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2008

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Full-Text Articles in Medicine and Health Sciences

Download Entire Pdf Prescriptions For Excellence In Health Care-Spring 2008, Issue 3. Apr 2008

Download Entire Pdf Prescriptions For Excellence In Health Care-Spring 2008, Issue 3.

Prescriptions for Excellence in Health Care Newsletter Supplement

No abstract provided.


Chylopericardium--A Rare Complication After Ventricular Septal Defect Repair, Saqib A Gowani, Ameer A Khowaja, Asmatullah Khan, Saulat H Fatimi Apr 2008

Chylopericardium--A Rare Complication After Ventricular Septal Defect Repair, Saqib A Gowani, Ameer A Khowaja, Asmatullah Khan, Saulat H Fatimi

Section of Cardiothoracic Surgery

Chylopericardium is a rare complication of cardiac surgery. It may be caused by a lesion in the thoracic duct or its tributaries or by thrombosis in the confluence of the jugular and left subclavian veins, obstructing the drainage of the thoracic duct. The treatment may be conservative or surgical, depending on the duration and on the volume of the effusion. We report the case of a 1 1/2 year-old male, who, in the late postoperative period of VSD repair, was hospitalized with low-grade fever and breathlessness for one week due to the presence of chylopericardium. The clinical findings and treatment …


Application Of The Asset Mapping Model To Church Based Hiv/Aids Prevention And Control In Aba, Abia State, Nigeria, Godwin Nwadibia Aja Apr 2008

Application Of The Asset Mapping Model To Church Based Hiv/Aids Prevention And Control In Aba, Abia State, Nigeria, Godwin Nwadibia Aja

Loma Linda University Electronic Theses, Dissertations & Projects

This study examined whether HIV/AIDS activities were more frequent among churches with needs and assets for HIV/AIDS prevention and control in Aba, Nigeria and whether this connection was mediated by collective efficacy. A cross-sectional design was used to obtain data in two phases. First, a three-step forum focus group discussion (FFGD) method was used to obtain data from 32 representatives of five denominations. Second, a quantitative survey questionnaire was constructed based on the result of the FFGD and the collective efficacy model. This questionnaire was administered to 830 members aged 18 years and above from 83 churches that had operated …


An Experimental Juvenile Probation Program: Effects On Parent And Peer Relationships, Eve M. Brank, Jodi Lane, Susan Turner, Terry Fain, Amber Sehgal Apr 2008

An Experimental Juvenile Probation Program: Effects On Parent And Peer Relationships, Eve M. Brank, Jodi Lane, Susan Turner, Terry Fain, Amber Sehgal

Department of Psychology: Faculty Publications

In an effort to provide a wider range of services to youth and their families than is traditionally available in routine probation, the South Oxnard Challenge Project (SOCP) employed a team approach to service delivery of an intensive probation program. The researchers interviewed juveniles who were randomly assigned to either the SOCP experimental condition or the control condition of a routine probation program. The intensive probation program, among other goals, focused on improving parent-child relationships and teaching youth how to choose better peers. At 1 year post random assignment, experimental and control youth were not significantly different on key family …


Self-Medication Amongst University Students Of Karachi: Prevalence, Knowledge And Attitudes, Syed Nabeel Zafar, Reema Syed, Sana Waqar, Akbar Jaleel Zubairi, Talha Vaqar, Mehrine Shaikh, Wajeeha Yousaf, Saman Shahid, Sarah Saleem Apr 2008

Self-Medication Amongst University Students Of Karachi: Prevalence, Knowledge And Attitudes, Syed Nabeel Zafar, Reema Syed, Sana Waqar, Akbar Jaleel Zubairi, Talha Vaqar, Mehrine Shaikh, Wajeeha Yousaf, Saman Shahid, Sarah Saleem

Community Health Sciences

OBJECTIVE: To determine the prevalence, attitude and knowledge of self-medication amongst university students of Karachi, Pakistan.

METHODS: This cross-sectional, study was conducted from Jan-Feb 2007. A convenience sample was taken from 2 medical and 2 non-medical universities of the city of Karachi, Pakistan. Data was analyzed using SPSS v 14 and associations were tested using the Chi square test.

RESULTS: Of the 572 participants (mean age=21 +/- 1.8 years, Male: Female ratio=1:1.5), 295 were medical and 277 were non-medical students. The prevalence of self-medication was 76%. Forty three percent students stated that they alter the regimen of prescribed medicines while …


Program Mitigasi Bagi Anak Terpapar Hiv/Aids, Fentiny Nugroho Apr 2008

Program Mitigasi Bagi Anak Terpapar Hiv/Aids, Fentiny Nugroho

Jurnal Ilmu Kesejahteraan Sosial

Mitigation services for children living with HIV/ AIDS who have done such as health and psychosocial services for children and also training and financial assistance for economic improvement for the child's parent Especially psychosocial services for children, not all agencies provide this service, so it's a service aspect that still needs to be developed. Mitigation model that has been done in general is family-based care, while community-based have limitations because there still exists the stigma from society. In implementation, the mitigation program experienced a number of obstacles, besides there is also a supporting factor


Types And Measurement Of Poverty In Australia, Isbandi Rukminto Adi Apr 2008

Types And Measurement Of Poverty In Australia, Isbandi Rukminto Adi

Jurnal Ilmu Kesejahteraan Sosial

During Millennium Summit 2000 the United Nations (UN) has declared the Millennium Development Goals. The UN acknowledges the importance of poverty problems. The first goal of MDGs is to eradicate extreme poverty and hunger The declaration also mentioned that proportion of people whose income is less than one dollar a day and people who suffer from hunger should decrease by half in 25 years (from 1990 to 2015) Related to poverty problems The 8th goal of MDGs is to develop a global partnership for development Global Partnership, in this case, could be seen by giving opportunities for people from developing …


Kebijakan Hiv/Aids Dan Prevention Mother To Child Transmision (Pmtct) Di Indonesia, Triyanti Anugrahini Apr 2008

Kebijakan Hiv/Aids Dan Prevention Mother To Child Transmision (Pmtct) Di Indonesia, Triyanti Anugrahini

Jurnal Ilmu Kesejahteraan Sosial

The various policies which related to HIV/AIDS in Indonesia is continue to be developed in line with the increasing number of HIV/AIDS cases in Indonesia since the cases were first found in 1987 By using the framework of a retrospective policy analysis (analysis of policy), this paper will review the formulation of the policy and its contents, seen from several dimensions that are interconnected with one another, ie the contents of the policy (content), national and international contextual conditions (context), policy-making (process) and the actors that play the role and influence in the policy-making (actors) Policy analysis is described based …


Pemahaman Bullying Di Sekolah, Fitriyah Fitriyah Apr 2008

Pemahaman Bullying Di Sekolah, Fitriyah Fitriyah

Jurnal Ilmu Kesejahteraan Sosial

This research was conducted to determine the understanding of the concept of bullying from the teachers, students and the perpetrator, the victim's parent and also the efforts to prevent bullying and the constraints to eliminate bullying in schools. This research was conducted with qualitative research approach and descriptive research with research sites in SMUN in South Jakarta. The survey results revealed that the school including teachers, perpetrators and victims of bullying and parents do not understand about bullying which is still a lot of bullying occurred at school However the school has sought to minimize with various efforts such as …


The Effect Of Acute Resistance Training On Resting Metabolic Rate In Men, Steven William Ball Apr 2008

The Effect Of Acute Resistance Training On Resting Metabolic Rate In Men, Steven William Ball

Masters Theses

The purpose of this study was to investigate the effect of different frequencies of resistance training on an individual's resting metabolic rate (RMR). Six healthy males between the ages of 18 and 35 participated in two separate trials. The first trial involved two full-body resistance training bouts, 48 hours apart with RMR measurements pre- and post-bout and a RMR measurement 24 hours following each. The second trial consisted of four split-body resistance training bouts on four consecutive mornings with RMR measurements pre- and post-bout each morning with a fifth morning for one final RMR measurement, 24 hours after the final …


Intracytoplasmic Sperm Injection Outcome Using Ejaculated Sperm And Retrieved Sperm In Azoospermic Men., Tahira Naru, M. Nasir Sulaiman, Atiya Kidwai, M. Hammad Ather, Sana Waqar, Saadia Virk, Javed H Rizvi Apr 2008

Intracytoplasmic Sperm Injection Outcome Using Ejaculated Sperm And Retrieved Sperm In Azoospermic Men., Tahira Naru, M. Nasir Sulaiman, Atiya Kidwai, M. Hammad Ather, Sana Waqar, Saadia Virk, Javed H Rizvi

Department of Obstetrics & Gynaecology

Introduction:We aimed to determine pregnancy and miscarriage rates following intracytoplasmic sperm injection (ICSI) cycles using retrieved epididymal and testicular sperm in azoospermic men and ejaculated sperm in oligospermic and normospermic men. Materials And
Methods: This retrospective study was carried out on 517 couples who underwent ICSI. They included 96 couples with azoospermia and 421 with oligospermia or normal sperm count in the male partner. Of the men with azoospermia, 69 underwent percutaneous epididymal aspiration (PESA) and 47 underwent testicular sperm extraction (TESE). In the 421 men with oligospermia or normal sperm count, ejaculated sperm was used for ICSI. The …


Frequency Of Various Types Of Headaches Inpostgraduate Medical Students Of A Tertiary Care Hospital, Sidra Aurangzeb, Muhammad Tariq, Ayesha Gul, Mehwish Hameed Apr 2008

Frequency Of Various Types Of Headaches Inpostgraduate Medical Students Of A Tertiary Care Hospital, Sidra Aurangzeb, Muhammad Tariq, Ayesha Gul, Mehwish Hameed

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.


Seasonal Variation And Sex Distribution Inpatients With Guillain-Barre Syndrome, Mohsin Zaheer, Muhammad Naeem, Muhammad Nasrullah Apr 2008

Seasonal Variation And Sex Distribution Inpatients With Guillain-Barre Syndrome, Mohsin Zaheer, Muhammad Naeem, Muhammad Nasrullah

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.


Hyperacute Extradural Hematoma Mimickingacute Subdural Hematoma, Amit Agrawal Apr 2008

Hyperacute Extradural Hematoma Mimickingacute Subdural Hematoma, Amit Agrawal

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.


Neurosurgery, Manzar Hussain Apr 2008

Neurosurgery, Manzar Hussain

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.


An Audit Of The Quality Of Care Indicators For The Management Of Diabetes In Family Practice Clinics In Karachi, Pakistan, Raheem H Dhanani, Mohammad Mustafa Qureshi, Ali Khan Khuwaja, Badar Sabir Ali, Riaz Qureshi Apr 2008

An Audit Of The Quality Of Care Indicators For The Management Of Diabetes In Family Practice Clinics In Karachi, Pakistan, Raheem H Dhanani, Mohammad Mustafa Qureshi, Ali Khan Khuwaja, Badar Sabir Ali, Riaz Qureshi

Department of Family Medicine

BACKGROUND: Management of diabetes is a painstaking and careful approach. This study was aimed to evaluate the quality of care for the management of diabetes provided by family practitioners to their patients having diabetes. This is a retrospective audit of medical records conducted in a tertiary care teaching hospital of private sector in Karachi for one month.

METHODS: For this study, 150 medical records of patients with type 2 diabetes that visited family practice clinics for their diabetes care were examined. A total of 88 patient's medical records were selected and analyzed who attended the studied clinics for at least …


Chediak-Higashi Syndrome, Emaduddin Siddiqui, Shaheena Hanif Apr 2008

Chediak-Higashi Syndrome, Emaduddin Siddiqui, Shaheena Hanif

Department of Emergency Medicine

Chediak Higashi Syndrome is a rare inherited autosomal recessive disorder of immune system. Susceptibility to infection due to phagocyte dysfunction ranges from recurrent skin infection to over whelming fatal systemic infection. A five years old male child was admitted on 31st March 2006 with the complaints of pallor, fever & ear discharge for 6 month. He was treated by several medications but had temporary relief. The ear discharge was bilateral, foul smelling and of yellowish color. Past history was significant with episodes of abscess involving the different parts of body. Myeloid precursors shows giant, purple stained granules mainly in metamyelocytes, …


Preventing Cardiovascular Disease In Kentucky: Epidemiology, Trends, And Strategies For The Future, Sarah Sartini Rugg, Alison L. Bailey, Steven R. Browning Apr 2008

Preventing Cardiovascular Disease In Kentucky: Epidemiology, Trends, And Strategies For The Future, Sarah Sartini Rugg, Alison L. Bailey, Steven R. Browning

Internal Medicine Faculty Publications

Cardiovascular disease (CVD) is the leading cause of death in the United States despite dramatic improvements in the treatment of heart disease in recent years. Kentucky leads the nation in the prevalence of several individual risk factors for cardiovascular disease, the prevalence of multiple risk factors, and in cardiovascular mortality. While trends in the prevalence of some of these cardiac risk factors have shown improvement, others have remained unchanged or have worsened. The increased prevalence of obesity and diabetes, especially among young persons, is one of the most worrisome trends. The prevalence of smoking in Kentucky remains high, and has …


Ocular Aberrations Wavefront Sensor In Clinical Application, Matthew Sheehan Apr 2008

Ocular Aberrations Wavefront Sensor In Clinical Application, Matthew Sheehan

Masters

A versatile Hartmann-Shack (HS) wavefront sensor (WFS) was designed and constructed. Its advantages include simultaneous pupil centre determination, off-axis capability, realtime data displays, and efficient lenslet sampling orientation. The instrument is compact and transportable, making it convenient for use in a clinical setting. Subject alignment is achieved by the use of a parallel channel that is recombined with the sensing channel to simultaneously image the external eye and the HS spots onto a single charge coupled device (CCD). The pupil centre is determined using this image of the eye, rather than the HS spots. Off-axis measurements are possible throughout an …


Implementing A Practice Doctorate Program At A Distance Through An Urban-Rural Partnership, Beth Ann Swan, Anthony J. Frisby, Lori S. Lauver, Margaret M. West, Mary Powell, Ksenia Zukowsky, Alexis Marsella Apr 2008

Implementing A Practice Doctorate Program At A Distance Through An Urban-Rural Partnership, Beth Ann Swan, Anthony J. Frisby, Lori S. Lauver, Margaret M. West, Mary Powell, Ksenia Zukowsky, Alexis Marsella

The Selected Works of Anthony J. Frisby, PhD

The purposes of this poster presentation are to 1) describe the implementation of a doctor of nursing practice (DNP) program by providing access to rigorous distance education to students living in rural Pennsylvania; 2) discuss building a critical mass of doctorally prepared advanced practice nurse experts in both urban and rural communities; and 3) share formative and summative evaluation information.

Through funding from the U.S. Department of Health and Human Services, Health Resources and Services Administration, Bureau of Health Professions, Division of Nursing, the Jefferson School of Nursing (JSN) expanded its DNP program currently offered at the urban Philadelphia campus …


Knowledge About Osteoporosis Among Healthy Women Attending A Tertiary Care Hospital, Mehmood Riaz, Naushad Abid, Muhammad Junaid Patel, M. Tariq, Muhammad Shoaib Khan, Lubna Zuberi Apr 2008

Knowledge About Osteoporosis Among Healthy Women Attending A Tertiary Care Hospital, Mehmood Riaz, Naushad Abid, Muhammad Junaid Patel, M. Tariq, Muhammad Shoaib Khan, Lubna Zuberi

Section of Internal Medicine

INTRODUCTION: To determinate the knowledge on osteoporosis-risk factors and disease in three age groups of Pakistani women.METHODS: In this exploratory cross-sectional study, an osteoporosis knowledge assessment questionnaire (OKAT) was used to collect data and it was delivered through a face-to-face interview. Questions were asked about symptoms of osteoporosis, knowledge of risk factors, preventive factors and treatment. A convenience sample (n =320) comprising of three groups of healthy women aged 25-35 years, 36-45 years, and over 45 years was taken. The scoring range was 0 to 20. Among-group comparisions of means were analyzed by two-way ANOVA. To determine the overall influence …


Ly2109761, A Novel Transforming Growth Factor Beta Receptor Type I And Type Ii Dual Inhibitor, As A Therapeutic Approach To Suppressing Pancreatic Cancer Metastasis, Davide Melisi, Satoshi Ishiyama, Guido M Sclabas, Jason B Fleming, Qianghua Xia, Giampaolo Tortora, James L Abbruzzese, Paul J Chiao Apr 2008

Ly2109761, A Novel Transforming Growth Factor Beta Receptor Type I And Type Ii Dual Inhibitor, As A Therapeutic Approach To Suppressing Pancreatic Cancer Metastasis, Davide Melisi, Satoshi Ishiyama, Guido M Sclabas, Jason B Fleming, Qianghua Xia, Giampaolo Tortora, James L Abbruzzese, Paul J Chiao

Faculty, Staff and Student Publications

Most pancreatic cancer patients present with inoperable disease or develop metastases after surgery. Conventional therapies are usually ineffective in treating metastatic disease. It is evident that novel therapies remain to be developed. Transforming growth factor beta (TGF-beta) plays a key role in cancer metastasis, signaling through the TGF-beta type I/II receptors (TbetaRI/II). We hypothesized that targeting TbetaRI/II kinase activity with the novel inhibitor LY2109761 would suppress pancreatic cancer metastatic processes. The effect of LY2109761 has been evaluated on soft agar growth, migration, invasion using a fibroblast coculture model, and detachment-induced apoptosis (anoikis) by Annexin V flow cytometric analysis. The efficacy …


Drinking-Water Arsenic Exposure Modulates Gene Expression In Human Lymphocytes From A U.S. Population, Angeline S. Andrew, David A. Jewell, Rebecca A. Mason, Michael L. Whitfield, Jason H. Moore, Margaret R. Karagas Apr 2008

Drinking-Water Arsenic Exposure Modulates Gene Expression In Human Lymphocytes From A U.S. Population, Angeline S. Andrew, David A. Jewell, Rebecca A. Mason, Michael L. Whitfield, Jason H. Moore, Margaret R. Karagas

Dartmouth Scholarship

Background:

Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 μg/L in the northeastern, western, and north central regions of the United States.

Objectives:

We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression.

Methods:

We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999–2002) …


Nursing In Uganda: My Summer Of Unexpected Discoveries, Emily Roberts Apr 2008

Nursing In Uganda: My Summer Of Unexpected Discoveries, Emily Roberts

Inquiry Journal 2008

No abstract provided.


Clear Cell Papillary Cystadenoma Of Epididymis, A Mimic Of Metastatic Renal Cell Carcinoma, Nausheen Yaqoob, Aamir Ahsan, Zubair Ahmad, Ambreen Nasir Khan Apr 2008

Clear Cell Papillary Cystadenoma Of Epididymis, A Mimic Of Metastatic Renal Cell Carcinoma, Nausheen Yaqoob, Aamir Ahsan, Zubair Ahmad, Ambreen Nasir Khan

Department of Pathology and Laboratory Medicine

We discuss a case of 25 year old male who was evaluated for primary infertility following marriage. He had no previous history of urogenital complaints or abnormalities. In fact, his past medical history was unremarkable. On examination epididymal masses were found. Semen analysis showed azoospermia. Right epididymal mass was surgically excised. Histopathology showed an epididymal neoplasm composed of simple and complex papillary processes lining and filling the ducts. The tumor cells were clear and positive for cytoplasmic glycogen. Immunohistochemistry was also supportive. Diagnosis of clear cell papillary cystedenoma was made based on histopathological and immunohistochemical features.


Adaptation Interventions To Promote Participation In Natural Settings, Philippa H. Campbell, Ph.D, Suzanne Milbourne, M.S, M. Jeanne Wilcox, Ph.D. Apr 2008

Adaptation Interventions To Promote Participation In Natural Settings, Philippa H. Campbell, Ph.D, Suzanne Milbourne, M.S, M. Jeanne Wilcox, Ph.D.

Department of Occupational Therapy Faculty Papers

Children's participation in everyday activities and routines in home and community settings is an important focus of services for infants and young children with disabilities. Data indicate that assistive technology (AT) is not widely used nor do early intervention service providers report frequent use of AT devices with infant-toddlers. Adaptation interventions combine environmental accommodations and AT in ways that promote children's participation in activities and routines and provide functional skill-building learning opportunities. A decision-making process for planning and implementing adaptation interventions is outlined with examples of strategies and formats that service providers can use to create successful interventions for infants …


Drug Metabolism In Human Brain: High Levels Of Cytochrome P4503a43 In Brain And Metabolism Of Anti-Anxiety Drug Alprazolam To Its Active Metabolite, Varsha Agarwal, Reddy P. Kommaddi, Khader Valli, Daniel Ryder, Thomas M. Hyde, Joel E. Kleinman, Henry W. Strobel, Vijayalakshmi Ravindranath Apr 2008

Drug Metabolism In Human Brain: High Levels Of Cytochrome P4503a43 In Brain And Metabolism Of Anti-Anxiety Drug Alprazolam To Its Active Metabolite, Varsha Agarwal, Reddy P. Kommaddi, Khader Valli, Daniel Ryder, Thomas M. Hyde, Joel E. Kleinman, Henry W. Strobel, Vijayalakshmi Ravindranath

Faculty, Staff and Student Publications

Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are …


Disruption Of C-Jun Reduces Cellular Migration And Invasion Through Inhibition Of C-Src And Hyperactivation Of Rock Ii Kinase., Xuanmao Jiao, Sanjay Katiyar, Manran Liu, Susette C Mueller, Michael P. Lisanti, Anping Li, Timothy G Pestell, Kongming Wu, Xiaoming Ju, Zhiping Li, Erwin F Wagner, Tatsuo Takeya, Chenguang Wang, Richard G Pestell Apr 2008

Disruption Of C-Jun Reduces Cellular Migration And Invasion Through Inhibition Of C-Src And Hyperactivation Of Rock Ii Kinase., Xuanmao Jiao, Sanjay Katiyar, Manran Liu, Susette C Mueller, Michael P. Lisanti, Anping Li, Timothy G Pestell, Kongming Wu, Xiaoming Ju, Zhiping Li, Erwin F Wagner, Tatsuo Takeya, Chenguang Wang, Richard G Pestell

Kimmel Cancer Center Faculty Papers

The spread of metastatic tumors to different organs is associated with poor prognosis. The metastatic process requires migration and cellular invasion. The protooncogene c-jun encodes the founding member of the activator protein-1 family and is required for cellular proliferation and DNA synthesis in response to oncogenic signals and plays an essential role in chemical carcinogenesis. The role of c-Jun in cellular invasion remains to be defined. Genetic deletion of c-Jun in transgenic mice is embryonic lethal; therefore, transgenic mice encoding a c-Jun gene flanked by LoxP sites (c-jun(f/f)) were used. c-jun gene deletion reduced c-Src expression, hyperactivated ROCK II signaling, …


Poster Abstracts, Sigma Xi Research Day 2008 Apr 2008

Poster Abstracts, Sigma Xi Research Day 2008

Sigma Xi Student Research Day

No abstract provided.


Trail Mediates Liver Injury By The Innate Immune System In The Bile Duct-Ligated Mouse., Alisan Kahraman, Fernando J. Barreyro, Steven F. Bronk, Nathan W. Werneburg, Justin L. Mott, Yuko Akazawa, Howard C Masuoka, Charles L Howe, Gregory J. Gores Apr 2008

Trail Mediates Liver Injury By The Innate Immune System In The Bile Duct-Ligated Mouse., Alisan Kahraman, Fernando J. Barreyro, Steven F. Bronk, Nathan W. Werneburg, Justin L. Mott, Yuko Akazawa, Howard C Masuoka, Charles L Howe, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

The contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand expressed by cells of the innate immune system, to cholestatic liver injury has not been explored. Our aim was to ascertain if TRAIL contributes to liver injury in the bile duct-ligated (BDL) mouse. C57/BL6 wild-type (wt), TRAIL heterozygote (TRAIL(+/-)), and TRAIL knockout (TRAIL(-/-)) mice were used for these studies. Liver injury and fibrosis were examined 7 and 14 days after BDL, respectively. Hepatic TRAIL messenger RNA (mRNA) was 6-fold greater in BDL animals versus sham-operated wt animals (P < 0.01). The increased hepatic TRAIL expression was accompanied by an increase in liver accumulation of natural killer 1.1 (NK 1.1)-positive NK and natural killer T (NKT) cells, the predominant cell types expressing TRAIL. Depletion of NK 1.1-positive cells reduced hepatic TRAIL mRNA expression and serum alanine aminotransferase (ALT) values. Consistent with a role for NK/NKT cells in this model of liver injury, stress ligands necessary for their recognition of target cells were also up-regulated in hepatocytes following BDL. Compared to sham-operated wt mice, BDL mice displayed a 13-fold increase in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and an 11-fold increase in caspase 3/7-positive hepatocytes (P < 0.01). The number of TUNEL and caspase 3/7-positive cells was reduced by >80% in BDL TRAIL knockout animals (P < 0.05). Likewise, liver histology, number of bile infarcts, serum ALT values, hepatic fibrosis, and animal survival were also improved in BDL TRAIL(-/-) animals as compared to wt animals. Conclusion: These observations support a pivotal role for TRAIL in cholestatic liver injury mediated by NK 1.1-positive NK/NKT cells.