A novel scavenger of nitric oxide decreases heme protein nitrosylation and prolongs graft survivial during cardiac transplant rejection.
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Journal Article↗
Biomedical subjects
G Hilton
Publications and source records attributed to G Hilton.
Antioxidant treatment inhibits activation of myocardial nuclear factor kappa B and inhibits nitrosylation of myocardial heme protein in cardiac transplant rejection.
Nitric oxide production via inducible nitric oxide synthase (iNOS) is believed to play a role in cardiac allograft rejection. Previously, we showed that antioxidants can significantly prolong cardiac graft survival, but the nature of this protection is unknown. In the present study, we examined the protective effect of another antioxidant, dimethylthiourea (DMTU), in a model of cardiac allograft rejection. Specifically, we hypothesized that DMTU would prolong graft survival and decrease activation of nuclear factor-kappa B (NF-kappa B), an important redox-sensitive transcription factor necessary for iNOS gene expression. NF-kappa B was activated by twofold as early as postoperative day 2 in allografts. NF-kappa B activation in allografts progressed to a peak of ninefold by postoperative day and remained increased until postoperative day 6. No activation of NF-kappa B was observed in isografts for comparable time periods. Treatment with DMTU resulted in a significant prolongation of graft survival. This beneficial effect was associated with diminished activation of myocardial NF-kappa B. Treatment with DMTU also resulted in decreased formation of iron-nitrosylprotein complexes as evidenced by electron paramagnetic resonance spectroscopy. These studies provide evidence that reactive oxygen plays a significant role in signal transduction for activation via the transcription factor, NF-kappa B, thereby modulating distal actions and consequences of iNOS-derived nitric oxide.
Animals↗
Emergency. Acute head injury.
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Accidents, Traffic↗
NOX 100, a nitric oxide scavenger, enhances cardiac allograft survival and promotes long-term graft acceptance.
BACKGROUND: We examined the role of nitrosative stress in allograft destruction. METHODS: Rats undergoing cardiac transplants received NOX-100, a water-soluble nitric oxide (NO) scavenger with antioxidant properties, with or without low-dose cyclosporine (CsA). Graft survival, NO production, and nuclear factor kappa B (NF-kappaB) activity were studied. RESULT: Using NOX-100 daily until rejection prolonged graft survival (11.6+/-0.6 vs. 7.4+/-0.2 days; P<0.05). Daily low-dose CsA (2.5 mg/kg im) for 7 days or until rejection also prolonged survival (12.6+/-0.5 and 21.6+/-1.6 days, respectively; P<0.01 vs. Controls). Low-dose CsA for 7 days and NOX-100 for 30 days prolonged graft survival (45.0+/-4.7 days; P<0.01 vs. all groups.). NOX-100 had no effect on whole blood CsA levels. Combination therapy until Day 100 resulted in 1 graft loss at Day 116 and indefinite survival in 3 animals (>300 days), which accepted a second WF strain heart without further immunosuppressive therapy but promptly rejected a third party (ACI) cardiac allograft. NOX-100 and CsA reduced nitrate and nitrite, and combination therapy completely normalized NO through to Day 30. Electron paramagnetic resonance spectroscopic analysis demonstrated reduction of signals for nitrosylmyoglobin and nitrosyl-heme with NOX-100 and elimination of signals with CsA alone or combination therapy. Activity of myocardial NF-kappaB decreased with monotherapy vs. untreated allografts. Combination therapy resulted in further inhibition of NF-kappaB up to Day 30. The extent of graft survival correlated with the extent of NO scavenging and NF-kappaB inhibition. Short-term combination therapy had no effect on graft lymphocytic infiltrate on Days 15, 20, and 30. CONCLUSION: These data support a role for both oxidative and nitrosative stress in rejection and the immunoregulatory potential of antioxidant therapy after transplantation.
Animals↗
Cerebral oxygenation in the traumatically brain-injured patient: are ICP and CPP enough?
Secondary brain injury results in increased morbidity and mortality in the traumatically brain-injured (TBI) patient. Research has shown that prevention of secondary brain injury, as characterized by cerebral ischemia and edema, can improve neurologic outcomes. The standard of care in many facilities is to monitor intracranial pressure and cerebral perfusion pressure as indirect measures of cerebral oxygenation and perfusion and to therefore manage secondary brain injury via these parameters. Yet these may not be the most accurate or reliable measures of cerebral oxygenation. Scientifically, brain tissue oxygenation can be directly measured via the partial pressure of oxygen in brain tissue (PbO2) probe. This provides a rapid, potentially more accurate indicator of cerebral oxygenation, thereby allowing for earlier intervention into the prevention of secondary brain injury.
Blood Gas Analysis↗
Pharmacologic management of seizure disorders.
Patients who experience seizures constitute a significant segment of the healthcare population. A thorough understanding of the causes and categories of seizures helps to ensure optimal pharmacologic management. This article addresses the categories of seizures as well as first-line and alternative pharmacologic agents. It also addresses the newer and experimental agents under development.
Adult↗
The discharge process for palliative care patients.
This article describes the response of staff at a specialist palliative care service to the need for effective discharge planning. Hospice and community nurses were invited to give their views on the discharge of palliative care patients. The authors discuss the strategy for change and how it was implemented and evaluated.
Hospice Care↗
Seizure disorders in adults: evaluation and management of new onset seizures.
The adult patient with first-time seizures often presents to the primary care and urgent care settings. It is estimated that 1% of the population of the United States has a diagnosed seizure disorder, with more than 125,000 new cases identified each year. Because of the complexity of assessment and intervention required for the patient with seizures, it behooves the health care practitioner to be aware of diagnostic criteria, current management techniques, and evaluation of treatment protocols. This article discusses various types of seizures, offers information regarding a differential diagnosis, and addresses the implementation of pharmacologic therapies as well as ongoing care of the patient.
Activities of Daily Living↗
Cross utilization in critical care.
Fluctuations in inpatient census are occurring across the nation, necessitating innovative approaches to staffing. At our facility, fluctuations were most acute in the critical care units. In order to meet the staffing needs of these units and ensure competency of staff, a cross-utilization program was implemented.
Clinical Competence↗
MELAS: a mitochondrial encephalomyopathy syndrome.
MELAS, a syndrome characterized by Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes, is one of a group of diseases known as mitochondrial encephalopathies. These genetically-transmitted diseases result in metabolic abnormalities associated with mitochondrial dysfunction, which contribute to neuronal destruction. Clinical manifestations include dementia, seizures, muscle weakness and stroke-like episodes. Accurate diagnosis is difficult to make and effective treatment is nonexistent at this time. The focus of care is supportive and the nurse's role centers on identification of deficits and maintenance of existing function.
Adult↗
Secondary brain injury and the role of neuroprotective agents.
Secondary brain injury is associated with high mortality and morbidity rates. Reversible causes of secondary injury, including hypoxemia, hypotension and increased intracranial pressure need to be anticipated and prevented, when at all possible. In addition, further understanding of the cellular and metabolic alterations associated with delayed brain injury and the role of neuroprotective agents in the prevention of said injury will hopefully result in improved neurologic care. One challenge for health care providers in the years ahead will be to limit the extent of injury after the initial event, thereby improving outcomes.
Brain Injuries↗
Development of a surgical/trauma intermediate care unit.
During these times of escalating health care costs and increased demand for critical care beds, hospitals are often unable to provide the intensive level of nursing care that is required. One large urban trauma center found that 36% of the surgical intensive care unit patients required a level of nursing care intermediate between the intensive care unit and the general ward. A multidisciplinary team met to plan and develop a surgical/trauma intermediate care unit to provide this level of care. Goals, objectives, specific admission, discharge criteria, and administrative responsibility were determined. An educational program was developed based on a needs assessment of the staff. During the implementation phase and throughout the unit's operation, advanced practice nurses performed an integral role as resource personnel. The purpose of this paper is to describe the multidisciplinary process used in the development of a new unit and to highlight the advanced practice role in this activity.
Intermediate Care Facilities↗
Clue: unusually severe wound pain.
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Adult↗
Antiphospholipid antibody syndrome: a case study.
Antiphospholipid antibody syndrome includes a spectrum of autoantibody reactions associated with vascular thrombosis, thrombocytopenia and recurrent fetal loss. Neurologic manifestations include strokes, transient ischemic attacks and multi-infarct dementia. Treatment involves prolonged anticoagulation, and prognosis is poor. A case study of a 21-year-old female with antiphospholipid antibody syndrome is provided.
Adult↗
Methylprednisolone for acute spinal cord injury.
Treatment with high-dose intravenous methylprednisolone is safe and may be associated with significant neurologic improvement in acute spinal cord injury patients. Accurate calculation and administration of the prescribed therapy and identification and assessment of complications should be incorporated into the overall standard of care for the acute spinal cord injury patient.
Acute Disease↗
Review of neurobehavioral assessment tools.
Behavioral, cognitive, and memory deficits are frequently observed sequelae of brain injury. Yet in most critical care settings, neurologic assessment is limited to evaluation of arousal, pupillary response, orientation, and motor capability. Behavior, cognition, and memory are not routinely evaluated. Several brief, bedside assessment tools are reviewed. All may be used in the critical care setting to evaluate the type and extent of residual deficits in the neurologically impaired patient. Nursing implications, based on the evaluation of deficits, are also discussed.
Brain Injuries↗
High-dose methylprednisolone in the treatment of spinal cord injuries.
The Second National Acute Spinal Cord Injury Study (NASCIS II), published in 1990, illustrated the benefits of high-dose steroids in the treatment of acute spinal cord injury. Research into the use of high-dose steroids is reviewed, and proposed mechanisms of action are addressed. Implications for nursing include method and timing of administration and expected complications. A case study is also provided.
Acute Disease↗