Oral submucous fibrosis: an overview of the aetiology, pathogenesis, classification, and principles of management

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Arakeri, G.; Brennan, P.A.

2013-01-01

Oral submucous fibrosis (OSMF) is a complex, debilitating, and precancerous condition. Formerly confined to the Indian subcontinent, it is now often seen in the Asian populations of the United Kingdom, USA, and other developed countries, and is therefore a serious problem for global health. The

Role of drinking water copper in pathogenesis of oral submucous fibrosis: a prospective case control study

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Arakeri, G.; Hunasgi, S.; Colbert, S.; Merkx, M.A.W.; Brennan, P.A.

2014-01-01

Although oral submucous fibrosis (OSMF) is thought to be multifactorial in origin, the chewing of areca nut is thought to be the main cause. Alkaloids and tannins in areca nut are responsible for fibrosis, but recent evidence has suggested that copper ions are also an important mediator, and in a

The Role of Serum Copper and Iron in Oral Submucous Fibrosis

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Master Luquman

2004-01-01

Full Text Available Oral submucous fibrosis (OSMF is a chronic insidious disease of multifactorial etiology. The habit of chewing arecanut is thought to be one of the most important etiologic factors. Copper and iron are elements in the human body that form part of important enzymes. We estimated the serum copper and iron in patients with OSMF as well as normal controls and discuss the role of these elements in the etiology of OSMF.

Dietary copper: a novel predisposing factor for oral submucous fibrosis?

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Arakeri, Gururaj; Brennan, Peter A

2013-03-01

Oral submucous fibrosis (OSMF) is known devastating disorder commonly seen in South Asian developing countries. It is directly linked to areca nut chewing and the contents of areca are subjected to multitude of investigations. Among all the contents of areca nut, the copper element has been extensively studied. Most of the published studies have validated its association with OSMF because of its local action. In this paper we postulate a novel biological pathway through which copper is thought to predispose oral mucosa to OSMF. The hypothesis is instructive in explaining various unexplored aspects of the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Oral Submucous Fibrosis (OSMF : A study of 101 cases

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J V Tupkari

2007-01-01

The study showed male preponderance affecting individuals in second and third decades of life. All the patients had the habit of chewing betel leaves, betel nuts, tobacco, gutkha, alone or in various combinations. The associated causative factors were high chilli intake, nutritional deficiencies, and the clinical features were varied such as burning sensation, intolerance to spicy food, restricted mouth opening and difficulty in speech and deglutition. Histopathology was the characteristic of OSMF and was consistent with clinical grades of the disease but could not be corelated to the degree of mouth opening. The study of 101 cases of oral submucous fibrosis is reported.

Does Clinical Staging and Histological Grading Show Parallelism In Oral Submucous Fibrosis? A Retrospective Study from an Indian City

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Manish Narayan

2014-06-01

Conclusions: There was no correlation between clinical staging and histopathological grading of oral submucous fibrosis. The test results were statistically not significant. (p=0.635 This may be due to difference in severity and extent of fibrosis in different parts of the oral mucosa. [J Interdiscipl Histopathol 2014; 2(3.000: 145-149

Correlation of areca habit, clinical grading, anorexia, and fatique in oral submucous fibrosis

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Rashmi S Sathe; Harshkant P Gharote; Preeti P Nair; Karthik J Hegde; Meenakshi S Sood; Palak A Gangwal

2015-01-01

Aim: The aim was to correlate the habit index (HI), clinical grading with anorexia, and fatigue in oral submucous fibrosis (OSMF). Settings and Design: Hospital-based study including a total of 60 individuals, out of which 30 patients were with OSMF, (27 males and 3 females). A group of 30 individuals, with areca chewing habit but without any oral lesions were selected as a control group. Subjects and Methods: Detailed case history was recorded. Height and weight measurements were made to ass...

Oral submucous fibrosis: An update on pathophysiology of malignant transformation.

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Arakeri, Gururaj; Patil, Shekar Gowda; Aljabab, Abdulsalam S; Lin, Kuan-Chou; Merkx, M A W; Gao, Shan; Brennan, Peter A

2017-07-01

Oral submucous fibrosis (OSMF) is a potentially malignant condition associated with areca nut chewing. Formerly confined to the Indian subcontinent, it is now often seen in Asian populations of the United Kingdom, USA and other developed countries, and is therefore a serious problem for global health. What makes it more sinister is the malignant transformation rate, which has been reported to be around 7.6% over a 17-year period. In this concise article, we review the current trends in the pathophysiology of malignant transformation of OSMF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical and Histologic Features Compared with AgNOR Count in Oral Leukoplakia, Erosive Lichen Planus, Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma

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Sarbjeet Singh

2006-01-01

The aim of the study was to correlate and compare AgNOR count in speckled leukoplakia, oral lichen planus, oral submucous fibrosis and in oral squamous cell carcinoma and to assess if AgNOR count could contribute to the pre-therapeutic assessment of the biologic aggressiveness of the disease and to detect malignant potential of premalignant lesion and conditions which could render us to assess the prognosis of the disease.

Limited mouth opening in oral submucous fibrosis: reasons, ramifications, and remedies.

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Sharma, Mohit; Radhakrishnan, Raghu

2017-07-01

Limited mouth opening (LMO) in oral submucous fibrosis (OSF) has been attributed to both the submucosal and muscle fibrosis (MF). While reflectory trismus was proposed before as an auxiliary mechanism by another group, the stretch-mediated muscle damage (MSD), histopathological changes in blood vessels (such as endothelial dysfunction, endothelial hypertrophy, and endarteritis obliterans), and upregulated anaerobic isoforms of lactate dehydrogenase (LDH) have been proposed by us as complementary events leading to MF. Additionally, the amount of hypoxia-mediated upregulation of anaerobic isoforms of LDH determines the extent of MF. Radiotherapy (RT)-mediated release of reactive oxygen species causes vascular damage thereby worsening hypoxia. While the alteration in LDH levels secondary to hypoxia enhances fibrosis, RT worsens it. Oral squamous cell carcinoma occurring in the background of OSF is an absolute contraindication for RT as it augurs unfavorable prognosis. An algorithm to demonstrate this with evidence is clearly depicted. The role of HIF-1α in the progression of OSF and its malignant transformation, and the consideration of hyperbaric oxygen therapy as a therapeutic remedy in OSF are underscored. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Malignant transformation of oral submucous fibrosis in Taiwan: A nationwide population-based retrospective cohort study.

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Yang, Po-Yu; Chen, Yi-Tzu; Wang, Yu-Hsun; Su, Ni-Yu; Yu, Hui-Chieh; Chang, Yu-Chao

2017-11-01

Oral submucous fibrosis (OSF) is one of the well-recognized oral potentially malignant disorders. In this study, we investigated the malignant transformation of OSF in a Taiwanese population. A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort was randomly frequency-matched with the OSF cohort according to age, sex, and index year. Oral leukoplakia (OL) was further stratified to evaluate for the possible synergistic effects of OSF-associated malignant transformation. In this cohort, 71 (9.13%) of 778 cases of OSF were observed to transform into oral cancer. The malignant transformation rate was 29.26-fold in the OSF cohort than in the comparison cohort after adjustment (95% confidence intervals 20.55-41.67). To further stratify with OL, OSF with OL (52.46%; 95% confidence intervals 34.88-78.91) had higher risk of malignant transformation rate than OSF alone (29.84%; 95% confidence intervals 20.99-42.42). The Kaplan-Meier plot revealed the rate free of malignant transformation was significant over the 13-year follow-up period (log-rank test, Ptransformation was 5.1, 2.7, and 2.2 years for non-OSF, OSF alone, and OSF with OL, respectively. Oral submucous fibrosis patients exhibited a significantly higher risk of malignant transformation than those without OSF. OL could enhance malignant transformation in patients with OSF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy of curcumin in the treatment for oral submucous fibrosis - A randomized clinical trial

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Hazarey, Vinay K; Sakrikar, Aditee R; Ganvir, Sindhu M

2015-01-01

Introduction: Oral submucous fibrosis (OSF) is a chronic, insidious disease that is associated with significant functional morbidity and an increased risk for malignancy. Turmeric and its active ingredient "curcumin′′ are being studied upon as chemopreventive agents in various diseases. The present study aims to determine the efficacy of curcumin in the treatment of OSF. Materials and Methods: Thirty clinically diagnosed OSF patients were divided into two groups, 15 patients in each group fro...

Pentoxifylline therapy : A new adjunct in the treatment of oral submucous fibrosis

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Rajendran R

2006-01-01

Full Text Available OBJECTIVE : This study was designed to determine the effect of pentoxifylline (Trental on the clinical and pathologic course of oral submucous fibrosis. This drug is a methylxanthine derivative that has vasodilating properties and was envisaged to increase mucosal vascularity. STUDY DESIGN : This investigation was conducted as a randomized clinical trial incorporating a control group (Standard drug group SDG, multivitamin, and local heat therapy in comparison to pentoxifylline test cases (Experimental drug group EDG, 400mg 3 times daily, as coated, sustained release tablets. The stipulated treatment period was 7 months and a total of 29 cases of advanced fibrosis (14 test subjects and 15 age and sex matched diseased controls were included in this study and 100% compliance was reported at the end ofthe test period. RESULTS : Mild gastric irritation that could be managed by diet protocols was the only untoward symptom reported during this trial. Review of the patients and controls was done at an interval of 30 days and subjective and objective measurements were recorded. The follow up data at each visit with respect to each other and to base-line values was calibrated using a nonparametric test of Mann-Whitney (Kruskal-Wallis test. Significant comparisons with regard to improvement were recorded as objective criteria of mouth opening (t=11.285, p= 0.000, tongue protrusion (t= 3.898, p = 0.002, and relief from perioral fibrotic bands (p = 0.0001554. Subjective symptoms of intolerance to spices (p = 0.0063218, burning sensation of mouth (p = 0.0005797, tinnitus (p=0.000042, difficulty in swallowing (p=0.0000714. and difficulty in speech (p=0.0000020 were also recorded significant improvement at the end of the trial period. CONCLUSION : This pilot investigation points to the effectiveness of pentoxifylline as an adjunct therapy in the routine management of oral submucous fibrosis.

Oral submucous fibrosis: an overview of the aetiology, pathogenesis, classification, and principles of management.

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Arakeri, Gururaj; Brennan, Peter A

2013-10-01

Oral submucous fibrosis (OSMF) is a complex, debilitating, and precancerous condition. Formerly confined to the Indian subcontinent, it is now often seen in the Asian populations of the United Kingdom, USA, and other developed countries, and is therefore a serious problem for global health. The well-known causative agent of the disease, areca-nut is now recognised as a group one carcinogen. We review and discuss all components of OSMF, including the terminology, presentation, aetiology, and pathogenesis, and provide a brief overview of its management. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Oral Submucous Fibrosis – The Indian Scenario: Review and Report of Three Treated Cases

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Kamala Rawson

2017-01-01

Full Text Available Oral submucous fibrosis (OSF is a premalignant condition mainly associated with the practice of chewing betel quid containing areca nut, a habit common among south Asian people. It is characterized by inflammation, increased deposition of submucosal collagen, and formation of fibrotic bands in the oral and paraoral tissues, which increasingly limit mouth opening. In this paper, we review literature on OSF and the different stages of the disease to help dentists make an early diagnosis and reduce the morbidity and mortality associated with this condition. We also present three cases after treatment with biweekly intralesional injections which resulted in improvement of the subjective symptoms.

Oral submucous fibrosis: A clinico-histopathological study in Chennai

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Kiran Kumar K

2007-01-01

Full Text Available Background: Oral submucous fibrosis (OSF is a precancerous condition associated with the use of areca nut in various forms. There are very few reports to correlate the clinical stage to histopathological grading in OSF. Materials and Methods: A hospital-based study was conducted on 75 OSF cases who visited our hospital in Chennai from 2000-2003. A detailed history of each patient was recorded along with a clinical examination. Biopsy was performed for histopathological correlation. Clinical stage of the disease in terms of the ability to open one′s mouth was correlated with histopathological grading. Results: The male to female ratio of OSF cases was 6:1. All forms of areca nut products were associated with OSF. Chewing of paanmasala was associated with early presentation of OSF as compared to chewing of the betel nut. Out of 57 cases, which were in clinical stage II, 91.2% had histological grading of I and II in equal proportions and 8.8% had histological grade III. Out of 13 cases that showed a clinical stage of III, 52% showed a histological grade of II, 40% grade III and 8% grade I. Conclusion: In the present study, there was no direct correlation between clinical stages and histopathological grading. The possibility of difference in the severity and extent of fibrosis in different regions of the oral mucosa and involved muscles were considered as contributory factors for this variation.

Prosthetic rehabilitation of oral submucous fibrosis patients: A systematic review of published case reports and case series.

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Shankargouda Patil

Full Text Available Oral submucous fibrosis (OSF is an insidious chronic condition characterized by restricted mouth opening. Prosthetic rehabilitation is challenging for OSF patients as obtaining a good impression requires adequate mouth opening. The aim of the present review is to systematically present the data from case reports published in the English-language literature.A comprehensive search of the literature databases (PubMed, Medline, SCOPUS, Web of Science and Google Scholar along with the references of published articles on prosthetic rehabilitation in OSF patients published to date was conducted. Keywords included a combination of 'Oral submucous fibrosis', 'prosthesis', 'dentures' and/or 'restricted mouth opening'. Citations from selected references and bibliographic linkages taken from similar cases were included in this review. The inclusion criteria selected for case reports on prosthetic rehabilitation in OSF patients, and cases of restricted mouth opening due to causes other than OSF were excluded from the study.A total of 21 cases were identified and analysed from 17 papers published in the English-language literature. Of these, 9 cases employed the sectional denture technique, 4 cases emphasized the need-based treatment approach in which conventional methods were modified, and 4 cases used mouth exercising devices. Finally, 1 case each involved, flexible denture, oral screen prosthesis, oral stents, surgery in conjunction with dentures.Prosthetic rehabilitation in OSF patients is a multifaceted approach and should be patient specific, although sectional dentures have achieved the best results.

Prosthetic rehabilitation of oral submucous fibrosis patients: A systematic review of published case reports and case series.

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Patil, Shankargouda; Sarode, Sachin Chakradhar; Sarode, Gargi S; Bhandi, Shilpa; Awan, Kamran Habib; Ferrari, Marco

2017-01-01

Oral submucous fibrosis (OSF) is an insidious chronic condition characterized by restricted mouth opening. Prosthetic rehabilitation is challenging for OSF patients as obtaining a good impression requires adequate mouth opening. The aim of the present review is to systematically present the data from case reports published in the English-language literature. A comprehensive search of the literature databases (PubMed, Medline, SCOPUS, Web of Science and Google Scholar) along with the references of published articles on prosthetic rehabilitation in OSF patients published to date was conducted. Keywords included a combination of 'Oral submucous fibrosis', 'prosthesis', 'dentures' and/or 'restricted mouth opening'. Citations from selected references and bibliographic linkages taken from similar cases were included in this review. The inclusion criteria selected for case reports on prosthetic rehabilitation in OSF patients, and cases of restricted mouth opening due to causes other than OSF were excluded from the study. A total of 21 cases were identified and analysed from 17 papers published in the English-language literature. Of these, 9 cases employed the sectional denture technique, 4 cases emphasized the need-based treatment approach in which conventional methods were modified, and 4 cases used mouth exercising devices. Finally, 1 case each involved, flexible denture, oral screen prosthesis, oral stents, surgery in conjunction with dentures. Prosthetic rehabilitation in OSF patients is a multifaceted approach and should be patient specific, although sectional dentures have achieved the best results.

Matrix metalloproteinase-1 expression in oral submucous fibrosis: An immunohistochemical study

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Mishra Gauri

2010-01-01

Full Text Available Context: Oral submucous fibrosis (OSF is a form of pathological fibrosis affecting the oral mucosa. There is compelling evidence to implicate the habitual chewing of areca nut with the development of OSF. Because collagens are the major structural components of connective tissues, including oral submucosa, the composition of collagen within each tissue needs to be precisely regulated to maintain tissue integrity. Arecoline stimulates fibroblasts to increase the production of collagen by 150%. Aim: As the role of collagenase is implicated in cleaving the collagen under physical conditions, this study was carried out to evaluate the role of collagenase-1 (matrix metalloproteinase [MMP]-1 in a pathologic condition like OSF. Settings and Design: A total of 40 patients were included in the study, comprising of 30 OSF as Group 1 and 10 normal buccal mucosa tissue as Group 2. Materials and Methods: Both the groups were stained for MMP-1 by the immunohistochemical method using the streptavidin HRP-biotin labeling technique. MMP-1 expression intensity in the epithelium and connective tissue was decreased in Group 1 when compared to Group 2. Statistical Analysis Used: Chi-square test of association was used to determine the difference in the expression of MMP-1 between OSF and normal buccal mucosa and among different histological gradings of OSF. Results: The results were statistically significant. However, there was no statistically significant difference between the expression of MMP-1 among different histological grades of OSF in Group 1.

Oral submucous fibrosis: An update on current theories of pathogenesis.

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Arakeri, Gururaj; Rai, Kirthi Kumar; Hunasgi, Santosh; Merkx, M A W; Gao, Shan; Brennan, Peter A

2017-07-01

Over the last 40 years, many theories linking oral submucous fibrosis (OSMF) to various risk factors have been proposed. Spicy, pungent foods and irritants such as supari (areca nut), paan (betel leaves), tobacco (through chewing or smoking)-the common Asian habits of chewing the aforementioned agents-have all been incriminated as causative agents. Systemic factors such as nutritional deficiency, genetic predisposition and autoimmunity have also been proposed in the pathogenesis of OSMF. However, the precise aetiology of OSMF is still unknown, and no conclusive evidence has been found despite many extensive investigations on implicated factors. Most of the ideas proposed have been derived from the existing clinical and epidemiological data. We present a comprehensive review of the various theories regarding the pathogenesis of the condition, but have not concentrated on malignant transformation in this article. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Helicobacter pylori coinfection is a confounder, modulating mucosal inflammation in oral submucous fibrosis

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Rajendran R

2009-01-01

Full Text Available The oral cavity has been considered a potential reservoir for Helicobacter pylori (H pylori , from where the organism causes recurrent gastric infections. Aim: With this case-control study we tried to evaluate the role of H pylori in the etiology of mucosal inflammation, a condition that compounds the morbid state associated with oral submucous fibrosis (OSF. Materials and Methods : Subjects ( n = 150 were selected following institutional regulations on sample collection and grouped into test cases and positive and negative controls based on the presence of mucosal fibrosis and inflammation. The negative controls had none of the clinical signs. All patients underwent an oral examination as well as tests to assess oral hygiene/periodontal disease status; a rapid urease test (RUT of plaque samples was also done to estimate the H pylori bacterial load. We used univariate and mutivariate logistic regression for statistical analysis of the data and calculated the odds ratios to assess the risk posed by the different variables. Results : The RUT results differed significantly between the groups, reflecting the variations in the bacterial loads in each category. The test was positive in 52% in the positive controls (where nonspecific inflammation of oral mucosa was seen unassociated with fibrosis, in 46% of the test cases, and in 18% of the negative controls (healthy volunteers (χ2 = 13.887; P < 0.01. A positive correlation was seen between the oral hygiene/periodontal disease indices and RUT reactivity in all the three groups. Conclusions: The contribution of the H pylori in dental plaque to mucosal inflammation and periodontal disease was significant. Logistic regression analysis showed gastrointestinal disease and poor oral hygiene as being the greatest risk factors for bacterial colonization, irrespective of the subject groups. A positive correlation exists between RUT reactivity and the frequency of mucosal inflammation.

Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge.

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Ramani, Priya; Krithika, C; Ananthalakshmi, R; Singaram, Mamta; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

2016-11-04

Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

Evaluation of cachexia in oral submucous fibrosis

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Pooja Singh

2012-01-01

Full Text Available Introduction: Patients with cancer suffer from a wasting syndrome associated with anorexia/cachexia. Anorexia is associated with a marked loss of appetite and/or an aversion to food. Cachexia is associated with loss of body mass and is often associated with weakness, fatigue leading to poor quality of life. It has been observed in those individuals with oral submucous fibrosis (OSMF, a premalignant condition, are generally thin and there seems to be a relation between loss of appetite and consumption of areca nut in these individuals. Aims: Evaluation of cachexia in OSMF patients based on the criteria given for defining cachexia by group of scientists and clinicians in the cachexia consensus conference. Materials and methods: Twenty OSMF cases (group I and 20 healthy individuals with areca nut chewing habit (group II were assessed for body mass index (BMI, hemoglobin and serum albumin level. Their fatigue and anorexia scores were calculated by using structured questionnaires. Results: Correlation between fatigue and anorexia was statistically significant for OSMF group but was statistically not significant in group 11. Comparisons of BMI, hemoglobin, fatigue and anorexia between two groups were statistically not significant, however, serum albumin was found to be statistically significant. Conclusion: From the present study it can be concluded that the early process of cachexia begins during the progression of OSMF. The areca nut chewing practice associated with OSMF may play some role in this context.

Breath Alkane as an index of severity for oral submucous fibrosis: A new perspective?

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Arakeri, Gururaj; Boraks, George; Aljabab, Abdulsalam S; Patil, Shekar Gowda; Merkx, M A W; Brennan, Peter A

2017-01-01

Oral submucous fibrosis (OSMF) is a devastating disease commonly seen in the Asian subcontinent that results in significant functional morbidity for patients and has a high potential for malignant transformation. Over the last three decades, different diagnostic methods have been described to quantify and grade OSMF severity. Some methods have been used with perceived favorable outcomes although recurrence and malignant transformation remains a problem in many cases, and OSMF presents a major therapeutic challenge. We present a simple, noninvasive and less time-consuming diagnostic method which measures the severity of OSMF, helping to predict its malignant transformation and monitoring the effect of medical therapy on this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral submucous fibrosis at pediatric age, now time to think: Series of two cases

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Gupta, Vinay K.; Malhotra, Seema; Patil, Ranjit; Tripathi, Anurag

2013-01-01

The younger generation is consuming areca nut and areca nut products, which is coming in the market with different multicolored attractive pouches and easily available in each and every corner of the road. For the children from the lower socioeconomic strata, areca nut use is rampant. Alarmingly, it has been seen that the highest period of risk for engaging in areca nut alone is between the ages of 5 and 12. Oral submucous fibrosis associated with areca nut in children is a great concern for the Society and the Government. Factors associated with this report for consuming areca nut are levels of awareness, household environment, peer pressure, low cost, easy availability etc. PMID:24049299

Immunohistochemical study of p21 and Bcl-2 in leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma.

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Sutariya, Rakesh V; Manjunatha, Bhari Sharanesha

2016-11-01

Oral Squamous cell carcinoma (OSCC) results from genetic damage, leading to uncontrolled cell proliferation of damaged cells and the cell death. In the course of its progression, visible changes are taking place at the cellular level (atypical) and the resultant at the tissue level (epithelial dysplasia). The Aim of the present study was to evaluate and compare the expressions of intensity of p21 and Bcl-2 in Leukoplakia, oralsubmucous fibrosis (OSMF) and oral squamous cell carcinoma. Total 60 cases, 30 cases of oral squamous cell carcinoma, 15 cases of oral submucous fibrosis and 15 cases of Leukoplakia were evaluated immunohistochemically for p21 and Bcl-2 expression. p21 showed positive expression in 13 (86.67%) cases out of 15 cases of OSMF, 12 (80%) cases of leukoplakia out of 15 cases and 24 (80%) cases out of 30 cases of OSCC. The Bcl-2 expression was positive in 13 (86.67%) cases of OSMF, all cases of Leukoplakia and 25 (83.33%) cases of OSCC. No statistical significance was noted in the expression of p21 and Bcl-2 positive expression between OSMF, Leukoplakia and OSCC. Statistical analysis for comparison of intensity of p21 expression in different grades of OSCC showed no significance. Statistical significance difference was found between the expressions of Bcl-2 in moderately and poorly differentiated SCC. The intensity of p21 and Bcl-2 expressions in different grades of OSCC indicates a key role in progression of oral neoplasia.

Mouth-opening device as a treatment modality in trismus patients with head and neck cancer and oral submucous fibrosis: a prospective study.

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Li, Yu-Hsuan; Chang, Wei-Chin; Chiang, Tien-En; Lin, Chiun-Shu; Chen, Yuan-Wu

2018-04-26

This study investigated the clinical effectiveness of intervention with an open-mouth exercise device designed to facilitate maximal interincisal opening (MIO) and improve quality of life in patients with head and neck (H&N) cancer and oral submucous fibrosis (OSF). Sixty patients with H&N cancer, OSF, and trismus (MIO cancer and OSF and improve mouth-opening range and quality of life.

An update on studies on etiological factors, disease progression, and malignant transformation in oral submucous fibrosis

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Samiha Bari

2017-01-01

Full Text Available Worldwide estimates of oral submucous fibrosis (OSMF show a confinement to Indians and Southeast Asians. In India, the prevalence of OSMF has increased over the past four decades from 0.03% to 6.42%. The condition is well recognized for its malignant potential rate of 7-30%. The condition has a multifactorial etiology and may remain either stationary or become severe, leaving an individual physically challenged both physically and psychologically. Hence, the study aims at reviewing studies done on various etiological factors leading to its onset. Their analysis may serve as an adjunct in defining the broad spectrum of the causation of this potentially malignant disorder.

Serum Iron and Haemoglobin Estimation in Oral Submucous Fibrosis and Iron Deficiency Anaemia: A Diagnostic Approach.

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Bhardwaj, Divya; Dinkar, Ajit D; Satoskar, Sujata K; Desai, Sapna Raut

2016-12-01

Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions. The aim of this study was to compare the haemoglobin and serum iron values of OSMF subjects with that of iron deficiency anaemia subjects. Total of 120 subjects were included, 40 subjects with the OSMF, 40 with the iron deficiency anemia without tobacco chewing habit, 40 healthy control subjects without OSMF and iron deficiency anaemia. A total of 5ml of venous blood was withdrawn from all the subjects and serum iron and haemoglobin levels were estimated for all the subjects. Estimation of iron was done using Ferrozine method and haemoglobin by Sahli's method. The statistical method applied were Kruskal Wallis, Mann Whitney and Pearson correlation coefficient test. There was a statistically significant difference in serum iron and haemoglobin level in all three groups (pauxillary test in assessment of prognosis of the disease.

Efficacy of aloe vera gel as an adjuvant treatment of oral submucous fibrosis.

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Alam, Sarwar; Ali, Iqbal; Giri, K Y; Gokkulakrishnan, S; Natu, Subodh S; Faisal, Mohammad; Agarwal, Anshita; Sharma, Himanshu

2013-12-01

Definitive therapy is not defined for the management of oral submucous fibrosis (OSMF). This study evaluated the efficacy of aloe vera gel as an adjuvant treatment of OSMF. A double-blind, placebo-controlled, parallel-group randomized controlled trial was conducted on 60 subjects with OSMF divided into medicinal treatment (submucosal injection of hyaluronidase and dexamethasone, n = 30) and surgical treatment (n = 30) categories. Each category was randomly divided into groups A (with aloe vera, n = 15 per category) and B (without aloe vera, n = 15 per category). Follow-up assessment for various symptoms was performed, and results were analyzed using paired and unpaired Student t tests. The group receiving aloe vera had a significant improvement in most symptoms of OSMF (P aloe vera group, in both the medicinal and surgical categories. Aloe vera gel was effective as an adjuvant in treatment of OSMF. Copyright © 2013 Elsevier Inc. All rights reserved.

MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis.

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Xie, Xiaoyan; Jiang, Yuchen; Yuan, Yao; Wang, Peiqi; Li, Xinyi; Chen, Fangman; Sun, Chongkui; Zhao, Hang; Zeng, Xin; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Mingye; Liu, Rui; Chen, Qianming

2016-09-13

Oral squamous cell carcinoma (OSCC) ranks among the most common cancer worldwide, and is associated with severe morbidity and high mortality. Oral submucous fibrosis (OSF), characterized by fibrosis of the mucosa of the upper digestive tract, is a pre-malignant lesion, but the molecular mechanisms underlying this malignant transformation remains to be elucidated. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was employed to profile the differentially expressed peptides/proteins between OSCC tissues and the corresponding adjacent non-cancerous OSF tissues. Sixty-five unique peptide peaks and nine proteins were identified with altered expression levels. Of them, expression of NCOA7 was found to be up-regulated in OSCC tissues by immunohistochemistry staining and western blotting, and correlated with a pan of clinicopathologic parameters, including lesion site, tumor differentiation status and lymph node metastasis. Further, we show that overexpression of NCOA7 promotes OSCC cell proliferation in either in vitro or in vivo models. Mechanistic study demonstrates that NCOA7 induces OSCC cell proliferation probably by activating aryl hydrocarbon receptor (AHR). The present study suggests that NCOA7 is a potential biomarker for early diagnosis of OSF malignant transformation, and leads to a better understanding of the molecular mechanisms responsible for OSCC development.

Transforming growth factor β2 (TGF-β2 in pathogenesis of oral submucous fibrosis: An immunohistochemical study

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Venkatesh V Kamath

2014-01-01

Full Text Available Background and Objectives: Oral Submucous Fibrosis (OSF is a potentially malignant oral disorder causing fibrosis of the oral mucosa. Commonly associated with the habit of chewing areca nut in its raw or refined forms, the progressive fibrosis causes intense debility and probable malignant transformation. Arecoline, flavinoids and tannins in the areca nut may activate pro-fibrotic cytokines like transforming growth factor beta (TGF-β leading to fibrosis. TGF-β and its isoforms probably represent the major pathway in the deposition of collagen fibers in this condition. Very little is known of the role of TGF-β2, as compared withTGF-β1, in OSF. The present study aims to evaluate TGF-β2 immunohistochemically in OSF with a view to understanding its role in the pathogenesis. Materials and Methods: TGF-β2 antibody was detected immunohistochemically on archival paraffin sections of 70 cases of various grades of OSF, 10 cases of normal oral mucosa and five cases of scar tissue. The presence and distribution of the antibody was noted and a quantification of the positive areas was also done using image analyses software and correlated in proportion to the rest of the tissue. Results: Expression of TGF-β2 was more in all grades of OSF when compared with that of normal oral mucosa but less than that expressed in scar tissue. The antibody was detected in epithelium, around the blood vessels, in areas of inflammatory infiltrate, fibroblasts and in muscles. The intensity and proportion of expression paralleled increasing grades of OSF. There was increased expression of the antibody in the epithelium, which is probably the source, but no correlation to epithelial changes (hyperplasia, atrophy or dysplasia was noted. Conclusion: TGF-β2 is a prominent cytokine in the TGF-β induced pathway of fibrosis but probably plays a contributory role to the main isoform TGF-β1. Its role as a marker of malignant transformation, as seen in other systemic malignant

Evaluation of matrix metalloproteinases-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 (TIMP-2) in oral submucous fibrosis and their correlation with disease severity.

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Shrestha, A; Carnelio, S

2013-01-01

Oral submucous fibrosis (OSF), a potentially malignant oral lesion, is a form of pathological fibrosis affecting the oral mucosa. It results from an imbalance in equilibrium of the normal process of synthesis and degradation of extra cellular matrix. Matrix metalloproteinases and its inhibitors play important role in remodeling of the extra cellular matrix which are important in progression and pathogenesis of potentially malignant lesions to malignancy. To evaluate the expression and distribution of Matrix metalloproteinases-2 (MMP- 2) and Tissue inhibitor of metalloproteinases-2 (TIMP-2) in different grades of Oral Submucous Fibrosis(OSF). Immunohistochemical analysis for MMP-2 and its TIMP-2 was performed in 30 histopathologically confirmed, formalin fixed, paraffin embedded specimens of OSF. A semi-quantitative analysis was done to assess the expression, distribution and comparison of these in various stages of this disease. All moderately advanced cases and 64.2% for MMP-2 and 78.5% for TIMP-2 of early stage cases showed positivity. Between two stages of OSF, statistically significant differences were noted in expression of TIMP-2 in lamina propria, deep connective tissue and supra basal layers (p<0.05) and basal and supra basal layers for MMP-2 (p<0.05). The simultaneous increase in expression of MMP-2 and TIMP-2 with advancing stages of OSF can provide a basis for considering the proteases as important mediators in the pathogenesis and progression of OSF which could aid in identifying the aggressiveness of the condition and elucidate its role in its malignant transformation.

Role of drinking water copper in pathogenesis of oral submucous fibrosis: a prospective case control study.

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Arakeri, Gururaj; Hunasgi, Santosh; Colbert, Serryth; Merkx, M A W; Brennan, Peter A

2014-07-01

Although oral submucous fibrosis (OSMF) is thought to be multifactorial in origin, the chewing of areca nut is thought to be the main cause. Alkaloids and tannins in areca nut are responsible for fibrosis, but recent evidence has suggested that copper ions are also an important mediator, and in a small pilot study we recently found that OSMF was significantly associated with a raised concentration of copper in drinking water. We have further investigated this association in a heterogeneous population in Hyderabad-Karnataka, India, a region with a high incidence of the condition. We evaluated 3 groups, each of 100 patients: those with OSMF who chewed gutkha, those who chewed gutkha but did not have OSMF, and healthy controls who did not chew gutkha. The difference between the groups in the mean concentration of copper in water measured by atomic absorption spectrometry was significant (p<0.001). There were also significant differences between the groups in mean concentrations of serum copper, salivary copper, and ceruloplasmin (p<0.001). Our results confirm that copper in drinking water contributes to the pathogenesis of OSMF, but ingestion of copper is unlikely to be the sole cause. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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

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

2015-05-01

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

Podoplanin expression in oral potentially malignant disorders and oral squamous cell carcinoma.

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A G, Deepa; Janardanan-Nair, Bindu; B R, Varun

2017-12-01

Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is specifically expressed in lymphatic endothelial cells. Studies have shown that assessment of podoplanin expression in the epithelial cells can be used to predict the malignant transformation of potentially malignant disorders and the metastatic tendency of primary head and neck squamous cell carcinoma. The aim of our study was to compare the expression of podoplanin in oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma with that in normal buccal mucosa by immunohistochemical methods. Immunohistochemical expression of podoplanin was analyzed in 20 cases each of oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma and normal buccal mucosa, with monoclonal antibody D2-40. The expression of podoplanin was graded from grade 0-4. There was a statistically significant upregulation of the grades of podoplanin expression in oral squamous cell carcinoma(100%), oral submucous fibrosis (90%) and oral leukoplakia (65%) when compared to that in normal mucosa(35%). Podoplanin expression increased with decrease in grades of differentiation in oral squamous cell carcinoma . Podoplanin expression in the samples of oral submucous fibrosis was higher than that in oral leukoplakia. Evaluation of podoplanin expression in the epithelial cells of oral dysplastic lesions may provide valuable information to predict their risk of malignant transformation. Key words: Immunohistochemistry, Oral leukoplakia, Oral submucous fibrosis, Podoplanin, Squamous cell carcinoma.

Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis

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Yu, Cheng-Chia; Yu, Chuan-Hang; Chang, Yu-Chao

2016-11-01

Oral submucous fibrosis (OSF), regarded as a precancerous condition, is characterized by juxta-epithelial inflammatory reaction followed by fibro-elastic change in the lamina properia and epithelial atrophy. The pathologic mechanisms of OSF still need to be further clarified. In the study, we investigated the functional expression of SSEA-4, which is a well-known stemness marker, in myofibroblast activity and the clinical significance in OSF tissues. The expression of SSEA-4 in OSF was evaluated by immunohistochemical staining. Functional analysis of SSEA-4 on myofibroblast activity of OSF was achieved by lentiviral silencing ST3GAL2. Immunohisitochemistry demonstrated that SSEA-4 expression was significantly higher expression in areca quid chewing-associated OSF tissues than those of normal oral mucosa tissues. From flow cytometry analysis, arecoline dose-dependently activated SSEA-4 expression in primary human normal buccal mucosal fibroblasts (BMFs). Sorted SSEA-4-positive cells from fibrotic BMFs (fBMFs) have higher colony-forming unit, collagen gel contraction, and α-smooth muscle actin (α-SMA) expression than SSEA-4-negative subset. Knockdown of ST3GAL2 in fBMFs suppressed SSEA-4 expression, collagen contraction, migration, invasiveness, and wound healing capability. Consistently, silencing ST3GAL2 was found to repress arecoline-induced myofibroblast activity in BMFs. The study highlights SSEA-4 as a critical marker for therapeutic intervention to mediate myofibroblast transdifferentiation in areca quid chewing-associated OSF.

TFM classification and staging of oral submucous fibrosis: A new proposal.

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Arakeri, Gururaj; Thomas, Deepak; Aljabab, Abdulsalam S; Hunasgi, Santosh; Rai, Kirthi Kumar; Hale, Beverley; Fonseca, Felipe Paiva; Gomez, Ricardo Santiago; Rahimi, Siavash; Merkx, Matthias A W; Brennan, Peter A

2018-04-01

We have evaluated the rationale of existing grading and staging schemes of oral submucous fibrosis (OSMF) based on how they are categorized. A novel classification and staging scheme is proposed. A total of 300 OSMF patients were evaluated for agreement between functional, clinical, and histopathological staging. Bilateral biopsies were assessed in 25 patients to evaluate for any differences in histopathological staging of OSMF in the same mouth. Extent of clinician agreement for categorized staging data was evaluated using Cohen's weighted kappa analysis. Cross-tabulation was performed on categorical grading data to understand the intercorrelation, and the unweighted kappa analysis was used to assess the bilateral grade agreement. Probabilities of less than 0.05 were considered significant. Data were analyzed using SPSS Statistics (version 25.0, IBM, USA). A low agreement was found between all the stages depicting the independent nature of trismus, clinical features, and histopathological components (K = 0.312, 0.167, 0.152) in OSMF. Following analysis, a three-component classification scheme (TFM classification) was developed that describes the severity of each independently, grouping them using a novel three-tier staging scheme as a guide to the treatment plan. The proposed classification and staging could be useful for effective communication, categorization, and for recording data and prognosis, and for guiding treatment plans. Furthermore, the classification considers OSMF malignant transformation in detail. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Correlation of areca habit, clinical grading, anorexia, and fatique in oral submucous fibrosis

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Rashmi S Sathe

2015-01-01

Full Text Available Aim: The aim was to correlate the habit index (HI, clinical grading with anorexia, and fatigue in oral submucous fibrosis (OSMF. Settings and Design: Hospital-based study including a total of 60 individuals, out of which 30 patients were with OSMF, (27 males and 3 females. A group of 30 individuals, with areca chewing habit but without any oral lesions were selected as a control group. Subjects and Methods: Detailed case history was recorded. Height and weight measurements were made to assess body mass index (BMI. Fatigue and anorexia scores were calculated using structured questionnaires. Clinical staging of OSMF was done according to Khanna JN and Andrade NN (1995 classification. The information related to the type of habit, site of placement of areca nut, and duration was recorded using HI. Statistical Analysis Used: Statistical analysis was done using Pearson's correlation and Student's t-test. Results: A statistically significant difference was found between anorexia in both the groups (P = 0.01 and a highly significant difference was seen in HI (P = 0.001. However, the comparison between other parameters was found to be statistically not significant. The correlation of HI, anorexia, and fatigue score in Grade I, Grade II, Grade III, and Grade IV OSMF within each group was not significant statistically. However, in Grade IV a strong correlation was found between BMI and anorexia score (P = 0.0188. Conclusion: The merits of this study include a positive correlation between anorexia and fatigue with disease progression and a congruent relation of HI with the grades of OSMF.

Levamisole and antioxidants in the management of oral submucous fibrosis: A comparative study

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Vasanti Jirge

2008-01-01

Full Text Available Background and Objectives: Oral submucous fibrosis (OSMF is a chronic condition of the oral cavity which results in permanent disability. The pathogenesis is poorly understood and the disease is difficult to treat. OSMF is associated with immunological changes (altered levels of serum immunoglobulins and the effect of treatment (especially antioxidants and levamisole on serum immunoglobulins (Ig is not known. This study was carried out to evaluate the clinical effects of levamisole (VERMISOL, and antioxidants (ANTOXID and its effect on serum immunoglobulins IgG, IgA and IgM. Meterials and Methods: Forty-five study subjects were included in the study. Patients were randomly assigned into three groups. There were 15 patients in each group; group I patients received levamisole, 50 mg three times daily for three alternate weeks, group II patients received 2 capsules of antoxid daily for six weeks, group III patients received levamisole and antoxid. The results were analyzed with paired ′t′ test and unpaired ′t′ test. Results: The results indicated that levamisole, antoxid and the combination of levamisole and antoxid showed significant improvement in mouth opening and reduction in burning sensation. Significant reduction of serum IgG, IgA and IgM was seen in the levamisole group and combination group whereas in the antoxid group significant reduction was observed only in serum IgA and IgM. Interpretation and Conclusion: Levamisole can bring about clinical improvement and is better than antoxid and the combination regimen. The addition of antoxid to the treatment regimen does not seem to have an added advantage over levamisole alone.

Oral squamous cell carcinoma in the background of oral submucous fibrosis is a distinct clinicopathological entity with better prognosis.

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Gadbail, Amol Ramchandra; Chaudhary, Minal; Gawande, Madhuri; Hande, Alka; Sarode, Sachin; Tekade, Satyajit Ashok; Korde, Sheetal; Zade, Prajakta; Bhowate, Rahul; Borle, Rajiv; Patil, Swati

2017-07-01

The aim of this study was to compare the clinicopathological features of oral squamous cell carcinoma in the background of oral submucous fibrosis (OSCC-OSMF) and oral squamous cell carcinoma (OSCC). A total of 217 cases of OSCC were retrieved from achieves for the analysis. OSCC-OSMF cases were segregated on the basis of history and clinicopathological parameters. The study included 217 patients of which 112 had OSCC and 105 OSCC-OSMF. OSCC-OSMFs were younger compared with OSCC. Overall oral cancer was noted predominantly in males compared to females. The number of OSCC-OSMF was more in clinical TNM stage I and stage II as compared to OSCC, whereas the number of OSCC was more in stage III and stage IV compared to OSCC-OSMF. Histological presentation of well-differentiated squamous cell carcinoma was significantly more in OSCC-OSMF compared to OSCC, whereas moderately differentiated squamous cell carcinoma was significantly more in OSCC compared to OSCC-OSMF. Regional lymph node metastasis was significantly higher in OSCC compared to OSCC-OSMF. Three-year disease-free survival rate was significantly higher in OSCC-OSMF compared to OSCC. The OSCC-OSMF was found to be a clinicopathologically distinct entity with a better grade of tumor differentiation, less incidence of nodal metastases, and early detection (early clinical TNM stage) compared to OSCC. All these factors probably contribute to a better prognosis and increased 3-year disease-free survival in OSCC-OSMF patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Salivary pooling: is it specific to particular regions in oral submucous fibrosis?

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Arakeri, Gururaj; Colbert, Serryth; Patil, Shekar Gowda; Hale, Beverley; Merkx, M A W; Brennan, Peter A

2015-03-01

Despite extensive research, the pathophysiology of oral submucous fibrosis (OSMF), a premalignant condition that primarily affects the mucosa, is still unclear, although the chewing of areca nut is known to be the primary cause. While a clear association exists between areca nut and OSMF, very little has been published on the reason for its sporadic incidence in the mouth. Many authors have suggested the site where quid is habitually placed, but this fails to explain multiple sites in those who chew on one side. We hypothesised that the pattern of salivary pooling might affect the distribution of OSMF by carrying the chemicals responsible for mucosal damage. In our study of 174 patients, we evaluated the sites where quid was habitually placed and the areas of salivary pooling, and their association with the incidence of OSMF. Most chewers (136/174, 78%) placed the quid in the buccal vestibule, although other sites were also used including the vestibule of the lip, tongue, and floor of the mouth. The standardised residuals suggested significant associations (p<0.001) between salivary pooling and OSMF, and indicated that salivary pooling affects the mucosal surfaces where it occurs. Our results show that the quid is not the only cause of OSMF. Salivary pooling also has an important role and provides a possible mechanism for the sporadic incidence of the condition. To our knowledge this is the first study to evaluate salivary pooling as a contributory factor in OSMF, and it may help to explain the pattern of distribution. Further work is needed in this area to understand the association more fully. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Role of oxidative stress in the pathogenesis of oral submucous fibrosis: A preliminary prospective study

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G K Shakunthala

2015-01-01

Full Text Available Background: In the current scenario pathogenesis of majority of the diseases is deeply linked with the oxidative stress, irrespective of its etiology. Enumerable data suggests that reactive oxygen species play a key role in multistage carcinogenesis. Oral submucous fibrosis (OSMF is considered as a potentially malignant disorder. Its increased incidence over recent years in the Indian subcontinent is a major health concern to oral physicians. However, the role of oxidative stress has not been widely investigated in OSMF. Aims: Is to evaluate both antioxidant and oxidant status in OSMF and to compare with controls. Settings and Design: Twenty patients and 20 controls of the same age group were enrolled in the study. Subjects and Methods: Five milliliters of blood were collected from each individual and serum was separated. Malondialdehyde (MDA estimation using thiobarbituric acid (TBA method, and antioxidant activity (AOA using principle of TBA reactive substances was done using this serum, with a calorimetric method. Statistical Analysis Used: Student's t-test and ANOVA test. Results: The mean serum AOA status was seen to significantly decrease in OSMF patients, as compared to controls (P = 0.013. The increase in mean serum MDA level was highly significant in OSMF patients, as compared to controls (P < 0.001. Conclusion: The disparity between AOA and MDA levels in the patients clearly demonstrates the role of oxidative stress in the disease process. The results also suggest the use of antioxidants in the management of OSMF.

Velar morphological variants in oral submucous fibrosis: A comparative digital cephalometric study

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Bhagyashree Mahadevappa Patil

2017-01-01

Full Text Available Context: Soft palate (velar plays a significant role in various important functions in the head and neck region. Its diverse morphology is implicated in a variety of diseases. Knowledge about the varied morphological pattern of soft palate in oral submucous fibrosis (OSMF patients can give us a clear understanding about disease progress in the oropharyngeal region for a proper diagnosis and also help the maxillofacial surgeon in successful structural and functional corrections associated with this disorder. Aim: (1 To evaluate the morphological variations of soft palate in OSMF patients using digital lateral cephalogram. (2 To assess the morphological variations of soft palate with respect to the different clinical stages of OSMF patients. Subjects and Methods: A total number of 300 patients were included in the study (150 participants each in study and control group, evaluated clinically, and subjected for digital lateral cephalogram for evaluating velar morphological variants. Statistical Analysis: The data were statistically evaluated using SPSS 11.5 software with Student's t-test, Chi-square test, and ANOVA. Results: Among Group I, 34 participants had Stage I OSMF, 90 participants had Stage II OSMF, and 26 participants had Stage III OSMF. Type I velar was commonly seen in Stage I OSMF, Type VI velar in Stage II OSMF, and Type III velar in Stage III OSMF. There was statistically highly significant decrease in anterior-posterior (AP length and increase in width of superior-inferior (SI measurement, as compared to the Group II. Conclusion: There was diminution in AP length and increase in SI measurement as the OSMF disease progressed.

Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy.

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Modak, Neha; Tamgadge, Sandhya; Tamgadge, Avinash; Bhalerao, Sudhir

2015-01-01

Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable ( P qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them.

Effectiveness of Aloe Vera and Antioxidant along with Physiotherapy in the Management of Oral Submucous Fibrosis.

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Singh, Nisha; Hebbale, Manjula; Mhapuskar, Amit; Ul Nisa, Shams; Thopte, Shameeka; Singh, Saumya

2016-01-01

Oral submucous fibrosis (OSMF) is a well-established precancerous condition affecting the oral mucosa. It is a disease that causes significant morbidity (in terms of loss of mouth function as tissues become rigid and mouth opening becomes difficult) and mortality (when transformation into squamous cell carcinoma occurs). The aim of the study is to compare the efficacy of Aloe vera with antioxidant when given along with physiotherapy in the management of OSMF. Forty patients presenting with clinical signs and symptoms of OSMF were included for the study after informed consent. Group A included 20 patients who received Aloe vera gel (forever living gel) along with physiotherapy. Group B included 20 patients who received antioxidant capsules twice daily for 3 months along with physiotherapy exercises four times in a day. The following parameters, that is, burning sensation, mouth opening, tongue protrusion and cheek flexibility were recorded at each visit. Majority of the participant enrolled were in the age range of 30 to 35 years. Improvement in all the parameters was seen with the individuals receiving Aloe vera gel in comparison to antioxidants. So, Aloe vera being a soothing, simple and safe mode of treatment along with proper habit restriction can be considered to be an effectual protocol in the management of OSMF. The analgesic effects of Aloe vera with the physiotherapy exercises provide better results in reducing burning sensation and improving mouth opening, tongue protrusion and cheek flexibility in comparison to antioxidants.

Analysis of serum copper and iron levels in oral submucous fibrosis patients: A case–control study

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Harshal Kumar

2016-01-01

Full Text Available Background: Oral submucous fibrosis (OSF is a chronic debilitating disease and a potentially malignant disorder of the oral cavity. The pathogenesis of the disease is not well established. Trace elements such as copper and iron play an important role in the pathogenesis of OSF. Estimation of these elements in serum of the patients may be helpful in understanding the pathologic mechanism. Therefore, a study was carried out to analyze the level of serum copper and iron in the population of Central India. Materials and Methods: A case–control study was carried out on 35 patients with clinically diagnosed of OSF and 35 healthy controls. OSF patients were categorized by clinical staging. Serum copper and iron concentrations were measured by atomic absorption spectrophotometry. Results: Results of the study shows that the mean serum copper concentration was greater in study group (133.3 ± 19.2 compared to control group (113.9 ± 22.1 and the mean serum iron was lower in study group (116.0 ± 24.1 compared to control group (128.2 ± 23.4. The result obtained was statistically significant. The serum copper level increases as the clinical staging of OSF progresses, whereas serum iron level decreases as clinical staging progresses. Conclusion: There was an increase in copper level and decrease in iron level in study group compared to control group; this suggests that there is an increase in copper level with the advancement of clinical staging of OSF.

Habit-associated salivary pH changes in oral submucous fibrosis-A controlled cross-sectional study.

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Donoghue, Mandana; Basandi, Praveen S; Adarsh, H; Madhushankari, G S; Selvamani, M; Nayak, Prachi

2015-01-01

Oral submucous fibrosis (OSF) is a multi-causal inflammatory reaction to the chemical or mechanical trauma caused due to exposure to arecanut containing products with or without tobacco (ANCP/T). Arecanut and additional components such as lime and chewing tobacco render ANCP/T highly alkaline. Fibrosing repair is a common reaction to an alkaline exposure in the skin. OSF may be related to the alkaline exposure by ANCP/T in a similar manner. The study was aimed at establishing the relationship of habit-associated salivary pH changes and OSF. The study design was controlled cross-sectional. Base line salivary pH (BLS pH), salivary pH after chewing the habitual ANCP/T substance, post chew salivary pH (PCSpH) for 2 min and salivary pH recovery time (SpHRT) were compared in 30 OSF patients and 30 sex-matched individuals with ANCP/T habits and apparently healthy oral mucosa. The group's mean BLSpH values were similar and within normal range and representative of the population level values. The average PCSpH was significantly higher (P ˂ 0.0001) than the average BLSpH in both groups. There was no significant difference (P = 0.09) between PCSpH of OSF patients and controls. OSF patients had a significantly longer (P = 0.0076) SpHRT than controls. Factors such as age, daily exposure, cumulative habit years, BLSpH and PCSpH, had varying effects on the groups. Chewing ANCP/T causes a significant rise in salivary pH of all individuals. SpHRT has a significant association with OSF. The effect of salivary changes in OSF patients differs with those in healthy controls.

Clinical evaluation of the role of tulsi and turmeric in the management of oral submucous fibrosis: A pilot, prospective observational study

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Adit Srivastava

2015-01-01

Full Text Available The aim of the present study was to investigate the clinical efficacy of herbal medicines (1 gm tulsi and 1 gm turmeric mixed in glycerine base for the treatment of oral submucous fibrosis (OSMF. Forty-one patients in the age group of 17- 56 years without any systemic complications were included in the study. The patients were treated with medicines, which were to be applied 3-4 times a day. Blood samples were collected before and after treatment to screen for any systemic changes due to these medications. Burning sensation and mouth opening were recorded before and after treatment. Patients were followed up on monthly subsequent visits for three months. Changes in the burning sensation on visual analogue scale (VAS scale and difference in the mouth opening were analyzed statistically. A statistically significant improvement was seen in both burning sensation and mouth opening. Tulsi and turmeric offers a safe and efficacious combination of natural products available for symptomatic treatment of OSMF.

Endorsing cellular competitiveness in aberrant epithelium of oral submucous fibrosis progression: neighbourhood analysis of immunohistochemical attributes.

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Anura, Anji; Kazi, Anees; Pal, Mousumi; Paul, Ranjan Rashmi; Sengupta, Sanghamitra; Chatterjee, Jyotirmoy

2018-04-23

Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant potentiality of OSF is yet to be resolved. Existing diagnostic conjectures lack precise diagnostic attributes which may be effectively resolved by substantiation of specific molecular pathology signatures. Present study elucidates existence of cellular competitiveness in OSF conditions using computer-assisted neighbourhood analysis in quantitative immunohistochemistry (IHC) framework. The concept of field cancerization was contributory in finding correspondence among neighbouring cells of epithelial layers with reference to differential expression of cardinal cancer-related genes [c-Myc (oncogene), p53 (tumour suppressor), and HIF-1α (hypoxia regulator)] which are known to be important sensors in recognizing cellular competitive interface. Our analyses indicate that different states of OSF condition may be associated with different forms of competitiveness within epithelial neighbouring cells which might be responsible to shape the present and future of the pre-malignant condition. Analytical findings indicated association of atrophic epithelium with stress-driven competitive environment having low c-Myc, high-p53, and stable HIF-1α (the looser cells) which undergo apoptosis. Whereas, the cells with high c-Myc + (winner cells) give rise to hyperplastic epithelium via possible mutation in p53. The epithelial dysplasia plausibly occurs due to clonal expansion of c-Myc and p53 positive supercompetitor cells. Present study proposes quantitative IHC along with neighbourhood analysis which might help us to dig deeper on to the interaction among epithelial cell population to provide a better understanding of field cancerization and malignant transformation of pre-malignancy.

Oral submucous fibrosis: Comparing clinical grading with duration and frequency of habit among areca nut and its products chewers

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Fareedi Mukram Ali

2013-01-01

Full Text Available Aims and objectives: To evaluate the effect of frequency, duration and type of areca nut products on the incidence and severity of oral submucous fibrosis (OSMF. Materials and methods: Patients with the limited mouth opening and associated blanched oral mucosa with palpable fibrous bands were included in this study. Biopsies were done and the informed consent was taken from each patient included in this study. The tissues were taken from the affected areas and then studied histopathologically. The data was analysed statistically using X 2 -test. Results: In this present prospective study done in 197 subjects (189 males and 8 females who were screened and diagnosed clinically having OSMF with age ranging from 22 to 61 years with mean 38.8 years. Gutkha-chewing habit alone was identified in 58 subjects and those associated with gutkha and tobacco were 33 with mean age of 28.2 years and 32.3 years, respectively. The number of people getting affected with OSMF is more associated with gutkha and areca nut with the P-value of the analysis ranging from 0.05 to 0.01. Conclusion: The occurrence of OSMF is related to areca nut and its products. The duration and frequency of its use and type of areca nut product has effect on the incidence and severity of OSMF. Gutkha and pan masala have more deleterious and faster effects on oral mucosa. The gutkha-chewing habit along with the other habits does not have any significant effect on the rate of occurrence and incidence and severity of the OSMF.

Quantitative proteomic analysis for novel biomarkers of buccal squamous cell carcinoma arising in background of oral submucous fibrosis

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Liu, Wen; Zeng, Lijuan; Li, Ning; Wang, Fei; Jiang, Canhua; Guo, Feng; Chen, Xinqun; Su, Tong; Xu, Chunjiao; Zhang, Shanshan; Fang, Changyun

2016-01-01

In South and Southeast Asian, the majority of buccal squamous cell carcinoma (BSCC) can arise from oral submucous fibrosis (OSF). BSCCs develop in OSF that are often not completely resected, causing local relapse. The aim of our study was to find candidate protein biomarkers to detect OSF and predict prognosis in BSCCs by quantitative proteomics approaches. We compared normal oral mucosa (NBM) and paired biopsies of BSCC and OSF by quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ) to discover proteins with differential expression. Gene Ontology and KEGG networks were analyzed. The prognostic value of biomarkers was evaluated in 94 BSCCs accompanied with OSF. Significant associations were assessed by Kaplan-Meier survival and Cox-proportional hazards analysis. In total 30 proteins were identified with significantly different expression (false discovery rate < 0.05) among three tissues. Two consistently upregulated proteins, ANXA4 and FLNA, were validated. The disease-free survival was negatively associated with the expression of ANXA4 (hazard ratio, 3.4; P = 0.000), FLNA (hazard ratio, 2.1; P = 0.000) and their combination (hazard ratio, 8.8; P = 0.002) in BSCCs. The present study indicates that iTRAQ quantitative proteomics analysis for tissues of BSCC and OSF is a reliable strategy. A significantly up-regulated ANXA4 and FLNA could be not only candidate biomarkers for BSCC prognosis but also potential targets for its therapy. The online version of this article (doi:10.1186/s12885-016-2650-1) contains supplementary material, which is available to authorized users

Computer vision approach to morphometric feature analysis of basal cell nuclei for evaluating malignant potentiality of oral submucous fibrosis.

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Muthu Rama Krishnan, M; Pal, Mousumi; Paul, Ranjan Rashmi; Chakraborty, Chandan; Chatterjee, Jyotirmoy; Ray, Ajoy K

2012-06-01

This research work presents a quantitative approach for analysis of histomorphometric features of the basal cell nuclei in respect to their size, shape and intensity of staining, from surface epithelium of Oral Submucous Fibrosis showing dysplasia (OSFD) to that of the Normal Oral Mucosa (NOM). For all biological activity, the basal cells of the surface epithelium form the proliferative compartment and therefore their morphometric changes will spell the intricate biological behavior pertaining to normal cellular functions as well as in premalignant and malignant status. In view of this, the changes in shape, size and intensity of staining of the nuclei in the basal cell layer of the NOM and OSFD have been studied. Geometric, Zernike moments and Fourier descriptor (FD) based as well as intensity based features are extracted for histomorphometric pattern analysis of the nuclei. All these features are statistically analyzed along with 3D visualization in order to discriminate the groups. Results showed increase in the dimensions (area and perimeter), shape parameters and decreasing mean nuclei intensity of the nuclei in OSFD in respect to NOM. Further, the selected features are fed to the Bayesian classifier to discriminate normal and OSFD. The morphometric and intensity features provide a good sensitivity of 100%, specificity of 98.53% and positive predicative accuracy of 97.35%. This comparative quantitative characterization of basal cell nuclei will be of immense help for oral onco-pathologists, researchers and clinicians to assess the biological behavior of OSFD, specially relating to their premalignant and malignant potentiality. As a future direction more extensive study involving more number of disease subjects is observed.

Assessment of Salivary Flow Rate and pH Among Areca Nut Chewers and Oral Submucous Fibrosis Subjects: A Comparative Study.

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Abdul Khader, Nishat Fatima; Dyasanoor, Sujatha

2015-09-01

To assess and compare the salivary flow rate (SFR) and salivary pH among areca nut chewers, oral submucous fibrosis (OSMF) patients and apparently healthy individuals. A comparative study was conducted to assess and compare the SFR and pH among 135 outpatients (45 areca nut chewers + 45 OSMF + 45 control) at The Oxford Dental College and Research Hospital, Bangalore, India. Subjects were interviewed using structural proforma and Modified Schirmer strips and pH paper were implemented for assessing SFR and pH respectively. Statistical analysis was done using IBM SPSS ver. 21.0 software. A statistically significant increase in SFR (35.7 mm at 3rd minutes) among areca nut group and a decrease in SFR among OSMF group (23.4 mm at 3rd minutes) when compared to apparently healthy subjects (30.7 mm at 3rd minutes). The mean pH among areca nut, OSMF and control groups was 6.76, 6.82, and 6.74 respectively with no statistical significance. The observation and findings of the study clearly showed hypersalivation among areca nut group and hyposalivation among OSMF group, with no significant change in salivary pH when compared to healthy subjects.

Efficacy of curcumin in the treatment for oral submucous fibrosis - A randomized clinical trial.

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Hazarey, Vinay K; Sakrikar, Aditee R; Ganvir, Sindhu M

2015-01-01

Oral submucous fibrosis (OSF) is a chronic, insidious disease that is associated with significant functional morbidity and an increased risk for malignancy. Turmeric and its active ingredient "curcumin" are being studied upon as chemopreventive agents in various diseases. The present study aims to determine the efficacy of curcumin in the treatment of OSF. Thirty clinically diagnosed OSF patients were divided into two groups, 15 patients in each group from the Outpatient Department. Test group patients were treated with Longvida (curcumin) lozenges and control group with Tenovate ointment (clobetasol propionate (0.05%). The treatment was given for 3 months duration and follow-up was done for 6 months. Both the groups were advised for physiotherapy exercises by mouth exercise device. The baseline and follow-up results were compared for IIO (interincisal distance on maximum mouth opening), Visual Analogue Scale (VAS) for normal food and VAS for spicy food. The test group showed 5.93 (±2.37) mm increase in mouth opening compared to 2.66 (±1.76) mm of the control group. In relation to VAS scale with spicy and normal food the average reduction was 64 (42-73) and 77 (70.5-82) as compared to 34 (14.5-64.5) and 64 (46-75.5) respectively in control group. The test group results achieved in the treatment span was sustained in the follow-up (P < 0.05) compared to control group which showed statistically significant (P < 0.05) relapse. It can be concluded that combination strategies for the management of OSF which include the stoppage of causative ill habits, appropriate medicinal and physiotherapy management is more efficient than single therapeutic modality. It is evident from the study that curcumin holds good promise in the treatment of OSF in future.

Evaluation of the possible role of copper ions in drinking water in the pathogenesis of oral submucous fibrosis: a pilot study.

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Arakeri, Gururaj; Patil, Shekhar Gowda; Ramesh, D N S V; Hunasgi, Santosh; Brennan, Peter A

2014-01-01

We aimed to investigate the concentration of copper ions in drinking water and to assess whether copper has a role in the pathogenesis of oral submucous fibrosis (OSMF). We studied 50 patients with clinically and histologically diagnosed OSMF from the Yadgir district of Karnataka in India. Fifty healthy people matched for age and sex were used as controls. In both groups concentrations of copper ions in serum, saliva, and home drinking water were measured using atomic absorption spectroscopy and intelligent nephelometry technology. Serum ceruloplasmin concentrations were also estimated in both groups. The mean (SD) concentration of copper in the home drinking water of patients with OSMF was significantly higher (764.3 (445.9)μmol/L) than in the controls (305.7 (318.5)μmol/L) (p<0.001). Patients with OSMF also had a significantly higher copper concentrations in serum and saliva, and serum ceruloplasmin than controls (p<0.001). For the first time these data have shown a positive association between copper concentrations in home drinking water and OSMF. It raises the possibility that increased copper in drinking water contributes to the development of OSMF, and adds to that ingested when areca nut is chewed. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Inhibition of Tanshinone IIA, Salvianolic Acid A and Salvianolic Acid B on Areca Nut Extract-Induced Oral Submucous Fibrosis in Vitro

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Jian-Ping Dai

2015-04-01

Full Text Available Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA, salvianolic acid A (Sal-A and salvianolic acid B (Sal-B, the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE-induced oral submucous fibrosis (OSF in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-β/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs, inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-β1, IL-6 and TNF-α; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-β/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.

Editorial. Oral submucous fibrosis: revised hypotheses as to its cause.

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Rajendran, R; Sukumaran, Anil

2013-09-01

Oral submucous fbrosis (OSF), being a prototype of pathological fbrosis, remains enigmatic as regards its causation. The connective tissue production is permanent and there is no reversal of the condition even after cessation of the habit of areca-nut usage; prime suspect in its causation.(1) The bulk of the connective tissue consists of type-1 collagen(2) and its formation does not appears to be caused by excessive proliferation of fbroblasts.(3) The effect of areca nut extract on in vitro fbroblasts varies on a concentration gradient, predominantly suppressing rather than stimulating the growth of the cells.(4) Based on morphological characteristics, the fbroblast population in the diseased mucosa has been classifed in to types F1, F2 and F3 with F3 cells producing signifcantly more collagen than the other two cell types. It was concluded that a change of fbroblast population has occurred in OSF and that this relative increase of F3 cells in humans, could be committed to the production of large quantities of collagen formation in OSF. It has been proposed that fbroblasts are functionally heterogeneous, the composition of any given normal or diseased connective tissue being a consequence in part of its particular mixture of fbroblast subtypes and density. Subtype deletion or amplifcation can result from selective cytotoxic or mitogenic responses induced by the binding environmental ligands.(5) Against this backdrop, we propose few de-novo attributes, hitherto unreported, and seem to be of relevance in the pathogenesis of OSF; namely the role of autophagy in basic cellular homeostatic process, important to cell fate decisions under conditions of stress and also ECM producing cells (fbroblasts, myofbroblasts and smooth muscle cells) derived from epithelial and endothelial cells through process termed epithelial and endothelial-mesenchymal transition.

The Use of Buccal Fat Pad in the Treatment of Oral Submucous Fibrosis: A Newer Method

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K. Saravanan

2012-01-01

Full Text Available Purpose of the study. This study was to evaluate the use of buccal fat pad as an interpositioning material in surgical management of oral sub mucous fibrosis. Materials and methods. A series of 8 cases with proven oral sub mucous fibrosis, with mouth opening less than 20 mm, involving the buccal mucosa were treated surgically in the Department of Oral and Maxillofacial Surgery, College of Dental Surgery, Saveetha University, Chennai. Pedicled buccal fat pad was used as an interpositioning material to cover the raw areas in the oral cavity after incision and release of fibrous bands. Results. In 8 patients, the range of pre operative mouth opening was 3–18 mm (mean 14 mm. As the result of the successful surgical procedure, the size of the intra operative mouth opening was ranged from 25–38 mm (mean 33.25 mm. The patients were discharged 5–7 days after the operation. The range of the mouth opening at this time was 25–36 mm (mean 30.63 mm. The results were evaluated using student’s t test and found to be statistically significant. The pedicled grafts took up uneventfull.

Estimation of serum, salivary immunoglobulin G, immunoglobulin A levels and total protein, hemoglobin in smokeless tobacco chewers and oral submucous fibrosis patients

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Chandrakanth Balakrishnan

2015-01-01

Full Text Available Background: Oral submucous fibrosis (OSMF is a debilitating, potentially cancerous oral condition. Although areca nut is the most important causative agent, it is also considered that the disease is immunologically mediated. Aim of the Study: To establish that autoimmunity and nutritional deficiency play a role in the etiopathogenesis of OSMF. Objectives of the Study: To show that serum immunoglobulin markers (immunoglobulin-G [IgG], immunoglobulin-A [IgA] and nutritional parameters such as total serum protein (TSP, Hemoglobin (Hb play a role in causing OSMF and also to correlate serum, salivary IgG, IgA levels in OSMF patients. Settings and Design: A case-control study was done with 50 patients (25 patients who were provisionally diagnosed as OSMF - Group I, and 25 patients who were chronic smokeless tobacco chewers and who did not have any intraoral lesion - Group II. Materials and Methods: Five milliliters of blood and saliva were collected from both the groups. Quantitative analysis of serum, and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hemoglobin (Hb were estimated by spectrophotometry. Statistical Analysis: Results were analyzed by independent samples t-test and one-way analysis of variance (ANOVA. Results: All patients of OSMF showed significant (P < 0.01 increase in serum IgG, IgA, and salivary IgG levels as compared to smokeless tobacco chewers. The salivary IgA levels showed a significant decrease in OSMF patients (P < 0.05. TSP and Hb levels showed significant (P < 0.01 decrease in OSMF patients as compared to smokeless tobacco chewers. Conclusion: The elevation of immunoglobulin levels supports the concept of autoimmunity. The decrease in TSP and Hb suggests that nutritional deficiency plays a defined role in the occurrence as well as a further progression of OSMF.

An Unusual Occurrence of OSMF with Oral Lichen Planus - A Case Report And Review of Literature

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L Ashok

2003-01-01

Full Text Available An unusual case of Oral submucous fibrosis and concomitant occurrence of oral lichen planus in a 18 year old male patient is presented. These conditions are defined and the clinical features on histopathology are discussed.

Incidence of bifid uvula and its relationship to submucous cleft palate and a family history of oral cleft in the Brazilian population.

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Sales, Sizina Aguiar G; Santos, Maria Luiza; Machado, Renato Assis; Dias, Verônica Oliveira; Nascimento, Jairo Evangelista; Swerts, Mario Sérgio Oliveira; Júnior, Hercílio Martelli; Martelli, Daniella Reis Barbosa

2017-08-24

Bifid uvula is a frequently observed anomaly in the general population and can be regarded as a marker for submucous cleft palate. In this study aimed to determine the frequency of bifid uvula and submucous cleft palate and their relationship with oral clefts in a Brazilian population. We conducted a transversal, descriptive and quantitative study of 1206 children between August 2014 and December 2015. A clinical examination of the children was conducted by means of inspection of the oral cavity with the aid of a tongue depressor and directed light. After the clinical examination in children, parents answered a questionnaire with questions about basic demographic information and their family history of oral clefts in their first-degree relatives. After application of the questionnaires, the information collected was archived in a database and analyzed by the statistical program SPSS ® version 19.0, by applying Chi-Square tests. Values with previews, with broader and diverse populations, seeking to associate the occurrence of bifid uvula, submucous cleft palate and oral clefts. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

The prevalence of oral mucosal lesions in patients visiting a dental school in Southern India

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Mathew Anuna

2008-01-01

Full Text Available The purpose of the present study was to evaluate the prevalence of oral mucosal lesions in Manipal, Karnataka State, India. A total of 1190 subjects who visited the department of oral medicine and radiology for diagnosis of various oral complaints over a period of 3 months were interviewed and clinically examined for oral mucosal lesions. The result showed the presence of one or more mucosal lesions in (41.2% of the population. Fordyce′s condition was observed most frequently (6.55% followed by frictional keratosis (5.79%, fissured tongue (5.71%, leukoedema (3.78%, smoker′s palate (2.77%, recurrent aphthae, oral submucous fibrosis (2.01%, oral malignancies (1.76%, leukoplakia (1.59%, median rhomboid glossitis (1.50%, candidiasis (1.3%, lichen planus (1.20%, varices (1.17%, traumatic ulcer and oral hairy leukoplakia (1.008%, denture stomatitis, geographic tongue, betel chewer′s mucosa and irritational fibroma (0.84%, herpes labialis, angular cheilitis (0.58%, and mucocele (0.16%. Mucosal lesions like tobacco-related lesions (leukoplakia, smoker′s palate, oral submucous fibrosis, and oral malignancies were more prevalent among men than among women. Denture stomatitis, herpes labialis, and angular cheilitis occurred more frequently in the female population.

Comparative evaluation of serum and salivary immunoglobulin G and A levels with total serum protein in oral submucous fibrosis patients: A case control study

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M Kandasamy

2016-01-01

Full Text Available Aim and Objective: The objective of this study is to estimate and compare the serum and salivary immunoglobulin G and A (IgG, IgA levels in various stages of oral submucous fibrosis (OSMF patients and relate it to total serum protein (TSP and hemoglobin (Hb levels. Materials and Methods: The sample for the present study comprised a total of 20 healthy controls, 20 OSMF patients. About 5 ml of blood and 2 ml of saliva were collected. Quantitative analysis of serum and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hb were estimated by Biuret and cyanmethemoglobin methods, respectively. Results: Serum and salivary IgA and IgG levels were statistically significantly increased (P < 0.001 in OSMF patients when compared to controls. Also serum and salivary IgG and IgA levels showed significantly increased (P < 0.01 in all the three staging of OSMF when compared to control group. Hb levels and TSP levels were significantly decreased (P < 0.001 in OSMF patients when compared to controls. One-way ANOVA, Pearson's correlation, and unpaired t -test were used for statistical analysis. Conclusion: The elevated levels of IgG and IgA are also in favor of polygammapathy, which are nonspecific and nondiagnostic objective reflections of an underlying disease. Decreased TSP is a result of host response and Hb, acts as an indicator of nutritional status plays an important role. It is also observed from the present study that the severity of OSMF was directly proportional to the estimated elevated levels of the major IgG and IgA. A need is also felt for the knowledge of immunoprofile estimation in etiology and pathogenesis that would prove a great asset in the proper assessment of this condition.

Comparative evaluation of serum and salivary immunoglobulin G and A levels with total serum protein in oral submucous fibrosis patients: A case control study.

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Kandasamy, M; Jaisanghar, N; Austin, Ravi David; Srivastava, Kumar Chandan; Anusuya, G Sai; Anisa, N

2016-10-01

The objective of this study is to estimate and compare the serum and salivary immunoglobulin G and A (IgG, IgA) levels in various stages of oral submucous fibrosis (OSMF) patients and relate it to total serum protein (TSP) and hemoglobin (Hb) levels. The sample for the present study comprised a total of 20 healthy controls, 20 OSMF patients. About 5 ml of blood and 2 ml of saliva were collected. Quantitative analysis of serum and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hb were estimated by Biuret and cyanmethemoglobin methods, respectively. Serum and salivary IgA and IgG levels were statistically significantly increased ( P < 0.001) in OSMF patients when compared to controls. Also serum and salivary IgG and IgA levels showed significantly increased ( P < 0.01) in all the three staging of OSMF when compared to control group. Hb levels and TSP levels were significantly decreased ( P < 0.001) in OSMF patients when compared to controls. One-way ANOVA, Pearson's correlation, and unpaired t -test were used for statistical analysis. The elevated levels of IgG and IgA are also in favor of polygammapathy, which are nonspecific and nondiagnostic objective reflections of an underlying disease. Decreased TSP is a result of host response and Hb, acts as an indicator of nutritional status plays an important role. It is also observed from the present study that the severity of OSMF was directly proportional to the estimated elevated levels of the major IgG and IgA. A need is also felt for the knowledge of immunoprofile estimation in etiology and pathogenesis that would prove a great asset in the proper assessment of this condition.

Treatment Outcome of Diode Laser for Symptomatic Relief in Oral Sub Mucous Fibrosis: A Pilot Study

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Jithender Mudigonda

2016-01-01

Full Text Available Aim : Oral submucous fibrosis (OSMF is a progressive premalignant condition largely occurring in Indian subcontinent due to habitual chewing of betel nut. Major symptoms of the condition include burning sensation to spicy food and progressive trismus. Since aetiology and pathogenesis of this condition is not fully understood; the management of patient focuses on symptomatic relief of trismus and burning sensation. Materials and Method : This was a pilot study to compare the outcome of diode laser (category A to steroid and hyaluronidase injections (category B in early stage of OSMF. Results : By the end of six months, patients in either of the categories showed significant improvement in reduction of symptoms, however; patients in category A showed greater significance in mouth opening ( p=0.002 vs. p=0.011 and reduction in burning sensation (p=0.002 vs. p=0.004. Conclusion: Although laser excision is not an answer for OSMF, it is a simple surgical procedure with effective results in the management of symptoms of OSMF. Improved mouth opening further facilitates periodic inspection of mucosa for initial signs of malignant transformation.

Textural pattern classification for oral squamous cell carcinoma.

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Rahman, T Y; Mahanta, L B; Chakraborty, C; DAS, A K; Sarma, J D

2018-01-01

Despite being an area of cancer with highest worldwide incidence, oral cancer yet remains to be widely researched. Studies on computer-aided analysis of pathological slides of oral cancer contribute a lot to the diagnosis and treatment of the disease. Some researches in this direction have been carried out on oral submucous fibrosis. In this work an approach for analysing abnormality based on textural features present in squamous cell carcinoma histological slides have been considered. Histogram and grey-level co-occurrence matrix approaches for extraction of textural features from biopsy images with normal and malignant cells are used here. Further, we have used linear support vector machine classifier for automated diagnosis of the oral cancer, which gives 100% accuracy. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Betel quid-induced oral lichen planus: a case report.

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Stoopler, Eric T; Parisi, Ernesta; Sollecito, Thomas P

2003-04-01

The social use of betel nut is relatively common in certain geographic areas, especially India and Southeast Asia. The term betel nut does not truly describe the product that is chewed; rather, the term quid is more accurate because it refers to a substance or mixture of substances, including the areca nut, that are chewed and remain in contact with the mucosa. Betel quid is a type of quid that contains betel leaf. Chewer's mucosa and oral submucous fibrosis are clinical entities that have been associated with betel quid use. We report a case of oral lichen planus induced by betel quid use in a 79-year-old Cambodian woman.

Malignant transformation of Taiwanese patients with oral leukoplakia: A nationwide population-based retrospective cohort study

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Tung-Yuan Wang

2018-05-01

Full Text Available Background/Purpose: Oral leukoplakia (OL is one of the clinically diagnosed oral potentially malignant disorders (OPMDs with an increased risk of oral cancer development. In this study, we investigated the malignant transformation of OL in Taiwanese population. Methods: A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort was randomly frequency-matched with the OL cohort according to age, sex, and index year. Oral submucous fibrosis (OSF and oral lichen planus (OLP were further stratified to evaluate the possible synergistic effects for OL-associated malignant transformation. Results: In this cohort, 102 (5.374% of 1898 OL patients were observed to transform into oral cancer. The malignant transformation rate was 26.40-fold in the OL cohort than in the comparison cohort after adjustment (95% confidence intervals 18.46–37.77. To further stratify with OSF and OLP, OL with OSF (58.38; 95% confidence intervals 34.61–98.50 and OL with OLP (36.88; 95% confidence intervals 8.90–152.78 had higher risk of malignant transformation rate than OL alone (27.01; 95% confidence intervals 18.91–38.59. The Kaplan–Meier plot revealed the free of malignant transformation rate was significant over the 13 years follow-up period (log-rank test, p < 0.001. Conclusion: OL patients exhibited a significantly higher risk of malignant transformation than those without OL. In addition, both OSF and OLP could enhance malignant transformation in patients with OL. However, further studies are required to identify the histopathological and clinical parameters in the pathogenesis of malignant transformation among OPMDs. Keywords: Oral leukoplakia, Oral submucous fibrosis, Oral lichen planus, Malignant transformation, Nationwide population, Cohort study, Taiwan

Prevalence of oral mucosal lesions among chewing tobacco users: A cross-sectional study

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Sujatha S Reddy

2015-01-01

Statistical Analysis Used: Chi-square and Fisher′s exact tests were used to assess the statistical significance. Results: Of the 901 subjects with CT habits, 55.8% revealed no clinically detectable oral mucosal changes and 44.1% showed mucosal changes of which 63.8% were males and 36.1% were females. The most common finding was chewers mucositis (59.5% followed by submucous fibrosis (22.8%, leukoplakia (8%, lichenoid reaction (6.5%, oral cancer (2.7%, and lichen planus (0.5%. Conclusion: This study provides information about different CT habits and associated mucosal lesions among this population.

Hinged and sectional complete dentures for restricted mouth opening: A case report and review

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Aditi Sharma

2013-01-01

Full Text Available Restricted mouth opening is a definite prosthodontic hindrance to carry out treatment successfully. Restricted mouth opening can be due to many reasons such as microstomia, oral submucous fibrosis, some genetic disorder, and as a result of some surgical treatment. In the past, various techniques for prosthetic rehabilitation of limited oral opening have been tried such as surgeries, use of dynamic opening devices, magnetic devices, and modification of denture design. Here we present; a simplified technique and simple design for fabrication of maxillary hinged and mandibular hinged and sectional complete denture for a patient with restricted mouth opening due to oral submucous fibrosis.

Oral calorie supplements for cystic fibrosis.

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Smyth, Rosalind L; Rayner, Oli

2017-05-04

Poor nutrition occurs frequently in people with cystic fibrosis and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. This is an update of a previously published review. To establish whether in people with cystic fibrosis, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements. We searched the Cochrane Cystic Fibrosis Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 18 October 2016. Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with cystic fibrosis. We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials. We identified 21 trials and included three, reporting results from 131 participants lasting between three months and one year. Two trials compared supplements to additional nutritional advice and one to no intervention. Two of the included trials recruited only children. In one trial the risk of bias was low across all domains, in a second trial the risk of bias was largely unclear and in the third mainly low. Blinding of participants was unclear in two of the trials. Also, in one trial the clinical condition of groups appeared to be unevenly balanced at baseline and in another trial there were

A novel wavelet neural network based pathological stage detection technique for an oral precancerous condition

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Paul, R R; Mukherjee, A; Dutta, P K; Banerjee, S; Pal, M; Chatterjee, J; Chaudhuri, K; Mukkerjee, K

2005-01-01

Aim: To describe a novel neural network based oral precancer (oral submucous fibrosis; OSF) stage detection method. Method: The wavelet coefficients of transmission electron microscopy images of collagen fibres from normal oral submucosa and OSF tissues were used to choose the feature vector which, in turn, was used to train the artificial neural network. Results: The trained network was able to classify normal and oral precancer stages (less advanced and advanced) after obtaining the image as an input. Conclusions: The results obtained from this proposed technique were promising and suggest that with further optimisation this method could be used to detect and stage OSF, and could be adapted for other conditions. PMID:16126873

Changing pattern of oral cavity lesions and personal habits over a decade: Hospital based record analysis from Allahabad

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Misra Vatsala

2009-01-01

Full Text Available Aim: To do a prospective clinicohistological study of premalignant and malignant lesions of the oral cavity, and compare it with a 10-year retrospective data, especially in terms of incidence, age distribution, personal habits, and site and type of lesion. Material and Methods: Sections from 776 lesions of the oral cavity, which included 647 lesions of a 10-year (1993 - 2003 retrospective study and 129 lesions of a one-year (2003 - 2004 prospective study, were observed clinically, and a histological correlation was carried out. Results: Premalignant lesions included 78 cases of leukoplakia, 68 cases of oral submucous fibrosis, and 76 cases of squamous papilloma. Their incidence has increased in the last decade from 0.15 to 0.53. These lesions commonly presented in the fourth decade of life, as white patches in leukoplakia and oral submucous fibrosis, and as a growth in squamous cell papilloma. Squamous cell carcinoma was the commonest lesion (57%. Its incidence has increased significantly in the last decade. The mean age of presentation was the sixth decade. A personal history of tobacco chewing was given by most of the patients in the retrospective group, while the use of pan masala was found to be maximum in the prospective group. The overall agreement between the clinical and histological diagnosis was 95.36% (740 / 776 and the kappa coefficient of agreement was 0.9256. Conclusion: Histology along with a detailed clinical workup was found to be a useful, reliable, and accurate diagnostic technique for lesions of the oral cavity. An increase in premalignant lesions in the prospective study, associated with increased pan masala intake is alarming and needs to be taken care of.

Submucous Clefts

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... Find Local Cleft/Craniofacial Specialists Booklets & Factsheets College Scholarships School-Age Support Resources Connections Conference View More… ... for speech problems, middle ear disease, and swallowing difficulties. However, there are some individuals with a submucous ...

Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes.

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Jeng, J H; Ho, Y S; Chan, C P; Wang, Y J; Hahn, L J; Lei, D; Hsu, C C; Chang, M C

2000-07-01

There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is associated with increased incidence of oral cancer and submucous fibrosis. In this study, areca nut (AN) extract (200-800 microg/ml) induced the prostaglandin E(2) (PGE(2)) production by 1. 4-3.4-fold and 6-keto-PGF(1 alpha) production by 1.1-1.7-fold of gingival keratinocytes (GK), respectively, following 24 h of exposure. Exposure of GK to AN extract (>400 microg/ml) led to cell retraction and intracellular vacuoles formation. At concentrations of 800 and 1200 microg/ml, AN extract induced cell death at 21-24 and 32-52% as detected by MTT assay and cellular lactate dehydrogenase release, respectively. Interestingly, AN-induced morphological changes of GK are reversible. GK can still proliferate following exposure to AN extract. Cytotoxicity of AN extract cannot be inhibited by indomethacin (1 microM) and aspirin (50 microM), indicating that prostaglandin (PG) production is not the major factor responsible for AN cytotoxicity. PGE(2) exhibited little effect on the growth of GK at concentrations ranging from 100-1000 pg/ml. Stimulating GK production of PGs by AN extract could be due to induction of cyclooxygenase-2 (COX-2) mRNA expression and protein production. These results suggest that AN ingredients are critical in the pathogenesis of oral submucous fibrosis and oral cancer via their stimulatory effects on the PGs, COX-2 production and associated tissue inflammatory responses. AN cytotoxicity to GK is not directly mediated by COX-2 stimulation and PG production.

Betel nut chewing and its deleterious effects on oral cavity

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Richa Anand

2014-01-01

Full Text Available The habit of chewing betel nut has a long history of use. Betel nut and products derived from it are widely used as a masticatory product among various communities and in several countries across the world. Over a long period, several additives have been added to a simple betel nut preparation; thus, creating the betel quid (BQ and encompassing chewing tobacco in the preparation. Betel nut has deleterious effects on oral soft tissues. Its effects on dental caries and periodontal diseases, two major oral diseases are less well-documented. Betel-induced lichenoid lesions mainly on buccal mucosa have been reported at quid retained sites. In chronic chewers, a condition called betel chewers mucosa is often found where the quid is placed. Betel nut chewing is implicated in oral submucous fibrosis (OSF and its use along with tobacco can cause leukoplakia, both of which are potentially malignant in the oral cavity. Oral cancer often arises from such precancerous changes. Thus, public health measures to quit betel use are recommended to control disabling conditions such as OSF and oral cancer.

Betel nut chewing and its deleterious effects on oral cavity.

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Anand, Richa; Dhingra, Chandan; Prasad, Sumanth; Menon, Ipseeta

2014-01-01

The habit of chewing betel nut has a long history of use. Betel nut and products derived from it are widely used as a masticatory product among various communities and in several countries across the world. Over a long period, several additives have been added to a simple betel nut preparation; thus, creating the betel quid (BQ) and encompassing chewing tobacco in the preparation. Betel nut has deleterious effects on oral soft tissues. Its effects on dental caries and periodontal diseases, two major oral diseases are less well-documented. Betel-induced lichenoid lesions mainly on buccal mucosa have been reported at quid retained sites. In chronic chewers, a condition called betel chewers mucosa is often found where the quid is placed. Betel nut chewing is implicated in oral submucous fibrosis (OSF) and its use along with tobacco can cause leukoplakia, both of which are potentially malignant in the oral cavity. Oral cancer often arises from such precancerous changes. Thus, public health measures to quit betel use are recommended to control disabling conditions such as OSF and oral cancer.

Betel nut chewing behaviour and its association with oral mucosal lesions and conditions in Ghaziabad, India.

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Prasad, Sumanth; Anand, Richa; Dhingra, Chandan

2014-01-01

To assess the practices and behaviour among Betel nut users in Ghaziabad and to detect the clinically associated oral mucosal lesions and conditions. A community-based survey was conducted in Ghaziabad among 332 betel nut users. Data on betel nut use was obtained through a self-administered questionnaire. Oral mucosal lesions and conditions were recorded using WHO criteria. Out of 332 betel nut users, 32.8% consumed Gutkha. 62.3% users used betel nut with tobacco. Most of the study population started chewing betel nut because of peer pressure and the habit started at the workplace or school. A majority found that there was no physical discomfort due to the habit. The significant oral diseases detected were oral leukoplakia in 11.7% and oral submucous fibrosis in 6.1% of individuals. The findings of the present study revealed that 74.7% of the participants were current chewers. 30.4% of all participants had oral mucosal lesions and conditions.

[Morphological classification and velopharyngeal function analysis of submucous cleft palate patients].

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Heng, Yin; Chunli, Guo; Bing, Shi; Yang, Li; Jingtao, Li

2016-10-01

To enhance the accuracy in diagnosis and management of submucous cleft palate via a thorough analysis of its anatomical and functional details. Two hundred seventy-six submucous cleft palate cases from 2008 to 2014 were retrospectively investigated. Subgroup analysis were performed on the basis of preoperative velopharyngeal function, palatal morphology, cleft lip concurrence, and patient motives for treatment. Among the included cases, 96 (34.78%) were presented as velopharyngeal competence (VPC), 151 (54.71%) as velopharyngeal insufficiency (VPI), and 29 (10.51%) as marginal VPI (MVPI). Eighty cases (28.99%) also demonstrated cleft lip deformity, and 196 cases (71.01%) were merely submucous cleft palate. Compared with patients with submucous cleft palate only, those with cleft lips exhibited higher rates of complete velopharyngeal closure. The pathological spectrum of submucous cleft palate varied significantly. Only 103 (37.32%) cases met all the three diagnostic criteria proposed by Calnan. Given that the velopharyngeal closure rate varies among the subgroups, the factors analyzed in this study should be considered in the personalized manage-ment of submucous cleft palate.

Laparoscopic Myomectomy for a Plethora of Submucous Myomas.

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Paul, P G; Paul, George; Radhika, K T; Bulusu, Saumya; Shintre, Hemant

To demonstrate a laparoscopic myomectomy technique for the removal of multiple submucous myomas. A step-by-step demonstration of the surgical procedure (Canadian Task Force classification III-C). In cases of multiple submucous myomas, hysteroscopic resection of myomas might not be a viable option, especially in cases requiring fertility preservation. It may cause significant damage to the endometrial surface, leading to the formation of endometrial synechiae [1]. The procedure is technically challenging and requires prolonged operating time owing to impaired visibility and the need for repeated specimen removal. This can lead to complications, such as fluid overload and, rarely, air embolism [2]. Thus, laparoscopic myomectomy may be a better option in such cases [1]. A 30-year-old nulligravida presented with a 3-year history of heavy menstrual bleeding and dysmenorrhea. She had received no symptom relief with hormonal medications and magnetic resonance-guided focused ultrasound. On examination, she was anemic, and her uterus was enlarged to 16-weeks gravid size. Ultrasonography revealed an intramural fundal myoma of 6 × 4.2 cm and numerous submucous myomas of 1 to 3.2 cm. During hysteroscopy, multiple submucous myomas of varying sizes ranging from type 0 to type 1 were seen. On laparoscopy, an incision was made on the uterine fundus with an ultrasonic device after injecting vasopressin (20 U in 200 mL dilution), and the fundal myoma was enucleated. The incision was then extended to open the endometrial cavity for the removal of the submucous myomas. Most of the myomas were removed with mechanical force, along with the minimal use of ultrasonic energy. A total of 46 myomas were removed, and the myometrium was closed in 2 layers. The duration of the surgery was 210 minutes, and estimated blood loss was 850 mL. The patient did not require blood transfusion, but was advised to take hematinics. At a 6-month follow-up, the patient reported significant improvement

Application of fuzzy consensus for oral pre-cancer and cancer susceptibility assessment

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Satarupa Banerjee

2016-11-01

Full Text Available Health questionnaire data assessment conventionally relies upon statistical analysis in understanding disease susceptibility using discrete numbers and fails to reflect physician’s perspectives and missing narratives in data, which play subtle roles in disease prediction. In addressing such limitations, the present study applies fuzzy consensus in oral health and habit questionnaire data for a selected Indian population in the context of assessing susceptibility to oral pre-cancer and cancer. Methodically collected data were initially divided into age based small subgroups and fuzzy membership function was assigned to each. The methodology further proposed the susceptibility to oral precancers (viz. leukoplakia, oral submucous fibrosis and squamous cell carcinoma in patients considering a fuzzy rulebase through If-Then rules with certain conditions. Incorporation of similarity measures using the Jaccard index was used during conversion into the linguistic output of fuzzy set to predict the disease outcome in a more accurate manner and associated condition of the relevant features. It is also expected that this analytical approach will be effective in devising strategies for policy making through real-life questionnaire data handling.

Congenital Palatal Fistula Associated with Submucous Cleft Palate

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Eshete, Mekonen; Camison, Liliana; Abate, Fikre; Hailu, Taye; Demissie, Yohannes; Mohammed, Ibrahim; Butali, Azeez; Losken, H. Wolfgang

2016-01-01

Background: Although cleft lip and cleft palate are among the most common congenital malformations, the presence of an isolated congenital palatal fistula along with a submucous cleft is very rare. This appears as an oval-shaped, full-thickness fenestration in the palatal midline that does not fully extend anteriorly or posteriorly, accompanied by the findings of a submucous cleft. Because of the uncommon nature of this entity, there is controversy about its etiology, diagnosis, and management. Methods: Two cases of children with congenital palatal fistulae and a submucous cleft palate are presented who were treated in different settings by different surgeons. Cases are discussed along with a thorough review of the available literature. Results: Patient 1 presented at 4 years of age with “a hole in the palate” since birth and abnormal speech. His palatal fistula and submucous cleft were repaired with a modified von Langenbeck technique in Ethiopia. At a 2-year follow-up, the palate remained closed, but hypernasal speech persisted. Patient 2 was a 1-year-old presenting with failure to thrive and nasal regurgitation, who underwent a Furlow palatoplasty in the United States with good immediate results. She was unfortunately lost to follow-up. Conclusions: A congenital fenestration of the palate is rare. Reports reveal suboptimal speech at follow-up, despite various types of repair, especially when combined with a submucous cleft. Available literature suggests that repair should not focus on fistula closure only but instead on providing adequate palate length to provide good velopharyngeal function, as in any cleft palate repair. PMID:27014542

Resectoscopic Resection of a Large Submucous Uterine Myoma

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Inocêncio, Gonçalo; Braga, António; Galvão, Ana; Zulmira, Rosa

2014-01-01

Submucous myoma(s) can decrease the chances of a spontaneous conception and, therefore, be a cause of reproductive failure.There are many different methods for submucous myoma(s) treatment. The choice for the best treatment approach should take into account the characteristics of the myoma: the size, number (single or multiple), location and its relationship with the myometrium/uterine cavity; Also, the age of the woman and her desire for procreation have great influence when choosing the bes...

Betel nut chewing, oral premalignant lesions, and the oral microbiome.

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Hernandez, Brenda Y; Zhu, Xuemei; Goodman, Marc T; Gatewood, Robert; Mendiola, Paul; Quinata, Katrina; Paulino, Yvette C

2017-01-01

Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes

Arecoline inhibits endothelial cell growth and migration and the attachment to mononuclear cells

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Shuei-Kuen Tseng

2014-09-01

Conclusion: Arecoline impaired vascular endothelial cells by inhibiting their growth and migration and their adhesion to U937 mononuclear cells. These results reveal that arecoline may contribute to the pathogenesis of oral submucous fibrosis and cardiovascular diseases by affecting endothelial cell function in BQ chewers.

Raman exfoliative cytology for oral precancer diagnosis

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Sahu, Aditi; Gera, Poonam; Pai, Venkatesh; Dubey, Abhishek; Tyagi, Gunjan; Waghmare, Mandavi; Pagare, Sandeep; Mahimkar, Manoj; Murali Krishna, C.

2017-11-01

Oral premalignant lesions (OPLs) such as leukoplakia, erythroplakia, and oral submucous fibrosis, often precede oral cancer. Screening and management of these premalignant conditions can improve prognosis. Raman spectroscopy has previously demonstrated potential in the diagnosis of oral premalignant conditions (in vivo), detected viral infection, and identified cancer in both oral and cervical exfoliated cells (ex vivo). The potential of Raman exfoliative cytology (REC) in identifying premalignant conditions was investigated. Oral exfoliated samples were collected from healthy volunteers (n=20), healthy volunteers with tobacco habits (n=20), and oral premalignant conditions (n=27, OPL) using Cytobrush. Spectra were acquired using Raman microprobe. Spectral acquisition parameters were: λex: 785 nm, laser power: 40 mW, acquisition time: 15 s, and average: 3. Postspectral acquisition, cell pellet was subjected to Pap staining. Multivariate analysis was carried out using principal component analysis and principal component-linear discriminant analysis using both spectra- and patient-wise approaches in three- and two-group models. OPLs could be identified with ˜77% (spectra-wise) and ˜70% (patient-wise) sensitivity in the three-group model while with 86% (spectra-wise) and 83% (patient-wise) in the two-group model. Use of histopathologically confirmed premalignant cases and better sampling devices may help in development of improved standard models and also enhance the sensitivity of the method. Future longitudinal studies can help validate potential of REC in screening and monitoring high-risk populations and prognosis prediction of premalignant lesions.

ABO blood groups and oral premalignancies: A clinical study in selected Indian population.

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Bhateja, S; Arora, G

2014-01-01

Background: The ABO blood group antigens are present on the surface of red blood cells and various epithelial cells. As the majority of human cancers are derived from epithelial cells, changes in blood group antigens constitute an important aspect of human cancers. The aim of the study was to establish clinical usefulness of ABO blood group as a predisposing factor in early diagnosis and management of patients with oral precancerous lesions/conditions. Materials and Methods: The study sample consisted of 50 control and 50 oral precancer (25 leukoplakia and 25 Oral Submucous Fibrosis) confirmed by histopathologic examination. All samples were subjected to blood group testing and their prevalence was compared by Z-test using STATA version 8. Results: The "A" blood group was prevalent among the precancerous group. Significant differences on prevalences of blood groups were found (P blood group. Conclusion: Blood group type should be considered along with other risk factors to understand the individual patient's risk and further studies in larger samples with inclusion of Rh factor is needed to elucidate the relationship with ABO blood group types.

Nutritional Aspects of Essential Trace Elements in Oral Health and Disease: An Extensive Review

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Preeti Tomar Bhattacharya

2016-01-01

Full Text Available Human body requires certain essential elements in small quantities and their absence or excess may result in severe malfunctioning of the body and even death in extreme cases because these essential trace elements directly influence the metabolic and physiologic processes of the organism. Rapid urbanization and economic development have resulted in drastic changes in diets with developing preference towards refined diet and nutritionally deprived junk food. Poor nutrition can lead to reduced immunity, augmented vulnerability to various oral and systemic diseases, impaired physical and mental growth, and reduced efficiency. Diet and nutrition affect oral health in a variety of ways with influence on craniofacial development and growth and maintenance of dental and oral soft tissues. Oral potentially malignant disorders (OPMD are treated with antioxidants containing essential trace elements like selenium but even increased dietary intake of trace elements like copper could lead to oral submucous fibrosis. The deficiency or excess of other trace elements like iodine, iron, zinc, and so forth has a profound effect on the body and such conditions are often diagnosed through their early oral manifestations. This review appraises the biological functions of significant trace elements and their role in preservation of oral health and progression of various oral diseases.

Modified hysteroscopic myomectomy of large submucous fibroids.

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Darwish, Atef

2003-01-01

To compare the efficacy, feasibility, operative time and possible complications of a modified technique of hysteroscopic removal of large submucus myomata versus traditional morcellation technique, and to assess the efficacy of preoperative sonohysterography (SHG). A prospective comparative study. Gynecologic Endoscopy Unit, Assiut University Hospital, Assiut, Egypt. One hundred forty-two women of childbearing age with a clinical and transvaginal sonographic diagnosis of large solitary submucous myomata (>3 cm in diameter) with or without an intramural element. The patients were divided into two groups. In group A (65 patients), a modified resectoscopic technique was used where the base of the myoma was excised followed by ring forceps extraction after misoprostol priming. In group B (77 patients), the myoma was cut using traditional resectoscopic morcellation. For each patient, operating time, intra- and postoperative complications and feasibility of the procedure were recorded. The accuracy of preoperative SHG in localizing submucous myoma and detecting intramural extension was assessed by diagnostic hysteroscopy. Transvaginal SHG showed good agreement with hysteroscopy in localizing submucous myomata and detecting intramural extension (k = 0.83). The operating time was significantly shorter in group A (15.6 +/- 3.02 min) than in group B (28.9 +/- 4.3 min). The procedure was completed in 60 (92%) and 51 patients (66%), whereas a second session was required in 2 (3%) and 20 patients (25.9%) in both groups respectively. Glycine volume was highly significantly less in group A (2.3 +/- 0.86 vs. 6.3+/- 1.7 liters, p = 0.001). Intraoperative complications were encountered in 9 (13.8%) and 22 patients (28.5%) in both groups respectively (p = 0.03). Cervical laceration was diagnosed in 3 cases (4.6%) in group A. Postoperative visual disturbances were diagnosed in 4 cases (5%) in group B. Hysteroscopic resection of large submucous myomata with minimal intramural

Paan without tobacco: an independent risk factor for oral cancer.

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Merchant, A; Husain, S S; Hosain, M; Fikree, F F; Pitiphat, W; Siddiqui, A R; Hayder, S J; Haider, S M; Ikram, M; Chuang, S K; Saeed, S A

2000-04-01

Oral cancer is the second most common cancer in women and the third most common in men in Pakistan. Tobacco is smoked and chewed extensively in Pakistan. Paan is a quid of piper betel leaf that contains areca nut, lime, condiment, sweeteners, and sometimes tobacco, which is also used extensively. We did this study to clarify the independent association of paan and oral cancer. Between July 1996 and March 1998, we recruited biopsy-proven, primary cases of oral squamous-cell carcinoma, from 3 tertiary teaching centers in Karachi, Pakistan, and controls pair-matched for age, gender, hospital and time of occurrence, excluding persons with a past or present history of any malignancy. There were 79 cases and 149 controls. Approximately 68% of the cases were men, 49 years old on average, the youngest being 22 years old and the eldest 80. People with oral submucous fibrosis were 19.1 times more likely to develop oral cancer than those without it, after adjusting for other risk factors. People using paan without tobacco were 9.9 times, those using paan with tobacco 8.4 times, more likely to develop oral cancer as compared with non-users, after adjustment for other covariates. This study identifies an independent effect of paan without tobacco in the causation of oral cancer. Its findings may be of significance in South Asian communities where paan is used, and among health-care providers who treat persons from South Asia.

Immunohistochemical Analysis of Vimentin in Oral Sub mucous Fibrosis

International Nuclear Information System (INIS)

Nayak, M. T.; Singh, A.; Desai, R. S.; Vanaki, S. S.

2013-01-01

Oral sub mucous fibrosis (OSF), a precancerous condition, is characterized by abnormal accumulation of collagen fibers in oral sub mucosa. Vimentin is a Class 2 intermediate filament (IF) and primarily expressed in cells of mesenchymal origin. Vimentin is also found to be involved in cell growth, cell cycling, and tumour differentiation. Objective. The purpose of the study was to compare the expression of vimentin in various histological grades of OSF. Materials and Methods. To assess the immunohistochemical expression of vimentin in 20 mild cases of OSF, 20 severe cases of OSF, and ten cases of normal oral buccal mucosa. Results. The overall staining intensity of vimentin significantly increased statistically (P<0.01) in OSF cases over normal control. A significant increase in the staining intensity of vimentin was also noted in the fibroblasts of severe cases of OSF (P=0.03). Conclusion. Considering the marked vimentin expression in the present study, future studies should include cytoskeleton IF and other filaments in the fibroblasts of OSF.

Total, direct, and indirect effects of paan on oral cancer.

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Merchant, Anwar T; Pitiphat, Waranuch

2015-03-01

Paan (betel leaf and betel nut quid) used with or without tobacco has been positively associated with oral cancer. Oral submucous fibrosis (OSMF), a precancerous condition caused by paan, lies on the causal pathway between paan use and oral cancer. The purpose of this analysis was to estimate the effect of paan consumption on oral cancer risk when it is mediated by OSMF. We used mediation methods proposed by VanderWeele, which are based on causal inference principles, to characterize the total, direct, and indirect effects of paan, consumed with and without tobacco, on oral cancer mediated by OSMF. We reanalyzed case-control data collected from three hospitals in Karachi, Pakistan, between July 1996 and March 1998. For paan without tobacco, the total effect on oral cancer was OR 7.39, 95 % CI 1.01, 38.11, the natural indirect effect (due to OSMF among paan users) was OR 2.48, 95 % CI 0.99, 10.44, and the natural direct effect (due to paan with OSMF absent) was OR 3.32, 95 % CI 0.68, 10.07. For paan with tobacco, the total direct effect was OR 15.68, 95 % CI 3.00, 54.90, the natural indirect effect was OR 2.18, 95 % CI 0.82, 5.52, and the natural direct effect was OR 7.27, 95 % CI 2.15, 20.43. Paan, whether or not it contained tobacco, raised oral cancer risk irrespective of OSMF. Oral cancer risk was higher among those who used paan with tobacco.

[Epidemiological investigation of chewing fresh or dried betel nut and oral mucosal disease].

Science.gov (United States)

Yongxiu, Du; Dongye, Sun; Xinchun, Jian; Qiuhua, Mao; Yanan, Cheng; Pu, Xu

2016-08-01

This study was conducted to investigate the effect of chewing fresh or dried betel nut on the inci-dence and canceration of oral mucosa disease in Haikou City in Hainan Province. Through a survey questionnaire, clinical examination, and regular follow-up, we collected clinical data from 1 722 cases and divided them into two groups, among which 704 of the afflicted people chew dried betel nut, whereas the other 1 018 chew fresh betel nut. The data were 
statistically analyzed using different variables which included age, number, time of onset of the disease, and the cancerous condition associated with common oral mucosa disease, including oral submucous fibrosis (OSF), oral leukoplakia (OLK), and oral Lichen planus (OLP). 1) The study found no significant difference in the prevalence of oral mucosa diseases between the dried betel nut group (n=704) and fresh betel nut group (n=1 018) among the 1 722 cases (P>0.05), but the peak age of oral mucosal disease was more advanced in the dried betel nut group (Pbetel nut group was significantly higher than that in the fresh betel nut group (Pbetel nut group was significantly higher than that in the fresh betel nut group (Pbetel nut is more pathogenic and carcinogenic than chewing fresh betel nut. The extremely harmful components of the dried betel nut synergistically play a vital role in the occurrence and carcinogenesis of oral mucosal diseases.

Oral Pirfenidone in patients with chronic fibrosis resulting from radiotherapy: a pilot study

International Nuclear Information System (INIS)

Simone, Nicole L; Soule, Benjamin P; Gerber, Lynn; Augustine, Elizabeth; Smith, Sharon; Altemus, Rosemary M; Mitchell, James B; Camphausen, Kevin A

2007-01-01

Fibrosis is a common side effect after treatment with ionizing radiation. Several methods to ameliorate debilitating fibrosis have been employed but without consistent results. The goal of this pilot study is to determine if Pirfenidone, a novel regulator of cytokine gene expression, has the potential to ameliorate established radiation-induced fibrosis. Open label, prospective pilot study of 800 mg three times/day, orally administered Pirfenidone was administered to enrolled patients who were had completed radiation therapy and who had established radiation-induced fibrosis. Range of motion (ROM) was assessed using standard measures, and subjective measures of pain, fatigue, disability and global health were measured every three months. Seven patients were enrolled of whom 3 had ROM assessments of 1 site and 2 had ROM assessments of 2 sites. Of these assessments, 6 revealed increased ROM during drug intervention while 1 revealed a decreased ROM. There was an overall improvement in the mental composite score of the SF36 while physical composite score was decreased and the vitality score was unchanged. Two patients were removed from the study because of syncopal episodes. Several patients experienced improved function of at least 25% and reported subjective improvement. Pirfenidone may benefit patients with radiation-induced fibrosis and is worthy of a larger well controlled trial

Changes in plasma steroids and cytokines levels in betel chewing patients in Taiwan.

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Hu, Sindy; Chen, Wen-Chyuan; Hwang, Guey-Shyang; Chen, Szu-Tah; Kuo, Song-Bor; Chen, Yifen; Idova, Galina; Wang, Shyi-Wu

2016-07-01

Betel nut is the second largest economic food product in Taiwan. In Southeast Asia, the habit of chewing betel nut seems to be highly correlated with oral submucous fibrosis and oral squamous cell carcinoma. Oral submucous fibrosis is characterized by abnormal accumulation of oral submucous collagen fibers and limitation of mouth opening. Although the mechanism responsible for tissue damage is still unknown, prolonged irritation caused by betel nut and tobacco is considered to be a major factor contributing to the pathogenesis of oral submucous fibrosis. The effect of betel nut chewing on immune system remains unknown. Present study aims to investigate the change of plasma hormones including cortisol, testosterone, and inflammatory cytokine concentrations in male chewing betel nut compared with normal subjects. Heparinized blood was obtained from control group (normal young+mid-aged individuals), betel nut-chewing, and oral cancer male subjects. The study was approved by the Ethics Committee of the Chang-Gung Memorial Hospital. Written informed consent was granted by the patients. Plasma cortisol and testosterone concentrations were detected by commercial enzyme-linked immunosorbent assay (ELISA). The inflammatory cytokines, including interleukin-1β (IL-1β), IL-15, tumor necrosis factor-α (TNF-α), were analyzed by ELISA with commercial monoclonal capture antibodies and polyclonal detection antibodies. The median concentrations of plasma IL-1β, IL-15, and TNF-α were 3.14pg/ml, 3.14pg/ml, and 6.85pg/ml, respectively, in patients with oral cancer, compared with median plasma IL-1β, IL-15, and TNF-α concentration of 2.64pg/ml, 5.86pg/ml, and 5.38pg/ml, respectively, in patients with betel nut-chewing habit. In contrast, the median concentrations of plasma IL-1β, IL-15, and TNF-α in mid-aged males (aged 30-50) were 7.00pg/ml, 10.64pg/ml, and 31.73pg/ml, respectively, compared with median plasma concentration of IL-1β, IL-15, and TNF-α of 4.48pg/ml, 33.36pg

A light microscopic study of fibrosis involving muscle in oral submucous fibrosis

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Rooban T

2005-01-01

Full Text Available Presence of two canals with type 11 pattern in mandibular canine is around 15%. Even though the incidence rate is high, multiple angled diagnostic radiographs are not regularly taken. This article highlights the importance of multiple-angled radiographs and indicates that the dentist should have a mind set to look out for extra canals in all root canal cases.

Office Hysteroscopic Laser Enucleation of Submucous Myomas without Mass Extraction: A Case Series Study

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Sergio Haimovich

2015-01-01

Full Text Available Background and Objectives. A new two-step hysteroscopic myomectomy carried out in the office setting and without anesthesia was feasible for the excision of submucous myomas. The objective of this study was to assess whether removal of submucous myomas from the uterine cavity after hysteroscopic laser enucleation is necessary. Methods. Between June 2009 and April 2013, all outpatients with symptomatic myomatosis (bleeding, pelvic pain, and infertility assessed ultrasonographically were eligible to participate in a prospective study. All patients underwent office hysteroscopic enucleation of submucous myomas. Enucleated myomas were left in the uterine cavity. Neither anesthesia nor antibiotic prophylaxis was used. Results. Sixty-one women (mean age: 47.3 years were included. Regardless of hysteroscopic localization and grading, all myomas were enucleated. The mean (standard deviation, SD diameter of the myoma as measured by the ultrasound scan was 22.6 (8.5 mm. In 29 cases (47.5%, the diameter of the resected myoma was >20 mm and in 10 cases (16.4% >30 mm. After a mean follow-up of 68.2 (16.5 days, none of the patients showed a residual myoma inside the uterine cavity. Conclusions. The present results indicate that leaving laser-enucleated submucous myoma in the uterine cavity is a feasible and safe therapeutic option.

Head and neck squamous cell carcinoma in chronic areca nut chewing Indian women: Case series and review of literature.

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Muttagi, Sidramesh Shivanand; Chaturvedi, Pankaj; Gaikwad, Rohith; Singh, Bikramjit; Pawar, Prashant

2012-01-01

Head and neck squamous cell carcinoma (HNSCC) is an important public health problem in India. Several risk factors such as tobacco, human papilloma virus, alcohol, areca nut usage have been extensively studied as causative agents. Though Areca nut chewing is known cause of oral cancer, its association with hypopharynx cancer has not been previously reported. Since areca nut is mostly consumed along with tobacco, it is uncommon to find patients who consume the areca nut alone. This is a prospective case series of ten women who presented to us with HNSCC with history of chewing of areca nut alone for several years. We have excluded all those cases where areca nut was consumed along with tobacco in any form. The data were prospectively collected with regard to clinical parameters, duration and frequency of areca nut usage, the socio-economic status and education level. All ten females had varying degree of submucous fibrosis and coexisting squamous cell carcinoma either in the oral cavity or hypopharynx. Submucous fibrosis was characterized by burning mouth, unhealthy oral mucosa, buried third molars, trismus, poor oral hygiene, etc. The disease presented in an advanced stage in majority of the cases. All patients were unaware of areca nut's deleterious effects. Areca nut chewing is an important risk factor for HNSCC in females. Despite plethora of information, little importance is given to areca nut control in cancer prevention campaigns in India.

Plasma enzymatic antioxidant levels in non smoke tobacco consuming Oral sub mucous fibrosis (OSMF

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Teklal Patel, Vikram Kulkarni

2013-04-01

Full Text Available Background: Globally Oral Cancer is the sixth most common cause death with India accounts for 86% of the world’s oral cancer cases. Chronic tobacco quid consumption often results in a progressive premalignant condition called Oral Sub mucous Fibrosis (OSMF whose malignant transformation rate of is around 7.6%. Free radicals released during the metabolism of tobacco and Areca nut my involved in the initiation and propagation of mucosal fibrosis. Objective: the objective of the present study is to measure antioxidant enzymes and lipid peroxidation levels in OSMF to assess oxidative stress like environment in OSMF patients. Materials and methods: for this study we invited 38 newly diagnosed OSMF patients both male and female consuming tobacco in the form of quid and the same number of age matched healthy non tobacco consuming were selected as a control group. In both groups plasma superoxide dismutase, Glutathione peroxidase, catalase levels and lipid peroxidation rate was measured. Results and conclusion: we observed very low antioxidant enzyme levels in OSMF patients when compared with healthy controls (P<0.01 and at the same time also observed very high lipid peroxidation rate in the study population (P<0.01 compare to control group indicating prevalence of oxidative stress like environment in tobacco consuming population, which might play a vital role in the initiation and propagation of various precancerous conditions like OSMF.

Prolapsed submucous uterine fibroid polyp associated with urinary ...

African Journals Online (AJOL)

A rare case of prolapsed submucous uterine fibroid polyp associated with intemittent acute urinary retention in a 34 year old Para 4+4 woman is described. She presented with one year history of increased menstrual blood loss and secondary dysmenorrhea and six months history of a mass protruding down the vagina, ...

Epithelial-mesenchymal transition: Understanding the basic concept

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Suresh Babu Ghanta

2012-01-01

Full Text Available The epithelial-mesenchymal transition (EMT is described as a rapid and reversible process of change of cell phenotype seen during embryonic development, organ fibrosis, and tumor progression. EMT was first described by Gary Greenberg and Elizabeth Hay in 1982. During EMT the epithelial cells alter their cell polarity, reorganize their cytoskeleton thus become isolated and motile. Depending upon the biological context in which they occur, EMT is divided into three types namely EMT type I, II, III. The article describes the process of EMT implicated in the oral cavity as in palate and root development (type I EMT, gingival fibromatosis and oral sub-mucous fibrosis (type II EMT, and oral squamous cell carcinoma (type III EMT. The reverse process of EMT is called as mesenchymal-epithelial transition seen in association with kidney formation.

Metabolic syndrome and health-related behaviours associated with pre-oral cancerous lesions among adults aged 20-80 years in Yunlin County, Taiwan: a cross-sectional study.

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Chang, Chang-Cheng; Lin, Ming-Shyan; Chen, Yu-Tsung; Tu, Liang-Tse; Jane, Su-Whi; Chen, Mei-Yen

2015-12-18

To explore the associations of health-related behaviours, metabolic syndrome and risk factors in adults with pre-oral cancerous (POC) lesions in rural, disadvantaged communities with a high prevalence of oral cancer. A cross-sectional observational study. Community-based health survey in the western coastal area of Yunlin County, Taiwan. 5161 adult residents participated in this study. Assessed parameters included oral leukoplakia, oral submucous fibrosis, fasting blood glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure and waist circumference. Statistical analyses included descriptive statistics, χ(2) tests and multivariate binary logistic regression. A high percentage of participants were found to have metabolic syndrome (40%) and POC lesions (7.3%). Participants with POC lesions tended to be male (psocioeconomic status are non-modifiable factors associated with POC and metabolic syndrome in adults, several factors, notably health behaviours, are modifiable. Clinicians can reduce the incidence and consequences of POC by developing programmes for early detection, encouraging regular dental check-ups, and initiating individualised, health-promoting behaviour modification programmes for reducing risky behaviours associated with oral cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Non-puerperal uterine inversion due to submucous myoma in a young woman: a case report

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Perquin Denise

2010-01-01

Full Text Available Abstract Introduction Inversion of the uterus is an uncommon complication of the puerperium and it is an even rarer complication of the non-puerperal period. A submucous myoma is mostly the cause of the non-puerperal inversion but diagnosis can be difficult. In young women, non-puerperal uterine inversion is likely associated with a malignancy. Case presentation A 19-year-old nulliparous woman presented with abnormal vaginal bleeding, dysmenorrhoea, and a large mass protruding from her cervix. The mass was interpreted as a prolapsed pedunculated submucosal myoma. After extirpation of the mass by clamping and twisting its pedicle, a laparotomy was required under suspicion of a uterine rupture. The diagnosis was confirmed and the patient's uterus could be preserved. Pathological examination revealed a submucous myoma. The uterine inversion happened when the uterus retracted to expel the submucous myoma with fundal attachment. By extirpating the stalk the fundus was also resected, causing a uterine rupture. Conclusion We report a case of non-puerperal uterine inversion associated with a benign submucous myoma. Non-puerperal uterine inversion is very uncommon in women of reproductive age and is usually caused by a malignant tumour. However, uterine-sparing surgery should be attempted in young women until the final pathology is known.

Tobacco Abuse and Associated Oral Lesions among Interstate Migrant Construction Workers.

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Ali, Anzil Ks; Mohammed, Arshad; Thomas, Archana A; Paul, Shann; Shahul, M; Kasim, K

2017-08-01

The present study was conducted to assess the prevalence of tobacco use and associated oral mucosal lesions among construction workers of Cochin, Kerala, India. A cross-sectional study was carried at various construction sites of Cochin and 2,163 workers were selected using multistage sampling method and were interviewed and examined. Information regarding demographic details, form, type, frequency of tobacco use, earlier attempt to quit, and willingness to quit tobacco use was obtained using predesigned questionnaire. The oral health status was recorded on the World Health Organization oral health assessment form 1997, and the examination was carried out under natural light using mouth mirrors and probe. Data thus collected were analyzed using Statistical Package for the Social Sciences version 17 (Chicago, Illinois, USA) statistical software package. Chi-square test was applied. Among the 2,163 workers, 1,952 were tobacco users and 211 were nonusers. Among the users, 1,021 use smokeless form, 372 use smoked form, and 559 use both. Premalignant lesions/conditions were more commonly seen with tobacco habit, with leukoplakia (14.75%) being the most common followed by oral submucous fibrosis in 201 (9.3%), candidiasis in 123 (5.7%), ulceration in 131 (6.05%), abscess in 59 (2.73%), smokers palate in 58 (2.68%), lichen planus in 21 (0.97%), and malignant tumor in 2 (0.1%). Commonness of abusive habits and oral premalig-nant lesions or conditions was considerable among the workers. Control and early diagnosis through workplace screening are the major backbones for the control of oral cancer. Building workers are unprotected from various health hazards at workplace. Lack of access to health services makes the situation unsatisfactory. Poor literacy and low socioeconomic status have resulted in practice of tobacco, smoking, and chewing in the majority of them. Hence, it is our responsibility to find and guide them with a proper oral health education.

Prevalence of oral soft tissue lesions and medical assessment of geriatric outpatients in North India

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Sameer Rastogi

2015-01-01

Full Text Available Introduction: Oral health reflects overall well-being for the elderly population. Compromised oral health may be a risk factor for systemic diseases commonly occurring in old age. Oral health evaluation should be an integral part of the physical examination, and dentistry is essential to qualify geriatric patient care. Aim: To determine the prevalence of oral soft tissue lesions and systemic diseases in institutionalized geriatric population in North India. Materials and Methods: Geriatric patients were clinically evaluated using a standard questionnaire and assessed for known medical illnesses and prevalence of oral soft tissue lesions. Four hundred patients (71% males and 29% females with age ranging from 60 to 100 years were considered in the study group. Twenty-two (33.8% patients were edentulous and seven patients (10.8% were denture wearers. Forty-four (67.69% patients reported with tobacco habits. Results: Most prevalent medical illness reported was diminished vision (15.5%, followed by hypertension (10% and diabetes mellitus (6.25%. Several oral soft tissue lesions were reported among the study population. The most prevalent lesions were leukoplakia (12%, smoker′s melanosis (10%, smoker′s palate (9%, pigmentation on tongue (6%, frictional keratosis (5%, lichen planus (3%, denture stomatitis (2.5%, aphthous ulcers (2%, angular chelitis (1.5%, oral submucous fibrosis (1.5%, melanotic macule (1.5%, candidiasis (1.5%, irritation fibroma (1%, geographic tongue (1%, median rhomboid glossitis (1%, and traumatic ulcer (1%. Conclusion: The findings observed in this population are important and can have a determinant effect on the overall quality of life in this population. This information is a crucial prerequisite for health awareness programs involving the community health workers, oral physicians, and medical professionals.

Clinical Effectiveness of Aloe Vera in the Management of Oral Mucosal Diseases- A Systematic Review

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Nair, Gopakumar Ramachandran; Naidu, Giridhar Seetharam; Jain, Supreet; Makkad, Ramanpal Singh; Jha, Abhishek

2016-01-01

Introduction Aloe vera is well known for its medicinal properties which lead to its application in treating various diseases. Its use in treating oral lesions has not been much documented in literature. Aim Although, systematic reviews on aloe vera and its extracts have been done earlier, but in relation to oral diseases this is the first systematic review. The aim of the present systematic review was to compile evidence based studies on the effectiveness of Aloe vera in treatment of various oral diseases. Materials and Methods Computerized literature searches were performed to identify all published articles in the subject. The following databases were used: PUBMED [MEDLINE], SCOPUS, COCHRANE DATABASE, EMBASE and SCIENCE DIRECT using specific keywords. The search was limited to articles published in English or with an English Abstract. All articles (or abstracts if available as abstracts) were read in full. Data were extracted in a predefined fashion. Assessment was done using Jadad score. Results Fifteen studies satisfied the inclusion criteria. Population of sample study ranged from 20 patients to 110 patients with clinically diagnosed oral mucosal lesions. Out of 15 studies, five were on patients with oral lichen planus, two on patients with oral submucous fibrosis, other studies were carried on patients with burning mouth syndrome, radiation induced mucositis, candida associated denture stomatitis, xerostomic patients and four were on minor recurrent apthous stomatitis. Most studies showed statistically significant result demonstrating the effectiveness of Aloe vera in treatment of oral diseases. Conclusion Although there are promising results but in future, more controlled clinical trials are required to prove the effectiveness of Aloe vera for management of oral diseases. PMID:27656587

[Velopharyngeal closure pattern and speech performance among submucous cleft palate patients].

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Heng, Yin; Chunli, Guo; Bing, Shi; Yang, Li; Jingtao, Li

2017-06-01

To characterize the velopharyngeal closure patterns and speech performance among submucous cleft palate patients. Patients with submucous cleft palate visiting the Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University between 2008 and 2016 were reviewed. Outcomes of subjective speech evaluation including velopharyngeal function, consonant articulation, and objective nasopharyngeal endoscopy including the mobility of soft palate, pharyngeal walls were retrospectively analyzed. A total of 353 cases were retrieved in this study, among which 138 (39.09%) demonstrated velopharyngeal competence, 176 (49.86%) velopharyngeal incompetence, and 39 (11.05%) marginal velopharyngeal incompetence. A total of 268 cases were subjected to nasopharyngeal endoscopy examination, where 167 (62.31%) demonstrated circular closure pattern, 89 (33.21%) coronal pattern, and 12 (4.48%) sagittal pattern. Passavant's ridge existed in 45.51% (76/167) patients with circular closure and 13.48% (12/89) patients with coronal closure. Among the 353 patients included in this study, 137 (38.81%) presented normal articulation, 124 (35.13%) consonant elimination, 51 (14.45%) compensatory articulation, 36 (10.20%) consonant weakening, 25 (7.08%) consonant replacement, and 36 (10.20%) multiple articulation errors. Circular closure was the most prevalent velopharyngeal closure pattern among patients with submucous cleft palate, and high-pressure consonant deletion was the most common articulation abnormality. Articulation error occurred more frequently among patients with a low velopharyngeal closure rate.

LITERATURE REVIEW ON STEM CELL TREATMENT & ORAL SUBMUCOUS FIBROSIS (OSMF)

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Prathipaty James; Kameswararao

2015-01-01

Stem cell therapy is a part of regenerative medicine that involves the use of undifferentiated cells in order to cure the disease. Stem cell - based therapies are being investigated for the treatment of many conditions, including neurodegenerative conditions such as Parkinson's disease, cardiovascular disease, liver disease, diabetes, autoimmune diseases and for nerve regeneration. (1) In orofacial region these therapies are being used for tooth and periodonta...

Immunohistochemical expression of ezrin in oral potentially malignant disorders-A descriptive study

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Raghini Mohanraj

2017-01-01

Full Text Available Introduction: Ezrin, also known as cytovillin, is a member of the ERM family of protein. Ezrin cross-links actin filament with the plasma membrane. They are involved in the formation of microvilli, cell–cell adhesion, maintenance of cell shape, cell motility, and membrane trafficking. Recent analysis reveals their involvement in signaling pathways. Ezrin is highly expressed in several types of human cancers, and correlation between its immunoreactivity and histopathological data as well as the patient outcome has previously been studied. Objective: The objective of the study was to analyze the immunohistochemical expression pattern of ezrin in oral potentially malignant disorders (OPMDs, namely, oral submucous fibrosis (OSMF with different grades and clinically leucoplakia (hyperkeratosis with various degree of dysplasia and its use as a predictive marker for malignant transformation. Subjects and Methods: Sample size n = 43, histopathologically confirmed cases of OPMDs (13 cases of OSMF with different grades and 30 cases of clinically leukoplakia were retrieved from the Department of Oral and Maxillofacial Pathology. Immunohistochemistry was done using anti-ezrin antibody, and the expression was graded in terms of proportion and intensity. Results: There was a significant expression of ezrin in OPMDs, and its cytoplasmic shift can be used as a predictive marker for malignant transformation. Conclusion: The findings of the current study revealed that the expression of ezrin in OPMDs may be related to the progression of the disease.

Malignant transformation of Taiwanese patients with oral leukoplakia: A nationwide population-based retrospective cohort study.

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Wang, Tung-Yuan; Chiu, Yu-Wei; Chen, Yi-Tzu; Wang, Yu-Hsun; Yu, Hui-Chieh; Yu, Chuan-Hang; Chang, Yu-Chao

2018-05-01

Oral leukoplakia (OL) is one of the clinically diagnosed oral potentially malignant disorders (OPMDs) with an increased risk of oral cancer development. In this study, we investigated the malignant transformation of OL in Taiwanese population. A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort was randomly frequency-matched with the OL cohort according to age, sex, and index year. Oral submucous fibrosis (OSF) and oral lichen planus (OLP) were further stratified to evaluate the possible synergistic effects for OL-associated malignant transformation. In this cohort, 102 (5.374%) of 1898 OL patients were observed to transform into oral cancer. The malignant transformation rate was 26.40-fold in the OL cohort than in the comparison cohort after adjustment (95% confidence intervals 18.46-37.77). To further stratify with OSF and OLP, OL with OSF (58.38; 95% confidence intervals 34.61-98.50) and OL with OLP (36.88; 95% confidence intervals 8.90-152.78) had higher risk of malignant transformation rate than OL alone (27.01; 95% confidence intervals 18.91-38.59). The Kaplan-Meier plot revealed the free of malignant transformation rate was significant over the 13 years follow-up period (log-rank test, p < 0.001). OL patients exhibited a significantly higher risk of malignant transformation than those without OL. In addition, both OSF and OLP could enhance malignant transformation in patients with OL. However, further studies are required to identify the histopathological and clinical parameters in the pathogenesis of malignant transformation among OPMDs. Copyright © 2018. Published by Elsevier B.V.

Prevalence of oral mucosal lesions in dental patients with tobacco smoking, chewing, and mixed habits: A cross-sectional study in South India

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Prashant B Patil

2013-01-01

Full Text Available Background: A variety of oral mucosal lesions and conditions are associated with the habit of smoking and chewing tobacco, and many of these carry a potential risk for the development of cancer. There have been no studies that report the prevalence of habits and associated oral changes in the population in Dharwad region, of Karnataka, south India. Materials and Methods: A hospital-based, cross-sectional study was carried out at SDM Dental College (Dharwad, Karnataka. A total of 2400 subjects (1200 subjects with and 1200 subjects without habits attending the dental hospital were interviewed and examined by trained professionals to assess any oral mucosal changes. Results: Oral mucosal lesions were found in 322 (26.8% subjects who had tobacco smoking and chewing habits as compared to 34 (2.8% subjects without those habits. Oral leukoplakia (8.2% and oral submucous fibrosis (OSF (7.1% were the prevalent oral mucosal lesions found in subjects who had those habits, while the other lesions (1.7% namely; oral candidiasis, median rhomboid glossitis, recurrent apthous ulcer, frictional keratosis, and oral lichen planus (0.9% were frequently reported among individuals without those habits. The odds of developing oral lesions in subjects with tobacco habits was nearly 11.92 times that of abstainers (odds ratio, OR = 11.92, 95% confidence intervals, CI = 10.61-14.59%. Conclusion: The study showed that the risk of the development of oral lesions associated with tobacco smoking, chewing, or both is quite high. Males who had one or more of these habits showed more frequent oral changes than females. The study reinforces the association of OSF with gutkha and areca nut chewing, and leukoplakia, erythroplakia, and oral cancer with tobacco smoking, chewing, or mixed habits.

White lesions in the oral cavity: A clinicopathological study from a tertiary care dermatology centre in Kerala, India

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S M Simi

2013-01-01

Full Text Available Context: White lesions in the oral cavity may be benign, pre-malignant or malignant. There are no signs and symptoms which can reliably predict whether a leukoplakia will undergo malignant change or not. Many systemic conditions appear initially in the oral cavity and prompt diagnosis and management can help in minimizing disease progression and organ destruction. Aim : The aim of the paper was to study the clinical and histopathological patterns of white lesions in the oral cavity presented at the study setting and to study the factors associated with the histopathological patterns of the lesions. Settings and Design: A hospital based cross-sectional study of patients with white lesions in the oral cavity attending the Department of Dermatology and Venereology, Medical College, Thiruvananthapuram was done. Materials and Methods: After taking a detailed history, microscopic examination of Potassium hydroxide smear and an oral biopsy with histopathologial examination was done. Results : Out of the 50 patients in the study, clinically the diagnoses made were Lichen planus (32 patients; 64%, Frictional Keratosis (4;8%, Dysplasia (2;4%, Oral Hairy Leukoplakia (1;2%, Pemphigus Vulgaris (2;4%, Cutaneous Lupus Erythematosus (1;2%, Oral Submucous fibrosis (3;6% and Oral Candidiasis alone (5;10%. Out of the 45 patients who had undergone biopsy, 25 (55.6% had Lichen planus, 9 (20% had Frictional Keratosis and mild Dysplasia was found in 4 (8.9% patients. Conclusion : The measure of agreement between the clinical and pathological diagnosis was only 32%. Older age, difficulty in opening the mouth, consumption of non-smoked tobacco, site of the lesion (gingival, floor of mouth or lingual vestibule and presence of tenderness on the lesion were significantly associated with Dysplasia.

Statistical analysis of textural features for improved classification of oral histopathological images.

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Muthu Rama Krishnan, M; Shah, Pratik; Chakraborty, Chandan; Ray, Ajoy K

2012-04-01

The objective of this paper is to provide an improved technique, which can assist oncopathologists in correct screening of oral precancerous conditions specially oral submucous fibrosis (OSF) with significant accuracy on the basis of collagen fibres in the sub-epithelial connective tissue. The proposed scheme is composed of collagen fibres segmentation, its textural feature extraction and selection, screening perfomance enhancement under Gaussian transformation and finally classification. In this study, collagen fibres are segmented on R,G,B color channels using back-probagation neural network from 60 normal and 59 OSF histological images followed by histogram specification for reducing the stain intensity variation. Henceforth, textural features of collgen area are extracted using fractal approaches viz., differential box counting and brownian motion curve . Feature selection is done using Kullback-Leibler (KL) divergence criterion and the screening performance is evaluated based on various statistical tests to conform Gaussian nature. Here, the screening performance is enhanced under Gaussian transformation of the non-Gaussian features using hybrid distribution. Moreover, the routine screening is designed based on two statistical classifiers viz., Bayesian classification and support vector machines (SVM) to classify normal and OSF. It is observed that SVM with linear kernel function provides better classification accuracy (91.64%) as compared to Bayesian classifier. The addition of fractal features of collagen under Gaussian transformation improves Bayesian classifier's performance from 80.69% to 90.75%. Results are here studied and discussed.

Treatment of velopharyngeal inadequacy in a patient with submucous cleft palate and myasthenia gravis.

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Rikihisa, Naoaki; Udagawa, Akikazu; Yoshimoto, Shinya; Ichinose, Masaharu; Kimura, Tomoe; Shimizu, Sara

2009-09-01

To describe the clinical course and management of a patient with submucous cleft palate who developed myasthenia gravis (MG) as an adult and suffered recurrent hypernasality. Few reports have described MG patients undergoing pharyngeal flap surgery for velopharyngeal incompetence, and these have described only slight speech improvement in such patients. Case report. The patient underwent primary pushback palatoplasty and superiorly based pharyngeal flap surgery for submucous cleft and short palate at age 7. Hypernasality showed major improvement after initial surgery. At age 19, the patient developed MG that triggered the recurrence of velopharyngeal incompetence. After MG was treated, revision pushback palatoplasty was performed for velopharyngeal incompetence when the patient was 24 years old. Preoperatively and postoperatively, the patient was evaluated by the same speech-language-hearing therapists, each with at least 5 years of clinical experience in cleft palate speech. After the second pushback palatoplasty, hypernasality and audible nasal air emission during speech decreased to mild. Primary pushback palatoplasty and pharyngeal flap surgery were performed for the submucous cleft palate. Revision pushback palatoplasty improved velopharyngeal inadequacy induced by MG. Decreased perceived nasality positively influenced the patient's quality of life. Combined pushback palatoplasty and pharyngeal flap surgery is thus an option in surgical treatment for velopharyngeal inadequacy to close the cleft and the velopharyngeal orifice in cases of cleft palate and MG.

Routine use of daily oral vitamin K to treat infants with cystic fibrosis.

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Cottam, Sophie T; Connett, Gary J

2015-10-01

Vitamin K is routinely administered after birth in the UK to prevent haemorrhagic disease of the newborn. Despite this, vitamin K-deficient coagulopathy still occurs in infants with high morbidity and mortality. Up to 50% of late onset bleeding presents with intracranial haemorrhage. The risk of developing vitamin K coagulopathy is higher in infants with cystic fibrosis (CF) and those that are exclusively breast fed due to low vitamin K levels in breast milk and intestinal changes in bacterial flora. Oral vitamin K supplementation is a simple addition to routine CF treatment during infancy to prevent complications from significant coagulopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Frequency of fungal infection in biopsies of oral mucosal lesions: A prospective hospital-based study

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Thimmarasa Venkappa Bhovi

2015-01-01

Full Text Available Aims and Objectives: To determine the frequency and common site of fungal infection in biopsies of oral mucosal lesions and also to detect the lesions most likely to be infected with fungal infection. Materials and Methods: A total of 100 patients with oral mucosal lesions were advised routine hematological examination followed by incisional biopsy under local anesthesia. The specimen were fixed in 10% neutral buffered formalin and processed. One section from the specimen was stained with hematoxylin and eosin staining for histopathological diagnosis of the lesion and a second section was stained with Periodic acid-Schiff (PAS stain for detection of fungal infection. Results: Out of the 100 patients, the most common mucosal lesion encountered was carcinoma (56% followed by lesions with dysplastic changes (28%, benign lesions (9%, squamous papilloma (2% and oral submucous fibrosis (5%. The most common anatomic location affected by the mucosal lesions were buccal mucosa, followed by the tongue, gingiva, maxillary tuberosity and floor of the mouth with values of 73%, 16%, 6%, 4% and 1%, respectively. Squamous papilloma had the highest positive association with fungal infection (100% followed by lesions with dysplastic changes (17.9% and carcinoma (8.9%. The maximum fungal positive association was encountered in the mucosal lesions over the tongue (18.7% followed by the buccal mucosa (12.3%. Conclusion: There is statistically significant association of fungal infection with dysplastic lesions and papilloma with the tongue and buccal mucosa as the most common sites. Hence a PAS stain should be performed whenever epithelial dysplasia on the tongue and buccal mucosa is diagnosed.

Automated oral cancer identification using histopathological images: a hybrid feature extraction paradigm.

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Krishnan, M Muthu Rama; Venkatraghavan, Vikram; Acharya, U Rajendra; Pal, Mousumi; Paul, Ranjan Rashmi; Min, Lim Choo; Ray, Ajoy Kumar; Chatterjee, Jyotirmoy; Chakraborty, Chandan

2012-02-01

Oral cancer (OC) is the sixth most common cancer in the world. In India it is the most common malignant neoplasm. Histopathological images have widely been used in the differential diagnosis of normal, oral precancerous (oral sub-mucous fibrosis (OSF)) and cancer lesions. However, this technique is limited by subjective interpretations and less accurate diagnosis. The objective of this work is to improve the classification accuracy based on textural features in the development of a computer assisted screening of OSF. The approach introduced here is to grade the histopathological tissue sections into normal, OSF without Dysplasia (OSFWD) and OSF with Dysplasia (OSFD), which would help the oral onco-pathologists to screen the subjects rapidly. The biopsy sections are stained with H&E. The optical density of the pixels in the light microscopic images is recorded and represented as matrix quantized as integers from 0 to 255 for each fundamental color (Red, Green, Blue), resulting in a M×N×3 matrix of integers. Depending on either normal or OSF condition, the image has various granular structures which are self similar patterns at different scales termed "texture". We have extracted these textural changes using Higher Order Spectra (HOS), Local Binary Pattern (LBP), and Laws Texture Energy (LTE) from the histopathological images (normal, OSFWD and OSFD). These feature vectors were fed to five different classifiers: Decision Tree (DT), Sugeno Fuzzy, Gaussian Mixture Model (GMM), K-Nearest Neighbor (K-NN), Radial Basis Probabilistic Neural Network (RBPNN) to select the best classifier. Our results show that combination of texture and HOS features coupled with Fuzzy classifier resulted in 95.7% accuracy, sensitivity and specificity of 94.5% and 98.8% respectively. Finally, we have proposed a novel integrated index called Oral Malignancy Index (OMI) using the HOS, LBP, LTE features, to diagnose benign or malignant tissues using just one number. We hope that this OMI can

Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25-27, 1996.

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Zain, R B; Ikeda, N; Gupta, P C; Warnakulasuriya, S; van Wyk, C W; Shrestha, P; Axéll, T

1999-01-01

A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.

Development of Orally Bioavailable Therapeutics by the Chloroplast Expression System to Counter Muscle Degeneration, Weakness, and Fibrosis in DMD

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2016-11-01

strength in the diaphragm muscles . However, by 2 months of treatment the benefits were reduced back to untreated controls. We are continuing to analyze...Enzyme 2 Angiotensin-(1-7) Fibrosis Duchenne Muscular Dystrophy Mdx Skeletal muscle Chloroplast expression Oral bioavailability 3... treatment regimen to determine if any acute functional benefit was achieved. While no significant improvement was observed in EDL muscles , the diaphragms

Ultrasonic Diagnosis of Masseteric Hypertrophy in Oral Submucous Fibrosis: A Preliminary Study

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K A Kamala

2010-01-01

Results: Study group showed higher thickness both on right and left side masseter muscle and also in relaxed and contracted state when compared to controls. The thickness of masseter muscle is more in contracted state than relaxed state which was highly significant.

Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

2015-05-26

Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma.

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Nayak, Seema; Goel, Madhu Mati; Makker, Annu; Bhatia, Vikram; Chandra, Saumya; Kumar, Sandeep; Agarwal, S P

2015-01-01

There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP.

Nigella sativa oil attenuates chronic nephrotoxicity induced by oral sodium nitrite: Effects on tissue fibrosis and apoptosis.

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Al-Gayyar, Mohammed M H; Hassan, Hanan M; Alyoussef, Abdullah; Abbas, Ahmed; Darweish, Mohamed M; El-Hawwary, Amany A

2016-03-01

Sodium nitrite, a food preservative, has been reported to increase oxidative stress indicators such as lipid peroxidation, which can affect different organs including the kidney. Here, we investigated the toxic effects of oral sodium nitrite on kidney function in rats and evaluated potential protective effects of Nigella sativa oil (NSO). Seventy adult male Sprague-Dawley rats received 80 mg/kg sodium nitrite orally in the presence or absence of NSO (2.5, 5, and 10 ml/kg) for 12 weeks. Morphological changes were assessed by hematoxylin and eosin, Mallory trichome, and periodic acid-Schiff staining. Renal tissues were used for measurements of oxidative stress markers, C-reactive protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3. NSO significantly reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as increasing normal appearance of renal tissue. NSO also prevented reductions in glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted in dose-dependent significant reductions in fibrosis markers after sodium nitrite-induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally, NSO partially reduced the elevated caspase-3 and pJNK/JNK. NSO ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative stress, attenuation of fibrosis/inflammation, restoration of glycogen level, amelioration of cytochrome C oxidase, and inhibition of apoptosis.

Intestinal permeability to [51Cr]EDTA in children with cystic fibrosis

International Nuclear Information System (INIS)

Leclercq-Foucart, J.; Forget, P.; Sodoyez-Goffaux, F.; Zappitelli, A.

1986-01-01

Intestinal permeability was investigated in 14 children with cystic fibrosis making use of [ 51 Cr]EDTA as probe molecule. Ten normal young adults and 11 children served as controls. After oral administration of [ 51 Cr]EDTA, 24 h urine was collected. Urinary radioactivity was calculated and results expressed as percentage of oral dose excreted in 24 h urine. Mean and SEM were as follows: 2.51 +/- 0.21, 2.35 +/- 0.24, and 13.19 +/- 1.72 for control children, normal adults, and cystic fibrosis patients, respectively. The permeability differences between cystic fibrosis patients and either control children or control adults are significant (p less than 0.001)

Oral administration of Saccharomyces boulardii ameliorates carbon tetrachloride-induced liver fibrosis in rats via reducing intestinal permeability and modulating gut microbial composition.

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Li, Ming; Zhu, Lin; Xie, Ao; Yuan, Jieli

2015-02-01

To investigate the effects of orally administrated Saccharomyces boulardii (S. boulardii) on the progress of carbon tetrachloride (CCl4)-induced liver fibrosis, 34 male Wistar rats were randomly divided into four experimental groups including the control group (n = 8), the cirrhotic group (n = 10), the preventive group (n = 8), and the treatment group (n = 8). Results showed that the liver expression levels of collagen, type I, alpha 1 (Col1A1), alpha smooth muscle actin (αSMA), transforming growth factor beta (TGF-β) and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) increased significantly in cirrhotic rats compared with control and decreased by S. boulardii administration. Treatment of S. boulardii also attenuated the increased endotoxin levels and pro-inflammatory cytokines in CCl4-treated rats. And, these were associated with the changes of intestinal permeability and fecal microbial composition. Our study suggested that oral administration of S. boulardii can promote the liver function of CCl4-treated rats, and the preventive treatment of this probiotic yeast may decelerate the progress of liver fibrosis.

Aloe vera is non-toxic to cells: A microculture tetrazolium technique colorimetric assay study

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Devi Gopakumar

2014-01-01

Full Text Available Introduction: Aloe vera (Av, a succulent of Liliaceae family is now a widely used medicinal plant. Its′ application covers a wide spectrum of human diseases, including oral mucosa, gastric mucosa and skin. Aloe vera preparations in the form of gel, mouth washes and cream are applied topically for many oral diseases. The applications include oral lichen planus, candidiasis, oral submucous fibrosis, geographic tongue, etc. Aims and Objectives: To evaluate the cytotoxicity of Av on human fibroblasts. Materials and Methods: Aloe vera preparation (70% was applied on the fibroblast cell lineage and the cell viability was evaluated by microculture tetrazolium technique (MTT colorimetric assay. Results: The cell viability at different concentrations was measured. The cells have maintained their viability at different concentrations used in the study. Conclusion: Our study shows the cell viability at different sample concentrations of Av. This could open up wide clinical applications of Av for reactive, inflammatory and potentially malignant oral and other mucocutaneous diseases.

Evaluation of stromal myofibroblasts in oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma - an immunohistochemical study

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Kanupriya Gupta

2015-01-01

Conclusion: These findings are suggestive of role of MFs with the creation of a permissive environment for tumor invasion in OSCC. Hence the presence of MF is a prognostic marker and evaluation of the frequency in the stroma can be used as therapeutic targets.

Exhaled nitric oxide in paediatric asthma and cystic fibrosis.

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Lundberg, J O; Nordvall, S L; Weitzberg, E; Kollberg, H; Alving, K

1996-01-01

Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases. PMID:8984919

Reduced responses of submucous neurons from irritable bowel syndrome patients to a cocktail containing histamine, serotonin, TNFα and tryptase (IBS-cocktail

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Daniela eOstertag

2015-12-01

Full Text Available Background & Aims:Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS. Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC.Methods:Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase and TNF-α (IBS-cocktail was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Results:Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P=0.097 or P=0.448. However, the neuronal response after application of the IBS-cocktail was significantly decreased (P=0.039 independent of whether diarrhea (n=12, constipation (n=5 or bloating (n=5 was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P=0.019 when compared to incubation with HC supernatant.Conclusion:We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis.

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Sroussi, Herve Y; Epstein, Joel B; Bensadoun, Rene-Jean; Saunders, Deborah P; Lalla, Rajesh V; Migliorati, Cesar A; Heaivilin, Natalie; Zumsteg, Zachary S

2017-12-01

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

DEFF Research Database (Denmark)

Johansen, H.K.; Gøtzsche, Peter C.; Johansen, Helle Krogh

2008-01-01

BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. OBJECTIVES......: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search May 2008) and PubMed using the terms vaccin* AND cystic...... fibrosis (last search May 2008). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently selected trials...

Role of dermatoglyphics as an indicator of precancerous and cancerous lesions of the oral cavity

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Ambika Gupta

2013-01-01

Full Text Available Background: Oral squamous cell carcinoma (SCC is one name that causes panic and holds an undeserved high ranking as a killer. Another important condition which has become a major public health issue in South East Asia is oral submucous fibrosis (OSF. Not all the people using tobacco suffer from these diseases. Genetic predisposition might explain such an individual variability that can be predicted by using various cytogenetic markers. However, these studies are far more costly and complicated. So, dermatoglyphics may be of immense clinical significance to segregate those individuals who are at an increased risk for developing these diseases. Aim: The present study was conducted to analyze the palmar dermatoglyphics in SCC and OSF and find a "dermatoglyphic marker", if any. Study Design: Cross sectional study. Materials and Methods: 120 individuals were divided into four groups based upon their habits of tobacco/areca nut usage and presence of OSF/SCC. Dermatoglyphic patterns were recorded using standard ink method. Various patterns were analysed statistically in the four groups. Results and Conclusion: In SCC, there was an increase in frequency of arch and ulnar loop patterns on fingertips, decrease in frequency of simple whorl patterns on fingertips, decrease in frequency of palmar accessory triradii on right and left hands. Significant findings in OSF included an increase in frequency of arch and ulnar loop pattern, decrease in frequency of simple whorl patterns on fingertips, decrease in atd angle on right hand, decrease in frequency of palmar accessory triradii on right hand. The results revealed that the field of dermatoglyphics holds promising results for determining the genetic susceptibility of individuals to develop SCC and OSF.

Bony defect of palate and vomer in submucous cleft palate patients.

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Ren, S; Ma, L; Zhou, X; Sun, Z

2015-01-01

The aim of this study was to visualize bony defects of the palate and vomer in submucous cleft palate patients (SMCP) by three-dimensional (3D) computed tomography (CT) reconstruction and to classify the range of bony defects. Forty-eight consecutive non-operated SMCP patients were included. Diagnosis was based on the presence of at least one of three classical signs of SMCP: bifid uvula, a translucent zone in the midline of the soft palate, and a palpable 'V' notch on the posterior border of the bony palate. Patients were imaged using spiral CT. 3D reconstruction models were created of the palate and vomer. The sagittal extent of the bony cleft in SMCP was classified into four types: type I, no V-shaped hard palate cleft (8.3%); type II, cleft involving the partial palate (43.8%); type III, cleft involving the complete palate and extending to the incisive foramen (43.8%); type IV, cleft involving the complete palate and the alveolar bone (4.2%). The extent of the vomer defect was classified into three types: type A, vomer completely fused with the palate (8.3%); type B, vomer partially fused with the palate (43.8%); type C, vomer not fused with the palate up to the incisive foramen (47.9%). Significant variability in hard palate defects in SMCP is the rule rather than the exception. The association of velopharyngeal insufficiency with anatomical malformations may be complex. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Betel: consumption and consequences.

Science.gov (United States)

Norton, S A

1998-01-01

Betel is a compound of natural substances chewed for its psychostimulating effects. Betel is composed of the nut of the areca palm (Areca catechu), the leaf of the betel pepper (Piper betle), and lime (calcium hydroxide). Approximately 200 million persons chew betel regularly throughout the western Pacific basin and south Asia. Only three drugs (nicotine, ethanol, and caffeine) are consumed more widely than betel. When betel is chewed, it produces mild psychoactive and cholinergic effects. There is copious production of a blood-red saliva that can stain oral structures. After years of chewing, the teeth may become red-brown to nearly black. Betel use is associated with oral leukoplakia, submucous fibrosis, and squamous cell carcinoma. Use of betel is discouraged in Western countries because of its alleged carcinogenic and perceived dysesthetic properties; nevertheless, betel is widely available in the West.

Developing a Betel Quid Cessation Program on the Island of Guam.

Science.gov (United States)

Moss, John; Kawamoto, Crissy; Pokhrel, Pallav; Paulino, Yvette; Herzog, Thaddeus

2015-01-01

Betel quid is a psychoactive drug preparation typically made up of a combination of areca quid, slaked lime, piper betel leaf and tobacco. It is the fourth most commonly consumed drug in the world with global use concentrated in the Asia-Pacific region (Boucher and Mannan, 2002; Warnakulasuriya and Peters, 2002). The International Agency for Research on Cancer has classified betel quid as a Group 1 carcinogen (IARC, 2004; Lin et al., 2006), and its use has been associated with oral and oropharyngeal cancer, oral lesions, oral leukoplakia, submucous fibrosis, gum disease, and cancer of the pharynx and esophagus (IARC, 2004; Oakley et al., 2005; Shah et al., 2002; Warnakulasuriya, 2002). This paper reports on the feasibility of an innovative betel quid cessation program carried on the U.S. territory of Guam, and is the first of its kind. The program is described, along with the challenges encountered during the implementation process.

Useful technique for submucous myomectomy under direct transcervical resectoscope observation

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Tatsuji Hoshino

2017-08-01

Full Text Available The transcervical resectoscope (TCR is used for resecting a submucous myoma (SMM. Safe grasping of an SMM with forceps and its complete resection under transabdominal ultrasound (TAUS guidance is not always easy. SMMs are slippery, making them difficult to grasp. The SMM moves right to left and anterior to posterior when the surgeon tries to grasp it with placental forceps. Surgeons could use small Martin forceps (65% smaller to grasp SMMs safely and tightly under direct TCR (transcervical resectoscope observation. We present a case in which this operative procedure was used to remove an SMM with Figure and Video. The benefits of this procedure are enormous and could be immeasurably important to hysteroscopists and gynecologists.

A Case of Placenta Increta Mimicking Submucous Leiomyoma

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Ali Ekiz

2014-01-01

Full Text Available In recent years with the increase in cesarean section rates, the frequency of placenta accreta cases rises. It causes 33–50% of all emergency peripartum hysterectomies. We present a 42-year-old case who was caught with early postpartum hemorrhage due to retained placental products. The ultrasonography showed a 65 × 84 mm mass in the uterine cavity after the delivery. Due to presence of early postpartum hemorrhage which needs transfusion, an intervention decision was made. The patient underwent curettage but the mass could not be removed so that placental retention was ruled out. Submucous leiomyoma was made as first-prediagnosis. Hysterectomy operation was performed as a curative treatment. Placenta increta diagnosis was made as a final diagnosis with pathological examination. As a result, placental attachment disorders may be overlooked if it is not a placenta previa case.

High-dose acetylcysteine in idiopathic pulmonary fibrosis

NARCIS (Netherlands)

Demedts, Maurits; Behr, Juergen; Buhl, Roland; Costabel, Ulrich; Dekhuijzen, Richard; Jansen, Henk M.; MacNee, William; Thomeer, Michiel; Wallaert, Benoit; Laurent, François; Nicholson, Andrew G.; Verbeken, Eric K.; Verschakelen, Johny; Flower, Christopher D. R.; Capron, Frédérique; Petruzzelli, Stefano; de Vuyst, Paul; van den Bosch, Jules M. M.; Rodriguez-Becerra, Eulogio; Corvasce, Giuseppina; Lankhorst, Ida; Sardina, Marco; Montanari, Mauro

2005-01-01

BACKGROUND Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added

Vitamin A supplementation for cystic fibrosis.

Science.gov (United States)

Bonifant, Catherine M; Shevill, Elizabeth; Chang, Anne B

2014-05-14

People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice. To determine if vitamin A supplementation in children and adults with cystic fibrosis:1. reduces the frequency of vitamin A deficiency disorders;2. improves general and respiratory health;3. increases the frequency of vitamin A toxicity. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 07 April 2014. All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency. No relevant studies for inclusion were identified in the search. No studies were included in this review. As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of

Fabrication of customized sectional impression trays in management of patients with limited mouth opening: a simple and unique approach.

Science.gov (United States)

Krishna Ch, Vamsi; Mahendranadh Reddy, K; Gupta, Nidhi; Mahadev Shastry, Y; Chandra Sekhar, N; Aditya, Venkat; Reddy, G V K Mohan

2013-01-01

Impression making is not only important but is also the most significant step in the fabrication of any fixed or removable prosthesis. Proper impression making may be hindered by certain pathologic conditions. Reduced mouth opening is one of the common mechanical obstructions for proper orientation of the impression tray in the patient's mouth. In patients with trismus induced by submucous fibrosis, the procedure may be even more difficult to carry out because of reduced tissue resiliency and obliteration of vestibular spaces. Use of sectional trays offers one of the alternatives to overcome the problem of restricted mouth opening. Fabrication of customized impression trays according to the patient dentition improves the accuracy of impression making. The present case reports describe the fabrication of sectional custom trays designed for dentulous patients with chronic tobacco-induced submucous fibrosis.

Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

DEFF Research Database (Denmark)

Johansen, Helle Krogh; Gøtzsche, Peter C

2015-01-01

BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed....... This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30...... March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic...

Intercountry prevalences and practices of betel-quid use in south, southeast and eastern Asia regions and associated oral preneoplastic disorders: an international collaborative study by Asian betel-quid consortium of south and east Asia.

Science.gov (United States)

Lee, Chien-Hung; Ko, Albert Min-Shan; Warnakulasuriya, Saman; Yin, Bang-Liang; Sunarjo; Zain, Rosnah Binti; Ibrahim, Salah Osman; Liu, Zhi-Wen; Li, Wen-Hui; Zhang, Shan-Shan; Kuntoro; Utomo, Budi; Rajapakse, Palandage Sunethra; Warusavithana, Supun Amila; Razak, Ishak Abdul; Abdullah, Norlida; Shrestha, Prashanta; Kwan, Aij-Lie; Shieh, Tien-Yu; Chen, Mu-Kuan; Ko, Ying-Chin

2011-10-01

Health risks stemming from betel-quid (BQ) chewing are frequently overlooked by people. Updated epidemiological data on the increased BQ use among Asian populations using comparable data collection methods have not been widely available. To investigate the prevalence, patterns of practice and associated types of oral preneoplastic disorders, an intercountry Asian Betel-quid Consortium study (the ABC study) was conducted for Taiwan, Mainland China, Malaysia, Indonesia, Nepal and Sri Lanka. A random sample of 8,922 subjects was recruited, and the data were analyzed using survey-data modules adjusted for the complex survey design. Chewing rates among men (10.7-43.6%) were significantly higher than women (1.8-34.9%) in Taiwan, Mainland China, Nepal and Sri Lanka, while women's rates (29.5-46.8%) were higher than that for men (9.8-12.0%) in Malaysia and Indonesia. An emerging, higher proportion of new-users were identified for Hunan in Mainland China (11.1-24.7%), where Hunan chewers have the unique practice of using the dried husk of areca fruit rather than the solid nut universally used by others. Men in the Eastern and South Asian study communities were deemed likely to combine chewing with smoking and drinking (5.6-13.6%). Indonesian women who chewed BQ exhibited the highest prevalence of oral lichen planus, oral submucous fibrosis and oral leukoplakia (9.1-17.3%). Lower schooling, alcohol drinking and tobacco smoking were identified as being associated with BQ chewing. In conclusion, the ABC study reveals the significant cultural and demographic differences contributing to practice patterns of BQ usage and the great health risks that such practices pose in the Asian region. Copyright © 2010 UICC.

The Effect of Furlow Palatoplasty Timing on Speech Outcomes in Submucous Cleft Palate.

Science.gov (United States)

Swanson, Jordan W; Mitchell, Brianne T; Cohen, Marilyn; Solot, Cynthia; Jackson, Oksana; Low, David; Bartlett, Scott P; Taylor, Jesse A

2017-08-01

Because some patients with submucous cleft palate (SMCP) are asymptomatic, surgical treatment is conventionally delayed until hypernasal resonance is identified during speech production. We aim to identify whether speech outcomes after repair of a SMCP is influenced by age of repair. We retrospectively studied nonsyndromic children with SMCP. Speech results, before and after any surgical treatment or physical management of the palate were compared using the Pittsburgh Weighted Speech Scoring system. Furlow palatoplasty was performed on 40 nonsyndromic patients with SMCP, and 26 patients were not surgically treated. Total composite speech scores improved significantly among children repaired between 3 and 4 years of age (P = 0.02), but not older than 4 years (P = 0.63). Twelve (86%) of 14 patients repaired who are older than 4 years had borderline or incompetent speech (composite Pittsburgh Weighted Speech Scoring ≥3) compared with 2 (29%) of 7 repaired between 3 and 4 years of age (P = 0.0068), despite worse prerepair scores in the latter group. Resonance improved in children repaired who are older than 4 years, but articulation errors persisted to a greater degree than those treated before 4 years of age (P = 0.01.) CONCLUSIONS: Submucous cleft palate repair before 4 years of age appears associated with lower ultimate rates of borderline or incompetent speech. Speech of patients repaired at or after 4 years of age seems to be characterized by persistent misarticulation. These findings highlight the importance of timely diagnosis and management.

The lymphoscintigraphy and intraoperative gamma detection of sentinel lymph node in oral cavity carcinoma

International Nuclear Information System (INIS)

Zhao Xinming; Zhang Jingmian; Wang Jianfang; Li Dezhi; Sun Li; Dai Chunnuan; He Yang

2006-01-01

Objective: To evaluate the role of lymphoscintigraphy and intraoperative gamma probe detection of sentinel lymph node (SLN) in oral cavity carcinoma. Methods: 99 Tc m labeled dextran (DX) was injected submucously at the center of oral cavity carcinoma before operation. The SLN identified by lymphoscintigraphy and intraoperative gamma counter probe were dissected out from the exited tissue. All sentinel and other lymph nodes were sent for pathological examination. Results: In all 33 cases, SLN and other lymph nodes were clear identified by lymphoscintigraphy. Forty-three SLNs were seen, among them 1 in 25 cases, 2 in 6 cases and 3 in 2 cases. Metastases were detected by biopsy in SLN in 9 cases, however, 11 cases showed positive neck lymph node metastases. The sensitivity of SLN gamma detection was 100% and in biopsy sensitivity was 81.82%, accuracy was 93.94%, false positive rate was 0, and false negative rate was 18.18%. Conclusions: Intraoperative gamma probe detection is the reliable approach to identify SLN in oral cavity carcinoma. Lymphoscintigraphy is the base of localization for oral cavity carcinoma. (authors)

Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4 Induced Hepatic Fibrosis in Mice.

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Leola N Chow

Full Text Available Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM-induced pulmonary fibrosis and carbon tetrachloride (CCl4-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC, the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis.

Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms.

Science.gov (United States)

Nair, Urmila; Bartsch, Helmut; Nair, Jagadeesan

2004-07-01

In south-east Asia, Taiwan and Papua New Guinea, smoking, alcohol consumption and chewing of betel quid with or without tobacco or areca nut with or without tobacco are the predominant causes of oral cancer. In most areas, betel quid consists of a mixture of areca nut, slaked lime, catechu and several condiments according to taste, wrapped in a betel leaf. Almost all habitual chewers use tobacco with or without the betel quid. In the last few decades, small, attractive and inexpensive sachets of betel quid substitutes have become widely available. Aggressively advertised and marketed, often claimed to be safer products, they are consumed by the very young and old alike, particularly in India, but also among migrant populations from these areas world wide. The product is basically a flavoured and sweetened dry mixture of areca nut, catechu and slaked lime with tobacco (gutkha) or without tobacco (pan masala). These products have been strongly implicated in the recent increase in the incidence of oral submucous fibrosis, especially in the very young, even after a short period of use. This precancerous lesion, which has a high rate of malignant transformation, is extremely debilitating and has no known cure. The use of tobacco with lime, betel quid with tobacco, betel quid without tobacco and areca nut have been classified as carcinogenic to humans. As gutkha and pan masala are mixtures of several of these ingredients, their carcinogenic affect can be surmised. We review evidence that strongly supports causative mechanisms for genotoxicity and carcinogenicity of these substitute products. Although some recent curbs have been put on the manufacture and sale of these products, urgent action is needed to permanently ban gutkha and pan masala, together with the other established oral cancer-causing tobacco products. Further, education to reduce or eliminate home-made preparations needs to be accelerated.

Screening of Oral Potentially Malignant Disorders Using Exfoliative Cytology: A Diagnostic Modality

International Nuclear Information System (INIS)

Kabiraj, A.

2016-01-01

Oral exfoliative cytology (OEC) has been implemented in the diagnosis of pathologic lesions for ages. The present study was undertaken to evaluate the cytomorphological features of some of the commonest potentially malignant disorders (leukoplakia, lichen planus, and oral sub mucous fibrosis) through a simple procedure and illustrate its importance in mass screening. Materials and Method. A total of 160 subjects with 25-50 years of age were included in the study. Among them, 40 were clinically diagnosed with oral leukoplakia, 40 were diagnosed with oral lichen planus, 40 were diagnosed with oral sub mucous fibrosis, and 40 were in the control group. The prepared smears were subjected to Papanicolaou stain and analyzed microscopically for the evaluation of the cytomorphological features. Results and Discussion. When analyzed microscopically, 36 (90%) out of the 40 oral leukoplakic lesions showed Class II cytological features whereas 4 (10%) revealed Class I features. Among 40 patients with oral lichen planus, 26 (65%) showed Class II features while the remaining 14 (35%) revealed Class I features. In 40 subjects with oral sub mucous fibrosis, 32 (80%) showed Class II features while the other 8 (20%) showed Class I features. All the 40 control subjects showed Class I features. Thus, OEC can be widely advocated as an addition to clinical conclusion and an adjunct to biopsy.

Quantitative Evaluation of Macrophage Expression Using CD68 in ...

African Journals Online (AJOL)

Submucous fibrosis is an insidious, chronic disease affecting any part of ... study suggest that CD68 plays a vital role in the pathogenesis of OSMF and can be regarded as a useful .... in lysosomes and to a lesser extent on surface membranes,.

Oral health and related factors in a group of children with cystic ...

African Journals Online (AJOL)

Oral health and related factors in a group of children with cystic fibrosis in Istanbul, Turkey. ... presented as a marker of wound healing and bleeding tendency of oral cavity. ... Caries experience, oral hygiene, and dental erosion were assessed.

Preventive effect of halofuginone on concanavalin A-induced liver fibrosis.

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Jie Liang

Full Text Available Halofuginone (HF is an active component of extracts derived from the plant alkaloid febrifugine and has shown therapeutic promise in animal models of fibrotic disease. Our main objectives were to clarify the suppressive effect of HF on concanavalin A (ConA-induced liver fibrosis. ConA injection into the tail vein caused a great increase in the serum aspartate aminotransferase (AST and alanine aminotransferase (ALT levels, while orally administration of HF significantly decreased the levels of the transaminases. In addition, the levels of hyaluronic acid (HA, procollagen III (PCIII and TGF-β1 in the serum and collagen I, α-SMA, tissue inhibitors of metalloproteinase 2 (TIMP2 and Smad3 in the liver tissue were significantly lowered with the treatment of HF. Histological examination also demonstrated that HF significantly reduced the severity of liver fibrosis. Since ConA-induced liver fibrosis is caused by the repeated activation of T cells, immunomodulatory substances might be responsible for the suppressive effect of HF. We found that the production of nuclear factor (NF-kB in the serum was increased in ConA-treated group, while decreased significantly with the treatment of HF. The changes of inflammatory cytokines tumor necrosis factor (TNF-α, IL-6 and IL-1β in the serum followed the same rhythm. All together, our findings indicate that orally administration HF (10ppm would attenuate the liver fibrosis by suppressing the synthesis of collagen I and inflammation-mediated liver injury.

Hyponatremia-associated rhabdomyolysis following exercise in an adolescent with cystic fibrosis.

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Kaskavage, Jillian; Sklansky, Daniel

2012-07-01

Adolescents with well-controlled cystic fibrosis, including good lung function and appropriate growth, commonly participate in competitive athletic activities. We present the case of an adolescent male with cystic fibrosis, hyponatremia, dehydration, and rhabdomyolysis after participating in football practice on a summer morning. The patient presented with severe myalgia and serum sodium of 129 mmol/L, chloride 90 mmol/L, and creatine phosphokinase 1146 U/L. Aggressive hydration with intravenous 0.9% saline resulted in clinical improvement with no renal or muscular sequelae. Health care providers need to educate patients with cystic fibrosis about maintaining adequate hydration and sodium repletion during exercise. Research is needed regarding the appropriate amount and composition of oral rehydration fluids in exercising individuals with cystic fibrosis, as the physiology encountered in these patients provides a unique challenge to maintaining electrolyte balance and stimulation of thirst.

Direct carotid cavernous fistula after submucous resection of the nasal septum.

Science.gov (United States)

Bizri, A R; al-Ajam, M; Zaytoun, G; al-Kutoubi, A

2000-01-01

A carotid cavernous fistula (CCF) is an abnormal arteriovenous anastomosis between the carotid artery and the cavernous sinus. Etiologies of this condition reported in the literature so far include facial trauma, rupture of an intracavernous aneurysm of the carotid artery, Ehler-Danlos syndrome and fibromuscular dysplasia of the cerebral arteries. Such fistulae were reported as complications of rhinoplasty, transsphenoidal surgery, embolization of cavernous sinus meningioma, and rhinocerebral mucormycosis. CCF may also occur spontaneously in children or as a congenital malformation. However, to our knowledge, submucous resection of the nasal septum has not been reported before to cause direct carotid-cavernous fistula. CT and angiographic findings are presented and a review of the literature for reported causes of CCF is made as well as a brief discussion of the possible pathophysiology.

Oral glucose tolerance test and continuous glucose monitoring to assess diabetes development in cystic fibrosis patients.

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Clemente León, María; Bilbao Gassó, Laura; Moreno-Galdó, Antonio; Campos Martorrell, Ariadna; Gartner Tizzano, Silvia; Yeste Fernández, Diego; Carrascosa Lezcano, Antonio

2018-01-01

Patients with cystic fibrosis (CF) undergo a slow and progressive process toward diabetes. Oral glucose tolerance test (OGTT) is recommended to diagnose impaired glucose levels in these patients. Continuous glucose monitoring (CGM) measures glucose profiles under real-life conditions. To compare OGTT and CGM results in CF patients. Paired OGTT and 6-day CGM profiles (146.2±9.1h/patient) were performed in 30 CF patients aged 10-18 years. According to OGTT, 14 patients had normal glucose tolerance (NGT), 14 abnormal glucose tolerance (AGT), and two cystic fibrosis-related diabetes (CFRD). In 27 patients (13 NGT, 13 AGT, 1 CFRD), CGM showed glucose values ranging from 140 to 200mg/dL during similar monitoring times (2%-14% with NGT, 1%-16.9% with AGT, and 3% with CFRD). Glucose peak levels ≥200mg/dL were seen in seven patients (3 NGT, 3 AGT, 1 CFRD). According to CGM, two patients had all glucose values under 140mg/dL (1 NGT, 1 AGT). Seventeen patients had glucose levels ranging from 140 to 200mg/dL (10 NGT, 6 AGT, 1 CFRD). Ten patients (3 NGT, 7 AGT) had glucose values ≥200mg/dL for ≤1% of the monitoring time and one (CFRD) for >1% of the monitoring time. OGTT results did not agree with those of the CGM. CGM allows for diagnosis of glucose changes not detected by OGTT. Such changes may contribute to optimize pre-diabetes management in CF patients. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of Oral Submucosal Fibrosis and Related Factors in Areca Nut Users

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Masoomeh Shirzaii

2013-01-01

Full Text Available Background: Oral Submucousal Fibrosis (OSF is a precancerous condition often created in consumers of different products containing arecanut. These products are commonly used in countries like India and Pakistan. In Iran, it is commonly consumed in cities which are in proximity of Pakistan border including Chabahar. The present study is done in order to study OSF and other relating factors in consumers of products containing areca nut. Materials and Methods: In this descriptive-analytical and cross-sectional study, 362 consumers of products containing areca nut (pan, supari, gutka and etc. were studied in order to examine the incidence of OSF. The diagnostic criteria were mouth-opening limitations, mucosa stiffness and touching the intramucous fibrotic bands. Information about the consumption amount, alternation, the type of consumed material and time of consumption was mentioned in the questionnaire. Finally, the data was analyzed using SPSS-14 and χ2 test. Results: Of 362 consumers of areca nut (227 men (62.7% and 135 women (37.3% in the age group 7-71 and average age of 27 years old, 61 person (16.9% including 33 men (54.1% and 28 women (45.9% were suffering OSF. There was a significant relationship between OSF incidence and time, dose and alternation of consumption (p˂0.05. Age and sex didn’t have a certain correlation with OSF.Conclusion: The recent study indicated a strong correlation between consumption of products containing areca nut and OSF.

Prevalence of precancerous lesions and conditions in Telangana region, Andhra Pradesh, India

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B Hari Vinay

2014-01-01

Full Text Available Aim: To assess the prevalence of oral precancerous lesions and conditions and to determine the potential risk factors associated among general population aged 20-70 years of Telangana region, Andhra Pradesh. Materials and Methods: An oral screening campaign was organized with the help of local general dental practitioners in each district. All the relevant information regarding the subject was documented and clinical examination of the oral soft tissues was carried out. Clinically diagnosed as precancerous lesion or condition were subjected to punch (incisional biopsy biopsy and evaluated histopathologically to confirm the diagnosis. Results: Among 1200 screened, 150 subjects were chewers and 136 subjects were smokers with 29 chewers and 16 smokers had precancerous lesions and conditions. An overall prevalence of oral precancerous lesions and conditions were found to be 4.2% (males 5.5%; females 2.5%. Leukoplakia was seen in 0.8%, Oral submucous fibrosis in 1.3% and lichen planus in 2% of the study population. Conclusions: The prevalence of precancerous lesions and conditions in our study is higher when compared with the reports from different parts of the country and in South East Asia. These lesions can be prevented from malignant transformation by mass screening, close monitoring, early detection, appropriate treatment plan and prognosis.

An Open-Label Investigation of the Pharmacokinetics and Tolerability of Oral Cysteamine in Adults with Cystic Fibrosis.

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Devereux, Graham; Steele, Sandra; Griffiths, Kairen; Devlin, Edward; Fraser-Pitt, Douglas; Cotton, Seonaidh; Norrie, John; Chrystyn, Henry; O'Neil, Deborah

2016-08-01

Cysteamine is licensed for use in nephropathic cystinosis but preclinical data suggest a role in managing cystic fibrosis (CF). This study aimed to determine whether oral cysteamine is absorbed in adult CF patients and enters the bronchial secretions. Tolerability outcomes were also explored. Patients ≥18 years of age, weighing >50 kg with stable CF lung disease were commenced on oral cysteamine bitartrate (Cystagon(®)) 450 mg once daily, increased weekly to 450 mg four times daily. Serial plasma cysteamine concentrations were measured for 24 h after the first dose. Participants were reviewed every week for 6 weeks, except at 4 weeks. Plasma cysteamine concentrations were measured 8 h after dosing when reviewed at 1, 2 and 3 weeks and 6 h after dosing when reviewed at 5 weeks. Sputum cysteamine concentration was also quantified at the 5-week assessment. Seven of the ten participants reported adverse reactions typical of cysteamine, two participants discontinued intervention. Following the first 450-mg dose, mean (SD) maximum concentration (C max) was 2.86 (1.96) mg/l, the time corresponding to C max (T max) was 1.2 (0.7) h, the half-life (t ½) was 3.7 (1.7) h, clearance (CL/F) 89.9 (30.5) L/h and volume of distribution (V d/F) 427 (129) L. Cysteamine appeared to accumulate in sputum with a median (interquartile range) sputum:plasma cysteamine concentration ratio of 4.2 (0.98-8.84). Oral cysteamine is absorbed and enters the bronchial secretions in patients with CF. Although adverse reactions were common, the majority of patients continued with cysteamine. Further trials are required to establish the risk benefit ratio of cysteamine therapy in CF.

Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in rats.

Science.gov (United States)

Hamza, Alaaeldin A

2010-01-01

This study was carried out to evaluate the effect of Moringa oleifera Lam (Moringa) seed extract on liver fibrosis. Liver fibrosis was induced by the oral administration of 20% carbon tetrachloride (CCl(4)), twice weekly and for 8 weeks. Simultaneously, M.oleifera Lam seed extract (1g/kg) was orally administered daily. The biochemical and histological results showed that Moringa reduced liver damage as well as symptoms of liver fibrosis. The administration of Moringa seed extract decreased the CCl(4)-induced elevation of serum aminotransferase activities and globulin level. The elevations of hepatic hydroxyproline content and myeloperoxidase activity were also reduced by Moringa treatment. Furthermore, the immunohistochemical study showed that Moringa markedly reduced the numbers of smooth muscle alpha-actin-positive cells and the accumulation of collagens I and III in liver. Moringa seed extract showed significant inhibitory effect on 1,1-diphenyl-2-picrylhydrazyl free radical, as well as strong reducing antioxidant power. The activity of superoxide dismutase as well as the content of both malondialdehyde and protein carbonyl, which are oxidative stress markers, were reversed after treatment with Moringa. Finally, these results suggested that Moringa seed extract can act against CCl(4)-induced liver injury and fibrosis in rats by a mechanism related to its antioxidant properties, anti-inflammatory effect and its ability to attenuate the hepatic stellate cells activation. Copyright 2009 Elsevier Ltd. All rights reserved.

Liver fibrosis after extracorporeal shock-wave lithotripsy of gallbladder stones - A case report

NARCIS (Netherlands)

P.W. Plaisier; J.F. Hamming (Jaap); R.L. van der Hul (René); R. den Toom (Rene); H.A. Bruining (Hajo)

1994-01-01

textabstractWe encountered significant liver fibrosis in a healthy young patient undergoing laparoscopic cholecystectomy for symptomatic gallstone disease. Twelve months prior to cholecystectomy the patient underwent multiple extracorporeal shock-wave lithotripsy (ESWL) sessions with adjuvant oral

Chronic hepatitis C and fibrosis: evidences for possible estrogen benefits

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Liana Codes

Full Text Available The main injury caused by hepatitis C virus is the hepatic fibrosis, as a result of a chronic inflammatory process in the liver characterized by the deposit of components from the extracellular matrix. The fibrosis development leads to the modification of the hepatic architecture, of the hepatocellular function and to irregularities in the microcirculation. The tissue remodeling process observed in fibrosis has stellate cells, located at the space of Disse, as main acting agents. These cells, in response to a harmful stimulus, undergo phenotypic changes from non-proliferating cells to proliferating cells that express a- smooth-muscle actin (a-SMA, a process called as transdifferentiation. There are evidences that the oxidative stress is involved in the chronic liver disease and serves as bond between the injury and the hepatic fibrosis. A number of studies suggest that the estrogen, at physiological levels, presents an antifibrogenic action probably through an antioxidant effect, decreasing the levels of lipid peroxidation products in the liver and blood, thus inhibiting the myofibroblastic transformation of stellate cells and contributing for gender-associated differences in relation to the fibrosis development. The aim of this paper was to describe data from literature concerning the interaction between chronic hepatitis C and estrogens, pregnancy, use of oral contraceptives, menopause and hormone reposition therapy.

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

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Nico Derichs

2013-03-01

Full Text Available Cystic fibrosis (CF is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the CFTR gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target CFTR mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-CFTR mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.

Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

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Wang, Xingqi; Ouyang, Zijun; You, Qian; He, Shuai; Meng, Qianqian; Hu, Chunhui; Wu, Xudong; Shen, Yan; Sun, Yang, E-mail: yangsun@nju.edu.cn; Wu, Xuefeng, E-mail: wuxf@nju.edu.cn; Xu, Qiang, E-mail: molpharm@163.com

2016-07-15

Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. - Highlights: • Obaculactone ameliorates bleomycin-induced pulmonary fibrosis in mice. • Obaculactone mitigates bleomycin-induced inflammatory response in lungs. • Obaculactone exerts inhibitory effects on TGF-β1 signaling and TGF-β1-induced EMT progress.

Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

International Nuclear Information System (INIS)

Wang, Xingqi; Ouyang, Zijun; You, Qian; He, Shuai; Meng, Qianqian; Hu, Chunhui; Wu, Xudong; Shen, Yan; Sun, Yang; Wu, Xuefeng; Xu, Qiang

2016-01-01

Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. - Highlights: • Obaculactone ameliorates bleomycin-induced pulmonary fibrosis in mice. • Obaculactone mitigates bleomycin-induced inflammatory response in lungs. • Obaculactone exerts inhibitory effects on TGF-β1 signaling and TGF-β1-induced EMT progress.

Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.

Science.gov (United States)

Chang, Mei-Chi; Chan, Chiu-Po; Chen, Yi-Jane; Hsien, Hsiang-Chi; Chang, Ya-Ching; Yeung, Sin-Yuet; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

2016-03-29

Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases.

Introduction to Pulmonary Fibrosis

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... page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a disease where there is scarring ... of pulmonary fibrosis. Learn more How Is Pulmonary Fibrosis Diagnosed? Pulmonary fibrosis can be difficult to diagnose, so it ...

Pulmonary Fibrosis Foundation

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... submissions. MORE We Imagine a World Without Pulmonary Fibrosis The Pulmonary Fibrosis Foundation mobilizes people and resources to provide ... its battle against the deadly lung disease, pulmonary fibrosis (PF). PULMONARY FIBROSIS WALK SURPASSES PARTICIPATION AND FUNDRAISING GOALS Nearly ...

Naja naja atra venom ameliorates pulmonary fibrosis by inhibiting inflammatory response and oxidative stress.

Science.gov (United States)

Cui, Kui; Kou, Jian-Qun; Gu, Jin-Hua; Han, Rong; Wang, Guanghui; Zhen, Xuechu; Qin, Zheng-Hong

2014-12-02

Naja naja atra venom (NNAV) displays diverse pharmacological actions including analgesia, anti-inflammation and immune regulation.In this study, we investigated the effects of NNAV on pulmonary fibrosis and its mechanisms of action. To determine if Naja naja atra venom (NNAV) can produce beneficial effects on pulmonary fibrosis, two marine models of pulmonary fibrosis were produced with bleomycin (BLM) and lipopolysaccharide (LPS). NNAV (30, 90, 270 μg/kg) was orally administered once a day started five days before BLM and LPS until to the end of experiment. The effects of NNAV treatment on pulmonary injury were evaluated with arterial blood gas analysis, hydroxyproline (HYP) content assessment and HE/Masson staining. The effects of NNAV treatment on inflammatory related cytokines, fibrosis related TGF-β/Smad signaling pathway and oxidative stress were examined. The results showed that NNAV improved the lung gas-exchange function and attenuated the fibrotic lesions in lung. NNAV decreased IL-1β and TNF-α levels in serum in both pulmonary fibrosis models. NNAV inhibited the activation of NF-κB in LPS-induced and TGF-β/Smad pathway in BLM-induced pulmonary fibrosis. Additionally, NNAV also increased the levels of SOD and GSH and reduced the levels of MDA in BLM-induced pulmonary fibrosis model. The present study indicates that NNAV attenuates LPS- and BLM-induced lung fibrosis. Its mechanisms of action are associated with inhibiting inflammatory response and oxidative stress. The study suggests that NNAV might be a potential therapeutic drug for treatment of pulmonary fibrosis.

Self‑perceived oral health and whole salivary immunoglobulin G ...

African Journals Online (AJOL)

2015-04-05

Apr 5, 2015 ... it has also been reported that self‑reported periodontal health is unreliable ..... fibrosis: A case‑control study. Quintessence Int ... Self‑perceived oral health and periodontal parameters in chronic periodontitis patients with and ...

Diagnosing subtle palatal anomalies: Validation of video-analysis and assessment protocol for diagnosing occult submucous cleft palate.

Science.gov (United States)

Rourke, Ryan; Weinberg, Seth M; Marazita, Mary L; Jabbour, Noel

2017-09-01

Submucous cleft palate (SMCP) classically involves bifid uvula, zona pellucida, and notched hard palate. However, patients may present with more subtle anatomic abnormalities. The ability to detect these abnormalities is important for surgeons managing velopharyngeal dysfunction (VPD) or considering adenoidectomy. Validate an assessment protocol for diagnosis of occult submucous cleft palate (OSMCP) and identify physical examination features present in patients with OSMCP in the relaxed and activated palate positions. Study participants included patients referred to a pediatric VPD clinic with concern for hypernasality or SMCP. Using an appropriately encrypted iPod touch, transoral video was obtained for each patient with the palate in the relaxed and activated positions. The videos were reviewed by two otolaryngologists in normal speed and slow-motion, as needed, and a questionnaire was completed by each reviewer pertaining to the anatomy and function of the palate. 47 patients, with an average age of 4.6 years, were included in the study over a one-year period. Four videos were unusable due to incomplete view of the palate. The most common palatal abnormality noted was OSMCP, diagnosed by each reviewer in 26/43 and 30/43 patients respectively. Using the assessment protocol, agreement on palatal diagnosis was 83.7% (kappa = 0.68), indicating substantial agreement, with the most prevalent anatomic features being vaulted palate elevation (96%) and visible notching of hard palate (75%). The diagnosis of subtle palatal anomalies is difficult and can be subjective. Using the proposed video-analysis method and assessment protocol may improve reliability of diagnosis of OSMCP. Copyright © 2017 Elsevier B.V. All rights reserved.

Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats

OpenAIRE

Nasri, Hamid-Reza; Joukar, Siyavash; Kheradmand, Hamid; Poursalehi, Hamid-Reza; Dabiri, Shahriar

2015-01-01

Objective The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats. Materials and Methods Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 we...

A case of acute exacerbation of idiopathic pulmonary fibrosis after proton beam therapy for non-small cell lung cancer

International Nuclear Information System (INIS)

Nagano, Tatsuya; Kotani, Yoshikazu; Fujii, Osamu

2012-01-01

There have been no reports describing acute exacerbations of idiopathic pulmonary fibrosis after particle radiotherapy for non-small cell lung cancer. The present study describes the case of a 76-year-old Japanese man with squamous cell carcinoma of the lung that relapsed in the left upper lobe 1 year after right upper lobectomy. He had been treated with oral prednisolone 20 mg/day every 2 days for idiopathic pulmonary fibrosis, and the relapsed lung cancer was treated by proton beam therapy, which was expected to cause the least adverse effects on the idiopathic pulmonary fibrosis. Fifteen days after the initiation of proton beam therapy, the idiopathic pulmonary fibrosis exacerbated, centered on the left upper lobe, for which intensive steroid therapy was given. About 3 months later, the acute exacerbation of idiopathic pulmonary fibrosis had improved, and the relapsed lung cancer became undetectable. Clinicians should be aware that an acute exacerbation of idiopathic pulmonary fibrosis may occur even in proton beam therapy, although proton beam therapy appears to be an effective treatment option for patients with idiopathic pulmonary fibrosis. (author)

Serologic and ultrasonographic parameters of praziquantel treatment of hepatic fibrosis in Schistosoma japonicum infection.

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Ohmae, H; Tanaka, M; Nara, T; Utsunomiya, H; Taguchi, H; Irie, Y; Yasuraoka, K

1991-09-01

We describe the parameters useful in evaluating the development of hepatic fibrosis in Schistosoma japonicum infection, as well as its improvement after treatment with praziquantel (PZQ). Various serologic parameters and ultrasonographic images were examined, and their changes were monitored using rabbits infected with 200 or 300 cercariae of S. japonicum. Infected rabbits were administered one oral treatment of PZQ at a dosage of 100 mg/kg at 6, 12, or 24 weeks after infection. Histopathologic examinations revealed that PZQ had a strong and rapid effect, even on damage that developed long after the infection. The improvement of moderate hepatic fibrosis that developed over 24 weeks after infection was also detected by histopathologic examinations. The serum level of total bile acid was the most sensitive parameter in evaluating the severity of hepatic fibrosis and its improvement after treatment with PZQ. The level of serum procollagen-III-peptide was also useful in evaluating the development of hepatic fibrosis, but not in its improvement. Ultrasonography revealed specific echogenic bands and nodules according to the progress of granuloma formation and fibrosis, and the reversal of these changes could also be observed after treatment with PZQ.

Familial Pulmonary Fibrosis

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... Education & Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... more members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

Estimation of serum superoxide dismutase and serum malondialdehyde in oral submucous fibrosis: A clinical and biochemical study

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M L Avinash Tejasvi

2014-01-01

Conclusions: From the present study, estimation of lipid peroxidation like MDA was done, which showed increased levels in the OSF group compared to the control group and antioxidant enzyme levels like SOD showed decreased levels in the OSF group compared to the control group. These can be considered as a subject of interest for their possible role in many of the precancerous and cancerous conditions.

The Role of Butylidenephthalide in Targeting Microenvironment Contributes to the Ameliorate of Liver Fibrosis

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Hong-Meng eChuang

2016-04-01

Full Text Available The treatment of liver fibrosis has clinical limitations because of its multiple etiologies, such as epithelial–mesenchymal transition (EMT promotion, cell regeneration and remodeling dysfunction, inflammatory cell activation, and scar tissue deposition. These factors might be considered as a new target for the fibrotic microenvironment, leading to increased fibrogenesis and liver fibrosis. Here, we investigate a small molecule named butylidenephthalide (BP and its multiple effects on liver fibrosis treatment. Thioacetamide was used in vivo to induce chronic liver fibrosis. BP was administered orally in rats for a period of 2 weeks and 4 weeks, which resulted in a significantly reduced fibrosis score (p<0.05 and (p<0.001, respectively. The inflammatory reaction of macrophage infiltration were reduced in the administration of BP, which led to the decrease in the transaminase levels. Moreover, we also found liver functions recovering (due to the increased serum albumin and reduced prothrombin time where liver cells regenerated, which can be seen in the increase of Ki-67 on Oval cell. In addition, the fibrotic scar was also reduced, along with the expression of matrix metalloprotease by hepatic stellate cell. Furthermore, regarding the mechanism/study of EMT reduced by BP, the knockdown of BMP-7, which could reduce α-SMA expression, was mediated by the regulation of TGF-β, which implies its major role on EMT. Finally, in the in vivo study, BP treatment of liver fibrosis was reduced by Bmp7 knockdown in zebrafish, suggesting that BP leads to the reduction of liver fibrosis, which also depends on BMP-7 induction. These results suggest that BP had multiple targets for treating liver fibrosis in the following ways: reduction of EMT, decreasing inflammatory reaction, and liver cell proliferation. This multiple targets approach provided a new mechanism to treat liver injury and fibrosis.

Nutritional Status Improved in Cystic Fibrosis Patients with the G551D Mutation After Treatment with Ivacaftor

NARCIS (Netherlands)

Borowitz, Drucy; Lubarsky, Barry; Wilschanski, Michael; Munck, Anne; Gelfond, Daniel; Bodewes, Frank; Schwarzenberg, Sarah Jane

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gating mutation G551D prevents sufficient ion transport due to reduced channel-open probability. Ivacaftor, an oral CFTR potentiator, increases the channel-open probability. To further analyze improvements in weight and body mass

Cystic Fibrosis (CF): Chloride Sweat Test

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... on this topic for: Parents Kids Teens Cystic Fibrosis Cystic Fibrosis and Nutrition Cystic Fibrosis (CF) Respiratory Screen: Sputum Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition View more Partner Message ...

Morphometry of submucous and myenteric esophagic plexus of dogs experimentally reinfected with Trypanosoma cruzi

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Machado Evandro MM

2001-01-01

Full Text Available We carried out a morphometric study of the esophagus of cross-bred dogs experimentally infected or consecutively reinfected with Trypanosoma cruzi 147 and SC-1 strains, in order to verify denervation and/or neuronal hypertrophy in the intramural plexus. The animals were sacrificed in the chronic stage, 38 months after the initial infection. Neither nests of amastigotes, nor myositis or ganglionitis, were observed in all third inferior portions of esophageal rings analyzed. No nerve cell was identified in the submucous of this organ. There was no significant difference (p>0.05 between the number, maximum diameter, perimeter, or area and volume of the nerve cells of the myenteric plexus of infected and/or reinfected dogs and of the non-infected ones. In view of these results we may conclude that the 147 and SC-1 strains have little neurotropism and do not determine denervation and/or hypertrophy in the intramural esophageal plexuses in the animals studied, independent of the reinfections.

Oral bacteria--the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis.

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Zetterquist, Wilhelm; Marteus, Helena; Kalm-Stephens, Pia; Näs, Elisabeth; Nordvall, Lennart; Johannesson, Marie; Alving, Kjell

2009-02-01

Nitrite in exhaled breath condensate (EBC) has been shown to be elevated in cystic fibrosis (CF), while exhaled nitric oxide (FENO) is paradoxically low. This has been argued to reflect increased metabolism of NO while its diffusion is obstructed by mucus. However, we wanted to study the possible influence of salivary nitrite and bacterial nitrate reduction on these parameters in CF patients by the intervention of an anti-bacterial mouthwash. EBC and saliva were collected from 15 CF patients (10-43 years) and 15 controls (9-44 years) before and 5 min after a 30s chlorhexidine mouthwash, in parallel with measurements of FENO. Nitrite and nitrate concentrations were measured fluorometrically. EBC nitrite, but not nitrate, was significantly higher in the CF patients (median 3.6 vs 1.3 microM in controls, p<0.05) and decreased after mouthwash in both groups (3.6-1.4 microM, p<0.01; 1.3-0.5 microM, p<0.01). Salivary nitrite correlated significantly to EBC nitrite (r=0.60, p<0.001) and decreased correspondingly after chlorhexidine, whereas salivary nitrate increased. FENO was lower in CF and the difference between patients and controls was accentuated after mouthwash (5.4 vs 8.4 ppb in controls, p<0.05). EBC nitrite mainly originates in the pharyngo-oral tract and its increase in CF is possibly explained by a regional change in bacterial activity. The limited lower airway contribution supports the view of a genuinely impaired formation and metabolism of NO in CF, rather than poor diffusion of the molecule.

Knowledge, Attitude, and Practice of Women in Slums of Pimpri, Chinchwad, Pune, Maharashtra, India, regarding Usage of Mishri.

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Chawla, Roshani M; Mitra, Pranjan; Shetiya, Sahana H; Agarwal, Deepti R; Narayana, D Satya; Bomble, Nikhil

2017-03-01

Mishri is one of the form of smokeless tobacco, which is a roasted, powdered preparation made by baking tobacco on a hot metal plate until it is uniformly black, after which it is powdered. It is noted that mishri use is more commonly used by the women of low socioeconomic status, hence the need was felt to conduct this study among women mishri users of slums. Also, the consequences of mishri use are little known, hence an effort is made to find out its ill-effect on oral health. To assess knowledge, attitude, and practice (KAP) among women using mishri regarding its effects on their oral and general health. A 6-month KAP study was conducted among 100 women who were using mishri. Snowball sampling was used. Oral examination of the participants was also done for oral potentially malignant disorders, such as leukoplakia, erythroplakia, oral submucous fibrosis, and hyperkeratinized pouch. About 61% of the population used mishri for cleaning the teeth and others used it as quid; 0.85% of the total participants knew that the use of mishri may lead to precancerous lesions/conditions. Only 17% knew that mishri use can cause gum disease; 84% of the population was willing to quit the habit of using mishri. It is concluded that all the participants had poor knowledge. Attitude toward quitting mishri use was found to be good. About 4% of the participants reported about quitting the habit. There is need to create awareness regarding harmful effects of mishri usage in this particular area to improve oral health status.

Glycemic variability is an independent predictive factor for development of hepatic fibrosis in nonalcoholic fatty liver disease.

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Motoi Hashiba

Full Text Available Patients with nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH often have metabolic disorders including insulin resistance and type 2 diabetes mellitus (T2DM. We clarified the predictive factors in glucose metabolism for progression of hepatic fibrosis in patients with NAFLD by the 75-g oral glucose tolerance test (75gOGTT and a continuous glucose monitoring system (CGMS. One hundred sixty-nine patients (68 female and 101 male patients with biopsy-proven NAFLD with performance with 75gOGTT were enrolled and divided into four groups according to the stage of hepatic fibrosis (F0-3. The proportion of patients with T2DM significantly gradually increased, HbA1c and the homeostasis model assessment of insulin resistance were significantly elevated, and 1,5-anhydroglucitol (1,5-AG was remarkably decreased with the progression of fibrosis. In the 75gOGTT, both plasma glucose and insulin secretion were remarkably increased with the progression of fibrosis. The only factor significantly associated with advanced fibrosis was 1,5-AG (P = 0.008 as determined by multivariate logistic regression analysis. We next evaluated the changes in blood glucose during 24 hours by monitoring with the CGMS to confirm the relationship between glycemic variability and progression of fibrosis. Variability of median glucose, standard deviation of median glucose (P = 0.0022, maximum blood glucose (P = 0.0019, and ΔMin-max blood glucose (P = 0.0029 were remarkably higher in severe fibrosis than in mild fibrosis.Hyperinsulinemia and hyperglycemia, especially glycemic variability, are important predictive factors in glucose impairment for the progression of hepatic fibrosis in NAFLD.

Cystic fibrosis: case report

International Nuclear Information System (INIS)

Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

2002-01-01

Cystic fibrosis is an autosomal recessive genetic disease. Among Caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among Caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

Cystic fibrosis: case report

International Nuclear Information System (INIS)

Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

2002-01-01

Cystic fibrosis is a autosomal recessive genetic disease. Among caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease.

Science.gov (United States)

Alazawi, William; Bernabe, Eduardo; Tai, David; Janicki, Tomasz; Kemos, Polychronis; Samsuddin, Salma; Syn, Wing-Kin; Gillam, David; Turner, Wendy

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) has a bidirectional association with metabolic syndrome. It affects up to 30% of the general population, 70% of individuals with diabetes and 90% with obesity. The main histological hallmark of progressive NAFLD is fibrosis. There is a bidirectional epidemiological link between periodontitis and metabolic syndrome. NAFLD, periodontitis and diabetes share common risk factors, are characterised by inflammation and associated with changes in commensal bacteria. Therefore we tested the hypothesis that periodontitis is associated with NAFLD and with significant fibrosis in two study groups. We analyzed data from a population-based survey and a patient-based study. NHANES III participants with abdominal ultrasound and sociodemographic, clinical, and oral examination data were extracted and appropriate weighting applied. In a separate patient-based study, consenting patients with biopsy-proved NAFLD (or with liver indices too mild to justify biopsy) underwent dental examination. Basic Periodontal Examination score was recorded. In NHANES, periodontitis was significantly associated with steatosis in 8172 adults even after adjusting for sociodemographic factors. However, associations were fully explained after accounting for features of metabolic syndrome. In the patient-based study, periodontitis was significantly more common in patients with biopsy-proven NASH and any fibrosis (F0-F4) than without NASH (p = 0.009). Periodontitis was more common in patients with NASH and significant fibrosis (F2-4) than mild or no fibrosis (F0-1, p = 0.04). Complementary evidence from an epidemiological survey and a clinical study show that NAFLD is associated with periodontitis and that the association is stronger with significant liver fibrosis.

Neck muscle atrophy and soft-tissue fibrosis after neck dissection and postoperative radiotherapy for oral cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Jinu; Shin, Eun Seow; Kim, Jeong Eon; Yoon, Sang Pil [Jeju National University School of Medicine, Jeju (Korea, Republic of); Kim, Young Suk [Dept. of Radiation Oncology, Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of)

2015-12-15

Late complications of head and neck cancer survivors include neck muscle atrophy and soft-tissue fibrosis. We present an autopsy case of neck muscle atrophy and soft-tissue fibrosis (sternocleidomastoid, omohyoid, digastric, sternohyoid, sternothyroid, and platysma muscles) within the radiation field after modified radical neck dissection type I and postoperative radiotherapy for floor of mouth cancer. A 70-year-old man underwent primary tumor resection of the left floor of mouth, left marginal mandibulectomy, left modified radical neck dissection type I, and reconstruction with a radial forearm free flap. The patient received adjuvant radiotherapy. The dose to the primary tumor bed and involved neck nodes was 63 Gy in 35 fractions over 7 weeks. Areas of subclinical disease (left lower neck) received 50 Gy in 25 fractions over 5 weeks. Adjuvant chemotherapy was not administered.

Oral manifestations of drug abuse disorders

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Nursyamsi Nursyamsi

2016-06-01

Full Text Available Narcotics is a highly addictive drug that acts as a stimulant or depresant for the central nervous system. The prevalence of various diseases found to be higher in the group of drug users then those who not use drugs such as endocarditis, hepatitis and HIV. Further evidence that the drug effects the oral health which includes the effect of the hard tissues by increased incidence of caries and periodontitis and the effect of the soft tissues in the form of leukoplakia and oral mucosal fibrosis, reduced production, especially the parotid salivary glands in amphetamine and cannabis users. In addition to the drug is a predisposing of oral infections such as candidiasis and gingivitis. Reduced volume of saliva on abusers may result in reduced immune function of saliva in maintaining oral health. Consequently the drug abusers increased number of bacteria and fungi in the oral cavity, including anaerobic bacteria and Candida albicans, especially in cases of abuse of cannabis. Gingival plaque formation and the growing colonies of anaerobic bacteria may increase the occurrence of gingivitis in the drug abusers. Lack of awareness of drug abusers in oral hygiene causing the gingivitis develops into periodontitis followed by alveolar bone loss.

Digital quantification of fibrosis in liver biopsy sections: description of a new method by Photoshop software.

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Dahab, Gamal M; Kheriza, Mohamed M; El-Beltagi, Hussien M; Fouda, Abdel-Motaal M; El-Din, Osama A Sharaf

2004-01-01

The precise quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease, as well as in evaluating the response to antifibrotic therapy. Because the recently described methods of digital image analysis of fibrosis in liver biopsy sections have major flaws, including the use of out-dated techniques in image processing, inadequate precision and inability to detect and quantify perisinusoidal fibrosis, we developed a new technique in computerized image analysis of liver biopsy sections based on Adobe Photoshop software. We prepared an experimental model of liver fibrosis involving treatment of rats with oral CCl4 for 6 weeks. After staining liver sections with Masson's trichrome, a series of computer operations were performed including (i) reconstitution of seamless widefield images from a number of acquired fields of liver sections; (ii) image size and solution adjustment; (iii) color correction; (iv) digital selection of a specified color range representing all fibrous tissue in the image and; (v) extraction and calculation. This technique is fully computerized with no manual interference at any step, and thus could be very reliable for objectively quantifying any pattern of fibrosis in liver biopsy sections and in assessing the response to antifibrotic therapy. It could also be a valuable tool in the precise assessment of antifibrotic therapy to other tissue regardless of the pattern of tissue or fibrosis.

A study to analyze the different patterns of quid usage among subjects with chewer′s mucosa

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Saba Khan

2012-01-01

Full Text Available Aim: Betel chewer′s mucosa, although not considered as a potentially malignant lesion, has been suggested to be a precursor of oral submucous fibrosis (OSMF. Thus a study was undertaken to asses various quid chewing patterns in patients with chewer′s mucosa and to evaluate possible association between chewer′s mucosa and a particular quid usage patter. Materials and methods: The study was done on 150 subjects clinically diagnosed of having chewers mucosa lesion. After complete oral examination, a detailed habit history was taken through preformed questionnaire. The data obtained was analyzed using Chi-square test. Results: Among the 150 subjects males to female ratio was 8:2- Majority of the subjects were within the age group of 20 to 30 years and chewed a combination of betel leaf, arecanut, tobacco, lime- Majority of the subjects of chewer′s mucosa used the quid for a duration of 1 to 5 years, a frequency of three to five quid per day. Conclusion: In the present study, chewers mucosa was seen in majority of the subjects who used the quid for a duration of 1 to 5 years, a frequency of three to five quid per day and chewed the quid containing betel leaf, arecanut, tobacco, lime as its constituents.

Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis.

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Johansen, Helle Krogh; Gøtzsche, Peter C

2015-08-23

Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review. To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. The authors independently selected trials, assessed them and extracted data. Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P Vaccines against

Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis.

Science.gov (United States)

Friedrich-Rust, Mireen; Schlueter, Nina; Smaczny, Christina; Eickmeier, Olaf; Rosewich, Martin; Feifel, Kirstin; Herrmann, Eva; Poynard, Thierry; Gleiber, Wolfgang; Lais, Christoph; Zielen, Stefan; Wagner, Thomas O F; Zeuzem, Stefan; Bojunga, Joerg

2013-09-01

Patients with cystic fibrosis (CF) have a relevant morbidity and mortality caused by CF-related liver-disease. While transient elastography (TE) is an established elastography method in hepatology centers, Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is a novel ultrasound-based elastography method which is integrated in a conventional ultrasound-system. The aim of the present study was to evaluate the prevalence of liver-fibrosis in patients with CF using TE, ARFI-imaging and fibrosis blood tests. 106 patients with CF were prospectively included in the present study and received ARFI-imaging of the left and right liver-lobe, ARFI of the pancreas TE of the liver and laboratory evaluation. The prevalence of liver-fibrosis according to recently published best practice guidelines for CFLD was 22.6%. Prevalence of significant liver-fibrosis assessed by TE, ARFI-right-liver-lobe, ARFI-left-liver-lobe, Fibrotest, Fibrotest-corrected-by-haptoglobin was 17%, 24%, 40%, 7%, and 16%, respectively. The best agreement was found for TE, ARFI-right-liver-lobe and Fibrotest-corrected-by-haptoglobin. Patients with pancreatic-insufficiency had significantly lower pancreas-ARFI-values as compared to patients without. ARFI-imaging and TE seem to be promising non-invasive methods for detection of liver-fibrosis in patients with CF. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Pathological assessment of liver fibrosis regression

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WANG Bingqiong

2017-03-01

Full Text Available Hepatic fibrosis is the common pathological outcome of chronic hepatic diseases. An accurate assessment of fibrosis degree provides an important reference for a definite diagnosis of diseases, treatment decision-making, treatment outcome monitoring, and prognostic evaluation. At present, many clinical studies have proven that regression of hepatic fibrosis and early-stage liver cirrhosis can be achieved by effective treatment, and a correct evaluation of fibrosis regression has become a hot topic in clinical research. Liver biopsy has long been regarded as the gold standard for the assessment of hepatic fibrosis, and thus it plays an important role in the evaluation of fibrosis regression. This article reviews the clinical application of current pathological staging systems in the evaluation of fibrosis regression from the perspectives of semi-quantitative scoring system, quantitative approach, and qualitative approach, in order to propose a better pathological evaluation system for the assessment of fibrosis regression.

Experimental models of liver fibrosis.

Science.gov (United States)

Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

2016-05-01

Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

Thoracic periaortal fibrosis and Ormond's disease

International Nuclear Information System (INIS)

Kacl, G.M.; Bino, M.; Salomon, F.; Risti, B.; Marincek, B.

1995-01-01

Two cases of thoracic periaortal fibrosis as a manifestation of retroperitoneal fibrosis (Ormond's disease) are shown on CT and MRI. Thoracic periaortal fibrosis can result in an inflammatory aneurysmo with chronic dissection. Manifestation of thoracic periaortal fibrosis may typically occur intermittently over decades. (orig.) [de

Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease.

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William Alazawi

Full Text Available Non-alcoholic fatty liver disease (NAFLD has a bidirectional association with metabolic syndrome. It affects up to 30% of the general population, 70% of individuals with diabetes and 90% with obesity. The main histological hallmark of progressive NAFLD is fibrosis. There is a bidirectional epidemiological link between periodontitis and metabolic syndrome. NAFLD, periodontitis and diabetes share common risk factors, are characterised by inflammation and associated with changes in commensal bacteria. Therefore we tested the hypothesis that periodontitis is associated with NAFLD and with significant fibrosis in two study groups.We analyzed data from a population-based survey and a patient-based study. NHANES III participants with abdominal ultrasound and sociodemographic, clinical, and oral examination data were extracted and appropriate weighting applied. In a separate patient-based study, consenting patients with biopsy-proved NAFLD (or with liver indices too mild to justify biopsy underwent dental examination. Basic Periodontal Examination score was recorded.In NHANES, periodontitis was significantly associated with steatosis in 8172 adults even after adjusting for sociodemographic factors. However, associations were fully explained after accounting for features of metabolic syndrome. In the patient-based study, periodontitis was significantly more common in patients with biopsy-proven NASH and any fibrosis (F0-F4 than without NASH (p = 0.009. Periodontitis was more common in patients with NASH and significant fibrosis (F2-4 than mild or no fibrosis (F0-1, p = 0.04.Complementary evidence from an epidemiological survey and a clinical study show that NAFLD is associated with periodontitis and that the association is stronger with significant liver fibrosis.

Role of cytokine gene (interferon-γ, transforming growth factor-β1, tumor necrosis factor-α, interleukin-6, and interleukin-10 polymorphisms in the risk of oral precancerous lesions in Taiwanese

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Han-Jen Hsu

2014-11-01

Full Text Available Oral squamous cell carcinoma can be preceded by some benign oral lesions with malignant potential, including leukoplakia, erythroplakia, oral lichen planus, and oral submucous fibrosis. There are different degrees of inflammatory cells infiltration in histopathology. Inflammatory cytokines may play a pathogenic role in the development of oral precancerous lesions (OPCLs. Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. We hypothesized that the risk of OPCLs might be associated with cytokine gene polymorphisms of interferon (IFN-γ, transforming growth factor (TGF-β1, tumor necrosis factor (TNF-α, interleukin (IL-6, and IL-10. In the present study, 42 OPCL patients and 128 controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874 T/A, TGF-β1 (codons 10 T/C and 25 G/C, TNF-α (−308 G/A, IL-6 (−174 G/C, and IL-10 (−1082 A/G, –819 T/C, and −592 A/C]. Cytokine genotyping was determined by the polymerase chain reaction sequence-specific primer technique using commercial primers. Allele and genotype data were analyzed for significance of differences between cases and controls using the Chi-square (χ2 test. Two-sided p < 0.05 were considered to be statistically significant. A series of multivariate logistic regression models, adjusted for age, sex, betel quid chewing, alcohol consumption, and smoking, was constructed in order to access the contribution of homozygous or heterozygous variant genotypes of polymorphisms. The TNF-α (−308 polymorphism was significantly associated with OPCLs. There were significant differences in the distribution of AA, GA, and GG genotypes between OPCL patients and controls (p = 0.0004. Patients with the AA or GA genotype had a 3.63-fold increased risk of OPCLs. The TGF-β1 (codon 10 and 25 polymorphism was also significantly associated with OPCLs (p < 0.001. The IL-6 polymorphism was significantly associated with OPCLs

Role of nitric oxide and KATP channel in the protective effect mediated by nicorandil in bile duct ligation-induced liver fibrosis in rats.

Science.gov (United States)

Mohamed, Yasmin S; Ahmed, Lamiaa A; Salem, Hesham A; Agha, Azza M

2018-05-01

Liver fibrosis is one of the most serious conditions affecting patients worldwide. In the present study, the role of nitric oxide and KATP channel was investigated for the first time in the possible protection mediated by nicorandil in bile duct ligation-induced liver fibrosis in rats. Nicorandil (3 mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed marked improvement in liver function tests, hepatic oxidative stress and inflammatory markers as well as inducible and endothelial nitric oxide synthase protein expressions. Furthermore, nicorandil administration led to significant decrement of phosphorylated protein kinase C, fibrosis and hepatic stellate cells activation as indicated by decreased alpha smooth muscle actin expression. Oral co-administration of glibenclamide (5 mg/kg/day) (a KATP channel blocker) with nicorandil mostly showed similar improvement though not reaching to that of nicorandil group. However, co-adminstration of L-NAME (15 mg/kg/day) (an inhibitor of nitric oxide synthase) completely abolished the protective effects of nicorandil and produced more or less similar results to that of untreated bile duct ligated group. In conclusion, nicorandil is an effective therapy against the development of bile duct ligation-induced liver fibrosis in rats where nitric oxide plays a more prominent role in the protective effect of nicorandil than KATP channel opening. Copyright © 2018 Elsevier Inc. All rights reserved.

Syndecans in heart fibrosis.

Science.gov (United States)

Lunde, Ida G; Herum, Kate M; Carlson, Cathrine C; Christensen, Geir

2016-09-01

Heart disease is a deadly syndrome affecting millions worldwide. It reflects an unmet clinical need, and the disease mechanisms are poorly understood. Cardiac fibrosis is central to heart disease. The four-membered family of transmembrane proteoglycans, syndecan-1 to -4, is believed to regulate fibrosis. We review the current literature concerning syndecans in cardiac fibrosis. Syndecan expression is up-regulated in response to pro-inflammatory stimuli in various forms of heart disease with fibrosis. Mice lacking syndecan-1 and -4 show reduced activation of pro-fibrotic signaling and increased cardiac rupture upon infarction indicating an important role for these molecules. Whereas the short cytoplasmic tail of syndecans regulates signaling, their extracellular part, substituted with heparan sulfate glycosaminoglycan chains, binds a plethora of extracellular matrix (ECM) molecules involved in fibrosis, e.g., collagens, growth factors, cytokines, and immune cell adhesion proteins. Full-length syndecans induce pro-fibrotic signaling, increasing the expression of collagens, myofibroblast differentiation factors, ECM enzymes, growth factors, and immune cell adhesion molecules, thereby also increasing cardiac stiffness and preventing cardiac rupture. Upon pro-inflammatory stimuli, syndecan ectodomains are enzymatically released from heart cells (syndecan shedding). Shed ectodomains affect the expression of ECM molecules, promoting ECM degradation and cardiac rupture upon myocardial infarction. Blood levels of shed syndecan-1 and -4 ectodomains are associated with hospitalization, mortality, and heart remodeling in patients with heart failure. Improved understanding of syndecans and their modifying enzymes in cardiac fibrosis might contribute to the development of compounds with therapeutic potential, and enzymatically shed syndecan ectodomains might constitute a future prognostic tool for heart diseases with fibrosis. Graphical Abstract Graphical abstract summarizing

Imaging pulmonary fibrosis

International Nuclear Information System (INIS)

Brauner, M.W.; Rety, F.; Naccache, J.M.; Girard, F.; Valeyre, D.F.

2001-01-01

Localized fibrosis of the lung is usually scar tissue while diffuse pulmonary fibrosis is more often a sign of active disease. Chronic infiltrative lung disease may be classified into four categories: idiopathic pneumonitis, collagen diseases, granulomatosis (sarcoidosis), and caused by known diseases (pneumoconiosis, hypersensitivity pneumonitis, drug-induced lung disease, radiation). (authors)

Nephrogenic systemic fibrosis

DEFF Research Database (Denmark)

Marckmann, Peter; Skov, Lone; Rossen, Kristian

2006-01-01

Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases...... of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75...... d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P

Fibrosis and Cancer

DEFF Research Database (Denmark)

Cox, Thomas R.; Erler, Janine T.

2016-01-01

The relation between fibrosis and cancer has long been debated, specifically whether desmoplasia precedes, accompanies, or succeeds tumourigenesis, progression, and metastasis. Recent reports have published opposing data, adding to the perplexity. However, what is emerging is that it is likely th...... the specific properties of the extracellular matrix (ECM) that determine the paradoxical nature of cancer-associated fibrosis....

Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats

Directory of Open Access Journals (Sweden)

Cheng-Jeng Tai

2016-02-01

Full Text Available Background: Advanced glycation end products (AGEs signal through the receptor for AGE (RAGE, which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs and hyperglycemia induced by high-fat diet with ethanol. Methods: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30% with ethanol (10%. Male Wistar rats (4 weeks of age were randomly divided into four groups (n = 6: (1 control (basal diet; (2 HFD (30% + ethanol (10% (HFD/ethanol; (3 HFD/ethanol + AESN (100 mg/kg, oral administration; and (4 HFD/ethanol + pioglitazone (10 mg/kg, oral administration and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. Results: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα, PPARγ co-activator (PGC-1α, carbohydrate response element-binding protein (ChREBP, acetyl-CoA carboxylase (ACC, and fatty acid synthase (FAS mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA inhibition and MMP-2 production. Conclusions: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.

Oral protein calorie supplementation for children with chronic disease.

Science.gov (United States)

Francis, Damian K; Smith, Joanne; Saljuqi, Tawab; Watling, Ruth M

2015-05-27

Poor growth and nutritional status are common in children with chronic diseases. Oral protein calorie supplements are used to improve nutritional status in these children. These expensive products may be associated with some adverse effects, e.g. the development of inappropriate eating behaviour patterns. This is a new update of a Cochrane review last updated in 2009. To examine evidence that in children with chronic disease, oral protein calorie supplements alter daily nutrient intake, nutritional indices, survival and quality of life and are associated with adverse effects, e.g. diarrhoea, vomiting, reduced appetite, glucose intolerance, bloating and eating behaviour problems. Trials of oral protein calorie supplements in children with chronic diseases were identified through comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Companies marketing these products were also contacted.Most recent search of the Group's Trials Register: 24 February 2015. Randomised or quasi-randomised controlled trials comparing oral protein calorie supplements for at least one month to increase calorie intake with existing conventional therapy (including advice on improving nutritional intake from food or no specific intervention) in children with chronic disease. We independently assessed the outcomes: indices of nutrition and growth; anthropometric measures of body composition; calorie and nutrient intake (total from oral protein calorie supplements and food); eating behaviour; compliance; quality of life; specific adverse effects; disease severity scores; and mortality; we also assessed the risk of bias in the included trials. Four studies (187 children) met the inclusion criteria. Three studies were carried out in children with cystic fibrosis and one study included children with paediatric malignant disease. Overall there was a low risk of bias for blinding and incomplete outcome data.Two studies had a high

Novel short chain fatty acids restore chloride secretion in cystic fibrosis

International Nuclear Information System (INIS)

Nguyen, Toan D.; Kim, Ug-Sung; Perrine, Susan P.

2006-01-01

Phenylalanine deletion at position 508 of the cystic fibrosis transmembrane conductance regulator (ΔF508-CFTR), the most common mutation in cystic fibrosis (CF), causes a misfolded protein exhibiting partial chloride conductance and impaired trafficking to the plasma membrane. 4-Phenylbutyrate corrects defective ΔF508-CFTR trafficking in vitro, but is not clinically efficacious. From a panel of short chain fatty acid derivatives, we showed that 2,2-dimethyl-butyrate (ST20) and α-methylhydrocinnamic acid (ST7), exhibiting high oral bioavailability and sustained plasma levels, correct the ΔF508-CFTR defect. Pre-incubation (≥6 h) of CF IB3-1 airway cells with ≥1 mM ST7 or ST20 restored the ability of 100 μM forskolin to stimulate an 125 I - efflux. This efflux was fully inhibited by NPPB, DPC, or glibenclamide, suggesting mediation through CFTR. Partial inhibition by DIDS suggests possible contribution from an additional Cl - channel regulated by CFTR. Thus, ST7 and ST20 offer treatment potential for CF caused by the ΔF508 mutation

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

OpenAIRE

Lee, Eunjo; Song, Min-ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

2016-01-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats...

Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study

DEFF Research Database (Denmark)

Pincikova, T; Nilsson, Kristine Kahr; Moen, I E

2011-01-01

Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis...

Subretinal fibrosis and uveitis: a spectral domain OCT study of its evolution and the minimal therapeutic effect of the off-label treatment with ranibizumab.

Science.gov (United States)

Symeonidis, Chrysanthos; Dastiridou, Anna; Konidaris, Vasilis; Brazitikos, Periklis; Androudi, Sofia

2014-12-01

The subretinal fibrosis and uveitis (SFU) syndrome is a rare multifocal posterior uveitis characterized by progressive subretinal fibrosis and significant visual loss. Slit-lamp examination, dilated fundoscopy, fluorescein angiography, Spectral Domain-Optical Coherence Tomography (SD-OCT) and laboratory testing were employed. A 52-year-old male presented with bilateral (best-corrected visual acuity: 2/10) visual loss. Clinical examination revealed bilateral anterior uveitis with posterior synechiae and posterior uveitis. Medical workup revealed no pathologic findings. Treatment included 1 gr intravenous prednisone followed by oral prednisone, immunosuppresive therapy and three ranibizumab injections in the right eye with no improvement. One year later, there was significant subretinal fibrosis. In the second year follow-up, the picture was slightly worse, with persisting bilateral macular edema and fibrosis. This is the first SFU syndrome report monitored with SD-OCT. This novel imaging modality can localize the lesion level, guide the therapeutic approach and may prove helpful in assessing disease prognosis.

Proteome analysis of Radiation-induced pulmonary fibrosis

International Nuclear Information System (INIS)

Song, Jie Young; Lim, Hee Soon; Kim, Hyung Doo; Shim, Ji Young; Han, Young Soo; Son, Hyeog Jin Son; Yun, Yeon Sook

2005-01-01

Pulmonary fibrosis is perhaps the most universal late effect of organ damage after both chemical insult and irradiation in the treatment of lung cancer. The use chemotherapy and radiation therapy, alone or combined, can be associated with clinically significant pulmonary toxicity, which leads to pneumonia and pulmonary fibrosis. It is also reported that about 100,000 people in the United States are suffered from pulmonary fibrosis. Therefore, pulmonary fibrosis will be more focused by medicinal researchers. Because current therapies, aimed at inhibiting pulmonary inflammation that often precedes fibrosis, are effective only in a minority of suffered patients, novel therapeutic methods are highly needed. Some researchers have used bleomycininduced pulmonary fibrosis as a basis for looking at the molecular mechanisms of fibrosis, and total gene expression was monitored using genomics method. However, radiation-induced pulmonary fibrosis has not been fully focused and investigated. Here, we have analyzed changes in gene expression in response to γ- irradiation by using proteomic analysis

Non-invasive tests in prediction of liver fibrosis in chronic hepatitis B and comparison with post-antiviral treatment results.

Science.gov (United States)

Başar, Omer; Yimaz, Bariş; Ekiz, Fuat; Giniş, Zeynep; Altinbaş, Akif; Aktaş, Bora; Tuna, Yaşar; Çoban, Sahin; Delibaş, Namik; Yüksel, Osman

2013-04-01

The aim of this study was to assess and compare the performance of a series of non-invasive tests to detect fibrosis in patients with chronic hepatitis B (CHB). Seventy-six patients with CHB, whose blood samples were collected and biopsies were done on the same day, were included in this study. Pre-treatment calculations of aspartate aminotransferase to platelet ratio index (APRI), Forn's index, FIB-4, S-index, Shanghai Liver Fibrosis Group's index (SLFG) and Hepascore(®) were done and relations with mild and advanced fibrosis and cirrhosis were assessed. Post-treatment values of APRI, Forn's index, FIB-4, S-index with oral antiviral agents were also investigated. APRI, S-index, SLFG, FIB-4, Forn's index and Hepascore(®) had 0.669, 0.669, 0.739, 0.741, 0.753, 0.780; retrospectively Area Under the Receiver Operating Characteristic Curve (AUROC) for significant fibrosis. APRI, Forn's index, S-index, FIB-4, SLFG, and Hepascore(®) had 0.681, 0.714, 0.715, 0.738, 0.747, 0.777 retrospectively AUROC for advanced fibrosis. APRI, SLFG, FIB-4, Forn's index, S-index, and Hepascore(®) had 0.741, 0.742, 0.768, 0.779, 0.792, 0.824 retrospectively AUROC for cirrhosis. APRI, Forn's index, FIB-4 and S-index were significantly lower in post-treatment group compared with pre-treatment group (P-values: fibrosis. Our study also suggests that the use of non-invasive test to predict fibrosis in patients with CHB may reduce the need for liver biopsy and may help to monitor the efficacy of treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis.

Science.gov (United States)

Locatelli, Luigi; Cadamuro, Massimiliano; Spirlì, Carlo; Fiorotto, Romina; Lecchi, Silvia; Morell, Carola Maria; Popov, Yury; Scirpo, Roberto; De Matteis, Maria; Amenduni, Mariangela; Pietrobattista, Andrea; Torre, Giuliano; Schuppan, Detlef; Fabris, Luca; Strazzabosco, Mario

2016-03-01

Congenital hepatic fibrosis (CHF) is a disease of the biliary epithelium characterized by bile duct changes resembling ductal plate malformations and by progressive peribiliary fibrosis, in the absence of overt necroinflammation. Progressive liver fibrosis leads to portal hypertension and liver failure; however, the mechanisms leading to fibrosis in CHF remain elusive. CHF is caused by mutations in PKHD1, a gene encoding for fibrocystin, a ciliary protein expressed in cholangiocytes. Using a fibrocystin-defective (Pkhd1(del4/del4)) mouse, which is orthologous of CHF, we show that Pkhd1(del4/del4) cholangiocytes are characterized by a β-catenin-dependent secretion of a range of chemokines, including chemokine (C-X-C motif) ligands 1, 10, and 12, which stimulate bone marrow-derived macrophage recruitment. We also show that Pkhd1(del4/del4) cholangiocytes, in turn, respond to proinflammatory cytokines released by macrophages by up-regulating αvβ6 integrin, an activator of latent local transforming growth factor-β1. While the macrophage infiltrate is initially dominated by the M1 phenotype, the profibrogenic M2 phenotype increases with disease progression, along with the number of portal myofibroblasts. Consistent with these findings, clodronate-induced macrophage depletion results in a significant reduction of portal fibrosis and portal hypertension as well as of liver cysts. Fibrosis can be initiated by an epithelial cell dysfunction, leading to low-grade inflammation, macrophage recruitment, and collagen deposition; these findings establish a new paradigm for biliary fibrosis and represent a model to understand the relationship between cell dysfunction, parainflammation, liver fibrosis, and macrophage polarization over time. © 2015 by the American Association for the Study of Liver Diseases.

Angiogenesis in liver fibrosis

NARCIS (Netherlands)

Adlia, Amirah

2017-01-01

Angiogenesis emerges in parallel with liver fibrosis, but it is still unclear whether angiogenesis is a defense mechanism of the body in response to fibrosis, or whether it aggravates the fibrotic condition. In this thesis, Amirah Adlia applied different approaches to elucidate the role of

Protein S is protective in pulmonary fibrosis.

Science.gov (United States)

Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

2016-08-01

Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar

Pulmonary fibrosis

International Nuclear Information System (INIS)

Yamakido, Michio; Okuzaki, Takeshi

1992-01-01

When the chest is exposed to x radiation and Co-60 gamma radiation, radiation damage may occur in the lungs 2 to 10 weeks after irradiation. This condition is generally referred to as radiation pneumonitis, with the incidence ranging from 5.4% to 91.8% in the literature. Then radiation pneumonitis may develop into pulmonary fibrosis associated with roentgenologically diffuse linear and ring-like shadows and strong contraction 6 months to one year after irradiation. Until recently, little attention has been paid to pulmonary pneumonitis as a delayed effect of A-bomb radiation. The recent study using the population of 9,253 A-bomb survivors have suggested that the prevalence of pulmonary fibrosis tended to be high in heavily exposed A-bomb survivors. Two other studies using the cohort of 16,956 and 42,728 A-bomb survivors, respectively, have shown that the prevalence of roentgenologically proven pulmonary fibrosis was higher in men than women (1.82% vs 0.41%), was increased with aging and had a higher tendency in heavily exposed A-bomb survivors. (N.K.)

Neonatal cystic fibrosis screening test

Science.gov (United States)

Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

Diagnosis of cystic fibrosis

NARCIS (Netherlands)

H.J. Veeze

1995-01-01

textabstractApplying the sweat-test as the first choice of test when a diagnosis of cystic fibrosis is suspected is still common practice and advisable. Since the cloning of the CFTR gene more than 400 different cystic fibrosis (CF) mutations have already been identified. The use of CF mutation

Fibrosis of Two: Epithelial Cell-Fibroblast Interactions in Pulmonary Fibrosis

Science.gov (United States)

Sakai, Norihiko; Tager, Andrew M.

2013-01-01

Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the “pas de deux” (steps of two), or perhaps more appropriate to IPF pathogenesis, the “folie à deux” (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their “fibrosis of two”, including transforming growth factor-β, connective tissue growth factor, sonic hedgehog, prostaglandin E2, angiotensin II and reactive oxygen species. PMID:23499992

Amlodipine decreases fibrosis and cardiac hypertrophy in spontaneously hypertensive rats: persistent effects after withdrawal.

Science.gov (United States)

Sevilla, María A; Voces, Felipe; Carrón, Rosalía; Guerrero, Estela I; Ardanaz, Noelia; San Román, Luis; Arévalo, Miguel A; Montero, María J

2004-07-02

Our objective was to examine the effect of chronic treatment with amlodipine on blood pressure, left ventricular hypertrophy, and fibrosis in spontaneously hypertensive rats and the persistence of such an effect after drug withdrawal. We investigated the effects of treatment with 2, 8 and 20 mg/kg/day of amlodipine given orally for six months and at three months after drug withdrawal. Systolic blood pressure was measured using the tail-cuff method. At the end of the study period, the heart was excised, the left ventricle was isolated, and the left ventricle weight/body weight ratio was calculated as a left ventricular hypertrophy index. Fibrosis, expressed as collagen volume fraction, was evaluated using an automated image-analysis system on sections stained with Sirius red. Age-matched untreated Wistar-Kyoto and SHR were used as normotensive and hypertensive controls, respectively. Systolic blood pressure was reduced in the treated SHR in a dose-dependent way and after amlodipine withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy was reduced by 8 and 20 mg/kg/day amlodipine, but when treatment was withdrawn only the group treated with 8 mg/kg/day maintained significant differences versus the hypertensive controls. All three doses of amlodipine reduced cardiac fibrosis and this regression persisted with the two highest doses after three months without treatment. We concluded that antihypertensive treatment with amlodipine is accompanied by a reduction in left ventricular hypertrophy and regression in collagen deposition. Treatment was more effective in preventing fibrosis than in preventing ventricular hypertrophy after drug withdrawal. Copyright 2004 Elsevier Inc.

Breakdown in Breathing: The Complexities of Cystic Fibrosis

Science.gov (United States)

... Healthier Lungs in Kids Wise Choices Living with Cystic Fibrosis In between checkups, practice good self-care and ... Links What Is Cystic Fibrosis? Learning About Cystic Fibrosis NIH Cystic Fibrosis Fact Sheet Genetic and Rare Diseases Information ...

Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1.

Science.gov (United States)

Peng, Wen-Huang; Tien, Yun-Chen; Huang, Chih-Yang; Huang, Tai-Hung; Liao, Jung-Chun; Kuo, Chao-Lin; Lin, Ying-Chih

2010-02-17

To investigate the effect of Fraxinus rhynchophylla ethanol extract (FR(EtOH)) on liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats. Rat hepatic fibrosis was induced by oral administration of CCl(4). Sixty SD rats were divided randomly into 6 groups: control, CCl(4) group, silymarin group and three FR(EtOH)-treated groups. Except for the rats in control group, all rats were administered orally with CCl(4) (20%, 0.2 mL/100g body weight) twice a week for 8 weeks. Rats in FR(EtOH) groups were treated daily with FR(EtOH) (0.1, 0.5 and 1.0 g/kg, p.o.) throughout the whole experimental period. Liver function parameters (such as activities of serum GOT and GPT levels), activities of liver anti-oxidant enzymes (such as catalase, SOD, GPx) and expressions of uPA, tPA, MMP-2, MMP-9 and TIMP-1, -2, -3, -4 in the liver fibrosis pathway were detected. The results showed that FR(EtOH) (0.1, 0.5 and 1.0 g/kg BW) significantly reduced the elevated activities of sGOT and sGPT caused by CCl(4). FR(EtOH) (0.1 and 0.5 g/kg BW) and significantly increased the activities of GSH-Px. The histopathological study showed that FR(EtOH) (0.1 and 0.5 g/kg BW) reduced the incidence of liver lesions, including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization hepatic necrosis and fibrous connective tissue proliferated induced by CCl(4) in rats. In our study it was showed that CCl(4)-treated group significantly increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FR(EtOH) (0.1 and 0.5 g/kg BW) could inhibit the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. Finally, the amount of esculetin in the FR(EtOH) was 33.54 mg/g extract. Oral administration of FR(EtOH) significantly reduces CCl(4)-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular fibrosis by its free radical scavenging ability. FR(EtOH) down-regulated the expressions of uPA, MMP-2 and MMP-9 in CCl(4)-induced liver fibrosis in rats

Serum markers of liver fibrosis

DEFF Research Database (Denmark)

Veidal, Sanne Skovgård; Bay-Jensen, Anne-Christine; Tougas, Gervais

2010-01-01

-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. METHODS: Pubmed was search for keywords; Liver fibrosis, neo......, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis....

A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis.

Science.gov (United States)

Calès, Paul; Boursier, Jérôme; Oberti, Frédéric; Moal, Valérie; Fouchard Hubert, Isabelle; Bertrais, Sandrine; Hunault, Gilles; Rousselet, Marie Christine

2018-04-01

Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis-stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi-FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeter V2G ) with those of a test targeted for cirrhosis (CirrhoMeter V2G ). In the derivation CHC population, we first compared Multi-FibroMeter V2G to FibroMeter V2G and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis-stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeter V2G and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi-FibroMeter V2G and FibroMeter V2G were the following: cirrhosis AUROC, 0.906 versus 0.878 ( P fibrosis AUROC, 0.833 versus 0.832 ( P = 0.366). Multi-FibroMeter V2G had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates

Voice Disorder in Cystic Fibrosis Patients

Science.gov (United States)

Lourenço, Bruna Mendes; Costa, Kauê Machado; da Silva Filho, Manoel

2014-01-01

Cystic fibrosis is a common autosomal recessive disorder with drastic respiratory symptoms, including shortness of breath and chronic cough. While most of cystic fibrosis treatment is dedicated to mitigating the effects of respiratory dysfunction, the potential effects of this disease on vocal parameters have not been systematically studied. We hypothesized that cystic fibrosis patients, given their characteristic respiratory disorders, would also present dysphonic symptoms. Given that voice disorders can severely impair quality of life, the identification of a potential cystic fibrosis-related dysphonia could be of great value for the clinical evaluation and treatment of this disease. We tested our hypothesis by measuring vocal parameters, using both objective physical measures and the GRBAS subjective evaluation method, in male and female cystic fibrosis patients undergoing conventional treatment and compared them to age and sex matched controls. We found that cystic fibrosis patients had a significantly lower vocal intensity and harmonic to noise ratio, as well as increased levels of jitter and shimmer. In addition, cystic fibrosis patients also showed higher scores of roughness, breathiness and asthenia, as well as a significantly altered general grade of dysphonia. When we segregated the results according to sex, we observed that, as a group, only female cystic fibrosis patients had significantly lower values of harmonic to noise ratio and an abnormal general grade of dysphonia in relation to matched controls, suggesting that cystic fibrosis exerts a more pronounced effect on vocal parameters of women in relation to men. Overall, the dysphonic characteristics of CF patients can be explained by dysfunctions in vocal fold movement and partial upper airway obstruction, potentially caused by the accumulation of mucus and chronic cough characteristic of CF symptomatology. Our results show that CF patients exhibit significant dysphonia and suggest they may

Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model.

Science.gov (United States)

Inoue, Ken; Naito, Yuji; Takagi, Tomohisa; Hayashi, Natsuko; Hirai, Yasuko; Mizushima, Katsura; Horie, Ryusuke; Fukumoto, Kohei; Yamada, Shinya; Harusato, Akihito; Hirata, Ikuhiro; Omatsu, Tatsushi; Yoshida, Naohisa; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Handa, Osamu; Konishi, Hideyuki; Wakabayashi, Naoki; Yagi, Nobuaki; Ichikawa, Hiroshi; Kokura, Satoshi; Yoshikawa, Toshikazu

2011-01-01

Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor β1 (TGF-β1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-β1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

Taurine attenuates radiation-induced lung fibrosis in C57/Bl6 fibrosis prone mice.

LENUS (Irish Health Repository)

Robb, W B

2010-03-01

The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine\\'s effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy.

Nilotinib counteracts thioacetamide-induced hepatic oxidative stress and attenuates liver fibrosis progression.

Science.gov (United States)

Shaker, Mohamed E; Salem, Hatem A; Shiha, Gamal E; Ibrahim, Tarek M

2011-04-01

The aim of this study was to evaluate and compare the effects of imatinib and nilotinib to that of silymarin on established liver fibrosis and oxidative stress in a thioacetamide (TAA) rat model. Male Wistar rats received intraperitoneal (i.p.) injections of TAA (150mg/kg, twice weekly) for 12weeks. Daily treatments with imatinib (10mg/kg), nilotinib (10mg/kg), and silymarin (100mg/kg) were administered orally during the last 4weeks of TAA-administration. At the end of the study, hepatic damage was evaluated by analysis of liver function tests in serum. Hepatic histopathology and collagen content were employed to quantify liver fibrosis. Hepatic oxidative stress was assessed by measuring malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), total nitrate/nitrite (NOx), and reduced glutathione (GSH) contents, as well as myeloperoxidase (MPO) and superoxide dismutase (SOD) activities. Nilotinib, silymarin and, to a lesser extent, imatinib treatments ameliorated TAA-induced hepatic oxidative stress and damage as indicated by hepatic MDA, 4-HNE, NOx, GSH, MPO and SOD levels, as well as liver function tests. Hepatic histopathology results revealed that nilotinib, imatinib, and silymarin treatments decreased the mean score of fibrosis in TAA-treated rats by 24, 14, and 3%, respectively. However, nilotinib and silymarin, but not imatinib, treatments decreased hepatic collagen content in TAA-treated rats by 17 and 36%, respectively. In conclusion, we demonstrated for the first time that nilotinib not only protected against hepatic oxidative stress, but also slowed down liver fibrosis progression. Thus, we provide the first evidence that nilotinib might be a promising anti-fibrotic drug. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression.

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Eraky, Salma M; El-Mesery, Mohamed; El-Karef, Amro; Eissa, Laila A; El-Gayar, Amal M

2018-05-01

Lysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis. Hepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks. Silymarin (50 mg/kg), caffeine (50 mg/kg), and their combination (50 mg/kg silymarin + 50 mg/kg caffeine) were orally given to rats every day for 8 weeks along with TAA injection. Liver functions were measured. Histopathological examination of liver tissues was performed using hematoxylin and eosin and Masson's trichrome staining. mRNA expressions of LPAR1, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), and alpha smooth muscle actin (α-SMA) were measured using RT-PCR. LPAR1 tissue expression was scored using immunohistochemistry. Silymarin, caffeine, and their combination significantly improved liver function. They caused significant decrease in fibrosis and necro-inflammatory scores. Combination of silymain and caffeine caused a significant decrease in the necro-inflammatory score than the single treatment with silymarin or caffeine. In addition, silymarin, caffeine, and their combination significantly decreased hepatic LPAR1, TGF-β1, CTGF, and α-SMA gene expressions and LPAR1 tissue expression. Silymarin, caffeine, and their combination protect against liver fibrosis through down-regulation of LPAR1, TGF-β1, and CTGF. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Serum adiponectin is increased in advancing liver fibrosis and declines with reduction in fibrosis in chronic hepatitis B.

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Hui, Chee-Kin; Zhang, Hai-Ying; Lee, Nikki P; Chan, Weng; Yueng, Yui-Hung; Leung, Kar-Wai; Lu, Lei; Leung, Nancy; Lo, Chung-Mau; Fan, Sheung-Tat; Luk, John M; Xu, Aimin; Lam, Karen S; Kwong, Yok-Lam; Lau, George K K

2007-08-01

Despite the possible role of adiponectin in the pathogenesis of liver cirrhosis, few data have been collected from patients in different stages of liver fibrosis. We studied the role of adiponectin in 2 chronic hepatitis B (CHB)-patient cohorts. Serum adiponectin was quantified by enzyme-linked immunosorbent assay. One-hundred liver biopsy specimens from CHB patients with different stages of fibrosis and 38 paired liver biopsies from hepatitis B e antigen-positive patients randomized to lamivudine (n=15), pegylated interferon alfa-2a (n=15) or pegylated interferon alfa-2a plus lamivudine (n=8) therapy for 48 weeks were assessed. Serum adiponectin was detected at levels ranging over fourfold magnitude with advancing fibrosis stage and correlated positively with fibrosis stage [r=0.45, p<0.001]. CHB patients with stage 0-1 fibrosis had higher composition of high molecular weight (HMW) form of adiponectin when compared with CHB patients with liver cirrhosis [mean+/-SEM 51.2+/-2.1% vs. 40.9+/-1.7%, respectively, p=0.001]. After antiviral therapy, patients with fibrosis reduction had marked decline in serum adiponectin level and increase in HMW form of adiponectin [mean+/-SEM 43.5+/-1.2% vs. 37.0+/-3.0%, respectively, p=0.04]. Serum adiponectin may have a role in fibrosis progression in CHB infection. A marked decline in serum adiponectin after antiviral therapy is associated with fibrosis reduction.

Endomyocardial fibrosis in infancy

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Jatene Marcelo Biscegli

2003-01-01

Full Text Available The patient was a 4-month-old infant, who underwent persistent ductus arteriosus interruption with titanium clips at the age of 13 days and, since the age of 2 months, had crises of hypoxia and hypertonicity. After clinical investigation, the presence of pulmonary hypertension was confirmed and left ventricular inflow tract obstruction was suspected. The patient underwent surgical treatment at the age of 4 months, during which right and left ventricular endocardial fibrosis was identified. The fibrosis was resected, but the infant had an unfavorable clinical evolution with significant diastolic restriction and died on the sixth postoperative day. Anatomicopathological and surgical findings suggested endomyocardial fibrosis, although that pathology is very rare at the patient's age.

Gastrointestinal Manifestations of Cystic Fibrosis

Science.gov (United States)

2016-01-01

Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

Therapeutic targets in liver fibrosis.

Science.gov (United States)

Fallowfield, Jonathan A

2011-05-01

Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

Antifibrotic effect of aloe vera in viral infection-induced hepatic periportal fibrosis

Science.gov (United States)

Hegazy, Sahar K; El-Bedewy, Mohamed; Yagi, Akira

2012-01-01

significantly after treatment. The expression of α-SMA was modified in patients before and after treatment as compared with the normal controls. In the conventional group, there was only thin and incomplete parenchymal α-SMA positive septum joining the thickened centrilobular veins, while in the AHM group, few α-SMA positive cells were present in sinusoid and lobule after treatment. CONCLUSION: Oral supplementation with AHM could be helpful in alleviating the fibrosis and inflammation of hepatic fibrosis patients. PMID:22563189

Non-Invasive Evaluation of Cystic Fibrosis Related Liver Disease in Adults with ARFI, Transient Elastography and Different Fibrosis Scores

OpenAIRE

Karlas, Thomas; Neuschulz, Marie; Oltmanns, Annett; Güttler, Andrea; Petroff, David; Wirtz, Hubert; Mainz, Jochen G.; Mössner, Joachim; Berg, Thomas; Tröltzsch, Michael; Keim, Volker; Wiegand, Johannes

2012-01-01

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is present in up to 30% of cystic fibrosis patients and can result in progressive liver failure. Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver fibrosis display an interesting diagnostic approach for CFLD detection. AIM: We evaluated transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and fibrosis indices for CFLD detection. METHODS: TE and ARFI were performed in 55 adult CF patient...

Nanoparticles for the treatment of liver fibrosis

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Poilil Surendran S

2017-09-01

Full Text Available Suchithra Poilil Surendran, Reju George Thomas, Myeong Ju Moon, Yong Yeon Jeong Department of Radiology, BioMolecular Theranostics (BiT Lab, Chonnam National University Medical School, Chonnam National University Hwasun Hospital (CNUHH, South Korea Abstract: Chronic liver diseases represent a global health problem due to their high prevalence worldwide and the limited available curative treatment options. They can result from various causes, both infectious and noninfectious diseases. The application of nanoparticle (NP systems has emerged as a rapidly evolving area of interest for the safe delivery of various drugs and nucleic acids for chronic liver diseases. This review presents the pathogenesis, diagnosis and the emerging nanoparticulate systems used in the treatment of chronic liver diseases caused by liver fibrosis. Activated hepatic stellate cell (HSC is considered to be the main mechanism for liver fibrosis. Ultrasonography and magnetic resonance imaging techniques are widely used noninvasive diagnostic methods for hepatic fibrosis. A variety of nanoparticulate systems are mainly focused on targeting HSC in the treatment of hepatic fibrosis. As early liver fibrosis is reversible by current NP therapy, it is being studied in preclinical as well as clinical trials. Among various nanoparticulate systems, inorganic NPs, liposomes and nanomicelles have been widely studied due to their distinct properties to deliver drugs as well as other therapeutic moieties. Liposomal NPs in clinical trials is considered to be a milestone in the treatment of hepatic fibrosis. Currently, NP therapy for liver fibrosis is updating fast, and hopefully, it can be the future remedy for liver fibrosis. Keywords: liver fibrosis, inorganic nanoparticles, liposomes, micelles

Tobacco use, Body Mass Index, and Potentially Malignant Disorders Among petrol fillers in Pimpri-Pune (India: A descriptive study

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Mamatha G. S. Reddy

2014-01-01

Full Text Available Background: Since petrol is combustible and smoking is banned at the petrol pumps, it may be predicted that use of smokeless tobacco is more prevalent among the petrol fillers. Also, smokeless tobacco is a major risk factor for developing oral potentially malignant disorders. The present study was conducted to determine the tobacco use, body mass index (BMI, and potentially malignant disorders among a cohort of petrol fillers and also to evaluate the interaction of tobacco use and BMI with the presence of potentially malignant disorders. Settings and Design: The study was conducted at 45 petrol stations located at Pimpri-Pune, India. A descriptive study design was used. Materials and Method: Four hundred and ten petrol fillers aged 17-64 years participated in the study. General information and tobacco history was obtained by interview. Height and weight were recorded to obtain BMI. Oral examination was conducted to identify the potentially malignant disorders. Statistical analysis: Chi-square test, Z test, and logistic regression were used. The level of significance was fixed at 5%. Results and Conclusions: It was found that 242 (59.02% used tobacco in different forms. 77.68% were tobacco chewers, and 8.26% were smokers. Leukoplakia was prevalent among 68.47%, oral submucous fibrosis among 27.45%, and 5.08% had erythroplakia. Age (χ2 = 11.46, P < 0.05, duration (χ2 = 17.46, P < 0.05, and frequency of tobacco chewing (χ2 = 14.16, P < 0.05 were significantly associated with potentially malignant disorders. Tobacco chewing was more prevalent as compared to smoking. It can be concluded that the petrol fillers are at a high risk for developing oral potentially malignant disorders.

Anti-fibrotic effects of a novel small compound on the regulation of cytokine production in a mouse model of colorectal fibrosis

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Imai, Jin [Center for Matrix Biology and Medicine, Tokai University School of Medicine, Kanagawa (Japan); Department of Gastroenterology, Tokai University School of Medicine, Kanagawa (Japan); Hozumi, Katsuto, E-mail: hozumi@is.icc.u-tokai.ac.jp [Center for Matrix Biology and Medicine, Tokai University School of Medicine, Kanagawa (Japan); Department of Immunology, Tokai University School of Medicine, Kanagawa (Japan); Sumiyoshi, Hideaki [Center for Matrix Biology and Medicine, Tokai University School of Medicine, Kanagawa (Japan); Department of Regenerative Medicine, Tokai University School of Medicine, Kanagawa (Japan); Yazawa, Masaki; Hirano, Ken-ichi [Department of Immunology, Tokai University School of Medicine, Kanagawa (Japan); Abe, Jun; Higashi, Kiyoshi [Environmental Health Science Laboratory, Sumitomo Chemical Company Limited, Osaka (Japan); Inagaki, Yutaka [Center for Matrix Biology and Medicine, Tokai University School of Medicine, Kanagawa (Japan); Department of Regenerative Medicine, Tokai University School of Medicine, Kanagawa (Japan); Mine, Tetsuya [Department of Gastroenterology, Tokai University School of Medicine, Kanagawa (Japan)

2015-12-25

Intestinal fibrotic stricture is a major complication of inflammatory bowel disease. Despite its clinical importance, anti-fibrotic therapy has not been implemented. Transforming growth factor-β (TGF-β) is considered to be a major factor contributing to tissue fibrosis. We have previously shown that the administration of a small compound, HSc025, which promotes the nuclear translocation of YB-1 as a downstream effector of IFN-γ and antagonizes TGF-β/Smad signaling, improves fibrosis in several murine tissues. In this study, we evaluated the anti-fibrotic effect of HSc025 on colorectal fibrosis in TNBS-induced murine chronic colitis. Daily oral administration of HSc025 (3, 15 and 75 mg/kg) suppressed collagen production and decreased the severity of colorectal fibrosis in a dose-dependent manner. In addition, the local production of TGF-β was decreased after HSc025 treatment, whereas that of IL-13 and TNF-α was not affected. HSc025 administration maintained the level of IFN-γ production, even at a late stage when IFN-γ production was lost without the drug treatment. These results demonstrate that HSc025 could be a therapeutic candidate for intestinal fibrosis in inflammatory bowel disease that acts by altering the local production of cytokines, as well as by directly suppressing collagen production. - Highlights: • Colorectal fibrosis of TNBS-induced colitis was attenuated by HSc025 administration. • Local production of TGF-b was suppressed by the modulation of TGF-b/IFN-g signaling. • Derepression of IFN-g production was induced by the drug treatment.

Anti-fibrotic effects of a novel small compound on the regulation of cytokine production in a mouse model of colorectal fibrosis

International Nuclear Information System (INIS)

Imai, Jin; Hozumi, Katsuto; Sumiyoshi, Hideaki; Yazawa, Masaki; Hirano, Ken-ichi; Abe, Jun; Higashi, Kiyoshi; Inagaki, Yutaka; Mine, Tetsuya

2015-01-01

Intestinal fibrotic stricture is a major complication of inflammatory bowel disease. Despite its clinical importance, anti-fibrotic therapy has not been implemented. Transforming growth factor-β (TGF-β) is considered to be a major factor contributing to tissue fibrosis. We have previously shown that the administration of a small compound, HSc025, which promotes the nuclear translocation of YB-1 as a downstream effector of IFN-γ and antagonizes TGF-β/Smad signaling, improves fibrosis in several murine tissues. In this study, we evaluated the anti-fibrotic effect of HSc025 on colorectal fibrosis in TNBS-induced murine chronic colitis. Daily oral administration of HSc025 (3, 15 and 75 mg/kg) suppressed collagen production and decreased the severity of colorectal fibrosis in a dose-dependent manner. In addition, the local production of TGF-β was decreased after HSc025 treatment, whereas that of IL-13 and TNF-α was not affected. HSc025 administration maintained the level of IFN-γ production, even at a late stage when IFN-γ production was lost without the drug treatment. These results demonstrate that HSc025 could be a therapeutic candidate for intestinal fibrosis in inflammatory bowel disease that acts by altering the local production of cytokines, as well as by directly suppressing collagen production. - Highlights: • Colorectal fibrosis of TNBS-induced colitis was attenuated by HSc025 administration. • Local production of TGF-b was suppressed by the modulation of TGF-b/IFN-g signaling. • Derepression of IFN-g production was induced by the drug treatment.

Collateral hepatic circulation with the portal hypertension syndrome in children

International Nuclear Information System (INIS)

Filippkin, M.A.; Kondakov, V.T.; Artamonov, Yu.A.

1990-01-01

The results of complex examination carried out in 80 children of different age with the extrahepatic form of portal hypertension and liver fibrosis are presented. Correspondence between clinical and roentgenoangiograph patterns of disease is detected. Dependence of the degree of varicose transformation of submucous veins of the esophagus and stomach on the value and the character of portal blood disposal is established. The risk group is detected. Clinico-X-ray comparisons carried out testify about advisability of the account of individual features of collateral hepatic circulation of the liver when developing medical treatment

The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease

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Pietrobattista Andrea

2009-05-01

Full Text Available Abstract Background Liver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center. Methods The study included 136 male and 67 female children with NAFLD aged 3.3 to 18.0 years; 141 (69% of them had fibrosis at liver biopsy. On the basis of biological plausibility, readily availability and evidence from adult studies, we evaluated the following potential predictors of liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin, triglycerides and cholesterol. A final model was developed using bootstrapped logistic regression with bias-correction. We used this model to develop the 'pediatric NAFLD fibrosis index' (PNFI, which varies between 0 and 10. Results The final model was based on age, waist circumference and triglycerides and had a area under the receiver operating characteristic curve of 0.85 (95% bootstrapped confidence interval (CI with bias correction 0.80 to 0.90 for the prediction of liver fibrosis. A PNFI ≥ 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to 201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0 could be used to rule in liver fibrosis without performing liver biopsy. Conclusion PNFI may help clinicians to predict liver fibrosis in children with NAFLD, but external validation is needed before it can be employed for this purpose.

Liver Fibrosis: Current Principles of Diagnosis

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A.K. Duda

2014-09-01

Full Text Available Liver fibrosis — a natural consequence of almost all liver diseases of any origin. We are faced with a number of standard stereotype processes that take place in the liver tissue. Mostly it is the processes of chronic inflammation, which oppose the processes of liver tissue regeneration. The basis of imbalance between the processes of fibrosis and regeneration is an accumulation of extracellular matrix. Liver fibrosis in its development leads to liver cirrhosis, hepatocellular carcinoma, and the increase in morbidity rate is observed worldwide. Furthermore, the process is genetically determined, but modifiable factors play an important role in the progression of this disease. Current data indicate the possibility of reversible liver fibrosis.

Otorhinolaryngologic manifestations of cystic fibrosis: literature review

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Carvalho, Carolina Pimenta

2008-12-01

Full Text Available Introduction: Cystic Fibrosis is the most common recessive autosomic genetic disease among Caucasians. It's caused by mutations in the gene that decodes regulatory protein for transmembrane conductance, resulting in defective transport of chlorine. Objective: Review the literature about Cystic Fibrosis, with emphasis on otorhinolaryngologic manifestations. Method: The online Pub Med databases were researched and we applied the following search terms Fibrosis Cystic and Sinusitis, and Mucoviscidosis and Sinusitis. Conclusions: Although it is not the main cause of death, the otorhinolaryngologic manifestations of the Cystic Fibrosis bring important morbidity to these patients.

Viral infection drives tissue fibrosis in vitro

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Andrea P. Malizia

2008-04-01

Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a refractory and lethal interstitial lung disease characterized by loss of alveolar epithelial cells, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. In this study we utilised a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV associated with lung fibrosis. A549 cells and an alveolar epithelial cell line infected with EBV (VAAK were used to identify genes whose expression was altered by EBV reactivation. EBV reactivation by TGFbeta1 drives alterations in expression of non-canonical Wnt pathway mediators, implicating it in epithelial mesenchymal transition (EMT, the molecular event underpinning scar production in tissue fibrosis. Cell invasion, EMT correlated transcripts expression, GSK-3b and c-Jun activation were altered in response to non-canonical Wnt pathway regulation. The role of EBV in promoting fibrosis can be attenuated by antiviral strategies and inhibition of Wnt signalling. Activation of non-canonical Wnt signalling pathway by EBV in epithelial cells suggests a novel mechanism of tissue fibrosis. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

Current Strategies for Quantitating Fibrosis in Liver Biopsy

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Yan Wang

2015-01-01

Full Text Available Objective: The present mini-review updated the progress in methodologies based on using liver biopsy. Data Sources: Articles for study of liver fibrosis, liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014. Study Selection: Key articles were selected mainly according to their levels of relevance to this topic and citations. Results: With the recently mounting progress in chronic liver disease therapeutics, comes by a pressing need for precise, accurate, and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients. Histopathological information is recognized as the most valuable data for fibrosis assessment. Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility. Morphometric assessment by computer assist digital image analysis, such as collagen proportionate area (CPA, detects change of fibrosis amount in tissue section in a continuous variable, and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis. Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort. Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging. Conclusions: With input from multidisciplinary innovation, liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated

Clinical application of noninvasive diagnosis of liver fibrosis

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ZHU Chuanlong

2015-03-01

Full Text Available Hepatic fibrosis is the common outcome of chronic liver diseases of various causes. At present, liver biopsy is the “gold standard” for the diagnosis of liver fibrosis, but it has limitations and is invasive, which leads to the development of noninvasive assessment of liver fibrosis. The article mainly introduces the technology and application of noninvasive diagnosis of liver fibrosis from the aspects of clinical manifestation, serology, and radiology. It has pointed out the clinical value of these noninvasive diagnosis techniques, and it discusses the progress in clinical research and its limitations for noninvasive diagnosis of liver fibrosis.

Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis.

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Eric Lefebvre

Full Text Available Interactions between C-C chemokine receptor types 2 (CCR2 and 5 (CCR5 and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC's anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC's antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05. At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05, and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls. CVC treatment had no notable effect on body or liver/kidney weight.CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC's antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475.

Imaging findings in idiopathic pelvic fibrosis

International Nuclear Information System (INIS)

Wiesner, W.; Bongartz, G.; Stoffel, F.

2001-01-01

Two patients presented with ureteric obstruction, and voiding symptoms and constipation, respectively, and were examined by means of intravenous urography and computed tomography. One patient was additionally examined by means of MR tomography. After CT (performed in both patients) and MRT (performed in one patient) had shown a diffuse, contrast-enhancing, infiltrating process in the small pelvis with infiltration of adjacent organs and vessels, surgical biopsy proved the diagnosis of idopathic pelvic fibrosis. Extension of retroperitoneal fibrosis below the pelvic rim is very rare. Clinical symptoms of pelvic fibrosis are variable and imaging findings may lead to a broad list of differential diagnoses. We present two patients with idiopathic pelvic fibrosis and discuss radiological findings and differential diagnoses of this rare disease. (orig.)

Imaging findings in idiopathic pelvic fibrosis

Energy Technology Data Exchange (ETDEWEB)

Wiesner, W.; Bongartz, G. [Inst. of Diagnostic Radiology University Hospital Basel (Switzerland); Stoffel, F. [Inst. of Urology, University Hospital Basel (Switzerland)

2001-04-01

Two patients presented with ureteric obstruction, and voiding symptoms and constipation, respectively, and were examined by means of intravenous urography and computed tomography. One patient was additionally examined by means of MR tomography. After CT (performed in both patients) and MRT (performed in one patient) had shown a diffuse, contrast-enhancing, infiltrating process in the small pelvis with infiltration of adjacent organs and vessels, surgical biopsy proved the diagnosis of idopathic pelvic fibrosis. Extension of retroperitoneal fibrosis below the pelvic rim is very rare. Clinical symptoms of pelvic fibrosis are variable and imaging findings may lead to a broad list of differential diagnoses. We present two patients with idiopathic pelvic fibrosis and discuss radiological findings and differential diagnoses of this rare disease. (orig.)

Idiopathic Pulmonary Fibrosis: The Association between the Adaptive Multiple Features Method and Fibrosis Outcomes.

Science.gov (United States)

Salisbury, Margaret L; Lynch, David A; van Beek, Edwin J R; Kazerooni, Ella A; Guo, Junfeng; Xia, Meng; Murray, Susan; Anstrom, Kevin J; Yow, Eric; Martinez, Fernando J; Hoffman, Eric A; Flaherty, Kevin R

2017-04-01

Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal lung densities were measured by AMFM and three radiologists, documenting baseline disease extent and postbaseline change. Disease progression includes composite mortality, hospitalization, and 10% FVC decline. Agreement between visual and AMFM measurements was moderate for GGR (Pearson's correlation r = 0.60, P fibrosis (as measured by GGR densities) is independently associated with elevated hazard for disease progression. Postbaseline change in AMFM-measured and visually measured GGR densities are modestly correlated with change in FVC. AMFM-measured fibrosis is an automated adjunct to existing prognostic markers and may allow for study enrichment with subjects at increased disease progression risk.

Automatic liver volume segmentation and fibrosis classification

Science.gov (United States)

Bal, Evgeny; Klang, Eyal; Amitai, Michal; Greenspan, Hayit

2018-02-01

In this work, we present an automatic method for liver segmentation and fibrosis classification in liver computed-tomography (CT) portal phase scans. The input is a full abdomen CT scan with an unknown number of slices, and the output is a liver volume segmentation mask and a fibrosis grade. A multi-stage analysis scheme is applied to each scan, including: volume segmentation, texture features extraction and SVM based classification. Data contains portal phase CT examinations from 80 patients, taken with different scanners. Each examination has a matching Fibroscan grade. The dataset was subdivided into two groups: first group contains healthy cases and mild fibrosis, second group contains moderate fibrosis, severe fibrosis and cirrhosis. Using our automated algorithm, we achieved an average dice index of 0.93 ± 0.05 for segmentation and a sensitivity of 0.92 and specificity of 0.81for classification. To the best of our knowledge, this is a first end to end automatic framework for liver fibrosis classification; an approach that, once validated, can have a great potential value in the clinic.

ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis.

Directory of Open Access Journals (Sweden)

Cecilia Riquelme

Full Text Available Duchenne muscular dystrophy (DMD is the most common inherited neuromuscular disease and is characterized by absence of the cytoskeletal protein dystrophin, muscle wasting, and fibrosis. We previously demonstrated that systemic infusion or oral administration of angiotensin-(1-7 (Ang-(1-7, a peptide with opposing effects to angiotensin II, normalized skeletal muscle architecture, decreased local fibrosis, and improved muscle function in mdx mice, a dystrophic model for DMD. In this study, we investigated the presence, activity, and localization of ACE2, the enzyme responsible for Ang-(1-7 production, in wild type (wt and mdx skeletal muscle and in a model of induced chronic damage in wt mice. All dystrophic muscles studied showed higher ACE2 activity than wt muscle. Immunolocalization studies indicated that ACE2 was localized mainly at the sarcolemma and, to a lesser extent, associated with interstitial cells. Similar results were observed in the model of chronic damage in the tibialis anterior (TA muscle. Furthermore, we evaluated the effect of ACE2 overexpression in mdx TA muscle using an adenovirus containing human ACE2 sequence and showed that expression of ACE2 reduced the fibrosis associated with TA dystrophic muscles. Moreover, we observed fewer inflammatory cells infiltrating the mdx muscle. Finally, mdx gastrocnemius muscles from mice infused with Ang-(1-7, which decreases fibrosis, contain less ACE2 associated with the muscle. This is the first evidence supporting ACE2 as an important therapeutic target to improve the dystrophic skeletal muscle phenotype.

Oral protein calorie supplementation for children with chronic disease

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Francis, Damian K; Smith, Joanne; Saljuqi, Tawab; Watling, Ruth M

2015-01-01

Background Poor growth and nutritional status are common in children with chronic diseases. Oral protein calorie supplements are used to improve nutritional status in these children. These expensive products may be associated with some adverse effects, e.g. the development of inappropriate eating behaviour patterns. This is a new update of a Cochrane review last updated in 2009. Objectives To examine evidence that in children with chronic disease, oral protein calorie supplements alter daily nutrient intake, nutritional indices, survival and quality of life and are associated with adverse effects, e.g. diarrhoea, vomiting, reduced appetite, glucose intolerance, bloating and eating behaviour problems. Search methods Trials of oral protein calorie supplements in children with chronic diseases were identified through comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Companies marketing these products were also contacted. Most recent search of the Group's Trials Register: 24 February 2015. Selection criteria Randomised or quasi-randomised controlled trials comparing oral protein calorie supplements for at least one month to increase calorie intake with existing conventional therapy (including advice on improving nutritional intake from food or no specific intervention) in children with chronic disease. Data collection and analysis We independently assessed the outcomes: indices of nutrition and growth; anthropometric measures of body composition; calorie and nutrient intake (total from oral protein calorie supplements and food); eating behaviour; compliance; quality of life; specific adverse effects; disease severity scores; and mortality; we also assessed the risk of bias in the included trials. Main results Four studies (187 children) met the inclusion criteria. Three studies were carried out in children with cystic fibrosis and one study included children with paediatric malignant disease

Factors Promoting Development of Fibrosis in Crohn’s Disease

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Gerhard Rogler

2017-07-01

Full Text Available The concepts on the pathophysiology of intestinal fibrosis in Crohn’s disease (CD have changed in recent years. Some years ago fibrosis was regarded to be a consequence of long-standing inflammation with subsequent destruction of the gut wall matrix followed by scar formation and collagen deposition. Fibrosis in CD patients appeared to be an irreversible process that could hardly be influenced. Therefore, the main target in CD therapy was to control inflammation to avoid fibrosis development. Many of these assumptions seem to be only partially true. Inflammation may be a necessary prerequisite for the initiation of fibrosis. However, when the pathophysiologic processes that lead to fibrosis in CD patients have been initiated fibrosis development may be independent of inflammation and may continue even when inflammation is under good medical control. Fibrosis in CD also may be reversible. After strictureplasty local collagen deposits decrease or even disappear. With new animal models for intestinal fibrosis on the horizon, we need to spend more efforts on understanding the factors influencing fibrosis in CD patients to finally find specific therapies. In this context, it will be as important to find markers and quantitative imaging tools to have reliable endpoints for clinical trials in fibrosing CD.

The effect of short-term, high-dose oral N-acetylcysteine treatment on oxidative stress markers in cystic fibrosis patients with chronic P. aeruginosa infection -- a pilot study.

Science.gov (United States)

Skov, Marianne; Pressler, Tacjana; Lykkesfeldt, Jens; Poulsen, Henrik Enghusen; Jensen, Peter Østrup; Johansen, Helle Krogh; Qvist, Tavs; Kræmer, Dorthe; Høiby, Niels; Ciofu, Oana

2015-03-01

Patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection have increased oxidative stress as a result of an imbalance between the production of reactive oxygen species caused by inflammation and their inactivation by the impaired antioxidant systems. Supplementation with anti-oxidants is potentially beneficial for CF patients. The effect of 4 weeks of oral N-acetylcysteine (NAC) treatment (2400 mg/day divided into two doses) on biochemical parameters of oxidative stress was investigated in an open-label, controlled, randomized trial on 21 patients; 11 patients in the NAC group and 10 in the control group. Biochemical parameters of oxidative burden and plasma levels of antioxidants were assessed at the end of the study and compared to the baseline values in the two groups. A significant increase in the plasma levels of the antioxidant ascorbic acid (p=0.037) and a significant decrease in the levels of the oxidized form of ascorbic acid (dehydroascorbate) (p=0.004) compared to baseline were achieved after NAC treatment. No significant differences were observed in the control group. The parameters of oxidative burden did not change significantly compared to baseline in either of the groups. A better lung function was observed in the NAC treated group with a mean (SD) change compared to baseline of FEV1% predicted of 2.11 (4.6), while a decrease was observed in the control group (change -1.4 (4.6)), though not statistically significant. Treatment with N-acetylcysteine 1200 mg×2/day for 30 days significantly decreased the level of oxidized vitamin C and increased the level of vitamin C (primary end-points) and a not statistically significant improvement of lung function was observed in this group of patients. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Serum hyaluronic acid as a marker of hepatic fibrosis

International Nuclear Information System (INIS)

Khan, J.A.; Khan, F.A.; Ijaz, A.; Khan, N.A.; Mehmood, T.

2007-01-01

To determine the serum hyaluronic acid (HA) levels as biochemical marker of hepatic fibrosis and cirrhosis and correlate it with the degree of hepatic fibrosis and cirrhosis. This study was performed on 100 patients of chronic liver disease whose liver biopsies had been carried out. Fifty healthy controls were also included in the study. Routine liver function tests, hepatitis serology and serum hyaluronic acid levels were carried out on patients and controls. Liver biopsy of 100 patients revealed that 21 were in stage 0 fibrosis, 38 in stage 1 fibrosis, 26 in stage 3 fibrosis and 15 in stage 4 fibrosis. Mean Serum HA (mean +- SD) concentration in patients were 189 +- 98 mg/L vs. 21 +- 10 mg/L of healthy controls. The difference observed was statistically significant (p < 0.001). Patients in stage 4 fibrosis had significantly higher (p <0.001) mean serum HA concentration as compared to other stages of liver fibrosis. Diagnostic accuracy of serum HA at marginally elevated level of 60 mg/L determined the sensitivity 78.4 %, specificity 80.9%, positive predicted value 93.9% and negative predicted value of 50%. Serum HA is a useful non-invasive marker of liver fibrosis. There is a strong positive correlation between serum HA levels and degree of liver fibrosis. The concentration of serum HA rises according to progression of liver fibrosis and levels are highest in patients with liver cirrhosis. (author)

Recommendations for quality improvement in genetic testing for cystic fibrosis European Concerted Action on Cystic Fibrosis

NARCIS (Netherlands)

Dequeker, E; Cuppens, H; Dodge, J; Estivill, [No Value; Goossens, M; Pignatti, PF; Scheffer, H; Schwartz, M; Schwarz, M; Tummler, B; Cassiman, JJ

These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external

Modeling the mechanical properties of liver fibrosis in rats.

Science.gov (United States)

Zhu, Ying; Chen, Xin; Zhang, Xinyu; Chen, Siping; Shen, Yuanyuan; Song, Liang

2016-06-14

The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading. Copyright © 2016 Elsevier Ltd. All rights reserved.

Costs, quality of life and treatment compliance associated with antibiotic therapies in patients with cystic fibrosis: a review of the literature.

Science.gov (United States)

Weiner, Jennifer R; Toy, Edmond L; Sacco, Patricia; Duh, Mei Sheng

2008-04-01

Cystic fibrosis is the most common incurable hereditary disease in the US. Persistent respiratory infection is the leading cause of morbidity and mortality in cystic fibrosis patients. This study aimed to review the literature on economic and quality of life outcomes and treatment compliance associated with antibiotic therapies for cystic fibrosis patients. A systematic literature review was conducted using keyword searches of the MEDLINE database and selected conference abstracts. The review covered studies published between January 1990 and May 2007. Evidence suggests that inhaled tobramycin, a key chronic suppressive therapy, can reduce other healthcare costs. The main determinants of the cost of care include disease severity and respiratory infection. Costs vary widely by country. There is evidence that inhaled tobramycin and oral azithromycin improve quality of life and that treatment setting and patient convenience may also impact on quality of life. Antibiotic treatment compliance varied significantly and depended on the method of measurement, with more subjective measures tending to be higher. This review concludes by offering directions for future research.

Computed tomography of cystic pancreatic fibrosis

International Nuclear Information System (INIS)

Brachlow, M.; Zaunbauer, W.; Haertel, M.

1984-01-01

The computer tomographic appearances of atrophic and lipomatous degeneration of the pancreas in cystic pancreatic fibrosis are described. CT exploration of the pancreas in recommended, particularly in differential diagnostic aspects of cystic fibrosis. (orig.) [de

Effect of Ganfukang on liver function and serum hepatic fibrosis markers levels in SD rats with experimental hepatic fibrosis

International Nuclear Information System (INIS)

Che Ying; Wang Shanju; Xu Tingting; Jiang Miaona; Jia Yujie

2004-01-01

Objective: To observe the effect of Ganfukang on liver function and serum hepatic fibrosis markers levels in SD rats with experimental hepatic fibrosis. Methods: SD rat models of liver fibrosis was induced by CCl 4 (n=57). Liver function (GPT, GOT) and serum hepatic fibrosis markers levels (HA, LN, C-IV, PC-III, with RIA) were tested in these models and 10 control rats. Eleven model rats were left untreated, the others were treated with Ganfukang of different concentrations and the above hepatic parameters were again determined after completion of treatment. Results: Lever function was much deteriorated and serum markers levels significantly increased in the model rats (vs controls, P<0.01). After treatment with Ganfukang, the improvement was significant (vs untreated models, P<0.01). Conclusion: Ganfukang is of definite therapeutic value for experimental hepatic fibrosis in rat models. (authors)

Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension.

Science.gov (United States)

Avouac, Jerome; Konstantinova, Irena; Guignabert, Christophe; Pezet, Sonia; Sadoine, Jeremy; Guilbert, Thomas; Cauvet, Anne; Tu, Ly; Luccarini, Jean-Michel; Junien, Jean-Louis; Broqua, Pierre; Allanore, Yannick

2017-11-01

To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH. Mice received two doses of IVA337 (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. IVA337 demonstrated at a dose of 100 mg/kg a marked protection from the development of lung fibrosis in both mouse models compared with mice receiving 30 mg/kg of IVA337 or vehicle. Histological score was markedly reduced by 61% in the bleomycin model and by 50% in Fra-2 transgenic mice, and total lung hydroxyproline concentrations decreased by 28% and 48%, respectively, as compared with vehicle-treated mice. IVA337 at 100 mg/kg also significantly decreased levels of fibrogenic markers in lesional lungs of both mouse models. In addition, IVA337 substantially alleviated PH in Fra-2 transgenic mice by improving haemodynamic measurements and vascular remodelling. In primary human lung fibroblasts, IVA337 inhibited in a dose-dependent manner fibroblast to myofibroblasts transition induced by TGF-β and fibroblast proliferation mediated by PDGF. We demonstrate that treatment with 100 mg/kg IVA337 prevents lung fibrosis in two complementary animal models and substantially attenuates PH in the Fra-2 mouse model. These findings confirm that the pan-PPAR agonist IVA337 is an appealing therapeutic candidate for these cardiopulmonary involvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical application of noninvasive diagnosis of liver fibrosis

OpenAIRE

ZHU Chuanlong

2015-01-01

Hepatic fibrosis is the common outcome of chronic liver diseases of various causes. At present, liver biopsy is the “gold standard” for the diagnosis of liver fibrosis, but it has limitations and is invasive, which leads to the development of noninvasive assessment of liver fibrosis. The article mainly introduces the technology and application of noninvasive diagnosis of liver fibrosis from the aspects of clinical manifestation, serology, and radiology. It has pointed out the clinical value o...

Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

Directory of Open Access Journals (Sweden)

Lili eGao

2015-10-01

Full Text Available Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA, a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition and activation of tansforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

Relationship of Antibiotic Treatment to Recovery after Acute FEV1 Decline in Children with Cystic Fibrosis.

Science.gov (United States)

Morgan, Wayne J; Wagener, Jeffrey S; Pasta, David J; Millar, Stefanie J; VanDevanter, Donald R; Konstan, Michael W

2017-06-01

Children with cystic fibrosis often experience acute declines in lung function. We previously showed that such declines are not always treated with antibiotics, but we did not assess whether treatment improves the likelihood of recovery. To determine whether new antibiotic treatment was associated with recovery from acute FEV 1 decline. We studied episodes of FEV 1 decline (≥10% from baseline) in the Epidemiologic Study of Cystic Fibrosis. Treatments were hospitalization, home intravenous antibiotic, new inhaled oral quinolone, or other oral antibiotic. We used logistic regression to evaluate whether treatment was associated with recovery to baseline or near baseline. Logistic regression of 9,875 patients showed that new antibiotic treatment was associated with an increased likelihood of recovery to 90% of baseline (P antibiotic (odds ratio [OR], 2.79; 95% confidence interval, 2.41-3.23). All four outpatient treatments were associated with greater likelihood of recovery compared with no treatment (OR, 1.27-1.64). Inpatient treatment was better than outpatient treatment (OR, 1.94; 95% confidence interval, 1.68-2.23). Treatment-type ORs were similar across recovery criteria and levels of baseline lung function. New antibiotic therapy, and especially inpatient treatment, is associated with greater likelihood of recovery after acute decline in FEV 1 . Benefits extend across all disease stages and are especially important in patients with high lung function, who are at greatest risk for FEV 1 decline.

[Combination of NAFLD Fibrosis Score and liver stiffness measurement for identification of moderate fibrosis stages (II & III) in non-alcoholic fatty liver disease].

Science.gov (United States)

Drolz, Andreas; Wehmeyer, Malte; Diedrich, Tom; Piecha, Felix; Schulze Zur Wiesch, Julian; Kluwe, Johannes

2018-01-01

Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent causes of chronic liver disease. Currently, therapeutic options for NAFLD patients are limited, but new pharmacologic agents are being investigated in the course of clinical trials. Because most of these studies are focusing on patients with fibrosis stages II and III (according to Kleiner), non-invasive identification of patients with intermediate fibrosis stages (II and III) is of increasing interest. Evaluation of NAFLD Fibrosis Score (NFS) and liver stiffness measurement (LSM) for prediction of fibrosis stages II/III. Patients with histologically confirmed NAFLD diagnosis were included in the study. All patients underwent a clinical and laboratory examination as well as a LSM prior to liver biopsy. Predictive value of NFS and LSM with respect to identification of fibrosis stages II/III was assessed. 134 NAFLD patients were included and analyzed. Median age was 53 (IQR 36 - 60) years, 55 patients (41 %) were female. 82 % of our patients were overweight/obese with typical aspects of metabolic syndrome. 84 patients (66 %) had liver fibrosis, 42 (50 %) advanced fibrosis. LSM and NFS correlated with fibrosis stage (r = 0.696 and r = 0.685, respectively; p stages II/III. If both criteria were met, probability of fibrosis stage II/III was 61 %. If none of the two criteria was met, chance for fibrosis stage II/III was only 6 % (negative predictive value 94 %). Combination of LSM and NFS enables identification of patients with significant probability of fibrosis stage II/III. Accordingly, these tests, especially in combination, may be a suitable screening tool for fibrosis stages II/III in NAFLD. The use of these non-invasive methods might also help to avoid unnecessary biopsies. © Georg Thieme Verlag KG Stuttgart · New York.

Transient elastography for liver fibrosis diagnosis

DEFF Research Database (Denmark)

Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

2008-01-01

Liver biopsy is considered the "golden standard" for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems....... Recently, a modified ultrasound scanner (transient elastography) has been developed to assess fibrosis. The device measures liver elasticity, which correlates well with the degree of fibrosis. Studies have shown that transient elastography is more accurate in diagnosing cirrhosis than minor to moderate...... to be a valuable diagnostic procedure and follow-up of patients with chronic liver diseases....

Transient elastography for liver fibrosis diagnosis

DEFF Research Database (Denmark)

Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

2009-01-01

Liver biopsy is considered the "golden standard" for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems....... Recently, a modified ultrasound scanner (transient elastography) has been developed to assess fibrosis. The device measures liver elasticity, which correlates well with the degree of fibrosis. Studies have shown that transient elastography is more accurate in diagnosing cirrhosis than minor to moderate...... to be a valuable diagnostic procedure and follow-up of patients with chronic liver diseases....

Pregnancy and cystic fibrosis: Approach to contemporary management

Science.gov (United States)

Tay, George; Callaway, Leonie; Bell, Scott C

2014-01-01

Over the previous 50 years survival of patients with cystic fibrosis has progressively increased. As a result of improvements in health care, increasing numbers of patients with cystic fibrosis are now considering starting families of their own. For the health care professionals who look after these patients, the assessment of the potential risks, and the process of guiding prospective parents through pregnancy and beyond can be both challenging and rewarding. To facilitate appropriate discussions about pregnancy, health care workers must have a detailed understanding of the various important issues that will ultimately need to be considered for any patient with cystic fibrosis considering parenthood. This review will address these issues. In particular, it will outline pregnancy outcomes for mothers with cystic fibrosis, issues that need to be taken into account when planning a pregnancy and the management of pregnancy for mothers with cystic fibrosis or mothers who have undergone organ transplantation as a result of cystic fibrosis. PMID:27512443

Performance of transient elastography and serum fibrosis biomarkers for non-invasive evaluation of recurrent fibrosis after liver transplantation: A meta-analysis.

Science.gov (United States)

Bhat, Mamatha; Tazari, Mahmood; Sebastiani, Giada

2017-01-01

Recurrent fibrosis after liver transplantation (LT) impacts on long-term graft and patient survival. We performed a meta-analysis to compare the accuracy of non-invasive methods to diagnose significant recurrent fibrosis (stage F2-F4) following LT. Studies comparing serum fibrosis biomarkers, namely AST-to-platelet ratio index (APRI), fibrosis score 4 (FIB-4), or transient elastography (TE) with liver biopsy in LT recipients were systematically identified through electronic databases. In the meta-analysis, we calculated the weighted pooled odds ratio and used a fixed effect model, as there was no significant heterogeneity between studies. Eight studies were included for APRI, four for FIB-4, and twelve for TE. The mean prevalence of significant liver fibrosis was 37.4%. The summary odds ratio was significantly higher for TE (21.17, 95% CI confidence interval 14.10-31.77, p = 1X10-30) as compared to APRI (9.02, 95% CI 5.79-14.07; p = 1X10-30) and FIB-4 (7.08, 95% CI 4.00-12.55; p = 1.93X10-11). In conclusion, TE performs best to diagnose recurrent fibrosis in LT recipients. APRI and FIB-4 can be used as an estimate of significant fibrosis at centres where TE is not available. Longitudinal assessment of fibrosis by means of these non-invasive tests may reduce the need for liver biopsy.

The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis

Directory of Open Access Journals (Sweden)

Lucy A. Murtha

2017-10-01

Full Text Available Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair. However, its continued activation is highly detrimental and a common final pathway of numerous disease states including cardiovascular and respiratory disease. Worldwide, fibrotic diseases cause over 800,000 deaths per year, accounting for ~45% of total deaths. With an aging population, the incidence of fibrotic disease and subsequently the number of fibrosis-related deaths will rise further. Although, fibrosis is a well-recognized cause of morbidity and mortality in a range of disease states, there are currently no viable therapies to reverse the effects of chronic fibrosis. Numerous predisposing factors contribute to the development of fibrosis. Biological aging in particular, interferes with repair of damaged tissue, accelerating the transition to pathological remodeling, rather than a process of resolution and regeneration. When fibrosis progresses in an uncontrolled manner, it results in the irreversible stiffening of the affected tissue, which can lead to organ malfunction and death. Further investigation into the mechanisms of fibrosis is necessary to elucidate novel, much needed, therapeutic targets. Fibrosis of the heart and lung make up a significant proportion of fibrosis-related deaths. It has long been established that the heart and lung are functionally and geographically linked when it comes to health and disease, and thus exploring the processes and mechanisms that contribute to fibrosis of each organ, the focus of this review, may help to highlight potential avenues of therapeutic investigation.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Science.gov (United States)

Jat, Kana R; Walia, Dinesh K; Khairwa, Anju

2018-03-18

study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Genetics Home Reference: idiopathic pulmonary fibrosis

Science.gov (United States)

... these health problems has idiopathic pulmonary fibrosis . Other respiratory diseases, some of which are less serious, can cause similar signs and symptoms. In people with idiopathic pulmonary fibrosis , scarring of the lungs increases over time until the lungs can no longer ...

Localization of substance P binding sites in submucous plexus of guinea pig ileum, using whole-mount autoradiography

International Nuclear Information System (INIS)

Burcher, E.; Bornstein, J.C.

1988-01-01

Whole mounts of guinea pig ileum submucosa were incubated with radiolabeled tachykinins, and binding sites were visualized using autoradiography. Very dense specific binding for [ 125 I]-Bolton-Hunter substance P (BHSP) was observed over ganglia of the submucous plexus, with weaker binding over internodal strands. Dense specific binding was also seen over occasional strands of circular muscle, with weak binding over clumps of mucosa. Although very weak binding was seen over some large blood vessels, no binding was associated with smaller blood vessels. Localization of binding was absent in whole-mounts coincubated with 1 microM substance P, used to define nonspecific binding. Localization of BHSP-specific binding was also abolished in whole-mounts coincubated with 1 nM substance P, but not with 1 nM neurokinin B, suggesting that binding was probably to an NK-1 tachykinin receptor. In whole-mounts incubated in [ 125 I]-iodohistidyl neurokinin A (INKA) or [ 125 I]-Bolton-Hunter neurokinin B (BHNKB), no specific binding over ganglia was observed. These binding sites for BHSP are probably identical with the neuronal substance P receptors mediating mucosal ion transport

Laparoscopic cholecystectomy in adult cystic fibrosis.

LENUS (Irish Health Repository)

McGrath, D S

2012-02-03

Two female patients with Cystic Fibrosis, attending the Adult Regional Cystic Fibrosis centre at the Cork University Hospital, were investigated for upper abdominal pain and found to have gallstones at ultrasonography. Laparoscopic cholecystectomy was performed successfully and, without complication, in both patients.

Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats.

Science.gov (United States)

Boigk, G; Stroedter, L; Herbst, H; Waldschmidt, J; Riecken, E O; Schuppan, D

1997-09-01

Silymarin (SIL), a standardized plant extract containing about 60% polyphenole silibinin, is used as a hepatoprotective agent. Its antifibrotic potential in chronic liver diseases has not been explored. Therefore, we applied SIL to adult Wistar rats that were subjected to complete bile duct occlusion (BDO) by injection of sodium amidotrizoate (Ethibloc). This treatment induces progressive portal fibrosis without significant inflammation. Rats with sham-operation that received SIL at 50 mg/kg/d (n = 10) and rats with BDO alone (n = 20) served as controls, whereas groups of 20 animals were fed SIL at a dose of 25 and 50 mg/kg/d during weeks 1 through 6 or doses of 50 mg/kg/d during weeks 4 through 6 of BDO. Animals were sacrificed after 6 weeks for determination of blood chemistries, total and relative liver collagen (as hydroxyproline [HYP]), and the serum aminoterminal propeptide of procollagen type III (PIIINP). BDO in untreated rats caused an almost ninefold increase in total liver collagen (16.1 +/- 3.1 vs. 1.8 +/- 0.4 mg HYP, P liver tissue, it acted as a true antifibrotic agent. The single value of PIIINP at killing paralleled the antifibrotic activity of SIL with 11.6 +/- 3.8 and 9.9 +/- 3.7 vs. 15.3 +/- 5.2 microg/L in both high-dose groups (P fibrosis score in the groups that received SIL, clinical-chemical parameters were not different among all groups with BDO. We therefore conclude that 1) BDO with Ethibloc is a suitable model to test for pure antifibrotic drugs because it induces progressive rat secondary biliary fibrosis without major inflammation; 2) oral SIL can ameliorate hepatic collagen accumulation even in advanced (biliary) fibrosis; and 3) PIIINP appears to be a suitable serum marker to monitor the inhibition of hepatic fibrogenesis in this model of biliary fibrosis.

Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C

OpenAIRE

Stauber, Rudolf E; Lackner, Carolin

2007-01-01

Assessment of hepatic fibrosis is important for determining prognosis, guiding management decisions, and monitoring disease. Histological evaluation of liver biopsy specimens is currently considered the reference test for staging hepatic fibrosis. Since liver biopsy carries a small but significant risk, noninvasive tests to assess hepatic fibrosis are desirable. This editorial gives an overview on noninvasive methods currently available to determine hepatic fibrosis and their diagnostic accur...

TGF-β/Smad signaling in renal fibrosis

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Xiao-Ming eMeng

2015-03-01

Full Text Available TGF-β (transforming growth factor-β is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF- signaling in progressive renal fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of myofibroblasts, overproduction of ECM (extracellular matrix, and reduction in ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for renal fibrosis in various models of kidney diseases. In contrast, another downstream effecter of TGF-β/Smad signaling pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3. Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3-mediated renal fibrosis in various mouse models of chronic kidney diseases. Taken together, TGF-/Smad signaling plays an important role in renal fibrosis. Targeting TGF-β/Smad3 signaling may represent a specific and effective therapy for chronic kidney diseases associated with renal fibrosis.

Accuracy of FibroScan for diagnosing liver fibrosis

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Jian ZHANG

2011-11-01

Full Text Available Objective To evaluate the accuracy of transient elastometry(FibroScan for the detection of liver fibrosis.Methods A total of 323 patients diagnosed with chronic liver disease based on pathological examination in the 302 Hospital of the People’s Liberation Army from April to December of 2009 were involved in the current study.Among them,141 patients were subjected to liver biopsy.Their liver function,coagulant index,B-ultrasound and blood cell count were examined clinically.Four examinations related to liver fibrosis were done on some of the patients.Meanwhile,FibroScan was used for liver stiffness measurement(LSM of every patient.The correlation between liver stiffness and the serologic index and liver fibrosis degree was analyzed.The Receive Operating Characteristic(ROC curve was adopted to analyze the accuracy of FibroScan for diagnosing liver fibrosis.Results Each serologic index was significantly correlated with liver stiffness(P < 0.001,and liver stiffness was closely related to the stage of liver fibrosis(r=0.74,P < 0.001.The statistical results of the 141 patients who underwent pathologic examination show that the areas under the ROC curve were 0.97(0.94,1.00 for patients with portal fibrosis(F1,0.96(0.93,0.99 for patients with significant fibrosis(F2,0.99(0.98,1.00 for patients with severe fibrosis(F3,and 0.97(0.94,0.99 for patients with cirrhosis(F4.The cutoff values were 4.4KPa,6.8KPa,9.7KPa,and 10.0KPa,respectively.Conclusion FibroScan is valuable for the diagnosis of liver fibrosis.It can be used as the basis for follow-up and management of patients with chronic liver diseases.

In-silico analysis of heat shock protein 47 for identifying the novel therapeutic agents in the management of oral submucous fibrosis

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Jayasankar P Pillai

2014-01-01

Conclusion: HSP47 can be a potential candidate to target, in order to control the production of abundance collagen in OSF. Hence, the binding sites of HSP47 with collagen are identified and some natural compounds with a potential to bind with these binding receptors are also recognized. These natural compounds might act as anti-HSP47 lead molecules in designing novel therapeutic agents for OSF, which are so far unavailable.

Hepatoprotective effect of Forsythiae Fructus water extract against carbon tetrachloride-induced liver fibrosis in mice.

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Zhang, Yi; Miao, Hui; Yan, Hongyu; Sheng, Yuchen; Ji, Lili

2018-05-23

The fruit of Forsythia suspensa (Thunb.) Vahl, named Forsythiae Fructus (Lian-Qiao), is a well-known traditional Chinese medicine (TCM) used for clearing away heat and toxic material, eliminating the mass and relieving swelling. This study aims to observe the attenuation of the water extract of Forsythiae Fructus (FSE) on carbon tetrachloride (CCl 4 )-induced hepatic fibrosis in male C57BL/6 mice. Hepatic fibrosis was induced in male C57BL/6 mice by intraperitoneal injection with 2 ml/kg CCl 4 (mixed 1: 3 in olive oil) twice a week for 4 weeks. At the same time, the mice were orally given with FSE (1, 2 g/kg) every day for 4 weeks. Serum biochemical parameters, gene and protein expression related to liver fibrosis were analyzed. The contents of forsythiaside A and forsythin in FSE were measured by high-performance liquid chromatography (HPLC). Results of serum alanine/aspartate aminotransferase (ALT/AST) activity and liver histological evaluation both showed the protection of FSE against CCl 4 -induced liver injury. Further, the anti-fibrotic effects of FSE was evidenced by the results of Masson's trichrome and Sirius red staining, liver hydroxyproline content, and serum amounts of hyaluronic acid, laminin, collagen Ⅳ and type III procollagen (PCIII). FSE also reduced the expression of α-smooth muscle actin (α-SMA) in livers from CCl 4 -injured mice. Additionally, FSE decreased the increased hepatic expression of fibroblast-specific protein 1 (FSP1) and vimentin induced by CCl 4 in mice. FSE attenuates CCl 4 -induced liver fibrosis in mice by inhibiting hepatic stellate cells (HSCs) activation, reducing hepatic extracellular matrix (ECM) disposition and reversing epithelial-mesenchymal transition (EMT). Copyright © 2018 Elsevier B.V. All rights reserved.

Congenital hepatic fibrosis associated with von Recklinghausen's disease Fibrosis hepática congénita asociada a enfermedad de von Recklinghausen

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O. A. Jorge

2006-09-01

Full Text Available Congenital hepatic fibrosis is characterized by a ductal plate malformation with duct-like structures and fibrosis. It manifests clinically with portal hypertension and may be associated with multiple congenital defects. We present the case of a 16-year-old male with splenomegaly, leukopenia and thrombocytopenia, esophageal varices, and a histopathological diagnosis of congenital hepatic fibrosis. He exhibits "café au lait' spots and "Lisch' nodules, with a diagnosis of von Recklinghausen's disease. Congenital hepatic fibrosis belongs to the so-called fibropolycystic diseases, in which there is a disordered interaction between cells and the extracellular matrix. Von Recklinghausen's disease affects tissues derived from the neural crest and its diagnosis is based on clinical criteria. It is associated with multiple diseases. We describe its association with congenital hepatic fibrosis for the first time.La fibrosis hepática congénita se origina como consecuencia de una malformación de la placa ductal con estructuras tipo ductales acompañadas de fibrosis. Se manifiesta con hipertensión portal y puede asociarse a múltiples defectos congénitos. Presentamos un varón de 16 años con esplenomegalia, leuco- y plaquetopenia, varices esofágicas y diagnóstico histopatológico de fibrosis hepática congénita. La exploración física mostraba la existencia de manchas de "café con leche' y nódulos de "Lisch' con diagnóstico de enfermedad de von Recklinghausen. La fibrosis hepática congénita forma parte de las enfermedades fibropoliquísticas donde existiría una alteración en la interacción entre las células y la matriz extracelular. La enfermedad de von Recklinghausen afecta a los tejidos derivados de la cresta neural y su diagnóstico se basa en criterios clínicos. Se asocia a múltiples patologías. Presentamos por primera vez su asociación con fibrosis hepática congénita.

Comparative study of Candida in oral submucous fibrosis and healthy individuals = Estudo comparativo de Candida em fibrose submucosa oral e indivíduos saudáveis

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Anila, K.

2011-01-01

Conclusão: A incidência e intensidade de Candida (primariamente C. albicans foi maior nos pacientes com FSO que nos sujeitos controle, mas estes achados estavam dentro dos limites normais (3-47%. Portanto, Candida pode não ser um fator etiológico na transformação maligna. Entretanto, ainda há controvérsias se o hábito de mascar ‘betel’ em casos de FSO teria um efeito inibidor ou promoveria a aderência e invasão de Candida

Comparative study of Candida in oral submucous fibrosis and healthy individuals = Estudo comparativo de Candida em fibrose submucosa oral e indivíduos saudáveis

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Anila, K.

2011-01-01

Conclusão: A incidência e intensidade de Candida (primariamente C. albicans foi maior nos pacientes com FSO que nos sujeitos controle, mas estes achados estavam dentro dos limites normais (3-47%. Portanto, Candida pode não ser um fator etiológico na transformação maligna. Entretanto, ainda há controvérsias se o hábito de mascar ‘betel’ em casos de FSO teria um efeito inibidor ou promoveria a aderência e invasão de Candida.

Oral and craniofacial manifestations and two novel missense mutations of the NTRK1 gene identified in the patient with congenital insensitivity to pain with anhidrosis.

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Li Gao

Full Text Available Congenital insensitivity to pain with anhidrosis (CIPA is a rare inherited disorder of the peripheral nervous system resulting from mutations in neurotrophic tyrosine kinase receptor 1 gene (NTRK1, which encodes the high-affinity nerve growth factor receptor TRKA. Here, we investigated the oral and craniofacial manifestations of a Chinese patient affected by autosomal-recessive CIPA and identified compound heterozygosity in the NTRK1 gene. The affected boy has multisystemic disorder with lack of reaction to pain stimuli accompanied by self-mutilation behavior, the inability to sweat leading to defective thermoregulation, and mental retardation. Oral and craniofacial manifestations included a large number of missing teeth, nasal malformation, submucous cleft palate, severe soft tissue injuries, dental caries and malocclusion. Histopathological evaluation of the skin sample revealed severe peripheral nerve fiber loss as well as mild loss and absent innervation of sweat glands. Ultrastructural and morphometric studies of a shed tooth revealed dental abnormalities, including hypomineralization, dentin hypoplasia, cementogenesis defects and a dysplastic periodontal ligament. Genetic analysis revealed a compound heterozygosity--c.1561T>C and c.2057G>A in the NTRK1 gene. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with CIPA and provides additional insight for clinical and molecular diagnosis.

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

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Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

2016-09-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Antifibrogenic Effects of the Antimicrobial Peptide Cathelicidin in Murine Colitis-Associated FibrosisSummary

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Jun Hwan Yoo

2015-01-01

Full Text Available Background & Aims: Cathelicidin (LL-37 in human and mCRAMP in mice represents a family of endogenous antimicrobial peptides with anti-inflammatory effects. LL-37 also suppresses collagen synthesis, an important fibrotic response, in dermal fibroblasts. Here, we determined whether exogenous cathelicidin administration modulates intestinal fibrosis in two animal models of intestinal inflammation and in human colonic fibroblasts. Methods: C57BL/6J mice (n = 6 per group were administered intracolonically with a trinitrobenzene sulphonic acid (TNBS enema to induce chronic (6–7 weeks colitis with fibrosis. We administered mCRAMP peptide (5 mg/kg every 3 day, week 5–7 or cathelicidin gene (Camp-expressing lentivirus (107 infectious units week 4 intracolonically or intravenously, respectively. We then infected 129Sv/J mice with Salmonella typhimurium orally to induce cecal inflammation with fibrosis. Camp-expressing lentivirus (107 infectious units day 11 was administered intravenously. Results: TNBS-induced chronic colitis was associated with increased colonic collagen (col1a2 mRNA expression. Intracolonic cathelicidin (mCRAMP peptide administration or intravenous delivery of lentivirus-overexpressing cathelicidin gene significantly reduced colonic col1a2 mRNA expression in TNBS-exposed mice compared with vehicle administration. Salmonella infection also caused increased cecal inflammation associated with collagen (col1a2 mRNA expression that was prevented by intravenous delivery of Camp-expressing lentivirus. Exposure of human primary intestinal fibroblasts and human colonic CCD-18Co fibroblasts to transforming growth factor-β1 (TGF-β1 and/or insulin-like growth factor 1 induced collagen protein and mRNA expression, which was reduced by LL-37 (3–5 μM through a MAP kinase-dependent mechanism. Conclusions: Cathelicidin can reverse intestinal fibrosis by directly inhibiting collagen synthesis in colonic fibroblasts. Keywords

Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

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Jamille Souza Fernandes

2014-01-01

Full Text Available A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14++CD16−, intermediate (CD14++CD16+, and nonclassical (CD14+CD16++. The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-α, and TGF-β was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

Combined Pulmonary Fibrosis and Emphysema Syndrome

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Rounds, Sharon I. S.

2012-01-01

There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?

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Mölleken, Christian; Poschmann, Gereon; Bonella, Francesco; Costabel, Ulrich; Sitek, Barbara; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Marcussen, Niels; Helmer, Michael; Nielsen, Ole; Hansen, Søren; Schlosser, Anders; Holmskov, Uffe; Sorensen, Grith Lykke

2016-03-29

Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in hepatitis C patients. The current study aimed to evaluate serum levels of MFAP4 in patients with pulmonary fibrosis in order to test its potential as biomarker in clinical practice. A further aim was to determine whether MFAP4 deficiency in mice affects the formation of pulmonary fibrosis in the bleomycin model of lung fibrosis. 91 patients with idiopathic pulmonary fibrosis (IPF), 23 with hypersensitivity pneumonitis (HP) and 31 healthy subjects were studied. In the mouse model, C57BL/6 Mfap4+/+ and Mfap4-/- mice between 6-8 weeks of age were studied. Serum levels of MFAP4 were measured by ELISA in patients and in mice. Surfactant protein D (SP-D) and LDH were measured as comparison biomarkers in patients with pulmonary fibrosis. Morphometric assessment and the Sircol kit were used to determine the amount of collagen in the lung tissue in the mouse model. Serum levels of MFAP4 were not elevated in lung fibrosis - neither in the patients with IPF or HP nor in the animal model. Furthermore no significant correlations with pulmonary function tests of IPF patients could be found for MFAP4. MFAP4 levels were increased in BAL of bleomycin treated mice with pulmonary fibrosis. MFAP4 is not elevated in sera of patients with pulmonary fibrosis or bleomycin treated mice with pulmonary fibrosis. This may be due to different pathogenic mechanisms of liver and lung fibrogenesis. MFAP4 seems to be useful as serum biomarker for hepatic but not for lung fibrosis.

Cystic fibrosis-related diabetes: a distinct condition.

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Cano Megías, Marta; González Albarrán, Olga

2015-01-01

Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

Noninvasive imaging of experimental lung fibrosis.

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Zhou, Yong; Chen, Huaping; Ambalavanan, Namasivayam; Liu, Gang; Antony, Veena B; Ding, Qiang; Nath, Hrudaya; Eary, Janet F; Thannickal, Victor J

2015-07-01

Small animal models of lung fibrosis are essential for unraveling the molecular mechanisms underlying human fibrotic lung diseases; additionally, they are useful for preclinical testing of candidate antifibrotic agents. The current end-point measures of experimental lung fibrosis involve labor-intensive histological and biochemical analyses. These measures fail to account for dynamic changes in the disease process in individual animals and are limited by the need for large numbers of animals for longitudinal studies. The emergence of noninvasive imaging technologies provides exciting opportunities to image lung fibrosis in live animals as often as needed and to longitudinally track the efficacy of novel antifibrotic compounds. Data obtained by noninvasive imaging provide complementary information to histological and biochemical measurements. In addition, the use of noninvasive imaging in animal studies reduces animal usage, thus satisfying animal welfare concerns. In this article, we review these new imaging modalities with the potential for evaluation of lung fibrosis in small animal models. Such techniques include micro-computed tomography (micro-CT), magnetic resonance imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and multimodal imaging systems including PET/CT and SPECT/CT. It is anticipated that noninvasive imaging will be increasingly used in animal models of fibrosis to gain insights into disease pathogenesis and as preclinical tools to assess drug efficacy.

Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

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Luciana Santos Cardoso

2013-01-01

Full Text Available The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process. Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis. Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The frequency of CD4+CD28+ T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4+ T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8+ T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8+ T cells, CD4+CD25high T cells, and CD4+CTLA-4+ T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4+CD25low cells did not differ between groups. Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.

Generalized morphea, lichen sclerosis et atrophicus associated with oral submucosal fibrosis in an adult male

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Virdi Sarvjit

2009-01-01

Full Text Available Generalized morphea is a disease characterized by wide-spread sclerosis of the skin. A 39-year-old man presented with history of multiple pigmented and bound-down plaques on the body along with mucosal involvement. Dermatological examination showed multiple indurated and sclerosed plaques with follicular plugging in few of them and gross thickened eroded and glazed tongue. The constellation of these findings with histopathological correlation led us to diagnosis of this spectrum of cutaneous involvement. The coexistence of localized morphea with lichen sclerosis et atrophicus has been reported earlier but existence of these entities with submucosal fibrosis in a same patient is documented here and is the first of its kind.

Effects of Zafirlukast on the Capsular Fibrosis of Silicone Breast Implants

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Emre Hocaoglu

2014-06-01

Methods: Forty-eight adult female Sprague-Dawley rats were divided into four groups. Smooth-surfaced, gel-filled prostheses were implanted in 36 rats. Group A: The day of the operation, 12 animals received Zafirlukast treatment for 14 weeks (oral gavage, once a day, 6 days a week, 4 mg/kg/day; Group B: 10 weeks after the operation, 12 animals received Zafirlukast treatment for 4 weeks; Group C: 12 animals were implanted but did not receive treatment; Group D: 12 animals did not have an operation, but for 14 weeks received oral gavage containing water instead of Zafirlukast. At the end of the 14 weeks, the implants with the surrounding capsules were extracted. Blind macroscopic inspectional evaluation of the capsules was performed, and microscopic capsular thickness measurements were made. Results: The mean capsular thickness was 0.033 mm (SD: 0.011 in Group A, and 0.089 mm (SD: 0.023 and 0.125 mm (SD: 0.025 in Groups B and C, respectively. Differences between Groups A and C and between Groups A and B were significant (p0.05. Similarly, Macroscopic Inspectional Fibrosis Scoring showed a significant difference between Groups A and C and a non-significant difference between Groups B and C. Conclusion: Daily prophylactic oral administration of Zafirlukast immediately after implantation significantly diminishes the development of fibrotic capsules around the silicone prostheses. [Arch Clin Exp Surg 2014; 3(3.000: 139-146

Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells.

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Jeng, J H; Wang, Y J; Chang, W H; Wu, H L; Li, C H; Uang, B J; Kang, J J; Lee, J J; Hahn, L J; Lin, B R; Chang, M C

2004-01-01

Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC-induced apoptosis and cell cycle arrest are associated with mitochondrial membrane potential (delta Psim) depolarization as revealed by a decrease in rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100 U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10-phenanthroline (200 microM) and desferrioxamine (0.5 mM) showed little effect on HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at moderate concentrations (0.05-0.1 mM), whereas at a concentration of 0.3 mM, inhibitory effects were noted. These results indicate that HC consumption may be associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS production, mitochondrial dysfunction, cell cycle disturbance and the induction of apoptosis. These events are related to the production of superoxide radicals and hydrogen peroxide.

Management of the Upper Airway in Cystic Fibrosis

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Illing, Elisa A.; Woodworth, Bradford A.

2015-01-01

Purpose of Review Upper airway disease engenders significant morbidity for patients with cystic fibrosis and is increasingly recognized as having a much greater role in pulmonary outcomes and quality of life than originally believed. Widespread disparate therapeutic strategies for cystic fibrosis chronic rhinosinusitis underscore the absence of a standardized treatment paradigm. This review outlines the most recent evidence-based trends in the management of upper airway disease in cystic fibrosis. Recent Findings The unified airway theory proposes that the sinuses are a focus of initial bacterial colonization which seeds the lower airway and may play a large role in maintaining lung infections. Mounting evidence suggests more aggressive treatment of the sinuses may confer significant improvement in pulmonary disease and quality of life outcomes in cystic fibrosis patients. However, there is a lack of high-level evidence regarding medical and surgical management of cystic fibrosis chronic rhinosinusitis that makes generalizations difficult. Summary Well designed clinical trials with long-term follow-up concerning medical and surgical interventions for cystic fibrosis sinus disease are required to establish standardized treatment protocols, but increased interest in the sinuses as a bacterial reservoir for pulmonary infections has generated considerable attention. PMID:25250804

Cystic Fibrosis-Related Diabetes (CFRD): Daily Management

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Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 This Web cast is supported by an unrestricted ... Moran, MD Professor, Pediatric Endocrinology University of Minnesota Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 ...

Outcome in cystic fibrosis liver disease.

LENUS (Irish Health Repository)

Rowland, Marion

2011-01-01

Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD.

[Genetic counseling in cystic fibrosis].

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Julia, S; Bieth, E

2000-08-01

Genetic counseling is an important part of health care in patients with cystic fibrosis or respiratory diseases associated with the CFTR (cystic fibrosis transmembrane conductance regulator) gene, including certain types of allergic bronchopulmonary aspergilloses or bronchial diseases (diffuse bronchiectasia). The basic goal is to provide patients with information on the transmission of cystic fibrosis and to asses the risk of recurrence. This risk is determined from molecular biology analyses examining the CFTR gene. Genotyping is the only means of screening for the heterozygous state, frequent in the French population (about 1/30). Because of the large number of mutated alleles not covered entirely by the genetic tests, there remains a question of probability expressed as a residual risk of a heterozygous state. A prenatal genotype diagnosis should be proposed to heterozygous couples who have a 25% risk of having a diseased child. Technically, this is almost always possible and the results are highly reliable. Nevertheless, there remains the risks related to sample taking and the ethical issue about which the patients must be informed. Management of these at risk couples who desire a child must be based on a multidisciplinary approach, particularly important when one of the parents has overt cystic fibrosis.

Radiation pneumonitis and fibrosis

International Nuclear Information System (INIS)

Shopova, V.; Salovsky, P.; Dancheva, V.

2001-01-01

The likelihood of toxic pulmonary lesions development as the result of radiation therapy for pulmonary carcinoma and breast cancer is discussed. Two possible forms of radiation induced changes are described, namely: classical radiation pneumonitis (RP) terminating with lung fibrosis circumscribed in the radiation zone, and sporadic RP giving rise to bilateral lymphatic alveolitis and manifestations outside the irradiation field. Attention is called to the fact that chemotherapy augments the risk of toxic lung damage occurrence. A number of markers for early RP diagnosis, including lactate dehydrogenase activity, KL-6, procollagen III, transforming growth factor β, C-reactive protein and partial oxygen pressure are listed. Therapeutic possibilities in coping with RP and pulmonary fibrosis are assayed. Apart from the standard therapeutic approach using corticosteroids and azatioprin, ideas are set forth concerning the application of some antioxidants, angiotensin converting enzyme inhibitors and γ-interferon. It is pointed out that radiation pneumonitis and pulmonary fibrosis treatment has an essential practical bearing on life expectancy and quality of life in a great number of cancer patients. (author)

Radiotherapy of breast fibrosis

International Nuclear Information System (INIS)

Heibel, J.H.

1979-01-01

In a retrospective study radiotherapy of breast fibrosis in hormone-treated men with histologically confirmed prostate carcinoma was examined. 10 patients had received hormones even before irradiation, 113 obtained hormone administration only after irradiation. The objective size of the glandular body and the overall size of the breast were measured with a special method developed by the author. 46 patients indicated complaints. With hypertrophic mamma and hypertrophic mamilla in 67 examined patients, 127 different symptoms resulted in total. Four patients of the group who had obtained hormones before irradiation, suffered from subjective symptoms. It resulted that radiotherapy of breast fibrosis carried out during hormone treatment is no gynecomastia prophylaxis, that already existent mamma hypertrophies are irreversible, but that existent sensations were notably reduced within 6 months after irradiation therapy. These results indicate the necessity of a radiotherapy of the mamma fibrosis before the hormone treatment is begun. Particularly in cases of higher operative risks, also the possibility of preferring radiotherapy to mastectomy should be fully utilized, in view of adequate or even better therapeutic results. (orig./MG) [de

Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

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Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

2008-01-01

Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

"Tipping" extracellular matrix remodeling towards regression of liver fibrosis

DEFF Research Database (Denmark)

Magdaleno, Fernando; Schierwagen, Robert; Uschner, Frank E

2018-01-01

Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established...... fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, together with other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration...

Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

Science.gov (United States)

Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

2018-06-01

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Chemical Composition of Golden Berry Leaves Against Hepato-renal Fibrosis.

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Khalaf-Allah, Abd El-Rahman M; El-Gengaihi, Souad E; Hamed, Manal A; Zahran, Hanan G; Mohammed, Mona A

2016-01-01

The role of Physalis peruviana (golden berry) as functional food against hepato-renal fibrosis induced by carbon tetrachloride (CCl4) was evaluated. The chemical composition of leaves referred the presence of withanolides and flavonoids. Two compounds, ursolic acid and lupeol, were isolated and their structures were elucidated by different spectral analysis techniques. The biological evaluation was conducted on different animal groups; control rats, control orally treated with plant extract (500 mg/kg body weight twice a week for six consecutive weeks), CCl4 (0.5 ml/kg body weight diluted to 1:9 (v/v) in olive oil and injected intraperitoneally) group, CCl4 treated with plant extract and CCl4 treated with silymarin as a reference herbal drug. The evaluation was done through measuring oxidative stress markers; malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO). Liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea and serum protein were also evaluated. The results revealed plant safety and decrease in NO, MDA, IgG, ALP, tissue protein, bilirubin, creatinine and urea levels. Increase in SOD, AST, ALT, GGT and serum protein levels were observed. Improvement in liver and kidney histopathological architectures were also seen. In conclusion, Physalis peruviana recorded a significant protective role in liver and kidney against fibrosis. Further studies are needed to evaluate its isolated compounds and its use in pharmacological applications and clinical uses.

The Interplay between Inflammation and Fibrosis in Kidney Transplantation

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Irina B. Torres

2014-01-01

Full Text Available Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

Cystic fibrosis Delta F508 heterozygotes, smoking, and reproduction

DEFF Research Database (Denmark)

Dahl, Morten; Tybjaerg-Hansen, A; Wittrup, H H

1998-01-01

Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested this hypot......Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested.......001). In conclusion, overall these results do not support a reproductive advantage for cystic fibrosis DeltaF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking DeltaF508 heterozygotes experience a reproductive advantage while smoking DeltaF508 heterozygotes experience...... the opposite, a reproductive disadvantage. Accordingly, the data suggest a previously undocumented role of smoking on fecundity among cystic fibrosis heterozygotes....

Role of Receptor Tyrosine Kinase Signaling in Renal Fibrosis

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Feng Liu

2016-06-01

Full Text Available Renal fibrosis can be induced in different renal diseases, but ultimately progresses to end stage renal disease. Although the pathophysiologic process of renal fibrosis have not been fully elucidated, it is characterized by glomerulosclerosis and/or tubular interstitial fibrosis, and is believed to be caused by the proliferation of renal inherent cells, including glomerular epithelial cells, mesangial cells, and endothelial cells, along with defective kidney repair, renal interstitial fibroblasts activation, and extracellular matrix deposition. Receptor tyrosine kinases (RTKs regulate a variety of cell physiological processes, including metabolism, growth, differentiation, and survival. Many studies from in vitro and animal models have provided evidence that RTKs play important roles in the pathogenic process of renal fibrosis. It is also showed that tyrosine kinases inhibitors (TKIs have anti-fibrotic effects in basic research and clinical trials. In this review, we summarize the evidence for involvement of specific RTKs in renal fibrosis process and the employment of TKIs as a therapeutic approach for renal fibrosis.

Liver Disease in Cystic Fibrosis: an Update

Science.gov (United States)

Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

2013-01-01

Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of

Fibrosis imaging : Current concepts and future directions

NARCIS (Netherlands)

Baues, Maike; Dasgupta, Anshuman; Ehling, Josef; Prakash, Jai; Boor, Peter; Tacke, Frank; Kiessling, Fabian; Lammers, Twan

2017-01-01

Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis

Cystic fibrosis with normal sweat chloride concentration: case report

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Silva Filho Luiz Vicente Ferreira da

2003-01-01

Full Text Available Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

Reversal of liver fibrosis: From fiction to reality.

Science.gov (United States)

Zoubek, Miguel Eugenio; Trautwein, Christian; Strnad, Pavel

2017-04-01

In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM. While animal models have been indispensable for our understanding of liver fibrosis, they possess several important limitations and need to be further refined. A better insight into the liver fibrogenesis resulted in a large number of clinical trials aiming at reversing liver fibrosis, particularly in patients with non-alcoholic steatohepatitis. Collectively, the current developments demonstrate that reversal of liver fibrosis is turning from fiction to reality. Copyright © 2017. Published by Elsevier Ltd.

Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.

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Jody Groenendyk

Full Text Available Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function.We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER homeostasis, transient activation of the unfolded protein response (UPR pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.

Self-management education for cystic fibrosis.

LENUS (Irish Health Repository)

Savage, Eileen

2011-01-01

Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted.

Effects and mechanisms of pirfenidone, prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models.

Science.gov (United States)

Yu, Wencheng; Guo, Fang; Song, Xiaoxia

2017-12-01

Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown. This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF. Rat IPF model was established by endotracheal injection of 5 mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100 mg/kg once daily), prednisone (H, 5 mg/kg once daily) and acetylcysteine (N, 4 mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay. After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p fibrosis scores of lung tissues, as well as expression of TGF-β1, TNF-α and PDGF, but the expression of Cav-1 was higher (p fibrosis score was significantly lower and the protein expression of Cav-1 was significantly higher in the P group (p fibrosis scores (r = -0.506, p pulmonary fibrosis in rat IPF models, which may be related with enhanced caveolin-1, reduced TNF-α, TGF-β1, PDGF.

Prediction of fibrosis progression in chronic viral hepatitis

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Grace Lai-Hung Wong

2014-09-01

Full Text Available Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

Endocytosis and intracellular protein degradation in cystic fibrosis fibroblasts

International Nuclear Information System (INIS)

Jessup, W.; Dean, R.T.

1983-01-01

Normal rates of pinocytosis of [ 3 H]sucrose were measured in cystic fibrosis fibroblasts, and were not affected by the addition of cystic fibrosis serum. Bulk protein degradation (a significant proportion of which occurs intralysosomally following autophagy) and its regulation by growth state were apparently identical in normal and cystic fibrosis cultures. (Auth.)

Do submucous myoma characteristics affect fertility and menstrual outcomes in patients underwent hysteroscopic myomectomy?

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Ahmed Namazov

2015-06-01

Full Text Available Background: Submucous myomas may be associated with menorrhagia, infertility and dysmenorrhea. Objective: The aim of this study was to determine the long term effects of submucousal myoma resection on menorrhagia and infertility; also to detect whether the type, size, and location of myoma affect the surgical success. Materials and Methods: .Totally 98 women referred to hysteroscopy for symptomatic submucousal fibroids (menorrhagia (n=51 and infertility (n=47 between 2005- 2010 were enrolled in this historical cohort study Pregnancy rates and menstrual improvement rates were compared according to myoma characteristics (size, type and location. Results: After a mean postoperative period of 23±10 months in 51 patients with excessive bleeding, 13 had recurrent menorrhagia (25%. In Other 38 patients excessive bleeding was improved (75%. The improvement rates by location and myoma type: lower segment 100%, fundus 92%, and corpus 63%; type 0 70%, type 1 78%, type 2 80%. The mean sizes of myoma in recurred and improved patients were 23.33 mm and 29.88 mm respectively. 28 of 47 infertile women spontaneously experienced thirty pregnancies (60%. Pregnancy rates according to myoma location and type: lower segment 50%, fundus 57%, and corpus 80%; type 0 75%, type 1 62%, type 2 50%. The mean myoma size in patients who became pregnant was 30.38 mm; in patients who did not conceive was 29.95 mm. Conclusion: The myoma characetesitics do not affect improvement rates after hysteroscopic myomectomy in patients with unexplained infertility or excessive uterine bleeding.

Hepatic fibrosis: Concept to treatment.

Science.gov (United States)

Trautwein, Christian; Friedman, Scott L; Schuppan, Detlef; Pinzani, Massimo

2015-04-01

Understanding the molecular mechanisms underlying liver fibrogenesis is fundamentally relevant to developing new treatments that are independent of the underlying etiology. The increasing success of antiviral treatments in blocking or reversing the fibrogenic progression of chronic liver disease has unearthed vital information about the natural history of fibrosis regression, and has established important principles and targets for antifibrotic drugs. Although antifibrotic activity has been demonstrated for many compounds in vitro and in animal models, none has been thoroughly validated in the clinic or commercialized as a therapy for fibrosis. In addition, it is likely that combination therapies that affect two or more key pathogenic targets and/or pathways will be needed. To accelerate the preclinical development of these combination therapies, reliable single target validation is necessary, followed by the rational selection and systematic testing of combination approaches. Improved noninvasive tools for the assessment of fibrosis content, fibrogenesis and fibrolysis must accompany in vivo validation in experimental fibrosis models, and especially in clinical trials. The rapidly changing landscape of clinical trial design for liver disease is recognized by regulatory agencies in the United States (FDA) and Western Europe (EMA), who are working together with the broad range of stakeholders to standardize approaches to testing antifibrotic drugs in cohorts of patients with chronic liver diseases. Copyright © 2015. Published by Elsevier B.V.

Nephrogenic systemic fibrosis

DEFF Research Database (Denmark)

Marckmann, Peter

2008-01-01

PURPOSE OF REVIEW: The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. RECENT FINDINGS: Epidemiological and histochemical studies demonstrated....... Increasingly poor renal function, aberrations in calcium-phosphate metabolism and erythropoietin treatment seem to increase the risk of the disease and its severity. Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. The figure...... that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. One particular agent, gadodiamide, caused the majority of cases, but gadopentetate dimeglumine has also been implicated in several cases...

Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction.

Science.gov (United States)

Kato, Noritoshi; Kosugi, Tomoki; Sato, Waichi; Ishimoto, Takuji; Kojima, Hiroshi; Sato, Yuka; Sakamoto, Kazuma; Maruyama, Shoichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji

2011-02-01

Regardless of their primary causes, progressive renal fibrosis and tubular atrophy are the main predictors of progression to end-stage renal disease. Basigin/CD147 is a multifunctional molecule-it induces matrix metalloproteinases and hyaluronan, for example-and has been implicated in organ fibrosis. However, the relationship between basigin and organ fibrosis has been poorly studied. We investigated basigin's role in renal fibrosis using a unilateral ureteral obstruction model. Basigin-deficient mice (Bsg(-/-)) demonstrated significantly less fibrosis after surgery than Bsg(+/+) mice. Fewer macrophages had infiltrated in Bsg(-/-) kidneys. Consistent with these in vivo data, primary cultured tubular epithelial cells from Bsg(-/-) mice produced less matrix metalloproteinase and exhibited less motility on stimulation with transforming growth factor β. Furthermore, Bsg(-/-) embryonic fibro blasts produced less hyaluronan and α-smooth muscle actin after transforming growth factor β stimulation. Together, these results demonstrate for the first time that basigin is a key regulator of renal fibrosis. Basigin could be a candidate target molecule for the prevention of organ fibrosis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

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Minrui Liang

2013-01-01

Full Text Available Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL- 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM- induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis.

[Endomyocardial fibrosis with massive calcification of the left ventricle].

Science.gov (United States)

Trigo, Joana; Camacho, Ana; Gago, Paula; Candeias, Rui; Santos, Walter; Marques, Nuno; Matos, Pedro; Brandão, Victor; Gomes, Veloso

2010-03-01

Endomyocardial fibrosis is a rare disease, endemic in tropical countries. It is characterized by fibrosis of the endocardium that can extend to myocardium. Important calcification of the endocardium is rare with only a few cases reported in the literature. We report a case of endomyocardial fibrosis in a european caucasian patient, associated with massive calcification of left ventricle.

Prevalence of areca nut chewing in the middle school-going children of Indore, India

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Ashok Khandelwal

2012-01-01

Full Text Available Objectives: To assess areca nut chewing habit among middle school-aged children in Indore, India. Areca nut is chewed by itself, and in various scented preparations. It is associated with carcinogenesis, foreign body aspiration in children, and oral submucous fibrosis and may aggravate asthma. Materials and Methods: A retrospective collection of data to evaluate the prevalence of areca nut chewing among 3896 children was done. A simple random sampling was done. Children of both sexes were included in this study. Results: 27.06% of the school-going children (1054/3896 had areca nut chewing habit. More boys chewed areca nut than girls (2:1. 45.42% of school going children of rural area pander to areca nut chewing habit, whereas in urban area 20.09% children are indulged. Government school children are more involved in areca nut chewing habit. 81.02% of the children used sweetened and flavoured form of areca nut. The majority of the users were not aware of harmful effects that the use of areca nut might be harmful for health Conclusion: To diminish the use of areca nut, the Indian Government should consider limiting trade, advertising, and actively communicating its health risks to the public and should deem heavy taxes on it.

Cystic Fibrosis-Related Diabetes

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Kayani Kayani

2018-02-01

Full Text Available Cystic fibrosis (CF is the most common autosomal recessive disorder in Caucasian populations. Individuals with CF have seen significant increases in life expectancy in the last 60 years. As a result, previously rare complications are now coming to light. The most common of these is cystic fibrosis-related diabetes (CFRD, which affects 40–50% of CF adults. CFRD significantly impacts the pulmonary function and longevity of CF patients, yet a lack of consensus on the best methods to diagnose and treat CFRD remains. We begin by reviewing our understanding of the pathogenesis of CFRD, as emerging evidence shows the cystic fibrosis transmembrane conductance regulator (CFTR also has important roles in the release of insulin and glucagon and in the protection of β cells from oxidative stress. We then discuss how current recommended methods of CFRD diagnosis are not appropriate, as continuous glucose monitoring becomes more effective, practical, and cost-effective. Finally, we evaluate emerging treatments which have narrowed the mortality gap within the CF patient group. In the future, pharmacological potentiators and correctors directly targeting CFTR show huge promise for both CFRD and the wider CF patient groups.

European Cystic Fibrosis Society Standards of Care

DEFF Research Database (Denmark)

Stern, Martin; Bertrand, Dominique Pougheon; Bignamini, Elisabetta

2014-01-01

Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful ...... to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons.......Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful...... therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference...

Immunoreactive trypsin and neonatalscreening for cystic fibrosis

International Nuclear Information System (INIS)

Travert, G.; Laroche, D.; Blandin, C.; Pasquet, C.

1988-01-01

Immunoreactive trypsin (IRT) was measured in dried blood spots from 160.822 five-day-old babies as a part of a regionwide neonatal screening program for cystic fibrosis. A second test was performed for 492 babies in whom blood IRT levels were found greater than 900 μg/l; retesting revealed persistent elevation in 55. Sweat testing confirmed cystic fibrosis in 43 babies, but results were normal in 12. During the course of this study, a total of 51 cystic fibrosis babies were identified: 43 by newborn screening, 6 because they had meconium ileus; so, early diagnosis was achieved in 49 cases out of 51. Two newborn babies did not have elevated IRT and they were missed by the screening test. Our results confirm that elevated blood IRT is characteristic of newborn babies with cystic fibrosis and show that this test has an excellent specificity (99.7%) and a good sensitivity (95%) when used as a neonatal screening test [fr

Molecular and cellular mechanisms of pulmonary fibrosis

Science.gov (United States)

2012-01-01

Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

Ormond's disease or secondary retroperitoneal fibrosis? An overview of retroperitoneal fibrosis

Energy Technology Data Exchange (ETDEWEB)

Heckmann, M.; Uder, M.; Kuefner, M.A.; Heinrich, M.C. [Universitaetsklinikum Erlangen (Germany). Radiologisches Inst.

2009-04-15

Retroperitoneal fibrosis represents a rare inflammatory disease. About two thirds of all cases seem to be idiopathic (= Ormond's disease). The remaining one third is secondary and may be ascribed to infections, trauma, radiation therapy, malignant diseases, and the use of certain drugs. Up to 15 % of patients have additional fibrotic processes outside the retroperitoneum. The clinical symptoms of retroperitoneal fibrosis are non-specific. In sonography retroperitoneal fibrosis appears as a retroperitoneal hypoechoic mass which can involve the ureters and thus cause hydronephrosis. Intravenous urography and MR urography can demonstrate the typical triad of medial deviation and extrinsic compression of the ureters and hydronephrosis. CT and MRI are the modalities of choice for the diagnosis and follow-up of this disease. The lesion typically begins at the level of the fourth or fifth lumbar vertebra and appears as a plaque, encasing the aorta and the inferior vena cava and often enveloping and medially displacing the ureters. In unenhanced CT, retroperitoneal fibrosis appears as a mass that is isodense with muscle. When using MRI, the mass is hypointense in T1-weighted images and of variable intensity in T2-weighted images according to its stage: it may be hyperintense in early stages, while the tissue may have a low signal in late stages. After the administration of contrast media, enhancement is greatest in the early inflammatory phase and minimal in the late fibrotic phase. Dynamic gadolinium enhancement can be useful for assessing disease activity, monitoring response to treatment, and detecting relapse. To differentiate retroperitoneal masses, diffusion-weighted MRI may provide useful information. (orig.)

Ivacaftor: A Novel Gene-Based Therapeutic Approach for Cystic Fibrosis

OpenAIRE

Condren, Michelle E.; Bradshaw, Marquita D.

2013-01-01

Ivacaftor is a new therapeutic agent that acts at the cystic fibrosis transmembrane conductance regulator (CFTR) channel to alter activity. It is approved for use in patients 6 years and older with cystic fibrosis who have at least 1 G551D mutation in the CFTR gene. It is unlike any other current pharmacologic agent for cystic fibrosis in that it specifically targets the gene defect associated with cystic fibrosis as opposed to treating resulting symptomology. Mucoactive agents, antibiotics, ...

Drug- and radiation-induced pulmonary fibrosis

International Nuclear Information System (INIS)

Uthgenannt, H.

1976-01-01

These two forms of pulmonary fibrosis which according to their type have nothing to do with one another, are presented as they are well suited to clarify the problems of the diagnosis of pulmonary fibrosis which is not a fixed concept for the pathologists. The frequent discrepancy found between the subjective clinical symptoms, clinical findings and X-ray and morphological pictures is indicated. (MG) [de

Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: impact of a "Top-Down" approach to intestinal fibrosis in mice.

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Johnson, Laura A; Luke, Amy; Sauder, Kay; Moons, David S; Horowitz, Jeffrey C; Higgins, Peter D R

2012-03-01

The natural history of Crohn's disease follows a path of progression from an inflammatory to a fibrostenosing disease, with most patients requiring surgical resection of fibrotic strictures. Potent antiinflammatory therapies reduce inflammation but do not appear to alter the natural history of intestinal fibrosis. The aim of this study was to determine the relationship between intestinal inflammation and fibrogenesis and the impact of a very early "top-down" interventional approach on fibrosis in vivo. In this study we removed the inflammatory stimulus from the Salmonella typhimurium mouse model of intestinal fibrosis by eradicating the S. typhimurium infection with levofloxacin at sequential timepoints during the infection. We evaluated the effect of this elimination of the inflammatory stimulus on the natural history of inflammation and fibrosis as determined by gross pathology, histopathology, mRNA expression, and protein expression. Fibrogenesis is preceded by inflammation. Delayed eradication of the inflammatory stimulus by antibiotic treatment represses inflammation without preventing fibrosis. Early intervention significantly ameliorates but does not completely prevent subsequent fibrosis. This study demonstrates that intestinal fibrosis develops despite removal of an inflammatory stimulus and elimination of inflammation. Early intervention ameliorates but does not abolish subsequent fibrosis, suggesting that fibrosis, once initiated, is self-propagating, suggesting that a very early top-down interventional approach may have the most impact on fibrostenosing disease. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

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Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang; Detlefsen, Sönke; Antonsen, Steen; Krag, Aleksander

2018-04-01

Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for

Blood Gene Expression Profiling of Breast Cancer Survivors Experiencing Fibrosis

International Nuclear Information System (INIS)

Landmark-Hoyvik, Hege; Dumeaux, Vanessa; Reinertsen, Kristin V.; Edvardsen, Hege; Fossa, Sophie D.; Borresen-Dale, Anne-Lise

2011-01-01

Purpose: To extend knowledge on the mechanisms and pathways involved in maintenance of radiation-induced fibrosis (RIF) by performing gene expression profiling of whole blood from breast cancer (BC) survivors with and without fibrosis 3-7 years after end of radiotherapy treatment. Methods and Materials: Gene expression profiles from blood were obtained for 254 BC survivors derived from a cohort of survivors, treated with adjuvant radiotherapy for breast cancer 3-7 years earlier. Analyses of transcriptional differences in blood gene expression between BC survivors with fibrosis (n = 31) and BC survivors without fibrosis (n = 223) were performed using R version 2.8.0 and tools from the Bioconductor project. Gene sets extracted through a literature search on fibrosis and breast cancer were subsequently used in gene set enrichment analysis. Results: Substantial differences in blood gene expression between BC survivors with and without fibrosis were observed, and 87 differentially expressed genes were identified through linear analysis. Transforming growth factor-β1 signaling was identified as the most significant gene set, showing a down-regulation of most of the core genes, together with up-regulation of a transcriptional activator of the inhibitor of fibrinolysis, Plasminogen activator inhibitor 1 in the BC survivors with fibrosis. Conclusion: Transforming growth factor-β1 signaling was found down-regulated during the maintenance phase of fibrosis as opposed to the up-regulation reported during the early, initiating phase of fibrosis. Hence, once the fibrotic tissue has developed, the maintenance phase might rather involve a deregulation of fibrinolysis and altered degradation of extracellular matrix components.

Loss of Matrix Metalloproteinase-13 Attenuates Murine Radiation-Induced Pulmonary Fibrosis

International Nuclear Information System (INIS)

Flechsig, Paul; Hartenstein, Bettina; Teurich, Sybille; Dadrich, Monika; Hauser, Kai; Abdollahi, Amir; Groene, Hermann-Josef; Angel, Peter; Huber, Peter E.

2010-01-01

Purpose: Pulmonary fibrosis is a disorder of the lungs with limited treatment options. Matrix metalloproteinases (MMPs) constitute a family of proteases that degrade extracellular matrix with roles in fibrosis. Here we studied the role of MMP13 in a radiation-induced lung fibrosis model using a MMP13 knockout mouse. Methods and Materials: We investigated the role of MMP13 in lung fibrosis by investigating the effects of MMP13 deficiency in C57Bl/6 mice after 20-Gy thoracic irradiation (6-MV Linac). The morphologic results in histology were correlated with qualitative and quantitative results of volume computed tomography (VCT), magnetic resonance imaging (MRI), and clinical outcome. Results: We found that MMP13 deficient mice developed less pulmonary fibrosis than their wildtype counterparts, showed attenuated acute pulmonary inflammation (days after irradiation), and a reduction of inflammation during the later fibrogenic phase (5-6 months after irradiation). The reduced fibrosis in MMP13 deficient mice was evident in histology with reduced thickening of alveolar septi and reduced remodeling of the lung architecture in good correlation with reduced features of lung fibrosis in qualitative and quantitative VCT and MRI studies. The partial resistance of MMP13-deficient mice to fibrosis was associated with a tendency towards a prolonged mouse survival. Conclusions: Our data indicate that MMP13 has a role in the development of radiation-induced pulmonary fibrosis. Further, our findings suggest that MMP13 constitutes a potential drug target to attenuate radiation-induced lung fibrosis.

Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis.

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Bei-Bei Zhang

Full Text Available Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson's trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (P<0.01. Importantly, increased Th2 subset and Treg subset all positively correlated with hydroxyproline contents (P<0.01. This result for the first time implied that the increased hepatic Th2 and Treg cell subsets were likely to play potential roles in the formation of biliary fibrosis in C. sinensis-infected mice.

PECULIARITIES OF ENT-DAMAGE IN CHILDREN WITH CYSTIC FIBROSIS

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I.V. Martynova

2011-01-01

Full Text Available Traditional approach to cystic fibrosis patients treatment doesn’t involve upper respiratory tract assessment, though abnormal changes — consequences of the cystic fibrosis transmembrane conductivity regulator gene mutation- do affect nasal and paranasal mucosa to the same extent. Approximately half of cystic fibrosis patients suffer from chronic rhinosinusitis and/or nasal polyposis that worsens the clinical course of already severe disease. Chronic hyperplasia in paranasal cavities can be quite extensive, recurrent and can lead to destruction of osseous walls of the cavity and of nasal septum. Thus increasing the amount of hospital admissions and and their duration. Low awareness of ENT-specialists working in polyclinics and in hospitals of ENT-pathology in cystic fibrosis patients leads to belated diagnostics, excessive manipulations, ineffective treatment, including surgery. All these lays grounds to implication of the early screening diagnostic program and development of proper treatment methods of ENT-complications of cystic fibrosis — therapeutic as well as surgical, with strict specification of indications and contraindications. Key words: cystic fibrosis, chronic rhino sinusitis, nasal polyposis. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 49–53.

Imaging pulmonary fibrosis; Imagerie des fibroses pulmonaires

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Brauner, M.W.; Rety, F.; Naccache, J.M.; Girard, F.; Valeyre, D.F. [Hopital Avicenne, 93 - Bobigny (France). Service de radiologie et de pneumologie

2001-02-01

Localized fibrosis of the lung is usually scar tissue while diffuse pulmonary fibrosis is more often a sign of active disease. Chronic infiltrative lung disease may be classified into four categories: idiopathic pneumonitis, collagen diseases, granulomatosis (sarcoidosis), and caused by known diseases (pneumoconiosis, hypersensitivity pneumonitis, drug-induced lung disease, radiation). (authors)

Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells

International Nuclear Information System (INIS)

Verhaeghe, Catherine; Tabruyn, Sebastien P.; Oury, Cecile; Bours, Vincent; Griffioen, Arjan W.

2007-01-01

Cystic fibrosis is a common genetic disorder characterized by a severe lung inflammation and fibrosis leading to the patient's death. Enhanced angiogenesis in cystic fibrosis (CF) tissue has been suggested, probably caused by the process of inflammation, as similarly described in asthma and chronic bronchitis. The present study demonstrates an intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells. Microarray experiments showed that CF airway epithelial cells expressed several angiogenic factors such as VEGF-A, VEGF-C, bFGF, and PLGF at higher levels than control cells. These data were confirmed by real-time quantitative PCR and, at the protein level, by ELISA. Conditioned media of these cystic fibrosis cells were able to induce proliferation, migration and sprouting of cultured primary endothelial cells. This report describes for the first time that cystic fibrosis epithelial cells have an intrinsic angiogenic activity. Since excess of angiogenesis is correlated with more severe pulmonary disease, our results could lead to the development of new therapeutic applications

Fibrosis quística que simula un síndrome de Bartter Cystic fibrosis mimicking Bartter syndrome

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Neri G Campañá Cobas

2008-12-01

Full Text Available La fibrosis quística es una enfermedad que se hereda como trastorno autosómico recesivo. La presentación clásica está caracterizada por enfermedad pulmonar crónica, deficiencia pancreática y concentraciones altas de electrolitos en sudor. En algunos pacientes la presentación puede ser monosíntomatica, por ejemplo, la depleción de electrolitos en sangre. El propósito de este informe es comunicar el caso de una lactante de 2 meses de edad diagnosticada de fibrosis quística, que inicialmente pareció ser un síndrome de Bartter. El motivo de ingreso fue un vómito, decaimiento y signos de deshidratación. Se realizó gasometría, estudio de electrolitos en sangre, determinación de concentración de electrolitos en la orina, prueba de electrolitos en sudor y estudio genético para fibrosis quística. La concentración de potasio (28 mEeq/L hizo pensar en un síndrome de Bartter y se comenzó tratamiento con indometacina y cloruro de potasio; se normalizaron todos los parámetros. Dos meses después reingresó con deshidratación ligera por un vómito, trastornos mixtos del equilibrio ácido-base, hiponatremia, hipocloremia y ligera hiperpotasemia. Se realizaron electrolitos en sudor en 3 ocasiones y fueron positivos, y el estudio genético para fibrosis quística demostró una mutación delta F508.Cystic fibrosis is a disease that is inherited as a recessive autosomal disorder. The classical presentation is characterized by chronic lung disease, pancreatic deficiency and high concentrations of electrolytes in sweat. In some patients, the presentation may be monosymptomatic as, for example, the depletion of electrolytes in blood. The objective of this paper is to report the case of a 2-months-old female infant with diagnosis of cystic fibrosis that initially seemed to be a Bartter syndrome. The reason to be admitted was vomit, dwindles and dehydration signs. Gasometry, study of electrolytes in blood, determination of concentration of

Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C.

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Petersen, John R; Stevenson, Heather L; Kasturi, Krishna S; Naniwadekar, Ashutosh; Parkes, Julie; Cross, Richard; Rosenberg, William M; Xiao, Shu-Yuan; Snyder, Ned

2014-04-01

The assessment of liver fibrosis in chronic hepatitis C patients is important for prognosis and making decisions regarding antiviral treatment. Although liver biopsy is considered the reference standard for assessing hepatic fibrosis in patients with chronic hepatitis C, it is invasive and associated with sampling and interobserver variability. Serum fibrosis markers have been utilized as surrogates for a liver biopsy. We completed a prospective study of 191 patients in which blood draws and liver biopsies were performed on the same visit. Using liver biopsies the sensitivity, specificity, and negative and positive predictive values for both aspartate aminotransferase/platelet ratio index (APRI) and enhanced liver fibrosis (ELF) were determined. The patients were divided into training and validation patient sets to develop and validate a clinically useful algorithm for differentiating mild and significant fibrosis. The area under the ROC curve for the APRI and ELF tests for the training set was 0.865 and 0.880, respectively. The clinical sensitivity in separating mild (F0-F1) from significant fibrosis (F2-F4) was 80% and 86.0% with a clinical specificity of 86.7% and 77.8%, respectively. For the validation sets the area under the ROC curve for the APRI and ELF tests was, 0.855 and 0.780, respectively. The clinical sensitivity of the APRI and ELF tests in separating mild (F0-F1) from significant (F2-F4) fibrosis for the validation set was 90.0% and 70.0% with a clinical specificity of 73.3% and 86.7%, respectively. There were no differences between the APRI and ELF tests in distinguishing mild from significant fibrosis for either the training or validation sets (P=0.61 and 0.20, respectively). Using APRI as the primary test followed by ELF for patients in the intermediate zone, would have decreased the number of liver biopsies needed by 40% for the validation set. Overall, use of our algorithm would have decreased the number of patients who needed a liver biopsy

Therapy of experimental NASH and fibrosis with galectin inhibitors.

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Peter G Traber

Full Text Available Non-alcoholic steatohepatitis (NASH and resultant liver fibrosis is a major health problem without effective therapy. Some data suggest that galectin-3 null mice are resistant to the development of NASH with fibrosis. We examined the ability of two complex carbohydrate drugs that bind galectin-3, GM-CT-01 and GR-MD-02, to treat NASH with fibrosis in a murine model. GR-MD-02 treatment resulted in marked improvement in liver histology with significant reduction in NASH activity and collagen deposition. Treatments seemed also to improve both glomerulopathy and interstitial fibrosis observed in kidneys. The improvement in liver histology was evident when animals were treated early in disease or after establishment of liver fibrosis. In all measures, GM-CT-01 had an intermediate effect between vehicle and GR-MD-02. Galectin-3 protein expression was increased in NASH with highest expression in macrophages surrounding lipid laden hepatocytes, and reduced following treatment with GR-MD-02, while the number of macrophages was unchanged. Treatment with GR-MD-02 also reduced the expression of pathological indicators including iNOS, an important TH1 inflammatory mediator, CD36, a scavenger receptor for lipoproteins on macrophages, and α-smooth muscle actin, a marker for activated stellate cells which are the primary collagen producing cells in liver fibrosis. We conclude that treatment with these galectin-3 targeting drugs improved histopathological findings of NASH and markedly reduced fibrosis in a murine model of NASH. While the mechanisms require further investigation, the treatment effect is associated with a reduction of galectin-3 expressed by activated macrophages which was associated with regression of NASH, including hepatocellular fat accumulation, hepatocyte ballooning, intra-portal and intra-lobular inflammatory infiltrate, and deposition of collagen. Similar effects were found with GM-CT-01, but with approximately four-fold lower potency than

Living with Cystic Fibrosis: A Guide for the Young Adult.

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Cystic Fibrosis Foundation, Atlanta, GA.

Intended for the young adult with cystic fibrosis, the booklet provides information on dealing with problems and on advances in treatment and detection related to the disease. Addressed are the following topics: description of cystic fibrosis; inheritance of cystic fibrosis; early diagnosis; friends, careers, and other matters; treatment;…

Unusual Presentation Of Idiopathic Retroperitoneal Fibrosis: Case ...

African Journals Online (AJOL)

Idiopathic retroperitoneal fibrosis (IRF) is an uncommon entity described as progressive proliferation of connective tissues leading to a fibrous plaque-like lesions that encases the aorta and inferior vena cava inferior to the level of the renal arteries. Mass forming retroperitoneal fibrosis is rare. We present a rare case of a ...

Role of histone deacetylases(HDACs) in progression and reversal of liver fibrosis

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Li, Xing; Wu, Xiao-Qin; Xu, Tao; Li, Xiao-Feng; Yang, Yang; Li, Wan-Xia; Huang, Cheng; Meng, Xiao-Ming; Li, Jun, E-mail: lijun@ahmu.edu.cn

2016-09-01

Liver fibrosis refers to a reversible wound healing process response to chronic liver injuries. Activation of hepatic stellate cells (HSCs) is closely correlated with the development of liver fibrosis. Histone deacetylases(HDACs) determine the acetylation levels of core histones to modulate expression of genes. To demonstrate the link between HDACs and liver fibrosis, CCl4-induced mouse liver fibrosis model and its spontaneous reversal model were established. Results of the current study demonstrated that deregulation of liver HDACs may involved in the development of liver fibrosis. Among 11 HDACs tested in our study (Class I, II, and IV HDACs), expression of HDAC2 was maximally increased in CCl4-induced fibrotic livers but decreased after spontaneous recovery. Moreover, expression of HDAC2 was elevated in human liver fibrotic tissues. In this regard, the potential role of HDAC2 in liver fibrosis was further evaluated. Our results showed that administration of HSC-T6 cells with transforming growth factor-beta1 (TGF-β1) resulted in an increase of HDAC2 protein expression in dose- and time-dependent manners. Moreover, HDAC2 deficiency inhibited HSC-T6 cell proliferation and activation induced by TGF-β1. More importantly, the present study showed HDAC2 may regulate HSCs activation by suppressing expression of Smad7, which is a negative modulator in HSCs activation and liver fibrosis. Collectively, these observations revealed that HDAC2 may play a pivotal role in HSCs activation and liver fibrosis while deregulation of HDACs may serve as a novel mechanism underlying liver fibrosis. - Highlights: • This is the first report to systematically examine expressions of HDACs during liver fibrosis and fibrosis reversal. • Aberrant expression of HDAC2 contributes to the development of liver fibrosis. • Provided important foundation for further liver fibrosis conversion studies.

Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2 production in keratinocyte is related to reactive oxygen species, CYP1A1, Src, EGFR and Ras signaling.

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Mei-Chi Chang

Full Text Available Chewing of betel quid (BQ increases the risk of oral cancer and oral submucous fibrosis (OSF, possibly by BQ-induced toxicity and induction of inflammatory response in oral mucosa.Primary gingival keratinocytes (GK cells were exposed to areca nut (AN components with/without inhibitors. Cytotoxicity was measured by 3-(4,5-dimethyl- thiazol- 2-yl-2,5-diphenyl-tetrazolium bromide (MTT assay. mRNA and protein expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR and western blotting. PGE2/PGF2α production was measured by enzyme-linked immunosorbent assays.Areca nut extract (ANE stimulated PGE2/PGF2α production, and upregulated the expression of cyclooxygenase-2 (COX-2, cytochrome P450 1A1 (CYP1A1 and hemeoxygenase-1 (HO-1, but inhibited expression of keratin 5/14, cyclinB1 and cdc25C in GK cells. ANE also activated epidermal growth factor receptor (EGFR, Src and Ras signaling pathways. ANE-induced COX-2, keratin 5, keratin 14 and cdc25C expression as well as PGE2 production were differentially regulated by α-naphthoflavone (a CYP 1A1/1A2 inhibitor, PD153035 (EGFR inhibitor, pp2 (Src inhibitor, and manumycin A (a Ras inhibitor. ANE-induced PGE2 production was suppressed by piper betle leaf (PBL extract and hydroxychavicol (two major BQ components, dicoumarol (aQuinone Oxidoreductase--NQO1 inhibitor and curcumin. ANE-induced cytotoxicity was inhibited by catalase and enhanced by dicoumarol, suggesting that AN components may contribute to the pathogenesis of OSF and oral cancer via induction of aberrant differentiation, cytotoxicity, COX-2 expression, and PGE2/PGF2α production.CYP4501A1, reactive oxygen species (ROS, EGFR, Src and Ras signaling pathways could all play a role in ANE-induced pathogenesis of oral cancer. Addition of PBL into BQ and curcumin consumption could inhibit the ANE-induced inflammatory response.

A Chinese Herbal Medicine, Jia-Wei-Xiao-Yao-San, Prevents Dimethylnitrosamine-Induced Hepatic Fibrosis in Rats

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Shu-Chen Chien

2014-01-01

Full Text Available Jia-wei-xiao-yao-san (JWXYS is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN- induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT and serum glutamic pyruvic transaminase (SGPT levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.

Pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis

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Chung, Myung Jin; Goo, Jin Mo E-mail: jmgoo@plaza.snu.ac.kr; Im, Jung-Gi

2004-11-01

Objectives: Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk of pulmonary tuberculosis. However, detecting pulmonary tuberculosis may be difficult due to the underlying fibrosis. The aim of this report is to describe the radiological and clinical findings of pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis. Materials and methods: We reviewed 143 consecutive patients in whom IPF was diagnosed by either the histological or radio-clinical criteria. Among them, nine patients were histologically (n=2) or bacteriologically (n=7) confirmed to have active pulmonary tuberculosis. The location and patterns of pulmonary tuberculosis were examined on a thin section CT scan. Results: The most common thin section CT findings were subpleural nodules (n=6; mean diameter, 3.2 cm) and a lobar or segmental consolidation (n=3). The lesions were located most commonly in the right lower lobe (n=4). The incidence of tuberculosis in patients with idiopathic pulmonary fibrosis was more than five times higher than that of the general population. Conclusion: The atypical manifestation of pulmonary tuberculosis is common in patients with idiopathic pulmonary fibrosis, which may mimic lung cancer or bacterial pneumonia.

Pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Chung, Myung Jin; Goo, Jin Mo; Im, Jung-Gi

2004-01-01

Objectives: Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk of pulmonary tuberculosis. However, detecting pulmonary tuberculosis may be difficult due to the underlying fibrosis. The aim of this report is to describe the radiological and clinical findings of pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis. Materials and methods: We reviewed 143 consecutive patients in whom IPF was diagnosed by either the histological or radio-clinical criteria. Among them, nine patients were histologically (n=2) or bacteriologically (n=7) confirmed to have active pulmonary tuberculosis. The location and patterns of pulmonary tuberculosis were examined on a thin section CT scan. Results: The most common thin section CT findings were subpleural nodules (n=6; mean diameter, 3.2 cm) and a lobar or segmental consolidation (n=3). The lesions were located most commonly in the right lower lobe (n=4). The incidence of tuberculosis in patients with idiopathic pulmonary fibrosis was more than five times higher than that of the general population. Conclusion: The atypical manifestation of pulmonary tuberculosis is common in patients with idiopathic pulmonary fibrosis, which may mimic lung cancer or bacterial pneumonia

MicroRNA mimicry blocks pulmonary fibrosis

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Montgomery, Rusty L; Yu, Guoying; Latimer, Paul A; Stack, Christianna; Robinson, Kathryn; Dalby, Christina M; Kaminski, Naftali; van Rooij, Eva

2014-01-01

Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis. PMID:25239947

Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

International Nuclear Information System (INIS)

Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G.; Castiglione, F.; Vanzi, E.; Bottoncetti, A.; Pupi, A.

2011-01-01

Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

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Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

2011-10-15

Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis

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Fang, Fan; Du, Ying; Ma, Rui; Li, Xiang-Yang; Yu, Qian; Meng, Di; Tang, Ren-Xian; Zheng, Kui-Yang

2017-01-01

Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells) and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice) induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson’s trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (Psinensis-infected mice. PMID:28151995

Gastroenterological endpoints in drug trials for cystic fibrosis

NARCIS (Netherlands)

Bodewes, Frank A. J. A.; Verkade, Henkjan J.; Wilschanski, Micheal

2016-01-01

The phenotype of cystic fibrosis includes a wide variety of clinical and biochemical gastrointestinal presentations. These gastrointestinal characteristics of the disease have come under renewed interest as potential outcome measures and clinical endpoints for therapeutic trials in cystic fibrosis.

Production site of radiation-induced pulmonary fibrosis

International Nuclear Information System (INIS)

Song Liangwen; Cui Xuemei; Gao Yabing; Yang Ruibiao; Xia Guowei; Wang Dewen

1997-01-01

Production site development and alterations of early pulmonary fibrosis were studied. Single irradiation was made at right thorax of rats with 0, 15 and 30 Gy of γ-irradiation, respectively. The rats were divided into three groups which were sacrificed 1, 3, 5 months post irradiation. Hydroxyproline in lungs was measured by biochemical method. Pulmonary type I and III collagens were measured by polarization method. Distribution of angiotensin II (A II) in pulmonary tissues was displayed by immunohistochemical method. Extent of pulmonary fibrosis relatively increased with irradiation dose and time elapse after irradiation. Ratio of type I to type III collagens increased with increasing fibrosis. Proliferating collagen fibers mainly came from fibroblasts of pulmonary bronchial and arterial adventitia, and extended into pulmonary parenchyma. Meanwhile, type I collagen substituted for type III collagen in interstitium of pulmonary alveoli. A II was positive for fibroblasts and macrophages in pulmonary interstitium. Irradiation can stimulate fibroblasts in interstitium proliferation, and type I collagen substitutes for type III collagen. Expression and synthesis of A II in interstitium may promote the course of pulmonary fibrosis

DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma

DEFF Research Database (Denmark)

Dahl, Morten; Tybjaerg-Hansen, A; Lange, P

1998-01-01

Cystic fibrosis is a recessive disorder mainly characterised by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease.......Cystic fibrosis is a recessive disorder mainly characterised by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease....

Matrix Remodeling in Pulmonary Fibrosis and Emphysema

Science.gov (United States)

O’Reilly, Philip; Antony, Veena B.; Gaggar, Amit

2016-01-01

Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

Pathogenic mechanism in lung fibrosis

International Nuclear Information System (INIS)

Witschi, H.; Haschek, W.M.; Meyer, K.R.; Ullrich, R.L.; Dalbey, W.E.

1979-01-01

The purpose of the study was to examine whether an interaction between two agents causing alveolar epithelial damage would produce lung fibrosis. In mouse lung, intraperitoneal injection of the antioxidant butylated hydroxytoluene causes diffuse alveolar type I cell necrosis, followed by proliferation of type II alveolar cells. In animals exposed to 70% O 2 or 100-200 rad x rays during the phase of type II cell proliferation following BHT, diffuse interstitial lung fibrosis developed within 2 weeks. Quantitative analysis of the lungs for hydroxyproline showed that the interaction between BHT and O 2 or x rays was synergistic. If exposure to O 2 or x rays was delayed until epithelial recovery was complete, no fibrosis was seen. Abnormally high levels of lung collagen persisted up to 6 months after one single treatment with BHT and 100 rad x rays. A commonly seen form of chronic lung damage may thus be caused by an acute interaction between a bloodborne agent which damages the alveolar cell and a toxic inhalant or x rays, provided a critically ordered sequence of exposure is observed

Assessment of cutaneous radiation fibrosis by 20 MHz-sonography

International Nuclear Information System (INIS)

Gottloeber, P.; Braun-Falco, B.; Plewig, G.; Kerscher, M.; Peter, R.U.; Nadeshina, N.

1996-01-01

Radiation fibrosis is the cardinal symptom of the chronicle stage of the cutaneous radiation syndrome. The degree of cutaneous fibrosis can clinically be estimated by palpation. High-frequency 20 MHz-sonography is an established, noninvasive procedure, which renders an exact determination of skin thickness and additionally densitometry is possible. We investigated 15 survivors of the Chernobyl accident in 1986, who developed symptoms of the chronic stage of the cutaneous radiation syndrome. We determined skin thickness and echogenicity of skin areas clinically suggestive of radiation fibrosis before, during and after treatment. 20 MHz-sonography showed a distinct enlargement of the echorich corium and a reduction of the subcutaneous fatty tissue in comparison with the unaffected, contralateral skin, here demonstrating typical features of radiation fibrosis, namely dermal fibrosis and reactive pseudoatrophy and fatty tissue. The histology presented an increase and swelling of the collagen fibers and atypical fibroblastic cells. The patients received treatment with low-dose interferon y (Polyfcron R , 3 x 50μg s.C., three times per week) up to 30 months. A marked reduction of skin thickness and echogenicity reaching nearly normal values could be observed. We conclude that 20 MHz-sonography is an easy to apply, noninvasive, well established procedure to quantify cutaneous radiation fibrosis and to assess therapeutic outcome

Physical exercise training for cystic fibrosis.

Science.gov (United States)

Radtke, Thomas; Nevitt, Sarah J; Hebestreit, Helge; Kriemler, Susi

2017-11-01

Physical exercise training may form an important part of regular care for people with cystic fibrosis. This is an update of a previously published review. To assess the effects of physical exercise training on exercise capacity by peak oxygen consumption, pulmonary function by forced expiratory volume in one second, health-related quality of life and further important patient-relevant outcomes in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 04 May 2017.We searched ongoing trials registers (clinicaltrials.gov and the WHO ICTRP). Date of most recent search: 10 August 2017. All randomised and quasi-randomised controlled clinical trials comparing exercise training of any type and a minimum duration of two weeks with conventional care (no training) in people with cystic fibrosis. Two authors independently selected studies for inclusion, assessed methodological quality and extracted data. The quality of the evidence was assessed using the GRADE system. Of the 83 studies identified, 15 studies which included 487 participants, met the inclusion criteria. The numbers in each study ranged from nine up to 72 participants; two studies were in adults, seven were in children and adolescents and six studies included all age ranges. Four studies of hospitalised participants lasted less than one month and 11 studies were outpatient-based, lasting between two months and three years. The studies included participants with a wide range of disease severity and employed differing levels of supervision with a mixture of types of training. There was also wide variation in the quality of the included studies.This systematic review shows very low- to low-quality evidence from both short- and long-term studies that in people

The role of metformin and resveratrol in the prevention of hypoxia‐inducible factor 1α accumulation and fibrosis in hypoxic adipose tissue

Science.gov (United States)

Li, Xiaole; Li, Jia; Wang, Lulu; Li, Aiyun; Qiu, Zhixia; Qi, Lian‐wen; Kou, Junping; Liu, Kang; Liu, Baolin

2016-01-01

Background and Purpose Hypoxic activation of hypoxia‐inducible factor 1α (HIF‐1α) and fibrosis in adipose tissue contribute to adipose dysfunction. This study was designed to investigate the effects of metformin and resveratrol on the regulation of HIF‐1α and fibrosis in hypoxic adipose tissue. Experimental Approach Mice were fed a high‐fat diet to induce hypoxia and fibrosis in adipose tissue; adipose tissue incubated in vitro in 1% O2 showed a similar change. The effects of metformin and resveratrol on hypoxia, HIF‐1α accumulation, endoplasmic reticulum stress and gene expressions of extracellular matrix components and pro‐inflammatory cytokines were examined. Key Results Oral administration of metformin or resveratrol prevented hypoxia and reduced HIF‐1α accumulation with dephosphorylation of inositol‐requiring enzyme 1α and eukaryotic initiation factor 2α, indicative of suppression of hypoxic HIF‐1α activation and endoplasmic reticulum stress. Metformin and resveratrol down‐regulated gene expressions of Col3α, Col6α, elastin and lysyl oxidase and thereby reduced collagen deposition in adipose tissue. The increased gene expressions of TNF‐α, IL‐6, monocyte chemoattractant protein 1 and F4/80 were also down‐regulated by metformin and resveratrol. Metformin and resveratrol had similar effects in adipose tissue exposed to 1% O2. Metformin reduced ATP production and prevented the reduction in oxygen tension in 3T3‐L1 cells, suggesting that it prevented hypoxia by limiting oxygen consumption, whereas resveratrol reduced HIF‐1α accumulation by promoting its proteasomal degradation via the regulation of AMPK/SIRT1. Conclusion and Implications Hypoxia and fibrosis are early causes of adipose dysfunction in obesity. Both metformin and resveratrol effectively inhibited HIF‐1α activation‐induced fibrosis and inflammation in adipose tissue, although by different mechanisms. PMID:27059094

The role of metformin and resveratrol in the prevention of hypoxia-inducible factor 1α accumulation and fibrosis in hypoxic adipose tissue.

Science.gov (United States)

Li, Xiaole; Li, Jia; Wang, Lulu; Li, Aiyun; Qiu, Zhixia; Qi, Lian-Wen; Kou, Junping; Liu, Kang; Liu, Baolin; Huang, Fang

2016-06-01

Hypoxic activation of hypoxia-inducible factor 1α (HIF-1α) and fibrosis in adipose tissue contribute to adipose dysfunction. This study was designed to investigate the effects of metformin and resveratrol on the regulation of HIF-1α and fibrosis in hypoxic adipose tissue. Mice were fed a high-fat diet to induce hypoxia and fibrosis in adipose tissue; adipose tissue incubated in vitro in 1% O2 showed a similar change. The effects of metformin and resveratrol on hypoxia, HIF-1α accumulation, endoplasmic reticulum stress and gene expressions of extracellular matrix components and pro-inflammatory cytokines were examined. Oral administration of metformin or resveratrol prevented hypoxia and reduced HIF-1α accumulation with dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α, indicative of suppression of hypoxic HIF-1α activation and endoplasmic reticulum stress. Metformin and resveratrol down-regulated gene expressions of Col3α, Col6α, elastin and lysyl oxidase and thereby reduced collagen deposition in adipose tissue. The increased gene expressions of TNF-α, IL-6, monocyte chemoattractant protein 1 and F4/80 were also down-regulated by metformin and resveratrol. Metformin and resveratrol had similar effects in adipose tissue exposed to 1% O2 . Metformin reduced ATP production and prevented the reduction in oxygen tension in 3T3-L1 cells, suggesting that it prevented hypoxia by limiting oxygen consumption, whereas resveratrol reduced HIF-1α accumulation by promoting its proteasomal degradation via the regulation of AMPK/SIRT1. Hypoxia and fibrosis are early causes of adipose dysfunction in obesity. Both metformin and resveratrol effectively inhibited HIF-1α activation-induced fibrosis and inflammation in adipose tissue, although by different mechanisms. © 2016 The British Pharmacological Society.

Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease.

Science.gov (United States)

Hossain, Noreen; Afendy, Arian; Stepanova, Maria; Nader, Fatema; Srishord, Manirath; Rafiq, Nila; Goodman, Zachary; Younossi, Zobair

2009-11-01

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We investigated factors associated with advanced fibrosis in NAFLD. The study included 432 patients with histologically proven NAFLD (26.8% with nonalcoholic steatohepatitis [NASH] and 17.4% with moderate-to severe fibrosis). NASH was defined as steatosis, lobular inflammation, and ballooning degeneration with or without Mallory-Denk bodies and/or fibrosis. Fibrosis was classified into 2 groups: those with no or minimal fibrosis and those with moderate-to-severe fibrosis. Groups were compared using Mann-Whitney and chi-square method analyses. A model was constructed using a stepwise bidirectional method; its predictive power was measured using a 10-fold cross-validation technique. Patients with NASH were more likely to be male (P < .0001); have lower hip-to-waist ratios (P = .03); were less likely to be African American (P = .06); have higher levels of alanine aminotransferase (ALT; P < .0001), aspartate aminotransferase (AST; P < .0001), and serum triglycerides (P = .0154), but lower levels of high-density lipoprotein cholesterol (P < .0001). Patients with moderate-to-severe fibrosis were older (P = .0245); more likely to be male (P = .0189), Caucasian (P = .0382), have diabetes mellitus (P = .0238), and hypertension (P = .0375); and have a lower hip-to-waist ratio (P = .0077) but higher serum AST (P < .0001) and ALT (P < .0001) levels. The multivariate analysis model to predict moderate-to-severe fibrosis included male sex, Caucasian ethnicity, diabetes mellitus, and increased AST and ALT levels (model P value < .0001). In patients with NAFLD, diabetes mellitus and aminotransferase levels are independent predictors of moderate-to-severe fibrosis. They can be used to identify NAFLD patients at risk for advanced fibrosis.

Ultrasound based evaluation of hepatic steatosis and fibrosis in hepatitis c non-responders

International Nuclear Information System (INIS)

Sohail, S.; Aziz, S.

2013-01-01

To determine the accuracy of ultrasound in the diagnosis and grading of steatosis and fibrosis in Hepatitis C (HCV) patients not responding to ribavarin-interferon therapy. Study Design: A cross-sectional, analytical study. Place and Duration of Study: Radiology Department, Civil Hospital, Karachi, from March 2008 to August 2010. Methodology: Patients with positive HCV RNA despite 24 weeks ribavarin-interferon therapy (non-responders) were subjected to ultrasound and biopsy prior to institution of pegylated interferon therapy for detection and grading of steatosis and fibrosis. Using histopathology as the gold standard, sensitivity, specificity, negative and positive predictive values for ultrasound were determined. Results: The sensitivity of ultrasound for hepatic steatosis was 90.9% for no steatosis (NS), 100% for moderate and gross steatosis and 84.4% for mild steatosis with 100% specificity. The senitivity for fibrosis was 25% for no fibrosis, 100% for mild fibrosis, 89.74% for moderate fibrosis and 100% for gross fibrosis. The overall accuracy for detection of steatosis was 95.39% and that for fibrosis was 98.02%. Hepatic vein showed increased dampening of flow with advancing grades of steatosis and fibrosis. Conclusion: Ultrasound has a high accuracy in the diagnosis and grading of steatosis and fibrosis in HCV nonresponders. Mild fibrosis may confound the diagnosis of mild steatosis. (author)

Adeno-associated virus for cystic fibrosis gene therapy

Directory of Open Access Journals (Sweden)

S.V. Martini

2011-11-01

Full Text Available Gene therapy is an alternative treatment for genetic lung disease, especially monogenic disorders such as cystic fibrosis. Cystic fibrosis is a severe autosomal recessive disease affecting one in 2500 live births in the white population, caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR. The disease is classically characterized by pancreatic enzyme insufficiency, an increased concentration of chloride in sweat, and varying severity of chronic obstructive lung disease. Currently, the greatest challenge for gene therapy is finding an ideal vector to deliver the transgene (CFTR to the affected organ (lung. Adeno-associated virus is the most promising viral vector system for the treatment of respiratory disease because it has natural tropism for airway epithelial cells and does not cause any human disease. This review focuses on the basic properties of adeno-associated virus and its use as a vector for cystic fibrosis gene therapy.

Appetite stimulants for people with cystic fibrosis.

Science.gov (United States)

Chinuck, Ruth; Dewar, Jane; Baldwin, David R; Hendron, Elizabeth

2014-07-27

Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index and nutritional status. However, these may have adverse effects on clinical status. The aim of this review is to systematically search for and evaluate evidence on the beneficial effects of appetite stimulants in the management of CF-related anorexia and synthesize reports of any side-effects. Trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, MEDLINE, Embase, CINAHL, handsearching reference lists and contacting local and international experts.Last search of online databases: 01 April 2014.Last search of the Cystic Fibrosis Trials Register: 08 April 2014. Randomised and quasi-randomised controlled trials of appetite stimulants, compared to placebo or no treatment for at least one month in adults and children with cystic fibrosis. Authors independently extracted data and assessed the risk of bias within eligible trials. Meta-analyses were performed. Three trials (total of 47 recruited patients) comparing appetite stimulants (cyproheptadine hydrochloride and megesterol acetate) to placebo were included; the numbers of adults or children within each trial were not always reported. The risk of bias of the included trials was graded as moderate.A meta-analysis of all three trials showed appetite stimulants produced a larger increase in weight z score at three months compared to placebo, mean difference 0.61 (95% confidence interval 0.29 to 0.93) (P children, appetite stimulants improved only two of the outcomes in this review - weight (or weight z score) and appetite; and side effects were insufficiently reported to determine the full extent of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice.

Science.gov (United States)

Gong, Ju-Hyun; Cho, In-Hee; Shin, Daekeun; Han, Seon-Young; Park, Sin-Hye; Kang, Young-Hee

2014-03-01

Chronic airway remodeling is characterized by structural changes within the airway wall, including smooth muscle hypertrophy, submucosal fibrosis and epithelial shedding. Epithelial-to-mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis, which can be induced by TGF-β. In the in vitro study, we investigated whether 1-20 μM kaempferol inhibited lipopolysaccharide (LPS)-induced bronchial EMT in BEAS-2B cells. The in vivo study explored demoting effects of 10-20 mg/kg kaempferol on airway fibrosis in BALB/c mice sensitized with ovalbumin (OVA). LPS induced airway epithelial TGF-β1 signaling that promoted EMT with concurrent loss of E-cadherin and induction of α-smooth muscle actin (α-SMA). Nontoxic kaempferol significantly inhibited TGF-β-induced EMT process through reversing E-cadherin expression and retarding the induction of N-cadherin and α-SMA. Consistently, OVA inhalation resulted in a striking loss of epithelial morphology by displaying myofibroblast appearance, which led to bronchial fibrosis with submucosal accumulation of collagen fibers. Oral administration of kaempferol suppressed collagen deposition, epithelial excrescency and goblet hyperplasia observed in the lung of OVA-challenged mice. The specific inhibition of TGF-β entailed epithelial protease-activated receptor-1 (PAR-1) as with 20 μM kaempferol. The epithelial PAR-1 inhibition by SCH-79797 restored E-cadherin induction and deterred α-SMA induction, indicating that epithelial PAR-1 localization was responsible for resulting in airway EMT. These results demonstrate that dietary kaempferol alleviated fibrotic airway remodeling via bronchial EMT by modulating PAR1 activation. Therefore, kaempferol may be a potential therapeutic agent targeting asthmatic airway constriction.

Non-invasive evaluation of cystic fibrosis related liver disease in adults with ARFI, transient elastography and different fibrosis scores.

Directory of Open Access Journals (Sweden)

Thomas Karlas

Full Text Available BACKGROUND: Cystic fibrosis-related liver disease (CFLD is present in up to 30% of cystic fibrosis patients and can result in progressive liver failure. Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver fibrosis display an interesting diagnostic approach for CFLD detection. AIM: We evaluated transient elastography (TE, acoustic radiation force impulse imaging (ARFI, and fibrosis indices for CFLD detection. METHODS: TE and ARFI were performed in 55 adult CF patients. In addition, AST/Platelets-Ratio-Index (APRI, and Forns' score were calculated. Healthy probands and patients with alcoholic liver cirrhosis served as controls. RESULTS: Fourteen CF patients met CFLD criteria, six had liver cirrhosis. Elastography acquisition was successful in >89% of cases. Non-cirrhotic CFLD individuals showed elastography values similar to CF patients without liver involvement. Cases with liver cirrhosis differed significantly from other CFLD patients (ARFI: 1.49 vs. 1.13 m/s; p = 0.031; TE: 7.95 vs. 4.16 kPa; p = 0.020 and had significantly lower results than individuals with alcoholic liver cirrhosis (ARFI: 1.49 vs. 2.99 m/s; p = 0.002. APRI showed the best diagnostic performance for CFLD detection (AUROC 0.815; sensitivity 85.7%, specificity 70.7%. CONCLUSIONS: ARFI, TE, and laboratory based fibrosis indices correlate with each other and reliably detect CFLD related liver cirrhosis in adult CF patients. CF specific cut-off values for cirrhosis in adults are lower than in alcoholic cirrhosis.

Non-Invasive Evaluation of Cystic Fibrosis Related Liver Disease in Adults with ARFI, Transient Elastography and Different Fibrosis Scores

Science.gov (United States)

Oltmanns, Annett; Güttler, Andrea; Petroff, David; Wirtz, Hubert; Mainz, Jochen G.; Mössner, Joachim; Berg, Thomas; Tröltzsch, Michael; Keim, Volker; Wiegand, Johannes

2012-01-01

Background Cystic fibrosis-related liver disease (CFLD) is present in up to 30% of cystic fibrosis patients and can result in progressive liver failure. Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver fibrosis display an interesting diagnostic approach for CFLD detection. Aim We evaluated transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and fibrosis indices for CFLD detection. Methods TE and ARFI were performed in 55 adult CF patients. In addition, AST/Platelets-Ratio-Index (APRI), and Forns' score were calculated. Healthy probands and patients with alcoholic liver cirrhosis served as controls. Results Fourteen CF patients met CFLD criteria, six had liver cirrhosis. Elastography acquisition was successful in >89% of cases. Non-cirrhotic CFLD individuals showed elastography values similar to CF patients without liver involvement. Cases with liver cirrhosis differed significantly from other CFLD patients (ARFI: 1.49 vs. 1.13 m/s; p = 0.031; TE: 7.95 vs. 4.16 kPa; p = 0.020) and had significantly lower results than individuals with alcoholic liver cirrhosis (ARFI: 1.49 vs. 2.99 m/s; p = 0.002). APRI showed the best diagnostic performance for CFLD detection (AUROC 0.815; sensitivity 85.7%, specificity 70.7%). Conclusions ARFI, TE, and laboratory based fibrosis indices correlate with each other and reliably detect CFLD related liver cirrhosis in adult CF patients. CF specific cut-off values for cirrhosis in adults are lower than in alcoholic cirrhosis. PMID:22848732

Enhanced liver fibrosis test using ELISA assay accurately discriminates advanced stage of liver fibrosis as determined by transient elastography fibroscan in treatment naïve chronic HCV patients.

Science.gov (United States)

Omran, Dalia; Yosry, Ayman; Darweesh, Samar K; Nabeel, Mohammed M; El-Beshlawey, Mohammed; Saif, Sameh; Fared, Azza; Hassany, Mohamed; Zayed, Rania A

2018-02-01

Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68-0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.

Lung adenocarcinoma mimicking pulmonary fibrosis-a case report

International Nuclear Information System (INIS)

Mehić, Bakir; Duranović Rayan, Lina; Bilalović, Nurija; Dohranović Tafro, Danina; Pilav, Ilijaz

2016-01-01

Lung cancer is usually presented with cough, dyspnea, pain and weight loss, which is overlapping with symptoms of other lung diseases such as pulmonary fibrosis. Pulmonary fibrosis shows characteristic reticular and nodular pattern, while lung cancers are mostly presented with infiltrative mass, thick-walled cavitations or a solitary nodule with spiculated borders. If the diagnosis is established based on clinical symptoms and CT findings, it would be a misapprehension. We report a case of lung adenocarcinoma whose symptoms as well as clinical images overlapped strongly with pulmonary fibrosis. The patient’s non-productive cough, progressive dyspnea, restrictive pattern of pulmonary function test and CT scans (showing reticular interstitial opacities) were all indicative of pulmonary fibrosis. The patient underwent a treatment consisting of corticosteroids and antibiotics, to no avail. Histopathology of the lung showed that the patient suffered from mucinous adenocarcinoma. Albeit the immunohistochemical staining was not consistent with lung adenocarcinoma, tumor’s morphological characteristics were consistent, and were used to make the definitive diagnosis. Given the fact that radiography cannot always make a clear-cut difference between pulmonary fibrosis and lung adenocarcinomas, and that clinical symptoms often overlap, histological examination should be considered as gold standard for diagnosis of lung adenocarcinoma

Phosphoproteomic biomarkers predicting histologic nonalcoholic steatohepatitis and fibrosis.

Science.gov (United States)

Younossi, Zobair M; Baranova, Ancha; Stepanova, Maria; Page, Sandra; Calvert, Valerie S; Afendy, Arian; Goodman, Zachary; Chandhoke, Vikas; Liotta, Lance; Petricoin, Emanuel

2010-06-04

The progression of nonalcoholic fatty liver disease (NAFLD) has been linked to deregulated exchange of the endocrine signaling between adipose and liver tissue. Proteomic assays for the phosphorylation events that characterize the activated or deactivated state of the kinase-driven signaling cascades in visceral adipose tissue (VAT) could shed light on the pathogenesis of nonalcoholic steatohepatitis (NASH) and related fibrosis. Reverse-phase protein microarrays (RPMA) were used to develop biomarkers for NASH and fibrosis using VAT collected from 167 NAFLD patients (training cohort, N = 117; testing cohort, N = 50). Three types of models were developed for NASH and advanced fibrosis: clinical models, proteomics models, and combination models. NASH was predicted by a model that included measurements of two components of the insulin signaling pathway: AKT kinase and insulin receptor substrate 1 (IRS1). The models for fibrosis were less reliable when predictions were based on phosphoproteomic, clinical, or the combination data. The best performing model relied on levels of the phosphorylation of GSK3 as well as on two subunits of cyclic AMP regulated protein kinase A (PKA). Phosphoproteomics technology could potentially be used to provide pathogenic information about NASH and NASH-related fibrosis. This information can lead to a clinically relevant diagnostic/prognostic biomarker for NASH.

Novel algorithm for non-invasive assessment of fibrosis in NAFLD.

Directory of Open Access Journals (Sweden)

Jan-Peter Sowa

Full Text Available INTRODUCTION: Various conditions of liver disease and the downsides of liver biopsy call for a non-invasive option to assess liver fibrosis. A non-invasive score would be especially useful to identify patients with slow advancing fibrotic processes, as in Non-Alcoholic Fatty Liver Disease (NAFLD, which should undergo histological examination for fibrosis. PATIENTS/METHODS: Classic liver serum parameters, hyaluronic acid (HA and cell death markers of 126 patients undergoing bariatric surgery for morbid obesity were analyzed by machine learning techniques (logistic regression, k-nearest neighbors, linear support vector machines, rule-based systems, decision trees and random forest (RF. Specificity, sensitivity and accuracy of the evaluated datasets to predict fibrosis were assessed. RESULTS: None of the single parameters (ALT, AST, M30, M60, HA did differ significantly between patients with a fibrosis score 1 or 2. However, combining these parameters using RFs reached 79% accuracy in fibrosis prediction with a sensitivity of more than 60% and specificity of 77%. Moreover, RFs identified the cell death markers M30 and M65 as more important for the decision than the classic liver parameters. CONCLUSION: On the basis of serum parameters the generation of a fibrosis scoring system seems feasible, even when only marginally fibrotic tissue is available. Prospective evaluation of novel markers, i.e. cell death parameters, should be performed to identify an optimal set of fibrosis predictors.

Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

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Claudio M. Mastroianni

2014-05-01

Full Text Available Chronic hepatitis C virus (HCV infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV. Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

Agmatine attenuates silica-induced pulmonary fibrosis.

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El-Agamy, D S; Sharawy, M H; Ammar, E M

2014-06-01

There is a large body of evidence that nitric oxide (NO) formation is implicated in mediating silica-induced pulmonary fibrosis. As a reactive free radical, NO may not only contribute to lung parenchymal tissue injury but also has the ability to combine with superoxide and form a highly reactive toxic species peroxynitrite that can induce extensive cellular toxicity in the lung tissues. This study aimed to explore the effect of agmatine, a known NO synthase inhibitor, on silica-induced pulmonary fibrosis in rats. Male Sprague Dawley rats were treated with agmatine for 60 days following a single intranasal instillation of silica suspension (50 mg in 0.1 ml saline/rat). The results revealed that agmatine attenuated silica-induced lung inflammation as it decreased the lung wet/dry weight ratio, protein concentration, and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid. Agmatine showed antifibrotic activity as it decreased total hydroxyproline content of the lung and reduced silica-mediated lung inflammation and fibrosis in lung histopathological specimen. In addition, agmatine significantly increased superoxide dismutase (p Agmatine also reduced silica-induced overproduction of pulmonary nitrite/nitrate as well as tumor necrosis factor α. Collectively, these results demonstrate the protective effects of agmatine against the silica-induced lung fibrosis that may be attributed to its ability to counteract the NO production, lipid peroxidation, and regulate cytokine effects. © The Author(s) 2014.

Subclinical anaemia of chronic disease in adult patients with cystic fibrosis.

LENUS (Irish Health Repository)

O'connor, T M

2012-02-03

Patients with chronic hypoxaemia develop secondary polycythaemia that improves oxygen-carrying capacity. Therefore, normal haemoglobin and haematocrit values in the presence of chronic arterial hypoxaemia in cystic fibrosis constitute \\'relative anaemia\\'. We sought to determine the cause of this relative anaemia in patients with cystic fibrosis. We studied haematological indices and oxygen saturation in healthy volunteers (n=17) and in adult patients with cystic fibrosis (n=15). Patients with cystic fibrosis had lower resting arterial oxygen saturation when compared with normal volunteers (P<0.0001), and exercise led to a greater reduction in arterial oxygen saturation (P<0.0001). However, haemoglobin and haematocrit values in patients with cystic fibrosis did not significantly differ from normal volunteers. Serum iron (P=0.002), transferrin (P=0.02), and total iron-binding capacity (P=0.01) were lower in patients with cystic fibrosis. There were no significant differences in serum ferritin, percentage iron saturation, serum erythropoietin or red cell volume between the groups. The data presented demonstrate a characteristic picture of anaemia of chronic disease in adult patients with cystic fibrosis, except for normal haemoglobin and haematocrit values. Normal haemoglobin and haematocrit values in patients with cystic fibrosis appear to represent a combination of the effects of arterial hypoxaemia promoting polycythaemia, counterbalanced by chronic inflammation promoting anaemia of chronic disease.

Idiopathic pulmonary fibrosis.

Science.gov (United States)

Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

2017-02-23

Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Fibrosis index based on four factors better predicts advanced fibrosis or cirrhosis than aspartate aminotransferase/platelet ratio index in chronic hepatitis C patients

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Chia-Chi Wang

2015-10-01

Conclusion: FIB-4 could predict hepatic fibrosis in CHC patients. By adding two parameters (age and alanine aminotransferase, FIB-4 better predicts advanced fibrosis and cirrhosis than APRI in CHC patients.

Origin and function of myofibroblasts in kidney fibrosis.

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LeBleu, Valerie S; Taduri, Gangadhar; O'Connell, Joyce; Teng, Yingqi; Cooke, Vesselina G; Woda, Craig; Sugimoto, Hikaru; Kalluri, Raghu

2013-08-01

Myofibroblasts are associated with organ fibrosis, but their precise origin and functional role remain unknown. We used multiple genetically engineered mice to track, fate map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Through this comprehensive analysis, we identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts through proliferation. The nonproliferating myofibroblasts derive through differentiation from bone marrow (35%), the endothelial-to-mesenchymal transition program (10%) and the epithelial-to-mesenchymal transition program (5%). Specific deletion of Tgfbr2 in α-smooth muscle actin (αSMA)(+) cells revealed the importance of this pathway in the recruitment of myofibroblasts through differentiation. Using genetic mouse models and a fate-mapping strategy, we determined that vascular pericytes probably do not contribute to the emergence of myofibroblasts or fibrosis. Our data suggest that targeting diverse pathways is required to substantially inhibit the composite accumulation of myofibroblasts in kidney fibrosis.

Higher Anti-Liver Fibrosis Effect of Cordyceps militaris-Fermented Product Cultured with Deep Ocean Water via Inhibiting Proinflammatory Factors and Fibrosis-Related Factors Expressions

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Yu-Ping Hung

2017-06-01

Full Text Available Deep ocean water (DOW has been shown to enhance the functional components of fungi, resulting in increased health benefits. Therefore, using DOW for culturing fungi can enhance the cordycepin and adenosine of Cordyceps militaris (CM and its protective effects on the liver. In this study, the antiliver fibrosis effects and mechanisms of ultrapure water-cultured CM (UCM, DOW-cultured CM (DCM, synthetic water-cultured CM, DOW, cordycepin, and adenosine were compared in the liver fibrosis mice induced by intraperitoneal injections of thioacetamide (TAA. The results indicated that DCM exhibited superior performance in reducing liver collagen accumulation, mitigating liver injuries, inhibiting proinflammatory factors and fibrosis-related factor (TGF-β1, Smad2/3, α-SMA, COL1A1 expression compared with UCM. DOW, cordycepin, and adenosine also performed antiliver fibrosis effect. Therefore, because DCM is rich in DOW and functional components, it can achieve anti-liver fibrosis effects through multiple pathways. These ameliorative effects are considerably superior to those of UCM.

Higher Anti-Liver Fibrosis Effect of Cordyceps militaris-Fermented Product Cultured with Deep Ocean Water via Inhibiting Proinflammatory Factors and Fibrosis-Related Factors Expressions.

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Hung, Yu-Ping; Lee, Chun-Lin

2017-06-08

Deep ocean water (DOW) has been shown to enhance the functional components of fungi, resulting in increased health benefits. Therefore, using DOW for culturing fungi can enhance the cordycepin and adenosine of Cordyceps militaris (CM) and its protective effects on the liver. In this study, the antiliver fibrosis effects and mechanisms of ultrapure water-cultured CM (UCM), DOW-cultured CM (DCM), synthetic water-cultured CM, DOW, cordycepin, and adenosine were compared in the liver fibrosis mice induced by intraperitoneal injections of thioacetamide (TAA). The results indicated that DCM exhibited superior performance in reducing liver collagen accumulation, mitigating liver injuries, inhibiting proinflammatory factors and fibrosis-related factor (TGF-β1, Smad2/3, α-SMA, COL1A1) expression compared with UCM. DOW, cordycepin, and adenosine also performed antiliver fibrosis effect. Therefore, because DCM is rich in DOW and functional components, it can achieve anti-liver fibrosis effects through multiple pathways. These ameliorative effects are considerably superior to those of UCM.

Utility of diffusion-weighted imaging in the evaluation of liver fibrosis

Energy Technology Data Exchange (ETDEWEB)

Bakan, Ayse Ahsen; Inci, Ercan; Cimilli, Tan [Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Department of Radiology, Istanbul (Turkey); Bakan, Selim [Istanbul University, Faculty of Medicine, Deparment of Radiology, Istanbul (Turkey); Gokturk, Suut [Istanbul University, Faculty of Medicine, Department of Internal Medicine, Division of Gastroenterohepatology, Istanbul (Turkey)

2012-03-15

To evaluate the usefulness of diffusion- weighted MRI (DWI) in the detection and staging of liver fibrosis and inflammation. DWI was performed with b-factors of 0, 500 and 1000 s/mm{sup 2}. ADC values were obtained by placing circular regions of interest in four segments of the liver. Differences between the study (n = 34) and control groups' (n = 25) ADC values were examined. Further, this study investigated if and how ADC values were related to fibrosis stages and histological activity index (HAI) scores. The mean ADC value of the liver was smaller in the study group compared with the control group (P < 0.001). Spearman rho correlation analyses showed lower ADC values were associated with higher fibrosis and HAI scores (P < 0.01). There were statistically significant differences in liver ADC values between each combination of fibrosis stages (e.g. stages 0 and 1, 0 and 2) except for stages 1 and 2. ADC values prove to be a valuable technique for the diagnosis of liver fibrosis and inflammation. They can also be useful in fibrosis staging, particularly in distinguishing later stages of fibrosis from intermediate and early stages. (orig.)

Festival food coma in cystic fibrosis.

Science.gov (United States)

Pandit, Chetan; Graham, Christie; Selvadurai, Hiran; Gaskin, Kevin; Cooper, Peter; van Asperen, Peter

2013-07-01

Children with cystic fibrosis liver disease and portal hypertension are at risk of developing acute hepatic encephalopathy. Even in the presence of normal synthetic liver function these children may have porto-systemic shunting. We report a case of an adolosecent who had cystic fibrosis liver disease and presented with life threatening hepatinc encephalopathy. This case illustrates that it is necessary to consider an appropriate dietary regimen in adolosecents with liver disease to prevent hepatic decompensation. Copyright © 2012 Wiley Periodicals, Inc.

The role of anaerobic bacteria in the cystic fibrosis airway.

Science.gov (United States)

Sherrard, Laura J; Bell, Scott C; Tunney, Michael M

2016-11-01

Anaerobic bacteria are not only normal commensals, but are also considered opportunistic pathogens and have been identified as persistent members of the lower airway community in people with cystic fibrosis of all ages and stages of disease. Currently, the role of anaerobic bacteria in cystic fibrosis lower airway disease is not well understood. Therefore, this review describes the recent studies relating to the potential pathophysiological role(s) of anaerobes within the cystic fibrosis lungs. The most frequently identified anaerobic bacteria in the lower airways are common to both cystic fibrosis and healthy lungs. Studies have shown that in cystic fibrosis, the relative abundance of anaerobes fluctuates in the lower airways with reduced lung function and increased inflammation associated with a decreased anaerobic load. However, anaerobes found within the lower airways also produce virulence factors, may cause a host inflammatory response and interact synergistically with recognized pathogens. Anaerobic bacteria are potentially members of the airway microbiota in health but could also contribute to the pathogenesis of lower airway disease in cystic fibrosis via both direct and indirect mechanisms. A personalized treatment strategy that maintains a normal microbial community may be possible in the future.

The Sociology and Entrenchment. A Cystic Fibrosis Test for Everyone?

DEFF Research Database (Denmark)

Koch, Lene; Stemerding, Dirk

1994-01-01

Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology......Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology...

Blood lipids analysis in patients with hepatitis and hepatic fibrosis

International Nuclear Information System (INIS)

Si Jianhong

2007-01-01

Objective: To investigate the correlationship between blood hepatic fibrosis markers and blood lipids levels. Methods: Serum hepatic fibrosis markers (HA, PC III, IV-C, LN) levels were determined with RIA and serum lipids (TG, TCh HDL; LDL, apoA1, apoB) were measured with biochemical methods in 98 patients with hepatitis in various stages and 50 controls. Liver biopsy was done in all the hepatitis patients. Results: Hepatic fibrosis was classified into 5 grades (S0-S4) according to the pathology shown in the biopsy specimen. The serum lipid levels decreased along with the increase of severity of fibrosis from S0 to S4. Levels in S4 patients were significantly lower than those in controls (P 0.05). Conclusion: The serum hepatic fibrosis markers levels increased and lipids levels decreased along with the progress of hepatitis from acute to cirrhosis. (authors)

Nephrogenic systemic fibrosis (NSF) and gadolinium-based contrast ...

African Journals Online (AJOL)

Nephrogenic systemic fibrosis (NSF), unknown before March 1997 and first described in 2000, is a systemic disorder characterised by widespread tissue fibrosis. The first known case occurred in 1997, after the use of gadolinium-based contrast agents (GBCAs) at high doses in patients with renal failure had become routine.

Gluteal muscle fibrosis with abduction contracture of the hip.

Science.gov (United States)

Al Bayati, Mohammed Ali; Kraidy, Bakir Kadhum

2016-03-01

Gluteal muscle fibrosis with hip contracture is a rare condition and causes major disability; literature reports are sparse. The aim of this study is to present, for the first time in Iraq and the region, a case series of gluteal fibrosis and the results of surgical treatment. Seven children--six boys and one girl--diagnosed as having gluteal muscle fibrosis with hip contracture, were investigated and treated by open surgical release of fibrotic bands and physiotherapy. All patients improved dramatically over the subsequent weeks, and were able to sit and squat in the normal position. Gluteal muscle fibrosis with hip contracture is present in Iraq and more awareness is needed for early diagnosis. Surgical treatment provided excellent results. More studies are needed to delineate the aetiology of the condition.

Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

Science.gov (United States)

Corcoran, B M; Dukes-McEwan, J; Rhind, S; French, A

1999-04-01

Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

Review: Quality of Life in Children with Non-cystic Fibrosis Bronchiectasis

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Anna Marie Nathan

2017-04-01

Full Text Available Non-cystic fibrosis bronchiectasis (NCFB has gained renewed interest, due to its increasing health-care burden. Annual mortality statistics in England and Wales showed that under 1,000 people die from bronchiectasis each year, and this number is increasing by 3% yearly. Unfortunately, there is a severe lack of well-powered, randomized controlled trials to guide clinicians how to manage NCFB effectively. Quality-of-life (QOL measures in NCFB are an important aspect of clinical care that has not been studied well. Commonly used disease-specific questionnaires in children with NCFB are the St George’s Respiratory Questionnaire, Short Form-36, the Leicester Cough Questionnaire, and the Parent Cough-Specific Quality of Life questionnaire (PC-QOL. Of these, only the PC-QOL can be used in young children, as it is a parent-proxy questionnaire. We reviewed pediatric studies looking at QOL in children with NCFB and cystic fibrosis. All types of airway clearance techniques appear to be safe and have no significant benefit over each other. Number of exacerbations and hospitalizations correlated with QOL scores, while symptom subscales correlated with lung function, worse QOL, frequent antibiotic requirements, and duration of regular follow-up in only one study. There was a correlation between QOL and age of diagnosis in children with primary ciliary dyskinesia. Other studies have shown no relationship between QOL scores and etiology of NCFB as well as CT changes. As for treatments, oral azithromycin and yoga have demonstrated some improvement in QOL scores. In conclusion, more studies are required to accurately determine important factors contributing to QOL.

induced pulmonary fibrosis in mice via regulation of IL

African Journals Online (AJOL)

TRAF6, IL-33 and ST2 in lung tissue were determined by western blotting assay. Serum levels of ..... facilitate excessive tissue repair and fibrosis [20]. Therefore ... to cancer biology. ... liver regeneration, fibrosis and carcinogenesis. Hepatol.

Fibrocytes in pulmonary fibrosis: a brief synopsis

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Shyam Maharaj

2013-12-01

Full Text Available Fibrocytes are bone marrow-derived, circulating mesenchymal progenitor cells that play a role in several fibrotic disorders, including lung fibrosis. They are attracted to injured tissue by various chemokines. It is likely that fibrocytes play a detrimental role in tissue homeostasis and promote fibrosis, although this paradigm needs further confirmation. This would make fibrocytes a possible novel treatment target for fibrotic disorders. Fibrocytes also have some potential as a biomarker for idiopathic pulmonary fibrosis (IPF and other diseases, but the promising preliminary data from single centre studies still require independent validation. Despite several, as yet, unresolved issues, it has become clear that fibrocytes are more than an incidental finding in lung injury and repair, and may hold great promise for the future of IPF management.

Post-radiation changes in oral tissues - An analysis of cancer irradiation cases

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Jay Ashokkumar Pandya

2014-01-01

Full Text Available Introduction: Radiation, commonly employed as neoadjuvant, primary, and adjuvant therapy for head and neck cancer causes numerous epithelial and stromal changes, prominent among which is fibrosis with its early and late consequences. Very little is known about the true nature of the fibrosed tissue and the type of fibers accumulated. Radiotherapy affects the supporting tumor stroma often resulting in a worsening grade of tumor post-radiation. Aim: To study epithelial, neoplastic, stromal, and glandular changes in oral cavity induced by radiation therapy for oral squamous cell carcinoma (OSCC using special stains. Materials and Methods: The study included 27 samples of recurrent OSCC following completion of radiotherapy (recurrence within an average span of 11 months, and 26 non-irradiated cases of OSCC. Patients with a history of combined radiotherapy and chemotherapy were not included in the study. The epithelial changes assessed included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The connective tissue was evaluated for amount of fibrosis, quality of fibers (using picrosirius red staining, fibrinous exudate, necrosis, pattern of invasion, vessel wall thickening, and salivary gland changes. The aforementioned changes were assessed using light and polarizing microscopy and tabulated. Statistical Analysis: Epithelial and connective tissue parameters were compared between the irradiated and non-irradiated cases using chi square and t-tests. Results: Epithelial and connective tissue parameters were found to be increased in irradiated patients. Pattern of invasion by tumor cells varied from strands and  cords between the two groups studied. The effect of radiation was seen to reflect on the maturity of fibers and the regularity of their distribution.

Retroperitoneal fibrosis with pancreatic involvement – radiological appearance

International Nuclear Information System (INIS)

Zielonko, Joanna; Obołończyk, Łukasz

2011-01-01

Retroperitoneal fibrosis or Ormond’s disease is an uncommon process characterized by fibrous tissue proliferation in the retroperitoneum, usually involving the aorta, inferior vena cava and iliac vessels. Obstructive hydronephrosis is often observed due to ureteral entrapment. This report presents a case of the peripancreatic location of the disease. The role of CT and MRI in establishing diagnosis of retroperitoneal fibrosis in an atypical site is discussed. A 52-year-old woman with Hashimoto’s thyroiditis was admitted to hospital because of pain suggesting renal colic. The patient was subjected to ultrasound, CT, and MRI which did not confirm urolithiasis but revealed pancreatic infiltration. Partial pancreatectomy, left-sided adrenalectomy and splenectomy were performed. Retroperitoneal fibrosis was diagnosed in the histopathological examination. A few weeks after surgery, a complication such as pancreatitis developed. Repeat CT confirmed it and showed right hydronephrosis secondary to ureteral involvement by a mass adjacent to the common iliac artery (defined as a typical manifestation of retroperitoneal fibrosis). Nephrostomy and conservative treatment improved the clinical state of the patient. No progression of the process was observed in the follow-up examinations. Atypical retroperitoneal fibrosis remains a diagnostic challenge. Imaging techniques CT and MRI are useful tools for evaluating the extent of Ormond’s disease. An unusual distribution of the process (e.g. peripancreatic location reported in this study) requires histopathological assessment to establish the final diagnosis

Nephrogenic systemic fibrosis

DEFF Research Database (Denmark)

Khurram, Misbah; Skov, Lone; Rossen, Kristian

2007-01-01

Nephrogenic systemic fibrosis (NSF) is a fibrotic disease seen in renal failure patients that may lead to severe physical disability. It has been demonstrated in recent studies that NSF can be caused by some gadolinium-containing MRI contrast agents. In this report we present one of a total of 26...

Assessment of myocardial fibrosis with T1 mapping MRI

International Nuclear Information System (INIS)

Everett, R.J.; Stirrat, C.G.; Semple, S.I.R.; Newby, D.E.; Dweck, M.R.; Mirsadraee, S.

2016-01-01

Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson–Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present.

Assessment of myocardial fibrosis with T1 mapping MRI.

Science.gov (United States)

Everett, R J; Stirrat, C G; Semple, S I R; Newby, D E; Dweck, M R; Mirsadraee, S

2016-08-01

Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present. Copyright © 2016 The Royal College

Localized bilateral perirenal fibrosis, a rare cause of idiopathic retroperitoneal fibrosis

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Maja Kveder

2014-08-01

Full Text Available Background: Idiopathic retroperitoneal fibrosis is an infrequent process of unknown aetiology characterised by fibrous tissue proliferation in the retroperitoneum. Even less frequent is a localized form of this disease by a proliferation of fibrous tissue around single or both kidneys.Case report: We describe a case of 46-year old man in whom medical management was started for accidentally discovered arterial hypertension, which turned out to be difficult to control.   During diagnostic work-up of hypertension, an abdominal ultrasound was obtained a year later demonstrating slight bilateral caliectasis without obvious visible cause for it. Laboratory exams have shown significantly impaired renal function, normocytic anaemia, slightly higher sedimentation rate, increased CRP and normal urinalysis. Nephrologist has decided for hospitalisation during which magnetic resonance imaging was performed  showing a few mm wide tissue coats surrounding both kidneys with fluid lying between the coat and kidney capsule. A biopsy of perirenal mass has confirmed a dense cellular lesion consisted of interweaved fascicles of spindle-shaped cells. After exclusion of tumours and other causes, a diagnosis of retroperitoneal fibrosis was confirmed. Clinical picture and laboratory data corresponded to idiopathic form of this disease. A treatment with tamoxifen was started after patient refused treatment with methylprednisolone. During tamoxifen monotherapy, there was gradual significant improvement of general symptoms, notable decline in inflammation markers, improvement of anaemia, normalisation of kidney function, and normalisation of blood pressure. Conclusion: Retroperitoneal fibrosis is still an obscure and multifaceted disease. A proper selection of diagnostic methods is the key to correct and fast diagnosis as well as good grounding for proper treatment.

FibroMeters: a family of blood tests for liver fibrosis.

Science.gov (United States)

Calès, P; Boursier, J; Oberti, F; Hubert, I; Gallois, Y; Rousselet, M-C; Dib, N; Moal, V; Macchi, L; Chevailler, A; Michalak, S; Hunault, G; Chaigneau, J; Sawadogo, A; Lunel, F

2008-09-01

FibroMeters are blood tests for liver fibrosis with several specificities: two main diagnostic targets (fibrosis stage and area of fibrosis); adaptation to specific causes; and results confirmed by an expert system. Thus, FibroMeters comprise six different tests: one for staging and one for quantitation of liver fibrosis in each of the three main causes of chronic liver disease-chronic viral hepatitis, alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). FibroMeters display a high overall diagnostic accuracy and are the only tests to correctly classify 100% of HCV patients without fibrosis or with cirrhosis. They have 90% predictive values in a higher proportion of patients than with other usual blood tests. A 90% correct classification is available in 100% of HCV patients with the following reliable diagnostic intervals: F0/1, F1/2, F2+/-1, F3+/-1. In real-life conditions, the reproducibility of FibroMeters is higher than that of liver biopsy or ultrasonographic elastometry. FibroMeters are robust tests with the most stable diagnostic performance across different centers. Optional tests are also available, such as a specific one for cirrhosis, which has a diagnostic accuracy of 93.0% (AUROC: 0.92) and a 100% positive predictive value for diagnosis of HCV cirrhosis. Determination by FibroMeters of the area of fibrosis - the only direct, non-invasive, quantitative measurement of liver fibrosis - are especially useful for following-up cirrhosis as it correlates well with clinical events. FibroMeters are also very accurate in HVB or HIV-HCV co-infected patients. The tests specific for ALD and NAFLD also have a high diagnostic accuracy (AUROCs: 0.96 and 0.94, respectively, for significant fibrosis).

Radiation-induced pulmonary fibrosis: examination of chemokine and chemokine receptor families.

Science.gov (United States)

Johnston, Carl J; Williams, Jacqueline P; Okunieff, Paul; Finkelstein, Jacob N

2002-03-01

Fibrosis is a common outcome of chronic inflammation or injury. Pulmonary fibrosis may be the result of abnormal repair after an acute inflammatory response. The process of repair initiated by a tissue insult is largely a function of the activation of cells to produce important biological mediators such as cytokines, growth factors and chemokines, which orchestrate most aspects of the inflammatory response. Consequently, altered regulation of the production of inflammatory cell cytokines and chemokines after injury and repair likely contributes to the fibrosis. Our hypothesis is that chronic expression of specific chemokine and chemokine receptors during the fibrotic phase induced by thoracic irradiation may perpetuate the recruitment and activation of lymphocytes and macrophages, which may contribute to the development of fibrosis. Fibrosis-sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single dose of 12.5 Gy to the thorax. Total lung RNA was prepared and hybridized using microarray analysis and RNase protection assays. At 26 weeks postirradiation, messages encoding the chemokines BLC (now known as Scyb13), C10 (now known as Scya6), IP-10 (now known as Scyb10), MCP-1 (now known as Scya2), MCP-3 (now known as Scya7), MIP-1gamma (now known as Scya9), and RANTES (now known as Scya5) and the chemokine receptors Ccr1, Ccr2, Ccr5 and Ccr6 were elevated in fibrosis-sensitive (C57BL/6) mice. In contrast, only the messages encoding SDF-1alpha (now known as Sdf1) and Ccr1 were elevated 26 weeks postirradiation in fibrosis-resistant (C3H/HeJ) mice. Our results point to the CC and CCR family members as the predominant chemokine responders during the development of fibrosis. These studies suggest that monocyte/macrophage and lymphocyte recruitment and activation are key components of radiation-induced fibrosis.

Guidelines for the medical treatment of idiopathic pulmonary fibrosis.

Science.gov (United States)

Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio

2017-05-01

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy

NARCIS (Netherlands)

T.C. Tran; G. van 't Hof; G. Kazemier (Geert); W.C.J. Hop (Wim); C.J. Pek (Chulja); A.W. van Toorenenbergen (Albert); H. van Dekken (Herman); C.H.J. van Eijck (Casper)

2008-01-01

textabstractBackground: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and

Influence of macrolides, nutritional support and respiratory therapies in diabetes and normal glucose tolerance in cystic fibrosis. A retrospective analysis of a cohort of adult and younger patients.

Science.gov (United States)

Megías, Marta Cano; Albarrán, Olga González; Vasco, Pablo Guisado; Ferreiro, Adelaida Lamas; Carro, Luis Maiz

2015-01-01

The development of cystic fibrosis related diabetes is associated with increased morbidity and mortality, worse nutritional status and lung function decline. It is known that patients with cystic fibrosis have a chronic inflammation status and that β pancreatic cells are very sensitive to oxidative stress. So these inflammatory mediators could contribute to the onset of progressive pancreatic fibrosis and, hence, to impair glucose metabolism. So, it could be hypothesized that the treatment with macrolides would protect and preserve β-cell function by decreasing pro-inflammatory cytokines and free oxidative radicals. We retrospectively analyzed a cohort of 64 patients affected of cystic fibrosis, older than 14 years, by using the first pathological 2-h oral glucose tolerance test; peripheral insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA - IR) and pancreatic β-cell function was estimated according to Wareham. The influence of macrolides, microbiological colonization, nutritional support and related clinical parameters were analyzed. Comparing CFRD without FPG and NGT, and after adjustment for microbial colonization, the significance of the use of macrolides was lost (p=0.1), as a risk or protective factor for any of the studied groups. Non-significative associations were found in the use of macrolides, inhaled corticosteroids and nutritional support therapies within the different disorders of carbohydrate metabolism. The anti-inflammatory and immunomodulating effect of macrolides did not seem to affect the β cell function or insulin resistance in patients with cystic fibrosis. The use of inhaled corticosteroids or nutritional supplements have not any influence in the carbohydrate metabolism. Further prospective studies are needed to analyze a potential protective role of macrolides in the development of carbohydrate metabolism alterations in cystic fibrosis. Copyright © 2014 Diabetes India. Published by

Nutrient Status of Adults with Cystic Fibrosis

Science.gov (United States)

GORDON, CATHERINE M.; ANDERSON, ELLEN J.; HERLYN, KAREN; HUBBARD, JANE L.; PIZZO, ANGELA; GELBARD, RONDI; LAPEY, ALLEN; MERKEL, PETER A.

2011-01-01

Nutrition is thought to influence disease status in patients with cystic fibrosis (CF). This cross-sectional study sought to evaluate nutrient intake and anthropometric data from 64 adult outpatients with cystic fibrosis. Nutrient intake from food and supplements was compared with the Dietary Reference Intakes for 16 nutrients and outcomes influenced by nutritional status. Attention was given to vitamin D and calcium given potential skeletal implications due to cystic fibrosis. Measurements included weight, height, body composition, pulmonary function, and serum metabolic parameters. Participants were interviewed about dietary intake, supplement use, pulmonary function, sunlight exposure, and pain. The participants’ mean body mass index (±standard deviation) was 21.8±4.9 and pulmonary function tests were normal. Seventy-eight percent used pancreatic enzyme replacement for malabsorption. Vitamin D deficiency [25-hydroxyvitamin D (25OHD)<37.5 nmol/L] was common: 25 (39%) were deficient despite adequate vitamin D intake. Lipid profiles were normal in the majority, even though total and saturated fat consumption represented 33.0% and 16.8% of energy intake, respectively. Reported protein intake represented 16.9% of total energy intake (range 10%–25%). For several nutrients, including vitamin D and calcium, intake from food and supplements in many participants exceeded recommended Tolerable Upper Intake Levels. Among adults with cystic fibrosis, vitamin D deficiency was common despite reported adequate intake, and lipid profiles were normal despite a relatively high fat intake. Mean protein consumption was adequate, but the range of intake was concerning, as both inadequate or excessive intake may have deleterious skeletal effects. These findings call into question the applicability of established nutrient thresholds for patients with cystic fibrosis. PMID:18060897

Episodic seasonal Pseudo-Bartter syndrome in cystic fibrosis.

Science.gov (United States)

Kintu, Brett; Brightwell, Alex

2014-06-01

Pseudo-Bartter syndrome (PBS) describes an uncommon but well recognised complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. Pseudo-Bartter syndrome is usually seen at initial presentation or within the first two years of life in children with cystic fibrosis. Risk factors for development of PBS include warm weather conditions, severe respiratory or pancreatic disease and gastrointestinal losses (e.g. vomiting and diarrhoea). PBS is rare in older children and adolescents although epidemics have been associated with heat wave conditions in warmer climates. In this era of climate change, it is crucial that clinicians consider Pseudo-Bartter syndrome when patients with cystic fibrosis present unwell during summer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Treatment and education reduce the severity of schistosomiasis periportal fibrosis

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Paula Carolina Valenca Silva

2013-07-01

Full Text Available Introduction This study evaluates the factors associated with the development of severe periportal fibrosis in patients with Schistosoma mansoni. Methods A cross-sectional study was conducted from April to December 2012 involving 178 patients infected with S. mansoni who were treated in the Hospital das Clínicas of Pernambuco, Brazil. Information regarding risk factors was obtained using a questionnaire. Based on the patients' epidemiological history, clinical examination, and upper abdomen ultrasound evaluation, patients were divided into 2 groups: 137 with evidence of severe periportal fibrosis and 41 patients without fibrosis or with mild or moderate periportal fibrosis. Univariate and multivariate analyses were conducted using EpiInfo software version 3.5.5. Results Illiterate individuals (30.1% and patients who had more frequent contact with contaminated water in towns in the Zona da Mata of Pernambuco (33.2% were at greater risk for severe periportal fibrosis. Based on multivariate analysis, it was determined that an education level of up to 11 years of study and specific prior treatment for schistosomiasis were preventive factors for severe periportal fibrosis. Conclusions The prevailing sites of the severe forms of periportal fibrosis are still within the Zona da Mata of Pernambuco, although there has been an expansion to urban areas and the state coast. Specific treatment and an increased level of education were identified as protective factors, indicating the need for implementing social, sanitary, and health education interventions aimed at schistosomiasis to combat the risk factors for this major public health problem.

Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.

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Ding, Hao; Jiang, Lei; Xu, Jing; Bai, Feng; Zhou, Yang; Yuan, Qi; Luo, Jing; Zen, Ke; Yang, Junwei

2017-09-01

Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. Copyright © 2017 the American Physiological Society.

Fibrosis endomiocárdica

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María Juliana Rodríguez-González

2017-07-01

Una de las formas más comunes de miocardiopatía restrictiva es la fibrosis endomiocárdica la cual es endémica en algunas zonas tropicales especialmente en África (países de bajos ingresos, pero en nuestro medio hay pocos reportes de aparición. Su etiología es desconocida, aunque existen diversos mecanismos que han sido involucrados en su fisiopatología. Su diagnóstico se basa en estudios imagenológicos (ecocardiograma transtorácico y resonancia magnética nuclear cardíaca. El pronóstico es muy pobre, y usualmente se diagnostica en etapas muy avanzadas de la enfermedad. Se describe el caso de una paciente femenina, adulta media, que debutó con cardiopatía restrictiva, cuyo diagnóstico final fue fibrosis endomiocárdica.

[Historical compilation of cystic fibrosis].

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Navarro, Salvador

2016-01-01

Cystic fibrosis is the most common life-shortening recessively inherited disorder in the Caucasian population. The genetic mutation that most frequently provokes cystic fibrosis (ΔF508) appeared at least 53,000years ago. For many centuries, the disease was thought to be related to witchcraft and the "evil eye" and it was only in 1938 that Dorothy H. Andersen characterized this disorder and suspected its genetic origin. The present article reviews the pathological discoveries and diagnostic and therapeutic advances made in the last 75 years. The review ends with some considerations for the future. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Thermodynamic Aspects and Reprogramming Cellular Energy Metabolism during the Fibrosis Process

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Alexandre Vallée

2017-11-01

Full Text Available Fibrosis is characterized by fibroblast proliferation and fibroblast differentiation into myofibroblasts, which generate a relaxation-free contraction mechanism associated with excessive collagen synthesis in the extracellular matrix, which promotes irreversible tissue retraction evolving towards fibrosis. From a thermodynamic point of view, the mechanisms leading to fibrosis are irreversible processes that can occur through changing the entropy production rate. The thermodynamic behaviors of metabolic enzymes involved in fibrosis are modified by the dysregulation of both transforming growth factor β (TGF-β signaling and the canonical WNT/β-catenin pathway, leading to aerobic glycolysis, called the Warburg effect. Molecular signaling pathways leading to fibrosis are considered dissipative structures that exchange energy or matter with their environment far from the thermodynamic equilibrium. The myofibroblastic cells arise from exergonic processes by switching the core metabolism from oxidative phosphorylation to glycolysis, which generates energy and reprograms cellular energy metabolism to induce the process of myofibroblast differentiation. Circadian rhythms are far-from-equilibrium thermodynamic processes. They directly participate in regulating the TGF-β and WNT/β-catenin pathways involved in energetic dysregulation and enabling fibrosis. The present review focusses on the thermodynamic implications of the reprogramming of cellular energy metabolism, leading to fibroblast differentiation into myofibroblasts through the positive interplay between TGF-β and WNT/β-catenin pathways underlying in fibrosis.

Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.

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Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza

2014-01-01

To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis

DEFF Research Database (Denmark)

Rambaldi, A; Gluud, C

2001-01-01

Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine...... evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis....

Spironolactone lowers portal hypertension by inhibiting liver fibrosis, ROCK-2 activity and activating NO/PKG pathway in the bile-duct-ligated rat.

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Wei Luo

Full Text Available OBJECTIVE: Aldosterone, one of the main peptides in renin angiotensin aldosterone system (RAAS, has been suggested to mediate liver fibrosis and portal hypertension. Spironolactone, an aldosterone antagonist, has beneficial effect on hyperdynamic circulation in clinical practice. However, the mechanisms remain unclear. The present study aimed to investigate the role of spionolactone on liver cirrhosis and portal hypertension. METHODS: Liver cirrhosis was induced by bile duct ligation (BDL. Spironolactone was administered orally (20 mg/kg/d after bile duct ligation was performed. Liver fibrosis was assessed by histology, Masson's trichrome staining, and the measurement of hydroxyproline and type I collagen content. The activation of HSC was determined by analysis of alpha smooth muscle actin (α-SMA expression. Protein expressions and protein phosphorylation were determined by immunohistochemical staining and Western blot analysis, Messenger RNA levels by quantitative real time polymerase chain reaction (Q-PCR. Portal pressure and intrahepatic resistance were examined in vivo. RESULTS: Treatment with spironolactone significantly lowered portal pressure. This was associated with attenuation of liver fibrosis, intrahepatic resistance and inhibition of HSC activation. In BDL rat liver, spironolactone suppressed up-regulation of proinflammatory cytokines (TNFα and IL-6. Additionally, spironolactone significantly decreased ROCK-2 activity without affecting expression of RhoA and Ras. Moreover, spironolactone markedly increased the levels of endothelial nitric oxide synthase (eNOS, phosphorylated eNOS and the activity of NO effector-protein kinase G (PKG in the liver. CONCLUSION: Spironolactone lowers portal hypertension by improvement of liver fibrosis and inhibition of intrahepatic vasoconstriction via down-regulating ROCK-2 activity and activating NO/PKG pathway. Thus, early spironolactone therapy might be the optional therapy in cirrhosis and

The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis

NARCIS (Netherlands)

Murtha, Lucy A.; Schuliga, Michael J.; Mabotuwana, Nishani S.; Hardy, Sean A.; Waters, David W.; Burgess, Janette K.; Knight, Darryl A.; Boyle, Andrew J.

2017-01-01

Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair.

Molecular basis of hepatic fibrosis and current status of its diagnosis and treatment

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LI Yan

2018-01-01

Full Text Available During the process of acute or chronic liver injury, hepatic stellate cells interact with various types of cells such as hepatic parenchymal cells, Kupffer cells, and liver sinusoidal endothelial cells to mediate extracellular matrix deposition and sinusoid capillarization and thus initiate the process of hepatic fibrosis. The nature of hepatic fibrosis is repair response after liver injury. Liver biopsy is regarded as the gold standard for the diagnosis of hepatic fibrosis; however, it is generally associated with the risk of bleeding and even death. Noninvasive diagnostic methods for liver fibrosis mainly include serum biomarkers, imaging techniques, and predictive statistical model, but such methods cannot completely replace liver biopsy. At present, the treatment of hepatic fibrosis focuses on the research and development of new drugs targeting primary disease, hepatic stellate cells, or balance of extracellular matrix synthesis/degradation. The research on the molecular mechanism of hepatic fibrosis provides a solid theoretical basis for exploring the treatment of hepatic fibrosis.

Epithelial-mesenchymal transition: An emerging target in tissue fibrosis

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Li, Meirong; Luan, Fuxin; Zhao, Yali; Hao, Haojie; Zhou, Yong; Han, Weidong

2016-01-01

Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibroses. Fibroblasts/myofibroblasts derived from epithelial cells contribute to the excessive accumulation of fibrous connective tissue in damaged tissue, which can lead to permanent scarring or organ malfunction. Therefore, EMT-related fibrosis cannot be neglected. This review highlights the findings that demonstrate the EMT to be a direct contributor to the fibroblast/myofibroblast population in the development of tissue fibrosis and helps to elucidate EMT-related anti-fibrotic strategies, which may enable the development of therapeutic interventions to suppress EMT and potentially reverse organ fibrosis. PMID:26361988

Effect of iron, taurine and arginine on rat hepatic fibrosis

International Nuclear Information System (INIS)

Song Liangwen; Wang Dewen; Cui Xuemei

1997-01-01

Objective: The promotion role of iron on pathogenesis of hepatic fibrosis and the protective role of taurine and L-arginine against hepatic fibrosis were studied. Method: The model of rat radiation hepatic fibrosis was used. Experimental rats were divided into 0 Gy, 30 Gy, 30 Gy + iron, 30 Gy + taurine and 30 Gy + L-arginine groups. Serum iron, liver tissue hydroxyproline (Hyp) and malondialdehyde (MDA) were measured one and three months respectively after irradiation of hepatic tissue, production and distribution characteristics of hepatic tissue type I and III collagen were observed with a polarizing microscope. Results: Administration of iron agent could significantly increase hepatic tissue MDA content and serum iron concentration, one month after irradiation, hepatic tissue Hyp in 30 Gy + iron group began to increase, and collagen in hepatic tissue obviously increased. Taurine and L-arginine could reduce serum iron concentration and decrease production of hepatic fissure Hyp. Conclusion: Exogenous iron agent could promote early development of radiation hepatic fibrosis; taurine and arginine could diminish pathologic alteration of hepatic fibrosis to a certain extent

Radiation-induced neck fibrosis in patients with nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Li Jian; Wang Rensheng; Gan Langge; Liu Wenqi; Zhang Yong

2005-01-01

Objective: To investigate the post-irradiation neck fibrosis in patients with nasopharyngeal carcinoma and its related factors. Methods: A total of 267 patients received conventional fractionated radiotherapy with D T 50-72 Gy on the neck a half year to 10 years ago were observed for the changes of cervical shape and functions. Results: Different degrees of post-irradiation neck fibrosis were seen in all patients. The rate of heavy degree of neck radiation fibrosis was 24.34 %, and it was 2.74% when received preventive dose on the neck. There was a very significant difference between patients who received late course of tangential irradiation on the neck and those who didn't receive (P=0.0001). The incidence of post-irradiation neck fibrosis didn't increase when patients received radiotherapy combined with chemotherapy (P=0.2678). The function of cervical muscles turned weak in patients received radiotherapy delivered by 6 MV accelerator in late course of tangential irradiation, whereas skin damage was severer in patients treated with 60 Co γ-rays. Conclusions: The incidence of heavy degree of post-irradiation neck fibrosis is high ,and is related closely to late course of tangential irradiation. The authors should avoid adopting this sort of irradiation on the neck. (authors)

A new model of progressive pulmonary fibrosis in rats

Energy Technology Data Exchange (ETDEWEB)

Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. (Univ. of California, Davis (United States))

1993-08-01

Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

Case series of omalizumab for allergic bronchopulmonary aspergillosis in cystic fibrosis patients.

Science.gov (United States)

Nové-Josserand, Raphaële; Grard, Soazic; Auzou, Lila; Reix, Philippe; Murris-Espin, Marlène; Brémont, François; Mammar, Benyebka; Mely, Laurent; Hubert, Dominique; Durieu, Isabelle; Burgel, Pierre-Régis

2017-02-01

Allergic bronchopulmonary aspergillosis (ABPA) affects up to 15% of patients with cystic fibrosis (CF). Corticosteroids are used as first-line therapy, but relapse and adverse effects commonly occur. Case reports have suggested the efficacy of the anti-IgE recombinant humanized monoclonal antibody omalizumab. A retrospective multicenter observational French study retrieved 32 CF patients (11 children and 21 adults) who have received omalizumab for more than 3 months in the context of ABPA. Clinical characteristics, concomitant medications (inhaled and oral corticosteroids, antifungal drugs), lung function, body mass index (BMI), and serum IgE were compared at the start and during the first year of omalizumab therapy. Omalizumab-related adverse effects and costs were also evaluated. No significant difference with omalizumab could be demonstrated with regard to lung function, BMI, or the number of patients receiving oral corticosteroids. At the time of initiation of omalizumab, 56% of patients were receiving oral corticosteroids. Five patients were able to discontinue corticosteroids during follow-up and nine patients were able to reduce their daily dose. A total of 78% of the patients had received antifungal therapy at the time of the initiation of omalizumab. Treatment tolerance was good (12.5% of patients experienced side effects). The median cost of omalizumab treatment was €3,620 per patient per month. Omalizumab may represent a steroid-sparing therapy in CF patients with ABPA. A randomized-controlled trial is urgently required to provide higher level of evidence regarding the efficacy and cost-effectiveness of omalizumab in CF patients with ABPA. Pediatr Pulmonol. 2017;52:190-197. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Role of NLRC5 in progression and reversal of hepatic fibrosis

Energy Technology Data Exchange (ETDEWEB)

Liu, Xuejiao, E-mail: liuxuejiao0615@163.com [School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032 (China); Institute for Liver Diseases, Anhui Medical University, Hefei 230032 (China); Wu, Yuting; Yang, Yang; Li, Wanxia; Huang, Cheng; Meng, Xiaoming [School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032 (China); Institute for Liver Diseases, Anhui Medical University, Hefei 230032 (China); Li, Jun, E-mail: lj@ahmu.edu.cn [School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032 (China); Institute for Liver Diseases, Anhui Medical University, Hefei 230032 (China); School of Pharmacy, Anhui Medical University, Mei Shan load, Hefei 230032, Anhui Province (China)

2016-03-01

Background: NLRC5, as the largest member of NLRs family, has recently been identified as a critical regulator of immune responses through negatively regulating NF-κB which is associated with the development of hepatic fibrosis. However, the expression and potential roles of NLRC5 in hepatic fibrosis and its reversal are still to be defined. Methods: C57BL/6 mice were treatment with carbon tetrachloride (CCl{sub 4}) induce hepatic fibrosis and its reversal. In vitro, models of hepatic fibrosis and its reversal are established by the treatment with TGF-β and MDI. The expression of NLRC5 was determined by RT-PCR, Western blot and immunohistochemistry. Consequently, NLRC5 was overexpressed or knockdown by transfecting PEGFP-C2-NLRC5 or NLRC5-siRNA respectively in the reversal of hepatic fibrosis, and the expression of fibrogenic genes such as α-SMA and Col1α1 was quantified. The NF-κB activity was detected as well. Results: Immunohistochemistry, RT-PCR and Western blot analysis with liver tissues and primary HSCs showed that NLRC5 was highly expressed in hepatic fibrosis and correspondingly decreased in the reversal stage. The differential expression of NLRC5 was confirmed in vitro. Enforced NLRC5 expression increased the expression of α-SMA and Col1α1, and blockade of NLRC5 reduced the fibrotic response. While the opposite expression of phosphorylated NF-kB p65 and phospho-IκBα was found. Conclusion: NLRC5 is differentially expressed in hepatic tissues and hepatic stellate cells during hepatic fibrosis and its reversal. All the data indicated that NLRC5 may play a crucial role in regulating the reversal of hepatic fibrosis through NF-κB signaling pathway. - Highlights: • The activated HSCs can be reverted to quiescent HSCs by MDI treatment. • NLRC5 expressed differentially during different stages of hepatic fibrosis and its reversal. • Enforced NLRC5 in reverted LX-c cells boosted the expression of α-SMA and Col1α1. • Blockade of NLRC5 diminished �

Deep learning for staging liver fibrosis on CT: a pilot study.

Science.gov (United States)

Yasaka, Koichiro; Akai, Hiroyuki; Kunimatsu, Akira; Abe, Osamu; Kiryu, Shigeru

2018-05-14

To investigate whether liver fibrosis can be staged by deep learning techniques based on CT images. This clinical retrospective study, approved by our institutional review board, included 496 CT examinations of 286 patients who underwent dynamic contrast-enhanced CT for evaluations of the liver and for whom histopathological information regarding liver fibrosis stage was available. The 396 portal phase images with age and sex data of patients (F0/F1/F2/F3/F4 = 113/36/56/66/125) were used for training a deep convolutional neural network (DCNN); the data for the other 100 (F0/F1/F2/F3/F4 = 29/9/14/16/32) were utilised for testing the trained network, with the histopathological fibrosis stage used as reference. To improve robustness, additional images for training data were generated by rotating or parallel shifting the images, or adding Gaussian noise. Supervised training was used to minimise the difference between the liver fibrosis stage and the fibrosis score obtained from deep learning based on CT images (F DLCT score) output by the model. Testing data were input into the trained DCNNs to evaluate their performance. The F DLCT scores showed a significant correlation with liver fibrosis stage (Spearman's correlation coefficient = 0.48, p deep learning model based on CT images, with moderate performance. • Liver fibrosis can be staged by a deep learning model based on magnified CT images including the liver surface, with moderate performance. • Scores from a trained deep learning model showed moderate correlation with histopathological liver fibrosis staging. • Further improvement are necessary before utilisation in clinical settings.

Microengineered in vitro model of cardiac fibrosis through modulating myofibroblast mechanotransduction

International Nuclear Information System (INIS)

Zhao, Hui; Li, Xiaokang; Zhao, Shan; Zeng, Yang; Ding, Haiyan; Du, Yanan; Zhao, Long; Sun, Wei

2014-01-01

Cardiac fibrosis greatly impairs normal heart function post infarction and there is no effective anti-fibrotic drug developed at present. The current therapies for cardiac infarction mainly take effect by eliminating occlusion in coronary artery by thrombolysis drugs, vascular stent grafting or heart bypass operation, which are capable to provide sufficient blood flow for intact myocardium yet showed subtle efficacy in ameliorating fibrosis condition. The advances of in vitro cell/tissue models open new avenues for drug assessment due to the low cost, good controllability and availability as well as the convenience for operation as compared to the animal models. To our knowledge, no proper biomimetic in vitro cardiac fibrosis model has been reported yet. Here we engineered an in vitro cardiac fibrosis model using heart-derived fibroblasts, and the fibrogenesis was recapitulated by patterning the substrate rigidity which mimicked the mechanical heterogeneity of myocardium post-infarction. Various biomarkers for cardiac fibrosis were assayed to validate the biomimicry of the engineered platform. Subsequent addition of Rho-associated protein kinase (ROCK) pathway inhibitor reduced the ratio of myofibroblasts, indicating the feasibility of applying this platform in screening anti-fibrosis drugs. (paper)

Breakthrough Therapies: Cystic Fibrosis (CF) Potentiators and Correctors

Science.gov (United States)

Solomon, George M.; Marshall, Susan G.; Ramsey, Bonnie W.; Rowe, Steven M.

2015-01-01

Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene resulting in abnormal protein function. Recent advances of targeted molecular therapies and high throughput screening have resulted in multiple drug therapies that target many important mutations in the CFTR protein. In this review, we provide the latest results and current progress of CFTR modulators for the treatment of cystic fibrosis, focusing on potentiators of CFTR channel gating and Phe508del processing correctors for the Phe508del CFTR mutation. Special emphasis is placed on the molecular basis underlying these new therapies and emerging results from the latest clinical trials. The future directions for augmenting the rescue of Phe508del with CFTR modulators is also emphasized. PMID:26097168

Noninvasive Assessment of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

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Elena Buzzetti

2015-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is prevalent in 20–25% of the general population and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. Histologically, NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH, fibrosis, and cirrhosis. As NASH develops in only 10–15% of patients with NAFLD, it is not practical to biopsy all patients who present with NAFLD. Noninvasive fibrosis tests have been extensively developed recently and offer alternatives for staging fibrosis. Despite their increasing use, such tests cannot adequately differentiate simple steatosis from NASH. At present, such tests can be used as first line tests to rule out patients without advanced fibrosis and thus prevent unnecessary secondary care referrals in a significant number of patients. In this review we present the evidence for the use of noninvasive fibrosis tests in patients with NAFLD.

Fibrosis of the pancreas: the initial tissue damage and the resulting pattern.

Science.gov (United States)

Klöppel, Günter; Detlefsen, Sönke; Feyerabend, Bernd

2004-07-01

Fibrosis in the pancreas is caused by such processes as necrosis/apoptosis, inflammation or duct obstruction. The initial event that induces fibrogenesis in the pancreas is an injury that may involve the interstitial mesenchymal cells, the duct cells and/or the acinar cells. Damage to any one of these tissue compartments of the pancreas is associated with cytokine-triggered transformation of resident fibroblasts/pancreatic stellate cells into myofibroblasts and the subsequent production and deposition of extracellular matrix. Depending on the site of injury in the pancreas and the involved tissue compartment, predominantly inter(peri)lobular fibrosis (as in alcoholic chronic pancreatitis), periductal fibrosis (as in hereditary pancreatitis), periductal and interlobular fibrosis (as in autoimmune pancreatitis) or diffuse inter- and intralobular fibrosis (as in obstructive chronic pancreatitis) develops.

[Cystic fibrosis--initial diagnosis in a 39-year-old patient].

Science.gov (United States)

Bargon, J; Rickmann, J; Jacobi, V; Straub, R; Arnemann, J; Wagner, T O

2000-12-15

Cystic fibrosis is the most common hereditary disorder among Caucasians. Most of the patients are diagnosed as children. However, some cases are going undiagnosed into adulthood and are then often misdiagnosed because the non-pediatricians do not know cystic fibrosis very well and do not consider this diagnosis in adult patients. We present the medical history of a woman, who was diagnosed with cystic fibrosis at the age of 39 years, although she had suffered from bronchiectasis, pancreatic insufficiency and liver cirrhosis since many years. Her medical history was long with some diagnosis, but because of her age nobody considered the final diagnosis. In adult patients with bronchiectasis, liver cirrhosis and pancreatic insufficiency in combination or with only one of these symptoms, cystic fibrosis should be included into the differential diagnosis.

TRIF Differentially Regulates Hepatic Steatosis and Inflammation/Fibrosis in MiceSummary

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Ling Yang

2017-05-01

Full Text Available Background & Aims: Toll-like receptor 4 (TLR4 signaling is activated through 2 adaptor proteins: MyD88 and TIR-domain containing adaptor-inducing interferon-β (TRIF. TLR4 and MyD88 are crucial in nonalcoholic steatohepatitis (NASH and fibrosis. However, the role of TRIF in TLR4-mediated NASH and fibrosis has been elusive. This study investigated the differential roles of TRIF in hepatic steatosis and inflammation/fibrosis. Methods: A choline-deficient amino acid defined (CDAA diet was used for the mouse NASH model. On this diet, the mice develop hepatic steatosis, inflammation, and fibrosis. TLR4 wild-type and TLR4-/- bone marrow chimeric mice and TRIF-/- mice were fed CDAA or a control diet for 22 weeks. Hepatic steatosis, inflammation, and fibrosis were examined. Results: In the CDAA diet–induced NASH, the mice with wild-type bone marrow had higher alanine aminotransferase and hepatic tumor necrosis factor levels than the mice with TLR4-/- bone marrow. The nonalcoholic fatty liver disease activity score showed that both wild-type and TLR4-/- bone marrow chimeras had reduced hepatic steatosis, and that both types of chimeras had similar levels of inflammation and hepatocyte ballooning to whole-body wild-type mice. Notably, wild-type recipients showed more liver fibrosis than TLR4-/- recipients. Although TRIF-/- mice showed reduced hepatic steatosis, these mice showed more liver injury, inflammation, and fibrosis than wild-type mice. TRIF-/- stellate cells and hepatocytes produced more C-X-C motif chemokine ligand 1 (CXCL1 and C-C motif chemokine ligand than wild-type cells in response to lipopolysaccharide. Consistently, TRIF-/- mice showed increased CXCL1 and CCL3 expression along with neutrophil and macrophage infiltration, which promotes liver inflammation and injury. Conclusions: In TLR4-mediated NASH, different liver cells have distinct roles in hepatic steatosis, inflammation, and fibrosis. TRIF promotes hepatic

Targeting Interleukin-13 with Tralokinumab Attenuates Lung Fibrosis and Epithelial Damage in a Humanized SCID Idiopathic Pulmonary Fibrosis Model

Science.gov (United States)

Zhang, Huilan; Oak, Sameer R.; Coelho, Ana Lucia; Herath, Athula; Flaherty, Kevin R.; Lee, Joyce; Bell, Matt; Knight, Darryl A.; Martinez, Fernando J.; Sleeman, Matthew A.; Herzog, Erica L.; Hogaboam, Cory M.

2014-01-01

The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung. PMID:24325475

Abdominal CT predictors of fibrosis in patients with chronic pancreatitis undergoing surgery

Energy Technology Data Exchange (ETDEWEB)

Sinha, Amitasha; Afghani, Elham [Johns Hopkins Medical Institutions, Division of Gastroenterology, Baltimore, MD (United States); Singh, Vikesh K. [Johns Hopkins Medical Institutions, Division of Gastroenterology, Baltimore, MD (United States); Johns Hopkins Medical Institutions, Pancreatitis Center, Baltimore, MD (United States); Cruise, Michael; Matsukuma, Karen [Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, MD (United States); Ali, Sumera; Raman, Siva P.; Fishman, Elliot K. [Johns Hopkins Medical Institutions, The Russel H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Andersen, Dana K. [National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States); Makary, Martin A. [Johns Hopkins Medical Institutions, Department of Surgery, Baltimore, MD (United States); Johns Hopkins Medical Institutions, Pancreatitis Center, Baltimore, MD (United States); Zaheer, Atif [Johns Hopkins Medical Institutions, The Russel H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Johns Hopkins Medical Institutions, Pancreatitis Center, Baltimore, MD (United States); Johns Hopkins Medical Institutions, Baltimore, MD (United States)

2015-05-01

To determine which abdominal CT findings predict severe fibrosis and post-operative pain relief in chronic pancreatitis (CP). Pre-operative abdominal CTs of 66 patients (mean age 52 ± 12 years, 53 % males) with painful CP who underwent the Whipple procedure (n = 32), Frey procedure (n = 32) or pancreatic head biopsy (n = 2), between 1/2003-3/2014, were evaluated. CT was evaluated for parenchymal calcifications, intraductal calculi, main pancreatic duct dilation (>5 mm), main pancreatic duct stricture, and abnormal side branch(es). The surgical histopathology was graded for fibrosis. CT findings were evaluated as predictors of severe fibrosis and post-operative pain relief using regression and area under receiver operating curve (AUC) analysis. Thirty-eight (58 %) patients had severe fibrosis. Parenchymal calcification(s) were an independent predictor of severe fibrosis (p = 0.03), and post-operative pain relief over a mean follow-up of 1-year (p = 0.04). Presence of >10 parenchymal calcifications had higher predictive accuracy for severe fibrosis than 1-10 parenchymal calcification(s) (AUC 0.88 vs. 0.59, p = 0.003). The predictive accuracy of >10 versus 1-10 parenchymal calcifications increased after adjusting for all other CT findings (AUC 0.89 vs. 0.63, p = 0.01). Parenchymal calcification(s) independently predict severe fibrosis and are significantly associated with post-operative pain relief in CP. The presence of >10 parenchymal calcifications is a better predictor of severe fibrosis than 1-10 parenchymal calcification(s). (orig.)

Abdominal CT predictors of fibrosis in patients with chronic pancreatitis undergoing surgery

International Nuclear Information System (INIS)

Sinha, Amitasha; Afghani, Elham; Singh, Vikesh K.; Cruise, Michael; Matsukuma, Karen; Ali, Sumera; Raman, Siva P.; Fishman, Elliot K.; Andersen, Dana K.; Makary, Martin A.; Zaheer, Atif

2015-01-01

To determine which abdominal CT findings predict severe fibrosis and post-operative pain relief in chronic pancreatitis (CP). Pre-operative abdominal CTs of 66 patients (mean age 52 ± 12 years, 53 % males) with painful CP who underwent the Whipple procedure (n = 32), Frey procedure (n = 32) or pancreatic head biopsy (n = 2), between 1/2003-3/2014, were evaluated. CT was evaluated for parenchymal calcifications, intraductal calculi, main pancreatic duct dilation (>5 mm), main pancreatic duct stricture, and abnormal side branch(es). The surgical histopathology was graded for fibrosis. CT findings were evaluated as predictors of severe fibrosis and post-operative pain relief using regression and area under receiver operating curve (AUC) analysis. Thirty-eight (58 %) patients had severe fibrosis. Parenchymal calcification(s) were an independent predictor of severe fibrosis (p = 0.03), and post-operative pain relief over a mean follow-up of 1-year (p = 0.04). Presence of >10 parenchymal calcifications had higher predictive accuracy for severe fibrosis than 1-10 parenchymal calcification(s) (AUC 0.88 vs. 0.59, p = 0.003). The predictive accuracy of >10 versus 1-10 parenchymal calcifications increased after adjusting for all other CT findings (AUC 0.89 vs. 0.63, p = 0.01). Parenchymal calcification(s) independently predict severe fibrosis and are significantly associated with post-operative pain relief in CP. The presence of >10 parenchymal calcifications is a better predictor of severe fibrosis than 1-10 parenchymal calcification(s). (orig.)