmann, Sandra; Petersen, Henning; Ryll, Martin; Rautenschlein, Silke

    2016-05-01

    Multiple respiratory infections have a significant impact on health and economy. Pathogenesis of co-infecting viruses and bacteria and their interaction with mucosal surfaces are poorly characterized. In this study we established a co-infection model based on pre-incubation of tracheal organ cultures (TOC) with Mycoplasma (M.) gallisepticum and a subsequent infection with avian influenza virus (AIV). Mycoplasma gallisepticum modified the pathogenesis of AIV as demonstrated in TOC of two different avian species (chickens and turkeys). Co-infection promoted bacterial growth in tracheal epithelium. Depending on the interaction time of M. gallisepticum with the host cells, AIV replication was either promoted or suppressed. M. gallisepticum inhibited the antiviral gene expression and affected AIV attachment to the host cell by desialylation of α-2,3 linked sialic acids. Ultrastructural analysis of co-infected TOC suggests that both pathogens may attach to and possibly infect the same epithelial cell. The obtained results contribute to better understanding of the interaction dynamics between M. gallisepticum and AIV. They highlight the importance of the time interval between infections as well as the biological properties of the involved pathogens as influencing factors in the outcome of respiratory infections. PMID:27079856

  7. Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus.

    Science.gov (United States)

    Wang, Hui; Zhang, Dunfang; Han, Qi; Zhao, Xin; Zeng, Xin; Xu, Yi; Sun, Zheng; Chen, Qianming

    2016-07-01

    Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment. PMID:26693958

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

    International Nuclear Information System (INIS)

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

  9. Acute radiation proctitis. A clinical, histopathological and histochemical study

    International Nuclear Information System (INIS)

    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

  10. Acute radiation proctitis. A clinical, histopathological and histochemical study

    Energy Technology Data Exchange (ETDEWEB)

    Hovdenak, Nils

    2004-07-01

    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.

  11. Psoriasis: Pathogenesis, Assessment, and Therapeutic Update.

    Science.gov (United States)

    Schleicher, Stephen M

    2016-07-01

    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. PMID:27215156

  12. Pathogenesis of nosocomial infections with Enterococcus faecalis

    NARCIS (Netherlands)

    Waar, Karola

    2004-01-01

    In this thesis, we analyzed the role of the different virulence factors of E. faecalis known in literature in the pathogenesis of infections. We investigated the prevalence of virulence factors in E. faecalis isolates from different hosts as well as their role in biomaterial related infections. The

  13. Transfusion-related acute lung injury; clinical perspectives.

    Science.gov (United States)

    Kim, Jeongmin; Na, Sungwon

    2015-04-01

    Transfusion-related acute lung injury (TRALI) was introduced in 1983 to describe a clinical syndrome seen within 6 h of a plasma-containing blood products transfusion. TRALI is a rare transfusion complication; however, the FDA has suggested that TRALI is the leading cause of transfusion-related mortality. Understanding the pathogenesis of TRALI will facilitate adopting preventive strategies, such as deferring high plasma volume female product donors. This review outlines the clinical features, pathogenesis, treatment, and prevention of TRALI. PMID:25844126

  14. Lassa fever presenting as acute abdomen: a case series

    OpenAIRE

    Andrew E. Dongo; Kesieme, Emeka B.; Iyamu, Christopher E; Okokhere, Peter O; Akhuemokhan, Odigie C.; Akpede, George O.

    2013-01-01

    Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefo...

  15. Pathogenesis of optic disc edema in raised intracranial pressure.

    Science.gov (United States)

    Hayreh, Sohan Singh

    2016-01-01

    Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with

  16. Oral manifestations of acute leukaemia

    Directory of Open Access Journals (Sweden)

    Ivanović Mirjana

    2011-01-01

    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.

  17. Contribution of Panton-Valentine leukocidin in community-associated methicillin-resistant Staphylococcus aureus pathogenesis.

    Directory of Open Access Journals (Sweden)

    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.

  18. Development of Mucosal Vaccines Based on Lactic Acid Bacteria

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Koshio, Shunsuke

    2015-01-01

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

  20. Infectious agents in coronary atheromas: a possible role in the pathogenesis of plaque rupture and acute myocardial infarction Agentes infecciosos em ateromas coronarianos: um possível papel na patogênese da ruptura da placa e infarto agudo do miocárdio

    OpenAIRE

    Maria de Lourdes HIGUCHI; Jose A. F. RAMIRES

    2002-01-01

    In this review we report our recent findings of histopathological features of plaque instability and the association with Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) infection, studying thrombosed coronary artery segments (CAS) of patients who died due to acute myocardial infarction. Vulnerable plaques are known to be associated with fat atheromas and inflammation of the plaque. Here we demonstrated that vulnerability is also related with focal positive vessel remodeling that mai...

  1. Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

    International Nuclear Information System (INIS)

    Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

  2. A national epidemiological survey of oral mucosal lesions in Malaysia

    OpenAIRE

    Zain, R. B.; Ikeda, N; I. A. Razak; Axell, T.; Majid, Z. A.; P C Gupta; Yaacob, M.

    1997-01-01

    The prevalence of oral mucosal lesions in Malaysia was determined by examining a representative sample of 11 707 subjects aged 25 years and above throughout the 14 states over a period of 5 months during 1993/1994. A two-stage stratified random sampling was undertaken. A predetermined number of enumeration blocks, the smallest population unit in the census publication was selected from each state. With the selected enumeration block, a systematic sample of living quarters was chosen with a ra...

  3. Endoscopic mucosal resection in the upper gastrointestinal tract

    OpenAIRE

    Ahmadi, Anis; Draganov, Peter

    2008-01-01

    Endoscopic mucosal resection (EMR) is a technique used to locally excise lesions confined to the mucosa. Its main role is the treatment of advanced dysplasia and early gastrointestinal cancers. EMR was originally described as a therapy for early gastric cancer. Recently its use has expanded as a therapeutic option for ampullary masses, colorectal cancer, and large colorectal polyps. In the Western world, the predominant indication for EMR in the upper gastrointestinal tract is the staging and...

  4. Oral mucosal precancer and cancer: a helpful discriminating clinical tool

    OpenAIRE

    Scully, Crispian; Sciubba, James; Bagán Sebastián, José Vicente

    2015-01-01

    The authors have collaborated with many colleagues in several countries in formulating a useful and practical clinical tool for evaluating oral mucosal findings on routine examination. Consideration of several factors including history, evolution of positive findings and clinical information allows placement of examination results into one of three categories which are graded by a color scheme along a spectrum of concerns (green to red, or no concern to serious concern). Afforded to the clini...

  5. Mucosal genetic immunization through microsphere–based oral carriers

    OpenAIRE

    Rosli, Rozita; Nograles, Nadine; Hanafi, Aimi; Nor Shamsudin, Mariana; Abdullah, Syahril

    2013-01-01

    Polymeric carriers in the form of cellulose acetate phthalate (CAP) and alginate (ALG) microspheres were used for encapsulation of plasmid DNA for oral mucosal immunization. Access into the intestinal mucosa by pVAX1 eukaryotic expression plasmid vectors carrying gene-coding sequences, either for the cholera enterotoxin B subunit (ctxB) immunostimulatory antigen or the green fluorescent protein (GFP), delivered from both types of microsphere carriers were examined in orally immunized BALB/c m...

  6. Mucosal reactive oxygen metabolite production in duodenal ulcer disease.

    OpenAIRE

    Davies, G. R.; Simmonds, N J; Stevens, T R; Grandison, A; D. R. Blake; Rampton, D S

    1992-01-01

    To investigate the hypothesis that reactive oxygen metabolites are important in the pathophysiology of duodenal ulcer disease, their production by duodenal mucosal biopsy specimens was measured using luminol and lucigenin amplified chemiluminescence. Luminol chemiluminescence, expressed as background corrected median photon emission/mg/min x 10(3) (95% confidence intervals), was increased in duodenal inflammation as assessed macroscopically: ulcers 20.3 (4.8 to 51.3), n = 29; severe duodeniti...

  7. Bleeding duodenal hemangioma: Morphological changes and endoscopic mucosal resection

    Institute of Scientific and Technical Information of China (English)

    Noriko Nishiyama; Hirohito Mori; Hideki Kobara; Shintarou Fujihara; Takako Nomura; Mitsuyoshi Kobayashi; Tsutomu Masaki

    2012-01-01

    Recently,the development of endoscopic procedures has increased the availability of minimally invasive treatments; however,there have been few case reports of duodenal hemangioma treated by endoscopic mucosal resection.The present report describes a case of duodenal hemangioma that showed various endoscopic changes over time and was treated by endoscopic mucosal resection.An 80-year-old woman presented with tarry stools and a loss of appetite.An examination of her blood revealed severe anemia,and her hemoglobin level was 4.2 g/dL.An emergency upper gastrointestinal endoscopy was performed.A red,protrusive,semipedunculated tumor (approximately 20 mm in diameter) with spontaneous bleeding on its surface was found in the superior duodenal angle.Given the semipedunculated appearance of the tumor,it was suspected to be an epithelial tumor with a differential diagnosis of hyperplastic polyp.The biopsy results suggested a telangiectatic hemangioma.Because this lesion was considered to be responsible for her anemia,endoscopic mucosal resection was performed for diagnostic and treatment purposes after informed consent was obtained.A histopathological examination of the resected specimen revealed dilated and proliferated capillary lumens of various sizes,which confirmed the final diagnosis of duodenal hemangioma.Neither anemia nor tumor recurrence has been observed since the endoscopic mucosal resection (approximately 1 year).Duodenal hemangiomas can be treated endoscopically provided that sufficient consideration is given to all of the possible treatment strategies.Interestingly,duodenal hemangiomas show morphological changes that are influenced by various factors,such as mechanical stimuli.

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

    OpenAIRE

    Koh, A.Y.; Kohler, J.R.; Coggshall, K.T.; Rooijen, van, N.; Pier, G B

    2008-01-01

    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 par...

  9. Molecular mechanism of interleukin-2-induced mucosal homeostasis

    OpenAIRE

    Mishra, Jayshree; Waters, Christopher M.; Kumar, Narendra

    2011-01-01

    Sustained damage to the mucosal lining in patients with inflammatory bowel disease (IBD) facilitates translocation of intestinal microbes to submucosal immune cells leading to chronic inflammation. Previously, we demonstrated the role of Jak3 in IL-2-induced intestinal epithelial cell (IEC) migration, one of the early events during intestinal wound repair. In this study, we demonstrate that IL-2 also plays a role in IEC homeostasis through concentration-dependent regulation of IEC proliferati...

  10. Effects of feminine hygiene products on the vaginal mucosal biome

    OpenAIRE

    Fichorova, Raina N.; Fashemi, Bisiayo; Delaney, Mary L.; Onderdonk, Andrew B

    2013-01-01

    Background: Over-the-counter (OTC) feminine hygiene products come with little warning about possible side effects. This study evaluates in-vitro their effects on Lactobacillus crispatus, which is dominant in the normal vaginal microbiota and helps maintain a healthy mucosal barrier essential for normal reproductive function and prevention of sexually transmitted infections and gynecologic cancer. Methods: A feminine moisturizer (Vagisil), personal lubricant, and douche were purchased OTC. A t...

  11. Mucosal immunity, intestinal microflora and inflammatory bowel disease

    Czech Academy of Sciences Publication Activity Database

    Tlaskalová, Helena; Štěpánková, Renata; Sokol, Dan; Rossmann, Pavel; Cukrowska, Božena; Hudcovic, Tomáš; Tučková, Ludmila; Kozáková, Hana; Řeháková, Zuzana; Hrnčíř, Tomáš; Drastich, Pavel; Frolová, Lenka; Powrie, F.; Uhlig, H.; Bland, P. W.

    Praha, 2005, s. 1-8. [Falk Symposium /135./. Praha (CZ), 12.09.2003-13.09.2003] R&D Projects: GA ČR GA310/01/0933; GA ČR GA310/01/0934; GA AV ČR IAA5020205; GA AV ČR IBS5020203 Institutional research plan: CEZ:AV0Z50200510 Keywords : intestinal microflora * mucosal immunity Subject RIV: EE - Microbiology, Virology

  12. Psittacid herpesviruses associated with mucosal papillomas in neotropical parrots

    International Nuclear Information System (INIS)

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

  13. Oral complications of cancer therapies. Management of mucositis during therapy

    International Nuclear Information System (INIS)

    This paper reviews the purposes of an oral care protocol, the major components of an oral care regimen, and oral care protocols and studies done to date. Many questions remain in the area of optimal oral care for the patient experiencing mucositis as a sequela of cancer treatment. Research is needed on types and use of mouth rinses, effective, harmless, and pleasant lip lubricants, appropriate analgesic and anti-inflammatory combinations, and the effectiveness of a variety of devices for oral cleansing, to name a few areas. As outpatient oncology services grow, oral care protocols must be developed to meet the needs of ambulatory patient populations. Oral care regimens must be safe, easy to use, and economical as well as effective to ensure patient and staff compliance. Research on the management of mucositis must be conducted in both inpatient and outpatient settings. Finally, in order to obtain sufficient sample sizes and optimize data collection, these studies will need to be conducted by multidisciplinary teams (including dentists, oncologists, radiation therapists, and nurses) across multiple sites. Not until large-scale clinical trials are done on the treatment of mucositis will we be able to optimize the therapeutic regimen for the patient. 43 references

  14. Role of mucosal dendritic cells in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Jan Hendrik Niess

    2008-01-01

    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.

  15. An overview of challenges limiting the design of protective mucosal vaccines for finfish

    Directory of Open Access Journals (Sweden)

    Hetron Mweemba Munang'andu

    2015-10-01

    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.

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

    Science.gov (United States)

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

    2006-12-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

  18. Lupus anticoagulants: pathogenesis and laboratory diagnosis.

    Science.gov (United States)

    Court, E L

    1997-12-01

    The pathogenesis of the lupus anticoagulant (LA) has been the focus of much research over the past decade, and a plethora of laboratory tests have been developed to detect it. This essay reviews the nature of LA and its pathogenesis, and a number of approaches employed in its diagnosis. These range from well established tests such as the kaolin clotting time (KCT), activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition test (TTI), to the 'newer' tests such as the dilute Russell's viper venom time (DRVVT) and more recent snake venom tests such as the textarin/ecarin ratio and Taipan snake venom time (TSVT). The criteria for diagnosis are discussed, including pre-analytical variables such as sample preparation, and the effects of therapeutic anticoagulants used to treat thrombotic manifestations of the syndrome or an underlying disease process. PMID:9624740

  19. Autophagy in the pathogenesis of ankylosing spondylitis.

    Science.gov (United States)

    Ciccia, Francesco; Haroon, Nigil

    2016-06-01

    The pathogenesis of ankylosing spondylitis (AS) is not well understood, and treatment options have met with limited success. Autophagy is a highly conserved mechanism of controlled digestion of damaged organelles within a cell. It helps in the maintenance of cellular homeostasis. The process of autophagy requires the formation of an isolation membrane. They form double-membraned vesicles called "autophagosomes" that engulf a portion of the cytoplasm. Beyond the role in maintenance of cellular homeostasis, autophagy has been demonstrated as one of the most remarkable tools employed by the host cellular defense against bacteria invasion. Autophagy also affects the immune system and thus is implicated in several rheumatic disease processes. In this article, we explore the potential role of autophagy in the pathogenesis of AS. PMID:27075464

  20. Aetio-pathogenesis of breast cancer

    Directory of Open Access Journals (Sweden)

    Imran Haruna Abdulkareem

    2013-01-01

    Full Text Available This is a literature review on the aetiology and pathogenesis of breast cancer, which is the most common cancer worldwide, and the second leading cause of cancer death, especially in Western countries. Several aetiological factors have been implicated in its pathogenesis, and include age, genetics, family history, diet, alcohol, obesity, lifestyle, physical inactivity, as well as endocrine factors. These factors act separately or together in the causation of breast cancer. More recently, triple negative breast cancer has been described in certain categories of patients and is associated with poorer prognosis and earlier recurrence compared with the conventional breast cancer. Therefore, adequate knowledge of these factors is important in identifying high risk groups and individuals, which will help in screening, early detection and follow-up. This will help to decrease the morbidity and mortality from this life-threatening disease.

  1. Pancreatic cancer: Pathogenesis, prevention and treatment

    International Nuclear Information System (INIS)

    Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-κB pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-κB, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer

  2. Theories on the Pathogenesis of Endometriosis

    Directory of Open Access Journals (Sweden)

    Samer Sourial

    2014-01-01

    Full Text Available Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition.

  3. Acne Scars: Pathogenesis, Classification and Treatment

    OpenAIRE

    Gabriella Fabbrocini; Annunziata, M. C.; V. D'Arco; V. De Vita; Lodi, G.; M. C. Mauriello; F. Pastore; G. Monfrecola

    2010-01-01

    Acne has a prevalence of over 90% among adolescents and persists into adulthood in approximately 12%–14% of cases with psychological and social implications. Possible outcomes of the inflammatory acne lesions are acne scars which, although they can be treated in a number of ways, may have a negative psychological impact on social life and relationships. The main types of acne scars are atrophic and hypertrophic scars. The pathogenesis of acne scarring is still not fully understood, but severa...

  4. Autophagy in lung disease pathogenesis and therapeutics

    OpenAIRE

    Ryter, Stefan W.; Augustine M K Choi

    2015-01-01

    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, an...

  5. The pathogenesis of tendinopathy. A molecular perspective

    OpenAIRE

    Riley, GP

    2003-01-01

    There are many publications that discuss the aetiology, diagnosis and treatment of the various forms of tendinopathy, but few are based on conclusive scientific evidence. The pathogenesis of tendinopathy is difficult to study because tendon biopsies are rarely obtained before a tendon has ruptured. There are interesting comparisons with animal tendinopathy, particularly in the equine athlete, although many animal models do not accurately reflect the human condition—the tendon lesions usually ...

  6. Vacuolar trafficking and Candida albicans pathogenesis

    OpenAIRE

    Palmer, Glen E.

    2011-01-01

    The vacuole is likely to play a variety of roles in supporting host colonization and infection by pathogenic species of fungi. In the human pathogen Candida albicans, the vacuole undergoes dynamic morphological shifts during the production of the tissue invasive hyphal form, and this organelle is required for virulence. Recent efforts in my lab have focused on defining which vacuolar trafficking pathways are required for C. albicans hyphal growth and pathogenesis. Our results indicate that th...

  7. Pathogenesis of Mycoplasma pneumoniae: An update

    Directory of Open Access Journals (Sweden)

    R Chaudhry

    2016-01-01

    Full Text Available Genus Mycoplasma, belonging to the class Mollicutes, encompasses unique lifeforms comprising of a small genome of 8,00,000 base pairs and the inability to produce a cell wall under any circumstances. Mycoplasma pneumoniae is the most common pathogenic species infecting humans. It is an atypical respiratory bacteria causing community acquired pneumonia (CAP in children and adults of all ages. Although atypical pneumonia caused by M. pneumoniae can be managed in outpatient settings, complications affecting multiple organ systems can lead to hospitalization in vulnerable population. M. pneumoniae infection has also been associated with chronic lung disease and bronchial asthma. With the advent of molecular methods of diagnosis and genetic, immunological and ultrastructural assays that study infectious disease pathogenesis at subcellular level, newer virulence factors of M. pneumoniae have been recognized by researchers. Structure of the attachment organelle of the organism, that mediates the crucial initial step of cytadherence to respiratory tract epithelium through complex interaction between different adhesins and accessory adhesion proteins, has been decoded. Several subsequent virulence mechanisms like intracellular localization, direct cytotoxicity and activation of the inflammatory cascade through toll-like receptors (TLRs leading to inflammatory cytokine mediated tissue injury, have also been demonstrated to play an essential role in pathogenesis. The most significant update in the knowledge of pathogenesis has been the discovery of Community-Acquired Respiratory Distress Syndrome toxin (CARDS toxin of M. pneumoniae and its ability of adenosine diphosphate (ADP ribosylation and inflammosome activation, thus initiating airway inflammation. Advances have also been made in terms of the different pathways behind the genesis of extrapulmonary complications. This article aims to comprehensively review the recent advances in the knowledge of

  8. Pathogenesis of Mycoplasma pneumoniae: An update.

    Science.gov (United States)

    Chaudhry, R; Ghosh, A; Chandolia, A

    2016-01-01

    Genus Mycoplasma, belonging to the class Mollicutes, encompasses unique lifeforms comprising of a small genome of 8,00,000 base pairs and the inability to produce a cell wall under any circumstances. Mycoplasma pneumoniae is the most common pathogenic species infecting humans. It is an atypical respiratory bacteria causing community acquired pneumonia (CAP) in children and adults of all ages. Although atypical pneumonia caused by M. pneumoniae can be managed in outpatient settings, complications affecting multiple organ systems can lead to hospitalization in vulnerable population. M. pneumoniae infection has also been associated with chronic lung disease and bronchial asthma. With the advent of molecular methods of diagnosis and genetic, immunological and ultrastructural assays that study infectious disease pathogenesis at subcellular level, newer virulence factors of M. pneumoniae have been recognized by researchers. Structure of the attachment organelle of the organism, that mediates the crucial initial step of cytadherence to respiratory tract epithelium through complex interaction between different adhesins and accessory adhesion proteins, has been decoded. Several subsequent virulence mechanisms like intracellular localization, direct cytotoxicity and activation of the inflammatory cascade through toll-like receptors (TLRs) leading to inflammatory cytokine mediated tissue injury, have also been demonstrated to play an essential role in pathogenesis. The most significant update in the knowledge of pathogenesis has been the discovery of Community-Acquired Respiratory Distress Syndrome toxin (CARDS toxin) of M. pneumoniae and its ability of adenosine diphosphate (ADP) ribosylation and inflammosome activation, thus initiating airway inflammation. Advances have also been made in terms of the different pathways behind the genesis of extrapulmonary complications. This article aims to comprehensively review the recent advances in the knowledge of pathogenesis of this

  9. Some observations on the pathogenesis of syringomyelia.

    OpenAIRE

    Newman, P K; Terenty, T R; Foster, J B

    1981-01-01

    The pathogenesis of most cases of syringomyelia remains obscure although a modification of the hydrodynamic theory of Gardner allows a logical surgical approach to treatment. Data are presented confirming a high incidence of traumatic birth in patients with syringomyelia who have a Chiari malformation or basal arachnoiditis, but demonstrating no increase in traumatic birth in patients with the Chiari malformation but no syringomyelia. A traumatic birth may be the factor responsible for creati...

  10. Diabetic Cataract—Pathogenesis, Epidemiology and Treatment

    OpenAIRE

    Ursula Schmidt-Erfurth; Andreas Pollreisz

    2010-01-01

    Cataract in diabetic patients is a major cause of blindness in developed and developing countries. The pathogenesis of diabetic cataract development is still not fully understood. Recent basic research studies have emphasized the role of the polyol pathway in the initiation of the disease process. Population-based studies have greatly increased our knowledge concerning the association between diabetes and cataract formation and have defined risk factors for the development of cataract. Diabet...

  11. New developments in the pathogenesis of preeclampsia.

    Science.gov (United States)

    Naljayan, Mihran V; Karumanchi, S Ananth

    2013-05-01

    Preeclampsia affects 3% to 5% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This disorder is characterized by a constellation of signs and symptoms, most notably new-onset hypertension and proteinuria during the last trimester of pregnancy. In this review, the molecular mechanisms of preeclampsia with an emphasis on the role of circulating antiangiogenic proteins in the pathogenesis of preeclampsia and its complications will be discussed. PMID:23928392

  12. NEW DEVELOPMENTS IN THE PATHOGENESIS OF PREECLAMPSIA

    OpenAIRE

    Naljayan, Mihran V.; Karumanchi, S. Ananth

    2013-01-01

    Preeclampsia affecting 3-5% of all pregnancies is a major cause of maternal and perinatal morbidity and mortality worldwide. This disorder is characterized by a constellation of signs and symptoms, most notably new onset hypertension and proteinuria during the last trimester of pregnancy. In this review, the molecular mechanisms of preeclampsia with an emphasis on the role of circulating anti-angiogenic proteins in the pathogenesis of preeclampsia and its complications will be discussed.

  13. Alzheimer's Disease: Genes, pathogenesis and risk prediction

    OpenAIRE

    Sleegers, Kristel; Duijn, Cock

    2001-01-01

    textabstractWith the aging of western society the contribution to morbidity of diseases of the elderly, such as dementia, will increase exponentially. Thorough preventative and curative strategies are needed to constrain the increasing prevalence of these disabling diseases. Better understanding of the pathogenesis of disease will enable development of therapy, prevention and the identification of high-risk groups in the population. Here, we review the genetic epidemiology of Alzheimer's dise...

  14. Autoantibodies and Resident Renal Cells in the Pathogenesis of Lupus Nephritis: Getting to Know the Unknown

    Directory of Open Access Journals (Sweden)

    Susan Yung

    2012-01-01

    Full Text Available Systemic lupus erythematosus is characterized by a breakdown of self-tolerance and production of autoantibodies. Kidney involvement (i.e., lupus nephritis is both common and severe and can result in permanent damage within the glomerular, vascular, and tubulo-interstitial compartments of the kidney, leading to acute or chronic renal failure. Accumulating evidence shows that anti-dsDNA antibodies play a critical role in the pathogenesis of lupus nephritis through their binding to cell surface proteins of resident kidney cells, thereby triggering the downstream activation of signaling pathways and the release of mediators of inflammation and fibrosis. This paper describes the mechanisms through which autoantibodies interact with resident renal cells and how this interaction plays a part in disease pathogenesis that ultimately leads to structural and functional alterations in lupus nephritis.

  15. A Mouse Model of Zika Virus Pathogenesis.

    Science.gov (United States)

    Lazear, Helen M; Govero, Jennifer; Smith, Amber M; Platt, Derek J; Fernandez, Estefania; Miner, Jonathan J; Diamond, Michael S

    2016-05-11

    The ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes, including Guillain-Barré syndrome and birth defects, has brought an urgent need for animal models. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking components of the antiviral response. Four- to six-week-old Irf3(-/-)Irf5(-/-)Irf7(-/-) triple knockout mice, which produce little interferon α/β, and mice lacking the interferon receptor (Ifnar1(-/-)) developed neurological disease and succumbed to ZIKV infection, whereas single Irf3(-/-), Irf5(-/-), and Mavs(-/-) knockout mice exhibited no overt illness. Ifnar1(-/-) mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The testes of Ifnar1(-/-) mice had the highest viral loads, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics as well as understanding disease pathogenesis. PMID:27066744

  16. Clinical features of the head and neck mucosal melanoma. А review

    Directory of Open Access Journals (Sweden)

    A. V. Ignatova

    2016-01-01

    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.

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27366048

  18. Acute glomerulonephritis, rapidly progressive emphasis on commitment

    Directory of Open Access Journals (Sweden)

    Adolfo León Castro

    2011-11-01

    Full Text Available Acute glomerulonephritis (GNA is a wide group of diseases with the common characteristics of abrupt onset and proliferation of endocapillary glomerular cells. Clinically, they usually manifest as acute nephritic syndrome: hematuria, acute renal failure, hypertension and mild proteinuria, although they can appear as recurrent hematuria. GNA can be present in association with a variety of bacterial and viral infections, but in most cases the initial antigenic initiating stimulus is unknown. Patients with rapidly progressive glomerulonephritis often present acute onset of manifestations of nephritis, such as azotemia, oliguria, edema, hypertension, proteinuria, and hematuria with «active» urine sediment that often contains red blood cell casts, pigmented casts, and cellular debris. This article, aimed at all primary care staff and seeking to increase their awareness of this disease, discusses in more detail the clinical, pathogenesis, pathology, and treatments available from one of the glomerulonephritis with greater impact on survival patient.

  19. Long-lived plasma cells are generated in mucosal immune responses and contribute to the bone marrow plasma cell pool in mice.

    Science.gov (United States)

    Lemke, A; Kraft, M; Roth, K; Riedel, R; Lammerding, D; Hauser, A E

    2016-01-01

    During systemic immune responses, plasma blasts are generated in secondary lymphoid organs and migrate to the bone marrow, where they can become long-lived, being responsible for the maintenance of long-term antibody titers. Plasma blasts generated in mucosal immune responses of the small intestine home to the lamina propria (LP), producing mainly immunoglobulin A. The migration of these antibody-secreting cells is well characterized during acute immune responses. Less is known about their lifetime and contribution to the long-lived bone marrow compartment. Here we investigate the lifetime of plasma cells (PCs) and the relationship between the PC compartments of the gut and bone marrow after oral immunization. Our findings indicate that PCs in the LP can survive for extended time periods. PCs specific for orally administered antigens can be detected in the bone marrow for at least 9 months after immunization, indicating that the mucosal PC compartment can contribute to the long-lived PC pool in this organ, independent of the participation of splenic B cells. Our findings suggest that the compartmentalization between mucosal and systemic PC pools is less strict than previously thought. This may have implications for the development of vaccines as well as for autoantibody-mediated diseases. PMID:25943272

  20. 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

    Energy Technology Data Exchange (ETDEWEB)

    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)

    2001-11-01

    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)