Publications by authors named "Ngoc Bich Nguyen"

22 Publications

  • Page 1 of 1

Hypospadias associated with partial bifid phallus: A case report.

Urol Case Rep 2021 Nov 9;39:101840. Epub 2021 Sep 9.

Department of Pediatric Surgery, Vietnam Germany Hospital, 40 TrangThi, Hoankiem, Hanoi, Viet Nam.

Diphallia is an extremely rare congenital anomaly. Bifid phallus is a type of diphallia and is rarely recorded in published studies. According to the degree of separation of the penises at the base of the shaft or just at the glans, bifid phallus is further classified into complete or partial forms. Bifid phallus is often associated with hypospadias or part of the exstrophy-epispadias complex. We are really lucky to have successfully treated a 2-year-old patient with penoscrotal hypospadias combined with partial bifid phallus in the shaft. After the surgery, the patient had no issues with penile function.
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http://dx.doi.org/10.1016/j.eucr.2021.101840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445837PMC
November 2021

Advancing family dementia caregiver interventions in low- and middle-income countries: A pilot cluster randomized controlled trial of Resources for Advancing Alzheimer's Caregiver Health in Vietnam (REACH VN).

Alzheimers Dement (N Y) 2020 23;6(1):e12063. Epub 2021 Jan 23.

Vietnam National Geriatric Hospital Hanoi Vietnam.

Introduction: Low- and middle-income countries have rapidly increasing numbers of people with dementia, yet little evidence on family caregiving interventions. We tested the preliminary efficacy and feasibility of a family caregiving intervention in northern Vietnam.

Methods: Nine clusters comprising 60 family caregivers were randomized to a culturally adapted version of a four- to six-session, multicomponent intervention delivered in-home over 2 to 3 months, or enhanced control. Eligible caregivers were ≥18 years of age and scored ≥6 on the Zarit Burden Inventory (ZBI).

Results: Fifty-one caregivers (85%) completed the study. Using analysis of covariance with 3-month assessment as the outcome and baseline assessment as a covariate, intervention group caregivers had an average ZBI (primary outcome) score 1.2 standard deviation (SD) lower (= .02) and Patient Health Questionnaire-4 (psychological distress) score 0.7 SD lower (= .03) than controls.

Discussion: In the first study of its kind in Vietnam, a culturally adapted, manualized, family caregiver intervention was both efficacious and feasible.
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http://dx.doi.org/10.1002/trc2.12063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825546PMC
January 2021

Change in Compliance of Staff at 4 Vietnam Universities after the Enactment of Smoke-free Environment Decree.

Environ Health Insights 2020 6;14:1178630220972957. Epub 2020 Dec 6.

University of Queensland, Saint Lucia, Australia.

Background: The Tobacco Control Law in Vietnam was adopted in 2012 and came into force from May 2013, followed by a number of guiding sub-law legal documents. Smoke-free campus policy in university is considered an important measure to protect people from secondhand smoking as well as staffs and students will be in favour of the policy. Furthermore, there has been evidence suggested that smoke-free policy had positive impact on active smoking as well as anti-smoking attitude.

Methods: A cross-sectional self-administered study of staff at 4 universities were conducted in 2 phases, Phase 1 as early introduction of the Law (n = 900) and Phase 2 as 1-year post (n = 885). Demographics, tobacco consumption, compliance status and compliance with awareness towards the campus smoking regulations were assessed in both phases.

Results: Daily smoking prevalence decreased significantly ( < .05) 1 year after implementing the smoke-free policy, while a significant increase in occasional smoking ( < .01). Compliance of staff to the regulation the campus should be indoor smoke-free was significantly increase at Phase 2 compared to Phase 1, however participants reported there would be places on campus that smokers frequently violated the smoke-free regulations.

Conclusions: The study indicated a significant positive change in compliance of staff at the 4 universities after the implementation of the Tobacco Control Law, included the smoke-free policy. Although the prevalence of tobacco smoking in this study was low, the proportion of respondents who reported to reduce infringement the smoke-free policy suggests support for staff smokers would be beneficial. Raising awareness and enforcement is likely to enhance the long-term outcomes of the implementation of smoke-free environment.
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http://dx.doi.org/10.1177/1178630220972957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724396PMC
December 2020

Treatment of complex complications after choledochal cyst resection by multiple minimal invasive therapies: A case report.

Int J Surg Case Rep 2020 11;73:130-133. Epub 2020 Jul 11.

Department of Hepatobiliary Surgery, Vietnam Germany Hospital, Hanoi, Viet Nam. Electronic address:

Introduction: Choledochal cyst is a rare benign congenital dilation of the bile duct, which causes recurring disturbing symptoms without totally resection. Nonetheless, postoperative complications are still a common issue. A step up management for patients with complex complications is required to address the problem.

Case Presentation: We report a 10-year-old child who suffered complex postoperative complications after choledochal cyst resection at the age of 5, including cholangitis, bilioenteric stenosis and cystolithiasis in remnant intrapancreatic duct cyst. She occasionally endured episodes of epigastric pain, fever and jaundice afterwards. As the symptoms and recurrent rate were worsen over time, the patient was admitted multiple times and various approaches (balloon dilation, percutaneous transhepatic biliary drainage, endoscopic retrograde cholangiopancreatography and laparoscopic surgery) were applied. Afterwards, patient recovered and discharged without any complications.

Conclusion: Our case presented sophisticated complications relating to choledochal cyst that were successfully treated by a combination of modern minimal invasive techniques. Despite operated by experienced surgeons, the post-op complications are still a concerned problem due to difficult laparoscopic techniques, injuries of hepatic artery, infection and risk of malignancy. We suggested that minimal-invasive procedures should be considered first with the aim of relieving symptoms, biliary drainage and preparing for the reoperation.
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http://dx.doi.org/10.1016/j.ijscr.2020.06.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365958PMC
July 2020

Stress, anxiety and depression in clinical nurses in Vietnam: a cross-sectional survey and cluster analysis.

Int J Ment Health Syst 2019 3;13. Epub 2019 Jan 3.

1Faculty of Environmental and Occupational Health, Hanoi University of Public Health, 1A Duc Thang Road, Duc Thang Ward, North Tu Liem District, Hanoi, Vietnam.

Background: Hospital nurses are exposed to various work-related factors that may be associated with increased risk of developing different mental disorders. Empirical evidence on the prevalence and correlates of individual mental health problems such as stress, anxiety and depression is widely reported, while a combined pattern of these conditions is unknown. This study aims to examine the co-occurrence of stress, anxiety and depression among clinical nurses, and to explore socio-demographic characteristics of, and working conditions experienced by, nurses that may be associated with these three mental health conditions.

Methods: A cross-sectional study was implemented in one tertiary hospital in Hanoi city, Vietnam, from May to September 2015. A self-reported questionnaire including a short version of the Depression, Anxiety and Stress scale 21 items and questions on demographic and work-related characteristics was delivered to 787 registered nurses. 600 completed questionnaires was used in the final analysis (76.2% response rate). The two-step clustering analysis was performed to identify sub groups. Chi square test and post hoc ANOVA analysis with Bonferroni correction were used to examine differences in psychological status, demographic characteristics and working conditions among the clusters (two-tailed p < 0.05).

Results: The prevalence of self-reported stress, anxiety and depression were 18.5%, 39.8% and 13.2%, respectively. 45.3% participants reported symptoms of at least one mental disorder, 7.3% had all three. Nurses in the first cluster (high prevalence of mental disorders), had high task demand and conflict at work with low job control and reward. The second cluster nurses (moderate percentage of mental strain) were significantly older and in marital relationship, high task demand and job control, and presence of chronic diseases. The lowest proportion of self-perceived mental disorders were observed in the cluster three who were younger and had fewer years of services, moderate task demand and low job control and better physical health in comparison with those in the other two clusters (p < 0.05).

Conclusions: Stress, anxiety and depression were prevalent among clinical nurses. Heterogeneity in demographic characteristics and working conditions were observed across clusters with different patterns of mental disorders. Institutional effort should be emphasized to support nurses in their career development to reduce psychological strains.
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http://dx.doi.org/10.1186/s13033-018-0257-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317201PMC
January 2019

Salience and Impact of Health Warning Label on Cigarette Packs in Vietnam: Findings From the Global Adult Tobacco Survey 2015.

Behav Med 2019 Jan-Mar;45(1):30-39. Epub 2018 Apr 13.

a Hanoi University of Public Health , Hanoi , Vietnam.

Viet Nam is among the countries having highest rate of male smokers in the world. The country has joined the Global Tobacco Surveillance System since 2010. Under this system, two rounds of Global Adult Tobacco Survey (GATS) were conducted in 2010 and 2015. Those two surveys provide excellent comparable data on tobacco usage and its related aspects in Vietnam. This study using the data from GATS 2015 to examine the salience and impact of cigarette pack health warnings on quitting intention in Vietnam. The Vietnam GATS 2015 was a nationally representative survey in which 9,513 households were selected using two-stage random systematic sampling method. Results of multivariate analysis showed that the strongest predictor for quit intention because of health warnings was "ever made a quit attempt in the past 12 months" followed by "believes that tobacco smoking causes serious illness". Compared to GATS 2010, GATS 2015 observed the increase in salience of cigarette health warnings. However, the current pictorial health warnings are losing their impact on motivating intention to quit. The results highlight that it is time to start the rotation cycle to refresh the current health warning set. Actions to select a new and more impressive set of pictorial health warnings should be developed as soon as possible.
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http://dx.doi.org/10.1080/08964289.2018.1434117DOI Listing
August 2019

Characteristics of greenhouse gas emissions from an anaerobic wastewater treatment system in a natural rubber processing factory.

Environ Technol 2019 Sep 11;40(22):2954-2961. Epub 2018 Apr 11.

g Department of Science of Technology Innovation, Nagaoka University of Technology , Nagaoka , Japan.

Greenhouse gas (GHG) emissions from both open-type and closed anaerobic wastewater treatment systems in a natural rubber processing factory in Vietnam were surveyed. In this factory, wastewater was treated by an open-type anaerobic baffled reactor (OABR) that comprised 60 compartments. A part of the wastewater was fed to a pilot-scale up-flow anaerobic sludge blanket (UASB) reactor to enable a comparison of the process performance and GHG emission characteristics with those of the OABR. In the OABR, 94.4% of the total chemical oxygen demand (COD) and 18.1% of ammonia nitrogen was removed. GHGs emitted from the OABR included both methane and nitrous oxide. The total GHGs emitted from the OABR was 0.153 t-COeq/m-wastewater. Nitrous oxide accounted for approximately 65% of the total GHGs emitted from the OABR. By contrast, 99.6% of the methane emission and 99.9% of nitrous oxide emission were reduced by application of the UASB. However, the ammonia removal efficiency of the UASB was only 2.2%. Furthermore, , which is known as a heterotrophic ammonia remover, was detected only in the OABR. These results indicated that high nitrous oxide emissions were caused by denitrification in the OABR and that application of the closed anaerobic system could drastically reduce the emissions of both methane and nitrous oxide.
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http://dx.doi.org/10.1080/09593330.2018.1459872DOI Listing
September 2019

Performance evaluation of the pilot scale upflow anaerobic sludge blanket - Downflow hanging sponge system for natural rubber processing wastewater treatment in South Vietnam.

Bioresour Technol 2017 Aug 7;237:204-212. Epub 2017 Mar 7.

Department of Civil and Environmental Engineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan; Department of Science of Technology Innovation, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan. Electronic address:

A pilot-scale upflow anaerobic sludge blanket (UASB)-downflow hanging sponge system (DHS) combined with an anaerobic baffled reactor (ABR) and a settling tank (ST) was installed in a natural rubber processing factory in South Vietnam and its process performance was evaluated for 267days. The UASB reactor achieved a total removal efficiency of 55.6±16.6% for chemical oxygen demand (COD) and 77.8±10.3% for biochemical oxygen demand (BOD) with an organic loading rate of 1.7±0.6kg-COD·m·day. The final effluent of the proposed system had 140±64mg·L of total COD, 31±12mg·L of total BOD, and 58±24mg-N·L of total nitrogen. The system could significantly reduce 92% of greenhouse gas emissions and 80% of hydraulic retention times compared with current treatment systems.
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http://dx.doi.org/10.1016/j.biortech.2017.02.058DOI Listing
August 2017

Development of downflow hanging sponge (DHS) reactor as post treatment of existing combined anaerobic tank treating natural rubber processing wastewater.

Water Sci Technol 2017 Jan;75(1-2):57-68

Department of Civil and Environmental Systems Engineering, Nagaoka University of Technology, 1603-1, Kamitomioka, Nagaoka, Niigata 940-2188, Japan E-mail: Department of Science of Technology Innovation, Nagaoka University of Technology, 1603-1, Kamitomioka, Nagaoka, Niigata 940-2188, Japan.

Conventional aerated tank technology is widely applied for post treatment of natural rubber processing wastewater in Southeast Asia; however, a long hydraulic retention time (HRT) is required and the effluent standards are exceeded. In this study, a downflow hanging sponge (DHS) reactor was installed as post treatment of anaerobic tank effluent in a natural rubber factory in South Vietnam and the process performance was evaluated. The DHS reactor demonstrated removal efficiencies of 64.2 ± 7.5% and 55.3 ± 19.2% for total chemical oxygen demand (COD) and total nitrogen, respectively, with an organic loading rate of 0.97 ± 0.03 kg-COD m day and a nitrogen loading rate of 0.57 ± 0.21 kg-N m day. 16S rRNA gene sequencing analysis of the sludge retained in the DHS also corresponded to the result of reactor performance, and both nitrifying and denitrifying bacteria were detected in the sponge carrier. In addition, anammox bacteria was found in the retained sludge. The DHS reactor reduced the HRT of 30 days to 4.8 h compared with the existing algal tank. This result indicates that the DHS reactor could be an appropriate post treatment for the existing anaerobic tank for natural rubber processing wastewater treatment.
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http://dx.doi.org/10.2166/wst.2016.487DOI Listing
January 2017

New strategy toward dioxin risk reduction for local residents surrounding severe dioxin hotspots in Vietnam.

Glob Health Action 2013 Jun 20;6:21105. Epub 2013 Jun 20.

Environmental Health Department, Hanoi School of Public Health, Hanoi, Vietnam.

Background: A public health intervention program with active involvement of local related stakeholders was piloted in the Bien Hoa dioxin hotspot (2007-2009), and then expanded to the Da Nang dioxin hotspot in Vietnam (2009-2011). It aimed to reduce the risk of dioxin exposure of local residents through foods. This article presents the results of the intervention in Da Nang.

Methodology: To assess the results of this intervention program, pre- and post-intervention knowledge, attitude, and practice (KAP) surveys were implemented in 400 households, randomly selected from four wards surrounding the Da Nang Airbase in 2009 and 2011, respectively.

Results: After the intervention, the knowledge on the existence of dioxin in food, dioxin exposure pathways, potential high-risk foods, and preventive measures significantly increased (P<0.05). Ninety-eight percent were willing to follow advice on preventing dioxin exposure. Practices to reduce the risk of dioxin exposure also significantly improved (P<0.05). After intervention, 60.4% of households undertook exposure preventive measures, significantly higher than that of the pre-intervention survey (39.6%; χ(2)=40.15, P<0.001). High-risk foods had quite low rates of daily consumption (from 0 to 2.5%) and were significantly reduced (P<0.05).

Conclusions: This is seen as an effective intervention strategy toward reducing the risk of human exposure to dioxin at dioxin hotspots. While greater efforts are needed for remediating dioxin-polluted areas inside airbases, there is also evidence to suggest that, during the past four decades, pollution has expanded to the surrounding areas. For this reason, this model should be quickly expanded to the remaining dioxin hotspots in Vietnam to further reduce the exposure risks in other areas.
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http://dx.doi.org/10.3402/gha.v6i0.21105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689901PMC
June 2013

Environmental health risk assessment of dioxin exposure through foods in a dioxin hot spot-Bien Hoa City, Vietnam.

Int J Environ Res Public Health 2010 05 14;7(5):2395-406. Epub 2010 May 14.

Hanoi School of Public Health, Hanoi, Vietnam.

This study used the Australian Environmental Health Risk Assessment Framework to assess the human health risk of dioxin exposure through foods for local residents in two wards of Bien Hoa City, Vietnam. These wards are known hot-spots for dioxin and a range of stakeholders from central government to local levels were involved in this process. Publications on dioxin characteristics and toxicity were reviewed and dioxin concentrations in local soil, mud, foods, milk and blood samples were used as data for this risk assessment. A food frequency survey of 400 randomly selected households in these wards was conducted to provide data for exposure assessment. Results showed that local residents who had consumed locally cultivated foods, especially fresh water fish and bottom-feeding fish, free-ranging chicken, duck, and beef were at a very high risk, with their daily dioxin intake far exceeding the tolerable daily intake recommended by the WHO. Based on the results of this assessment, a multifaceted risk management program was developed and has been recognized as the first public health program ever to have been implemented in Vietnam to reduce the risks of dioxin exposure at dioxin hot-spots.
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http://dx.doi.org/10.3390/ijerph7052395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898056PMC
May 2010

Deficiency in the divalent metal transporter 1 increases bleomycin-induced lung injury.

Biometals 2010 Aug 25;23(4):657-67. Epub 2010 Mar 25.

Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX 78229, USA.

Exposure to bleomycin can result in an inflammatory lung injury. The biological effect of this anti-neoplastic agent is dependent on its coordination of iron with subsequent oxidant generation. In lung cells, divalent metal transporter 1 (DMT1) can participate in metal transport resulting in control of an oxidative stress and tissue damage. We tested the postulate that metal import by DMT1 would participate in preventing lung injury after exposure to bleomycin. Microcytic anemia (mk/mk) mice defective in DMT1 and wild-type mice were exposed to either bleomycin or saline via intratracheal instillation and the resultant lung injury was compared. Twenty-four h after instillation, the number of neutrophils and protein concentrations after bleomycin exposure were significantly elevated in the mk/mk mice relative to the wild-type mice. Similarly, levels of a pro-inflammatory mediator were significantly increased in the mk/mk mice relative to wild-type mice following bleomycin instillation. Relative to wild-type mice, mk/mk mice demonstrated lower non-heme iron concentrations in the lung, liver, spleen, and splenic, peritoneal, and liver macrophages. In contrast, levels of this metal were elevated in alveolar macrophages from mk/mk mice. We conclude that DMT1 participates in the inflammatory lung injury after bleomycin with mk/mk mice having increased inflammation and damage following exposure. This finding supports the hypothesis that DMT1 takes part in iron detoxification and homeostasis in the lung.
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http://dx.doi.org/10.1007/s10534-010-9326-0DOI Listing
August 2010

The genome sequence of taurine cattle: a window to ruminant biology and evolution.

Science 2009 Apr;324(5926):522-8

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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http://dx.doi.org/10.1126/science.1169588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200PMC
April 2009

Antisense transcripts are targets for activating small RNAs.

Nat Struct Mol Biol 2008 Aug 6;15(8):842-8. Epub 2008 Jul 6.

Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.

Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) has been obscure. Other work has revealed noncoding transcripts that overlap mRNAs. The function of these noncoding transcripts is also not understood. Here we link these two sets of enigmatic results. We find that antisense transcripts are the target for agRNAs that activate or repress expression of progesterone receptor (PR). agRNAs recruit Argonaute proteins to PR antisense transcripts and shift localization of the heterogeneous nuclear ribonucleoprotein-k, RNA polymerase II and heterochromatin protein 1 gamma. Our data demonstrate that antisense transcripts have a central role in recognition of the PR promoter by both activating and inhibitory agRNAs.
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http://dx.doi.org/10.1038/nsmb.1444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574822PMC
August 2008

Hepcidin expression and iron transport in alveolar macrophages.

Am J Physiol Lung Cell Mol Physiol 2006 Sep 28;291(3):L417-25. Epub 2006 Apr 28.

Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, 78229, USA.

Alveolar macrophages express many proteins important in iron homeostasis, including the iron importer divalent metal transport 1 (DMT1) and the iron exporter ferroportin 1 (FPN1) that likely participate in lung defense. We found the iron regulatory hormone hepcidin (HAMP) is also produced by alveolar macrophages. In mouse alveolar macrophages, HAMP mRNA was detected at a low level when not stimulated but at a high level when exposed to lipopolysaccharide (LPS). LPS also affected the mRNA levels of the iron transporters, with DMT1 being upregulated and FPN1 downregulated. However, iron had no effect on HAMP expression but was able to upregulate both DMT1 and FPN1 in alveolar macrophages. IL-1 and IL-6, which are important in HAMP augmentation in hepatocytes, also did not affect HAMP expression in alveolar macrophages. In fact, the LPS-induced alterations in the expression of HAMP as well as DMT1 and FPN1 were preserved in the alveolar macrophages isolated from IL-1 receptor or IL-6-deficient mice. When alveolar macrophages were loaded with transferrin-bound (55)Fe, the subsequent release of (55)Fe was inhibited significantly by LPS. In addition, treatment of these cells with either LPS or HAMP caused the diminishment of the surface FPN1. These findings are consistent with the current model that HAMP production leads to a decreased iron efflux. Our studies suggest that iron mobilization by alveolar macrophages can be affected by iron and LPS via several pathways, including HAMP-mediated degradation of FPN1, and that these cells may use unique regulatory mechanisms to cope with iron imbalance in the lung.
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http://dx.doi.org/10.1152/ajplung.00484.2005DOI Listing
September 2006

The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa.

BMC Physiol 2006 Jan 18;6. Epub 2006 Jan 18.

Department of Physiology, The University Oklahoma Health Sciences Center, Oklahoma City, USA.

Background: An organ such as the bladder consists of complex, interacting set of tissues and cells. Inflammation has been implicated in every major disease of the bladder, including cancer, interstitial cystitis, and infection. However, scanty is the information about individual detrusor and urothelium transcriptomes in response to inflammation. Here, we used suppression subtractive hybridizations (SSH) to determine bladder tissue- and disease-specific genes and transcriptional regulatory elements (TRE)s. Unique TREs and genes were assembled into putative networks.

Results: It was found that the control bladder mucosa presented regulatory elements driving genes such as myosin light chain phosphatase and calponin 1 that influence the smooth muscle phenotype. In the control detrusor network the Pax-3 TRE was significantly over-represented. During development, the Pax-3 transcription factor (TF) maintains progenitor cells in an undifferentiated state whereas, during inflammation, Pax-3 was suppressed and genes involved in neuronal development (synapsin I) were up-regulated. Therefore, during inflammation, an increased maturation of neural progenitor cells in the muscle may underlie detrusor instability. NF-kappaB was specifically over-represented in the inflamed mucosa regulatory network. When the inflamed detrusor was compared to control, two major pathways were found, one encoding synapsin I, a neuron-specific phosphoprotein, and the other an important apoptotic protein, siva. In response to LPS-induced inflammation, the liver X receptor was over-represented in both mucosa and detrusor regulatory networks confirming a role for this nuclear receptor in LPS-induced gene expression.

Conclusion: A new approach for understanding bladder muscle-urothelium interaction was developed by assembling SSH, real time PCR, and TRE analysis results into regulatory networks. Interestingly, some of the TREs and their downstream transcripts originally involved in organogenesis and oncogenesis were also activated during inflammation. The latter represents an additional link between inflammation and cancer. The regulatory networks represent key targets for development of novel drugs targeting bladder diseases.
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http://dx.doi.org/10.1186/1472-6793-6-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1382248PMC
January 2006

Regulation of hepcidin and ferroportin expression by lipopolysaccharide in splenic macrophages.

Blood Cells Mol Dis 2005 Jul-Aug;35(1):47-56

Audie Murphy Veterans Administration Hospital, South Texas Veterans Health Care System, San Antonio, San Antonio, TX 78229, USA.

Acute and chronic inflammatory states are associated with many changes in intracellular iron metabolism including sequestration of iron in the mononuclear-phagocyte system (MPS) and a decline in serum iron. Previous work in rodent models of acute inflammation has demonstrated inflammation-induced downregulation of intestinal and MPS iron exporter, ferroportin 1, mRNA and protein. In addition, these models have also demonstrated hepatic induction of mRNA of the small 25 amino acid peptide hepcidin. Hepcidin has been hypothesized to be the mediator of iron- and inflammation-induced changes in iron metabolism. The molecular details of the connection between iron metabolism, hepcidin and inflammation have become clearer with the recent finding of hepcidin-induced internalization and degradation of FPN1. The work presented here demonstrates that the lipopolysaccharide-induced splenic macrophage FPN1 mRNA downregulation is not dependent upon the action of a single cytokine such as IL-6, IL-1 or TNF-alpha because mice deficient in these pathways downregulate FPN1 normally. Furthermore, hepcidin is also synthesized in the spleen of normal mice and induced by lipopolysaccharide. Additionally, in vitro, splenic adherent cells produce hepcidin in response to lipopolysaccharide in an IL-6-dependent manner. There appear to be both probable transcriptional and post-transcriptional control of FPN1 expression by lipopolysaccharide-induced inflammation. The former effect is on mRNA expression and is independent of hepcidin, whereas the latter is IL-6- and hepcidin-dependent.
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http://dx.doi.org/10.1016/j.bcmd.2005.04.006DOI Listing
October 2005

Gene expression profiling of inflammatory bladder disorders.

Expert Rev Mol Diagn 2003 Mar;3(2):217-35

Department of Physiology, College of Medicine, OUHSC, Oklahoma City, Ok 73190, USA.

Inflammation underlies all major bladder pathologies including malignancy and represents a defense reaction to injury caused by physical damage, chemical substances, micro-organisms or other agents. During acute inflammation, activation of specific molecular pathways leads to an increased expression of selected genes whose products attack the insult, but ultimately should protect the tissue from the noxious stimulus. However, once the stimulus ceases, gene-expression should return to basal levels to avoid tissue damage, fibrosis, loss of function, and chronic inflammation. If this down-regulation does not occur, tissue fibrosis occurs as a serious complication of chronic inflammation. Although sensory nerve and most cells products are known to be key parts of the inflammatory puzzle, other key molecules are constantly being described that have a role in bladder inflammation. Therefore, as the database describing the repertoire of inflammatory mediators implicated in bladder inflammation increases, the central mechanisms by which injury can induce inflammation, cell damage, and repair often becomes less rather than more clear. To make sense of the vast knowledge of the genes involved in the inflammatory response may require analysis of the patterns of change and the elucidation of gene networks far more than definition of additional members of inflammatory cascades. This review discuss the appropriate use of microarray technology, which promises to solve both of these problems as well as identifying key molecules and mechanisms involved in the transition between acute and chronic inflammation.
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http://dx.doi.org/10.1586/14737159.3.2.217DOI Listing
March 2003

Expression of protease-activated receptor-1, -2, -3, and -4 in control and experimentally inflamed mouse bladder.

Am J Pathol 2003 Mar;162(3):907-23

Johnson and Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania, USA.

Inflammation underlines all major bladder pathologies and represents a defense reaction to injury involving a mandatory participation of mast cells and sensory nerves. Mast cells are particularly frequent in close proximity to epithelial surfaces where they are strategically located in the bladder and release their mediators in response to inflammation. Tryptase is specifically produced by mast cells and modulates inflammation by activating protease-activated receptors (PARs). We recently found that PAR-4 mRNA is up-regulated in experimental bladder inflammation regardless of the initiating stimulus. Because it has been reported that PAR-1, PAR-2, and PAR-3 may also be involved in the processes of inflammation, we used immunohistochemistry to characterize the expression of all known PARs in normal, acute, and chronic inflamed mouse bladder. We found that all four PARs are present in the control mouse bladder, and follow a unique distribution. All four PARs are co-expressed in the urothelium, whereas PAR-1 and PAR-2 are predominant in the detrusor muscle, and PAR-4 is expressed in peripheral nerves and plexus cell bodies. The strong expression of PARs in the detrusor muscle indicates the need for studies on the role of these receptors in motility whereas the presence of PAR-4 in nerves may indicate its participation in neurogenic inflammation. In addition, PARs are differentially modulated during inflammation. PAR-1 and PAR-2 are down-regulated in acute inflammation whereas PAR-3 and PAR-4 are up-regulated. Bladder fibroblasts were found to present a clear demarcation in PAR expression secondary to acute and chronic inflammation. Our findings provide evidence of participation of PARs in the urinary system, provide a working model for mast cell tryptase signaling in the mouse bladder, and evoke testable hypotheses regarding the roles of PARs in bladder inflammation. It is timely to understand the role of tryptase signaling and PARs in the context of bladder biology.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868088PMC
http://dx.doi.org/10.1016/S0002-9440(10)63886-2DOI Listing
March 2003

Neurokinin 1 receptors and neprilysin modulation of mouse bladder gene regulation.

Physiol Genomics 2003 Feb 6;12(3):239-50. Epub 2003 Feb 6.

Oklahoma Medical Research Foundation, Microarray Research Facility, Oklahoma City, USA.

Neurokinin 1 (NK(1)) receptors play a fundamental role in neurogenic inflammation. We sought to determine the mechanisms downstream from NK(1) receptor (NK(1)R) activation using cDNA arrays and a novel statistical method to analyze gene expression. We used female NK(1)R(-/-) and wild-type (WT) mice that were sensitized actively by intraperitoneal injections of dinitrophenol 4 (DNP(4))-human serum albumin. Cystitis was induced by intravesical instillation of antigen of DNP(4)-ovalbumin, and control mice were challenged with saline. At 1, 4, and 24 h after instillation, bladders were removed for 1) RNA extraction (n = 3), 2) replicate of RNA extraction (n = 3), and 3) morphological analysis (n = 6). For cDNA array experiments, three bladders from each group were homogenized, and total RNA was obtained. DNase-treated RNA was reverse-transcribed to cDNA, labeled with [alpha-(32)P]dATP and hybridized to Atlas Mouse 1.2 Arrays (Clontech). After calculating the mean and SD for background spots, each experimental value was assigned a normalized score S using the formula S' = (S - Av)/SD, where S' is the original pixel value, and Av and SD are the mean and standard deviation of background spots, respectively. Only genes that expressed 3 SD values above background were used. Hypervariable genes were sorted by cluster analysis. Matrices of correlation coefficients were calculated and represented in a connectivity mosaic. As results, we found that in WT mice the most prominent gene cluster had neprilysin in a central position and positively correlated to a group of activator protein-1 (AP-1)-responsive genes, including laminin-alpha3, tissue plasminogen activator 11, fos-B, and TNF-beta. In WT mice, antigen-induced bladder inflammation led to a downregulation in neprilysin expression. In contrast, NK(1)R(-/-) mice failed to mount an inflammatory reaction and presented neprilysin negatively correlated with the same genes described in WT. In conclusion, this work indicates an overriding participation of NK(1)R and neprilysin in bladder inflammation, provides a working model for the involvement of AP-1 transcription factor, and evokes testable hypotheses regarding the role of NK(1)R and neprilysin in inflammation.
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http://dx.doi.org/10.1152/physiolgenomics.00141.2002DOI Listing
February 2003

Mast cells mediate substance P-induced bladder inflammation through an NK(1) receptor-independent mechanism.

Am J Physiol Renal Physiol 2002 Oct;283(4):F616-29

Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.

The role of neurokinin-1 receptors (NK1R) in the interaction between mast cells and substance P (SP) in bladder inflammation was determined. Mast cell-deficient Kit(W)/Kit(W-v), congenic normal (+/+), and Kit(W)/Kit(W-v) mice that were reconstituted with bone marrow cells isolated from NK1R(-/-) mice were challenged by instillation of SP, antigen, or saline into the urinary bladder. Twenty-four hours after challenge, the bladders were prepared for morphological assessment and gene expression. SP-induced bladder inflammation was mast cell dependent and did not require NK1R expression on the mast cell. Cluster analysis identified functionally significant genes that were dependent on the presence of mast cells for their upregulation regardless of stimulus. Those include serine protein inhibitor 2.2, maspin, mitogen- and stress-activated protein kinase 2, and macrophage colony-stimulating factor 1. Our findings demonstrate that while mast cells are essential for both antigen- and SP-induced bladder inflammation, there are common genes and unique genes expressed in each type of inflammatory reaction. When combined with unique animal models, gene array analysis provides a useful approach for identifying and characterizing pathways involved in bladder inflammation.
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http://dx.doi.org/10.1152/ajprenal.00096.2002DOI Listing
October 2002

Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation.

Am J Pathol 2002 Jun;160(6):2095-110

Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.

Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and is characterized by severe pain, increased frequency of micturition, and chronic inflammation. Characterizing the molecular fingerprint (gene profile) of IC will help elucidate the mechanisms involved and suggest further approaches for therapeutic intervention. Therefore, in the present study we used established animal models of cystitis to determine the time course of bladder inflammatory responses to antigen, Escherichia coli lipopolysaccharide (LPS), and substance P (SP) by morphological analysis and cDNA microarrays. The specific aim of the present study was to compare bladder inflammatory responses to antigen, LPS, and SP by morphological analysis and cDNA microarray profiling to determine whether bladder responses to inflammation elicit a specific universal gene expression response regardless of the stimulating agent. During acute bladder inflammation, there was a predominant infiltrate of polymorphonuclear neutrophils into the bladder. Time-course studies identified early, intermediate, and late genes that were commonly up-regulated by all three stimuli. These genes included: phosphodiesterase 1C, cAMP-dependent protein kinase, iNOS, beta-NGF, proenkephalin B and orphanin, corticotrophin-releasing factor (CRF) R, estrogen R, PAI2, and protease inhibitor 17, NFkB p105, c-fos, fos-B, basic transcription factors, and cytoskeleton and motility proteins. Another cluster indicated genes that were commonly down-regulated by all three stimuli and included HSF2, NF-kappa B p65, ICE, IGF-II and FGF-7, MMP2, MMP14, and presenilin 2. Furthermore, we determined gene profiles that identify the transition between acute and chronic inflammation. During chronic inflammation, the urinary bladder presented a predominance of monocyte/macrophage infiltrate and a concomitant increase in the expression of the following genes: 5-HT 1c, 5-HTR7, beta 2 adrenergic receptor, c-Fgr, collagen 10 alpha 1, mast cell factor, melanocyte-specific gene 2, neural cell adhesion molecule 2, potassium inwardly-rectifying channel, prostaglandin F receptor, and RXR-beta cis-11-retinoic acid receptor. We conclude that microarray analysis of genes expressed in the bladder during experimental inflammation may be predictive of outcome. Further characterization of the inflammation-induced gene expression profiles obtained here may identify novel biomarkers and shed light into the etiology of cystitis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850812PMC
http://dx.doi.org/10.1016/S0002-9440(10)61159-5DOI Listing
June 2002
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