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Find video protocols related to scientific articles indexed in Pubmed.
Clinical diagnostic decision-making in real life contexts: A trans-theoretical approach for teaching: AMEE Guide No. 95.
Med Teach
PUBLISHED: 11-14-2014
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Abstract Making an accurate clinical diagnosis is an essential skill for all medical students and doctors, with important implications for patient safety. Current approaches for teaching how to make a clinical diagnosis tend to lack the complexity that faces clinicians in real-life contexts. In this Guide, we propose a new trans-theoretical model for teaching how to make an appropriate clinical diagnosis that can be used by teachers as an additional technique to their current approach. This educational model integrates situativity theory, dual-information processing theory and socio-cognitive theory. Mapping and microanalysis help the teacher to identify the main processes involved in making an accurate clinical diagnosis, so that feedback can be provided that is focused on improving key aspects of the skill. An essential aspect of using the new educational model is the role of the experienced clinical teacher in making judgments about the appropriateness of the learner's attempts to make a clinical diagnosis.
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Nitrite therapy improves post-chlorine gas exposure survival.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 10-19-2014
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Exposure to relatively high levels of chlorine (Cl2) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown significant post-exposure injury phase to the airways, pulmonary and systemic vasculatures mediated in part by oxidative stress, inflammation and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field, and which display efficacy towards to post chlorine-exposure toxicity. In this study we tested if nitric oxide repletion using nitrite, by intramuscular injection post- Cl2 exposure, could prevent Cl2 gas toxicity. C57bl/6 male mice were exposed to 600ppm Cl2 gas for 45min and 24h survival determined with or without post-exposure intramuscular nitrite injection. A single injection of nitrite (10mg/Kg) administered either 30 or 60 min post exposure significantly improved 24h survival (from ?20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic prior to Cl2-exposure improved survival, and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl2 induced toxicity compared to males and were also less responsive to post-exposure nitrite therapy. These data provide evidence for efficacy, and define therapeutic parameters for a single intramuscular injection of nitrite as a post-Cl2 gas exposure therapeutic that is amenable to administration in mass-casualty scenarios.
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Utility of the Surgical Apgar Score for Patients who Undergo Surgery for Spinal Metastasis.
J Spinal Disord Tech
PUBLISHED: 10-14-2014
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Retrospective review of consecutive patients who underwent surgery for spinal metastasis 2005-2011.
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Peroxiredoxin-2 Recycling Is Inhibited During Erythrocyte Storage.
Antioxid. Redox Signal.
PUBLISHED: 09-30-2014
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Abstract Aims: Transfusion with stored red blood cells (RBCs) is associated with increased morbidity and mortality. Peroxiredoxin-2 (Prx-2) is a primary RBC antioxidant that limits hydrogen peroxide (H2O2)-mediated toxicity. Whether Prx-2 activity is altered during RBC storage is not known. Results: Basal and H2O2-induced Prx-2 activity was measured in RBCs (stored for 7-35 days). Basal Prx-2 thiol oxidation increased with RBC age, whereas H2O2-dependent formation of dimeric Prx-2 was similar. However, reduction of Prx-2 dimers to monomers became progressively slower with RBC storage, which was associated with increased H2O2-induced hemolysis. Surprisingly, no change in the NADPH-dependent thioredoxin (Trx)/Trx-reductase system, which recycles dimeric Prx-2, was observed in stored RBCs. Using mouse RBCs expressing human wild type (?93Cys) or hemoglobin (Hb) in which the conserved ?93Cys residue is replaced by Ala (?93Ala), a role for this thiol in modulating Prx-2 reduction was demonstrated. Specifically, Prx-2 recycling was blunted in ?93Ala RBC, which was reversed by carbon monoxide-treatment, suggesting that heme autoxidation-derived H2O2 maintains Prx-2 in the oxidized form in these cells. Moreover, assessment of the oxidative state of the ?93Cys in RBCs during storage showed that while it remained reduced on intraerythrocytic Hb in stored RBC, it was oxidized to dehydroalanine on hemolyzed or extracellular Hb. Innovation: A novel mechanism for regulated Prx-2 activity in RBC via the ?93Cys residue is suggested. Conclusion: These data highlight the potential for slower Prx-2 recycling and ?93Cys oxidation in modulating storage-dependent damage of RBCs and in mediating post-transfusion toxicity. Antioxid. Redox Signal. 00, 000-000.
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Formulation, optimization, and evaluation of a transdermal patch of heparin sodium.
Drug Discov Ther
PUBLISHED: 09-30-2014
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The purpose of this research was to develop a matrix-type transdermal therapeutic system containing drug heparin sodium with different ratios of hydrophilic polymeric systems by the solvent evaporation technique by using 30% (w/w) of PEG 400 LR to the dry polymer weight, incorporated as plasticizer. Different concentrations of oleic acid and isopropyl myristate were used to enhance the transdermal permeation of heparin sodium. The physicochemical compatibility of the drug and the polymers studied by differential scanning calorimetry and infrared spectroscopy suggested absence of any incompatibility. Formulated transdermal films were physically evaluated with regard to thickness, weight variation, drug content, flatness, tensile strength, folding endurance, percentage of moisture content and water vapour transmission rate. All prepared formulations indicated good physical stability. In-vitro permeation studies of formulations were performed by using diffusion cell apparatus. Formulation prepared with hydrophilic polymer containing permeation enhancer showed best in-vitro skin permeation through Wistar albino rat skin as compared to all other formulations. Formulation F9 showed highest flux among all the formulations and 1.369-fold enhancements in drug permeation. These results indicate that the formulation containing 10% of oleic acid with 10% isopropyl myristate give better penetration of heparin sodium through rat skin.
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Developmental student support in undergraduate medical education: AMEE Guide No. 92.
Med Teach
PUBLISHED: 07-29-2014
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Abstract Developmental student support has a focus on developing the whole person, not only academic and clinical competence. The positive and proactive developmental approach is in marked contrast to the deficit and reactive approach to student support which only targets identified students who are considered to be "at risk". The medical school is a nexus for personal development, combining the personal identity formation journey of early adulthood with the variety of new experiences in medical school. Important aspects of developmental student support are the development of resilience and ensuring reasonable adjustments for students with learning difficulties and disabilities. Careers guidance is an essential aspect of developmental student support, including students with doubts about a career in medicine and who are leaving because of poor performance. Developmental student support requires an organizational culture in which student support is considered as the responsibility of everyone, with further support from named personal tutors.
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HPTLC method for simultaneous determination of piperine, embeline, and carvone in the ayurvedic formulation Catpusphadhya churna.
J AOAC Int
PUBLISHED: 07-24-2014
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Churnas are an important group of formulations used by traditional physicians to treat various types of diseases. The principle of using a churna is based on the fact that the therapeutic value of most substances greatly increases when they are reduced to a very fine state of subdivision. Catpusphadhya churna, as per the Ayurvedic system of Indian medicine, is used for acute rheumatoid arthritis. In the present study, an attempt was made to develop an HPTLC method for the quantitative determination of piperine, embeline, and carvone in a laboratory-prepared formulation. Raw materials used in formulations were obtained from two different suppliers and were subjected to methanol extractions by using a Soxhlet apparatus. Piperine, embeline, and carvone were quantified in the extracts by using HPTLC. The detection and quantification were performed at 254 nm. The formulation contained 2.35% (w/w) of piperine, 4.86% (w/w) of embeline, and 1.48% (v/w) of carvone. Linearity studies indicated that piperine, embeline, and carvone were in the linear ranges, while the recovery studies revealed a recovery of 99.32% (w/w) of piperine, 101.82% (w/w) of embeline, and 100.09% (v/w) of carvone, thus proving the accuracy of the analysis. The developed HPTLC method resolved and quantified piperine, embeline, and carvone effectively, so it could be an important method for the QC of polyherbal formulations.
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Trigeminal nerve agenesis with absence of foramina rotunda in Gómez-López-Hernández syndrome.
Am. J. Med. Genet. A
PUBLISHED: 07-16-2014
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Gómez-López-Hernández syndrome (GLHS) is a clinical condition traditionally characterized by rhombencephalosynapsis (RS), parieto-occipital alopecia, and trigeminal anesthesia. It is a neurocutaneous disorder with no known etiology. The underlying cause of the trigeminal anesthesia in GLHS has not been examined or reported; it has merely been identified on clinical grounds. In this report, a 10-month-old white female born at 37 weeks gestational age with GLHS underwent a contrast-enhanced CT for the evaluation of craniofacial dysmorphic features. Thin-section bone algorithm images showed absence of bilateral foramina rotunda and trigeminal nerve fibers. The maxillary branch of the trigeminal nerve passes through the foramen rotundum and carries sensory information from the face. This case is unique because trigeminal nerve absence has not been suggested as a possible etiology for trigeminal anesthesia associated with GLHS. It is not known how many cases of GLHS have agenesis of the trigeminal nerve; however, a review of the literature suggests that this patient is the first. The triad of RS, alopecia, and trigeminal anesthesia is specific to GLHS; therefore, early identification of trigeminal nerve agenesis in patients with RS could expedite diagnosis of GLHS, particularly given that the clinical diagnosis of trigeminal anesthesia in neonates is a challenging one. Diagnosing alopecia in newborns is likewise challenging. Early diagnosis could allow for early intervention, especially for ophthalmic complications, which are known to have significant long-term effects. This case illustrates the benefits of CT imaging in the detection of trigeminal nerve and foramina rotunda abnormalities in neonates with suspected GLHS. © 2014 Wiley Periodicals, Inc.
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Polarization-sensitive multimodal imaging for detecting breast cancer.
Cancer Res.
PUBLISHED: 06-23-2014
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Intraoperative delineation of breast cancer is a significant problem in surgical oncology. A reliable method for demarcation of malignant breast tissue during surgery would reduce the re-excision rate due to positive margins. We present a novel method of identifying breast cancer margins using combined dye-enhanced wide-field fluorescence polarization imaging for en face cancer margins and polarization-sensitive (PS) optical coherence tomography (OCT) for cross-sectional evaluation. Tumor specimens were collected following breast surgery, stained with methylene blue, and imaged. Wide-field fluorescence polarization images were excited at 640 nm and registered between 660 and 750 nm. Standard and PS OCT images were acquired using a commercial 1,310-nm swept-source system. The imaging results were validated against histopathology. Statistically significant higher fluorescence polarization of cancer as compared with both normal and fibrocystic tumor tissue was measured in all the samples. Fluorescence polarization delineated lateral breast cancer margins with contrast superior to that provided by OCT. However, OCT complemented fluorescence polarization imaging by facilitating cross-sectional inspection of tissue. PS OCT yielded higher contrast between cancer and connective tissue, as compared with standard OCT. Combined PS OCT and fluorescence polarization imaging shows promise for intraoperative delineation of breast cancer.
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Cerebrospinal Fluid Leak Presenting as Epiphora.
Ophthal Plast Reconstr Surg
PUBLISHED: 06-10-2014
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A 52-year-old woman underwent a right frontotemporal craniotomy for microsurgical clip obliteration of a ruptured right dorsal variant ophthalmic segment carotid aneurysm. During the craniotomy, a defect involving the orbital roof was inadvertently created. The patient was noted postoperatively to have fluid egressing from her OD. The fluid was analyzed and based on glucose and chloride levels was determined to be cerebrospinal fluid (CSF). CT scan of the head demonstrated the orbital roof defect created during surgery. After placement of a lumbar drain, fluid egress from the eye significantly decreased, further confirming the suspicion for CSF leak. Patient was found to have a conjunctival defect of the OD, approximately 2.5 cm × 1.5 cm, extending to the fornix from 9 to 12 o'clock. The conjunctival defect and fornix were repaired with an amniotic membrane graft and a temporary tarsorrhaphy with subsequent resolution of CSF egress. The case report is in compliance with the Health Insurance Portability and Accountability Act.
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Hydroxyurea in sickle cell disease: drug review.
Indian J Hematol Blood Transfus
PUBLISHED: 05-20-2014
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Hydroxyurea, a myelosuppressive agent, is the only effective drug proven to reduce the frequency of painful episodes. It raises the level of HbF and the haemoglobin level. It usually decreases the rate of painful episodes by 50 %. It was first tested in sickle cell disease in 1984. It also decreases the rate of ACS episodes and blood transfusions by ~50 % in adults. It was developed as an anticancer drug and has been used to treat myeloproliferative syndromes-leukemia, melanoma, and ovarian cancer. It was approved for use by FDA in adults. Side effects includes neutropenia, bone marrow suppression, elevation of hepatic enzymes, anorexia, nausea, vomiting and infertility.
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Orbital histiocytic sarcoma in a 2-year-old child.
Ophthal Plast Reconstr Surg
PUBLISHED: 05-09-2014
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Histiocytic sarcoma (HS) is an exceedingly rare hematologic malignancy that typically presents in the skin, gastrointestinal tract, and lymph nodes. Few cases of HS have been reported in the head and neck. This study describes the case of a 2-year-old girl presenting with 2 weeks of left lower eyelid swelling. Diagnostic testing and biopsy revealed a large inferior orbital mass causing severe bony destruction with extension into the sinuses. Pathologic analysis revealed classic features of HS. To the best of knowledge, no previous case of HS occurring in the orbit of a child has been reported. This study presents an exceedingly rare case of HS in a young child presenting with eyelid swelling. In addition, this case report is in compliance with HIPAA regulations.
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A study of the efficacy of flashing lights to increase the salience of alcohol-gel dispensers for improving hand hygiene compliance.
Am J Infect Control
PUBLISHED: 04-22-2014
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Many interventions have been implemented to improve hand hygiene compliance, each with varying effects and monetary costs. Although some previous studies have addressed the issue of conspicuousness, we found only 1 study that considered improving hand hygiene by using flashing lights.
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Protracted Symptoms in Lymphocytic Choriomeningitis: A Case Report.
J. Child Neurol.
PUBLISHED: 04-17-2014
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Assumed to be underreported and underrecognized, lymphocytic choriomeningitis presents as a febrile illness transmitted by the common house mouse, Mus musculus. Although asymptomatic or mild febrile illnesses are commonplace, meningitis and meningoencephalitis may develop after symptoms have seemed to improve. Neurologic sequelae are not typical but have been reported and can persist for months. We report a documented case of lymphocytic choriomeningitis in which a previously healthy 17-year-old girl experienced debilitating recurrent headaches and arthralgias for more than a year after discharge. Neuropsychological testing and visual changes were also documented. Further research is needed to estimate the prevalence of this infection, although it has been estimated that 5% of American adults have antibodies to lymphocytic choriomeningitis virus. Education and awareness of the medical community as well as the general public will be critical in prevention as well as advancing future treatment modalities of lymphocytic choriomeningitis virus.
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Advanced locoregional therapies in breast.
Ann. Surg. Oncol.
PUBLISHED: 04-13-2014
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Advanced locoregional therapies continue to advance the treatment of breast cancer. These techniques are geared towards optimizing oncologic and aesthetic outcome as well as decreasing and treating morbidity. We present a selection of specialized locoregional therapies dedicated to the optimization of breast cancer treatment.
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Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature.
Toxicology
PUBLISHED: 04-04-2014
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Exposure to chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400 ppm, 30 min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24-48 h post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ?2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E+) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (?4 mmHg) lower in rats that had been exposed to Cl2 gas 24 h earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity.
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Cost-effectiveness of MRI to assess for posttraumatic ligamentous cervical spine injury.
Orthopedics
PUBLISHED: 04-01-2014
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Magnetic resonance imaging (MRI) has been shown to be sensitive in identifying ligamentous injury to the cervical spine. The major drawbacks to its routine use are cost and availability. The purpose of this study was to compare the cost of using MRI to rule out ligamentous injury of the cervical spine with the cost of immobilization in a cervical collar and outpatient follow-up. Neurologically intact and nonobtunded patients with neck pain and normal findings on radiographs evaluated for ligamentous injury of the cervical spine were studied. Patients were either evaluated with MRI or immobilized in a cervical collar and followed up for repeat clinical and radiographic evaluation as outpatients. The authors gathered year 2011 fees from their institution and 2011 Medicare reimbursement data and compared the costs of MRI with the costs of cervical collar and outpatient follow-up. In addition, the median income of the local community was used to estimate opportunity costs associated with cervical collar immobilization. After 7 days of lost wages at the median local income, MRI became a less costly option when comparing hospital fees. Alternatively, when considering Medicare reimbursement, MRI became less costly after only 2 days of lost wages at the median local income. On the basis of these findings, MRI of the cervical spine is less costly than other current management strategies when opportunity costs are considered.
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Redox therapeutics in hepatic ischemia reperfusion injury.
World J Hepatol
PUBLISHED: 03-22-2014
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Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.
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Ameliorative potential of aliskiren in experimental colitis in mice.
Eur. J. Pharmacol.
PUBLISHED: 02-27-2014
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In the present study, we investigated the ameliorative potential of aliskiren in dextran sulfate sodium (DSS) induced colitis in mice. Aliskiren (3 and 10mg/kg, i.p.) was administered for 10 days from the day of DSS administration. The severity of colitis in mice was assessed using body weight loss, colon and spleen weight, hematological parameters, food intake, stool consistency, rectal bleeding and colon shortening. Colonic malondialdehyde (MDA), myeloperoxidase (MPO) and renin mRNA levels were also estimated. Furthermore, TNF-? and IL-6 in plasma and colon were analyzed. The results showed that aliskiren (10mg/kg, i.p.) significantly improved the severity of colitis by, decrease in weight loss, improvement in food intake and stool consistency, decrease in rectal bleeding, decrease in relative colon and spleen weight and improvement in colonic shortening. Aliskiren (10mg/kg, i.p.) improved blood hemoglobin, red blood cells (RBC) and hematocrit. Colonic malondialdehyde (MDA), MPO and histolopathological score were significantly diminished by aliskiren (10mg/kg, i.p.). Furthermore, aliskiren (10mg/kg, i.p.) significantly diminished the elevated levels of TNF-?, IL-6 and renin mRNA in inflammed colon. These results indicate involvement of renin in colitis and inhibition of renin by aliskiren ameliorates colitis.
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Increased sensitivity of Apolipoprotein E knockout mice to swainsonine dependent immunomodulation.
Immunobiology
PUBLISHED: 02-23-2014
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The mechanisms that mediate accelerated atherosclerosis in autoimmune diseases remain unclear. One common mechanism that has been documented in autoimmune diseases and atherosclerosis is formation of hypoglycosyalted N-glycans on the cell surface. In this study we tested the effects of swainsonine, a class II ?-mannosidase inhibitor which results in formation of hypoglycosylated N-glycans, on atherogenesis and immune cell dynamics in the atheroprone and hypercholesterolemic ApoE -/- mouse. Wild type or ApoE-/- mice (8 weeks of age) were fed a normal chow diet and administered swainsonine via the drinking water for 8 weeks at which time, atherosclerosis, and systemic markers of markers of inflammation were evaluated. Interestingly, no change in the rate of atherosclerosis development was observed in ApoE -/- mice treated with swainsonine. However, swainsonine significantly increased the number of peripheral blood leukocytes in ApoE -/- mice, with trends toward similar increases in swainsonine treated wild type mice noted. Assessment of leukocyte subsets using specific markers of all major blood lineages indicated that the increase in circulating leukocytes was due to the elevated number of progenitor cells. Consistent with swainsonine having a greater effect in ApoE -/- vs. wild type mice, increases in circulating inflammatory markers (IgA, IgG and chemokines) were observed in the former. Collectively, these data demonstrate that predisposition of ApoE -/- mice to vascular disease is associated with sensitization to the immunomodulatory effects of swainsonine and indicate that changes in N-glycans may provide a mechanism linking autoimmunity to atherogenesis.
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A review of safety, quality management, and practice guidelines for high-dose-rate brachytherapy: executive summary.
Pract Radiat Oncol
PUBLISHED: 02-05-2014
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This white paper was commissioned by the American Society for Radiation Oncology (ASTRO) Board of Directors to evaluate the status of safety and practice guidance for high-dose-rate (HDR) brachytherapy. Given the maturity of HDR brachytherapy technology, this white paper considers, from a safety point of view, the adequacy of general physics and quality assurance guidance, as well as clinical guidance documents available for the most common treatment sites. The rate of medical events in HDR brachytherapy procedures in the United States in 2009 and 2010 was 0.02%, corresponding to 5-sigma performance. The events were not due to lack of guidance documents but failures to follow those recommendations or human failures in the performance of tasks. The white paper summarized by this Executive Summary reviews current guidance documents and offers recommendations regarding their application to delivery of HDR brachytherapy. It also suggests topics where additional research and guidance is needed.
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Lichen scrofulosorum presenting as pyrexia of unknown origin.
J Coll Physicians Surg Pak
PUBLISHED: 02-05-2014
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Cutaneous tuberculosis forms a subset of extra pulmonary tuberculosis. It accounts for about 1.5% of all the cases of extrapulmonary tuberculosis. Lichen Scrofulosorum is a rare form of cutaneous tuberculosis. It is usually seen in children or young adults and an important marker of occult tuberculosis. Usually, the eruption appears in children and adolescents with strong immune sensitivity to Mycobacterium tuberculosis and consists of tiny follicular papules. Underlying systemic involvement is more common in children, compared with adults. We report a case of 3 years old boy who was investigated for pyrexia of unknown origin and finally diagnosed as Lichen Scrofulosorum associated with tuberculous lymphadenitis of mediastinal lymph nodes. A skin biopsy showed extensive tuberculoid granulomas surrounding hair follicles which were consistent with the diagnosis of Lichen Scrofulosorum. The child was treated with antitubercular drugs and it showed improvement within 2 weeks of starting treatment with resolution of skin lesions.
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Renoprotective activity of aliskiren, a renin inhibitor in cyclosporine A induced hypertensive nephropathy in dTG mice.
Pharmacol Rep
PUBLISHED: 01-31-2014
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Hypertensive nephropathy is moving up the charts to number 2 after diabetic nephropathy in terms of diagnostic frequency cited as causing end stage renal disease (ESRD).
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Perioperative characteristics and complications in obese patients undergoing anterior cervical fusion surgery.
J Clin Neurosci
PUBLISHED: 01-30-2014
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In the USA, obesity rates have significantly increased in the last 15 years. Mirroring this trend, a large proportion of patients undergoing spinal surgery are obese. Concern exists for increased complications due to surgical challenges posed by obese patients and their often-prevalent comorbidities. Studies have shown associations between body mass index (BMI) and perioperative complications in lumbar and thoracolumbar fusion surgeries; however, few studies have evaluated the impact of obesity on anterior cervical fusion surgery. As such, this study aimed to evaluate complications and perioperative characteristics in obese patients undergoing anterior cervical fusion. We queried medical records to identify patients with BMI >30 who underwent anterior cervical fusion surgery. A total of 69 patients were included and subdivided based on obesity class: Class 1 (BMI 30-35), Class 2 (BMI 35-40), and Class 3 (BMI >40). Subgroup analysis included comorbidities, diagnosis, procedure, levels treated, and length of hospital stay. Overall mean BMI was 35.1, mean age was 54.3 years, and 43 (63.3%) were men. Disc herniation was the most common diagnosis. Length of stay differed significantly among obesity subgroups (p=0.02). Mean length of stay was 2.8, 3.5, and 4.0 days for Classes 1, 2, and 3, respectively. Three (4.3%) complications were observed, comprising of urinary tract infection, wound dehiscence, and neck hematoma. Complication rates by class were 5.5%, 0%, and 16.6% for Classes 1, 2, and 3, respectively (p=0.17). We found that obese patients undergoing anterior cervical spine surgery experience relatively few complications. Hospital stay, however, appears to lengthen with increased BMI.
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A novel model of chronic wounds: importance of redox imbalance and biofilm-forming bacteria for establishment of chronicity.
PLoS ONE
PUBLISHED: 01-01-2014
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Chronic wounds have a large impact on health, affecting ?6.5 M people and costing ?$25B/year in the US alone [1]. We previously discovered that a genetically modified mouse model displays impaired healing similar to problematic wounds in humans and that sometimes the wounds become chronic. Here we show how and why these impaired wounds become chronic, describe a way whereby we can drive impaired wounds to chronicity at will and propose that the same processes are involved in chronic wound development in humans. We hypothesize that exacerbated levels of oxidative stress are critical for initiation of chronicity. We show that, very early after injury, wounds with impaired healing contain elevated levels of reactive oxygen and nitrogen species and, much like in humans, these levels increase with age. Moreover, the activity of anti-oxidant enzymes is not elevated, leading to buildup of oxidative stress in the wound environment. To induce chronicity, we exacerbated the redox imbalance by further inhibiting the antioxidant enzymes and by infecting the wounds with biofilm-forming bacteria isolated from the chronic wounds that developed naturally in these mice. These wounds do not re-epithelialize, the granulation tissue lacks vascularization and interstitial collagen fibers, they contain an antibiotic-resistant mixed bioflora with biofilm-forming capacity, and they stay open for several weeks. These findings are highly significant because they show for the first time that chronic wounds can be generated in an animal model effectively and consistently. The availability of such a model will significantly propel the field forward because it can be used to develop strategies to regain redox balance that may result in inhibition of biofilm formation and result in restoration of healthy wound tissue. Furthermore, the model can lead to the understanding of other fundamental mechanisms of chronic wound development that can potentially lead to novel therapies.
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A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation.
PLoS ONE
PUBLISHED: 01-01-2014
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Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (n?=?20/center) or iNO (80 ppm, n?=?20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p<0.0001), surgical times were greater at Center B (7.7 vs. 4.5 hrs, p<0.001) and warm ischemia times were greater at Center B (95.4 vs. 69.7 min, p<0.0001). No adverse metabolic or hematologic effects from iNO occurred. iNO enhanced allograft function indexed by liver function tests (Center B, p<0.05; and p<0.03 for ALT with center data combined) and reduced complications at 9-months (Center A and B, p?=?0.0062, OR?=?0.15, 95% CI (0.04, 0.59)). ICU (p?=?0.47) and hospital length of stay (p?=?0.49) were not decreased. iNO increased concentrations of nitrate (p<0.001), nitrite (p<0.001) and nitrosylhemoglobin (p<0.001), with nitrite being postulated as a protective mechanism. Mean costs of iNO were $1,020 per transplant. iNO was safe and improved allograft function at one center and trended toward improving allograft function at the other. ClinicalTrials.gov with registry number 00582010 and the following URL:http://clinicaltrials.gov/show/NCT00582010.
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Mechanism of faster NO scavenging by older stored red blood cells.
Redox Biol
PUBLISHED: 01-01-2014
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The blood storage lesion involves morphological and biochemical changes of red blood cells (RBCs) that occur during storage. These include conversion of the biconcave disc morphology to a spherical one, decreased mean corpuscular hemoglobin concentration, varied mean corpuscular volume, reduced integrity of the erythrocyte membrane with formation of microparticles, and increased cell-free hemoglobin. We studied the extent that older stored red blood cells scavenge nitric oxide (NO) faster than fresher stored red blood cells. Using electron paramagnetic resonance spectroscopy and stopped-flow absorption spectroscopy to measure the rate of NO uptake and reaction with hemoglobin in red cells, we found that older stored red blood cells scavenge NO about 1.8 times faster than fresher ones. Based on these experimental data, we simulated NO scavenging by fresher or older stored red blood cells with a biconcave or spherical geometry, respectively, in order to explore the mechanism of NO scavenging related to changes that occur during blood storage. We found that red blood cells with a spherical geometry scavenges NO about 2 times slower than ones with a biconcave geometry, and a smaller RBC hemoglobin concentration or volume increases NO scavenging by red blood cells. Our simulations demonstrate that even the most extreme possible changes in mean corpuscular hemoglobin concentration and mean corpuscular volume that favor increased NO scavenging are insufficient to account for what is observed experimentally. Therefore, RBC membrane permeability must increase during storage and we find that the permeability is likely to increase between 5 and 70 fold. Simulations using a two-dimensional blood vessel show that even a 5-fold increase in membrane permeability to NO can reduce NO bioavailability at the smooth muscle.
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Postsurgical treatment of early-stage breast cancer with electronic brachytherapy: outcomes and health-related quality of life at 1 year.
Am. J. Clin. Oncol.
PUBLISHED: 11-15-2013
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This multicenter registry followed up patients with early-stage breast cancer treated with breast-conserving surgery and electronic brachytherapy (EBT). This report provides 1- and 2-year updates to the initial publication.
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The Transcription Factor E26 Transformation-Specific Sequence-1 Mediates Neointima Formation in Arteriovenous Fistula.
J. Am. Soc. Nephrol.
PUBLISHED: 11-07-2013
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Hemodialysis vascular access dysfunction contributes to increased morbidity and mortality in hemodialysis patients. Arteriovenous fistula (AVF) is the preferred type of vascular access for hemodialysis but has high rates of dysfunction, in part because of excessive neointima formation. The transcription factor E26 transformation-specific sequence-1 (ETS-1) is a mediator of proinflammatory responses in hypertension and endovascular injury. We examined the role of ETS-1 in the formation of neointima in AVF. Right carotid artery to internal jugular vein fistulas were created in C57BL/6 mice and assigned to treatment with an ETS-1-dominant negative peptide (ETS-DN), an inactive mutant peptide (ETS-MU), or vehicle (n=6 per group). After 7 and 21 days, AVFs or contralateral internal jugular veins were processed for PCR, immunofluorescence, immunohistochemistry, and morphometry. In AVFs, ETS-1 mRNA increased 2.5-fold at 7 days and 4-fold at 21 days. By immunofluorescence, we confirmed increased expression of ETS-1 predominantly in the neointima and overlying endothelium. Similarly, ETS-1 expression increased in human AVFs compared with normal veins. In mice, ETS-DN, but not ETS-MU, reduced neointima formation at days 7 and 21 and reduced the expression of nitric oxide synthase 2, NADPH oxidase (NOX) 2, NOX4, E-selectin, and monocyte chemotactic protein-1. Shear stress increased ETS-1 phosphorylation in human umbilical vein cells in a NOX-dependent manner, demonstrating a role for reactive oxygen species in ETS-1 activation. These results unveil the role of ETS-1 as a mediator of neointima formation in AVF and may result in the development of novel strategies for the treatment of AVF dysfunction.
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The deleterious effect of red blood cell storage on microvascular response to transfusion.
J Trauma Acute Care Surg
PUBLISHED: 10-26-2013
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The transfusion of relatively older red blood cells (RBCs) has been associated with both morbidity and mortality in trauma patients in observational studies. Although the mechanisms responsible for this phenomenon remain unclear, alterations in the microcirculation as a result of the transfusion of relatively older blood may be a causative factor. To assess this hypothesis, we evaluated microvascular perfusion in trauma patients during RBC transfusion.
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An Abscess Causing a Delayed Optic Neuropathy after Decompression for Thyroid Eye Disease.
Orbit
PUBLISHED: 10-21-2013
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ABSTRACT A 63-year-old female with Graves disease and chronic sinusitis presented with acute left orbital pain and proptosis five years after bilateral orbital decompression and sinus surgery. Imaging revealed bilateral frontal sinus opacification, frontoethmoidal mucoceles and left subperiosteal mass. Presence of an optic neuropathy drove emergent management with intravenous antibiotics and orbitotomy with exploration. Intra-operatively, a left orbital abscess and left frontal sinus purulence were drained. The patient regained her vision with relief of proptosis and pain.
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Treatment of C2 body fracture with unusual distractive and rotational components resulting in gross instability.
World J Orthop
PUBLISHED: 10-18-2013
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Cervical fractures can result in severe neurological compromise and even death. One of the most commonly injured segments is the C2 vertebrae, which most frequently involves the odontoid process. In this report, we present the unusual case of a 28-year-old female who sustained a C2 vertebral body fracture (comminuted transverse fracture through the body and both transverse processes) that had both a significant distractive and rotational component, causing the fracture to be highly unstable. Application of halo bracing was unsuccessful. The patient subsequently required a C1-C4 posterior spinal fusion. Follow-up computer tomography imaging confirmed fusion and the patient did well clinically thereafter.
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An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy.
Spine J
PUBLISHED: 08-07-2013
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The objective of the North American Spine Societys (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Lumbar Disc Herniation with Radiculopathy is to provide evidence-based recommendations to address key clinical questions surrounding the diagnosis and treatment of lumbar disc herniation with radiculopathy. The guideline is intended to reflect contemporary treatment concepts for symptomatic lumbar disc herniation with radiculopathy as reflected in the highest quality clinical literature available on this subject as of July 2011. The goals of the guideline recommendations are to assist in delivering optimum efficacious treatment and functional recovery from this spinal disorder.
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Heterogenic endothelial responses to inflammation: role for differential N-glycosylation and vascular bed of origin.
J Am Heart Assoc
PUBLISHED: 08-01-2013
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Endothelial cell responses during inflammation are heterogeneous and key for selectivity in how leukocytes hone in on specific sites and why vascular diseases are highly bed specific. However, mechanisms for this specificity remain unclear.
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Locoregional recurrence following accelerated partial breast irradiation for early-stage invasive breast cancer: significance of estrogen receptor status and other pathological variables.
Ann. Surg. Oncol.
PUBLISHED: 05-25-2013
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Understanding risk factors for locoregional recurrence (LRR) after accelerated partial breast irradiation (APBI) can help to guide patient selection for treatment with APBI. Published findings to date have not been consistent. More data are needed as these risk factors continue to be defined.
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Managing chronic pelvic pain following reconstructive pelvic surgery with transvaginal mesh.
Int Urogynecol J
PUBLISHED: 05-24-2013
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In 2001, the US Food and Drug Administration (FDA) approved the first transvaginal mesh kit to treat pelvic organ prolapse (POP). Since the introduction of vaginal mesh kits, some vaginal meshes have been associated with chronic pelvic pain after reconstructive pelvic floor surgery. Pelvic pain results in between 0 % and 30 % of patients following transvaginal mesh placement. Common causes of chronic pelvic pain include pelvic floor muscle spasm, pudendal neuralgia, and infection. Paucity of data exists on the effective management of chronic pelvic pain after pelvic reconstructive surgery with mesh. We outline the management of chronic pelvic pain after transvaginal mesh placement for reconstructive pelvic floor repair based on our clinical experience and adaptation of data used in other aspects of managing chronic pelvic pain conditions.
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Identification of a high-mannose ICAM-1 glycoform: effects of ICAM-1 hypoglycosylation on monocyte adhesion and outside in signaling.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 05-22-2013
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Endothelial adhesion molecules are critical effectors of inflammation ensuring coordinated interactions that allow leukocytes to home to sites of injury. These adhesion molecules are often extensively modified posttranslationaly by the addition of N-glycans, but if, or how, these modifications contribute to the protein function remains poorly understood. Herein we show that activated endothelial cells express two distinct N-glycoforms of intercellular adhesion molecule 1 (ICAM-1) that comprise a complex N-glycoform with ?-2,6 sialic acid present at relatively high levels and a second, less abundant and previously undescribed high-mannose glycoform (HM-ICAM-1). This novel HM-ICAM-1 glycoform was also detected in human coronary artery specimens and moreover appeared to be the dominant glycoform in vivo. Production of exclusively HM-ICAM-1 in cells by ?-mannosidase inhibition increased monocyte rolling and adhesion compared with mature ICAM-1 consistent with high-mannose epitopes providing leukocyte ligands. Cross-linking of ICAM-1 transmits outside-in signals that affect endothelial permeability and survival. Interestingly, cell signaling (assessed using ERK, VE-cadherin, and Akt phosphorylation) was maintained after cross-linking of HM-ICAM-1 compared with mature ICAM-1; however, interactions with the actin cytoskeleton were lost with HM-ICAM-1. These findings suggest that specific ICAM-1 N-glycoforms modulate distinct aspects of the inflammatory response and identify HM-ICAM-1 as a new therapeutic target for controlling leukocyte trafficking and endothelial inflammation.
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The musculoskeletal effects of cigarette smoking.
J Bone Joint Surg Am
PUBLISHED: 05-03-2013
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? Cigarette smoking decreases bone mineral density and increases the risk of sustaining a fracture or tendon injury, with partial reversibility of these risks with long-term cessation of smoking. ? Cigarette smoking increases the risk for perioperative complications, nonunion and delayed union of fractures, infection, and soft-tissue and wound-healing complications. ? Brief preoperative cessation of smoking may mitigate these perioperative risks. ? Informed-consent discussions should include notification of the higher risk of perioperative complications with cigarette smoking and the benefits of temporary cessation of smoking.
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Evaluation of digoxin concentration after loading dose in patients with renal dysfunction.
Can J Hosp Pharm
PUBLISHED: 04-26-2013
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Loading dose recommendations for digoxin are based on the volume of distribution, which is proportional to lean body weight, whereas maintenance dose recommendations depend on renal function. The volume of distribution of this drug is demonstrably reduced in severe renal dysfunction, but the threshold at which a reduction in loading dose is warranted remains unknown.
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Endovascular aortic aneurysm repair with chimney and snorkel grafts: indications, techniques and results.
Cardiovasc Intervent Radiol
PUBLISHED: 04-09-2013
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The chimney technique in endovascular aortic aneurysm repair (Ch-EVAR) involves placement of a stent or stent-graft parallel to the main aortic stent-graft to extend the proximal or distal sealing zone while maintaining side branch patency. Ch-EVAR can facilitate endovascular repair of juxtarenal and aortic arch pathology using available standard aortic stent-grafts, therefore, eliminating the manufacturing delays required for customised fenestrated and branched stent-grafts. Several case series have demonstrated the feasibility of Ch-EVAR both in acute and elective cases with good early results. This review discusses indications, technique, and the current available clinical data on Ch-EVAR.
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Effects of erythrocyte aging on nitric oxide and nitrite metabolism.
Antioxid. Redox Signal.
PUBLISHED: 03-04-2013
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Recent studies have suggested that in addition to oxygen transport, red blood cells (RBC) are key regulators of vascular function by both inhibiting and promoting nitric oxide (NO)-mediated vasodilation. Most studies assume that RBC are homogenous, but, in fact, they comprise cells of differing morphology and biochemical composition which are dependent on their age, parameters that control NO reactions. We tested the hypothesis that distinct RBC populations will have differential effects on NO signaling.
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Anti-nociceptive and anti-allodynic activity of aliskiren in various pain models.
Eur. J. Pharmacol.
PUBLISHED: 02-28-2013
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In the present study, we have investigated the anti-nociceptive and anti-allodynic activity of the renin inhibitor, aliskiren, in various pain models. The anti-nociceptive activity of aliskiren was investigated in chemically-induced pain, orofacial pain and centrally mediated pain models. Anti-allodynic activity was evaluated in post-operative and neuropathic pain models. The levels of TNF-? and IL-6 were measured in homogenates of hind paw as markers of inflammation in formalin injected mice. Intraperitoneal administration of aliskiren (1-50mg/kg) showed anti-nociceptive activity in the writhing test, formalin hind paw test, capsaicin induced pain, and orofacial pain tests in ICR mice in a dose dependent manner. Aliskiren (50mg/kg, i.p.) reduced levels of TNF-? and IL-6 in hind paw homogenates of formalin-injected mice. Aliskiren (50mg/kg, i.p.) did not show any analgesic activity in hot-plate and tail-flick tests, indicating the absence of centrally mediated anti-nociceptive effects. On the other hand, intra-plantar administration of aliskiren (0.1, 0.5 and 1mg) showed analgesic activity in rat formalin tests, indicating a locally mediated effect. Aliskiren (30-100mg/kg, i.p.) showed anti-allodynic activity in post-operative pain and chronic constriction injury-induced neuropathic pain in Sprague Dawley rats. This data suggests that aliskiren may have the potential to be used as an anti-nociceptive and anti-allodynic agent.
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Endothelial heterogeneity and adhesion molecules N-glycosylation: implications in leukocyte trafficking in inflammation.
Glycobiology
PUBLISHED: 02-27-2013
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Inflammation is a major contributing element to a host of diseases with the interaction between leukocytes and the endothelium being key in this process. Much is understood about the nature of the adhesion molecule proteins expressed on any given leukocyte and endothelial cell that modulates adhesive interactions. Although it is appreciated that these proteins are heavily glycosylated, relatively little is known about the roles of these posttranslational modifications and whether they are regulated, and if so how during inflammation. Herein, we suggest that a paucity in this understanding is one major reason for the lack of successful therapies to date for modulating leukocyte-endothelial interactions in human inflammatory disease and discuss developing paradigms of (i) how endothelial adhesion molecule glycosylation (with a focus on N-glycosylation) maybe a critical element in understanding endothelial heterogeneity between different vascular beds and species, (ii) how adhesion molecule N-glycosylation may be under distinct, and as yet, unknown modes of regulation during inflammatory stress to affect the inflammatory response in a vascular bed- and disease-specific manner (analogous to a "zip code" for inflammation) and finally (iii) to underscore the concept that a fuller appreciation of the role of adhesion molecule glycoforms is needed to provide foundations for disease and tissue-specific targeting of inflammation.
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The remediation challenge: theoretical and methodological insights from a systematic review.
Med Educ
PUBLISHED: 02-13-2013
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Remediation is usually offered to medical students and doctors in training who underperform on written or clinical examinations. However, there is uncertainty and conflicting evidence about the effectiveness of remediation. The aim of this systematic review was to synthesise the available evidence to clarify how and why remediation interventions may have worked in order to progress knowledge on this topic.
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Incidence of and risk factors for superior facet violation in minimally invasive versus open pedicle screw placement during transforaminal lumbar interbody fusion: a comparative analysis.
J Neurosurg Spine
PUBLISHED: 02-08-2013
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A reported risk factor for adjacent-segment disease is injury to the superior facet joint from pedicle screw placement. Given that the facet joint is not typically visualized during percutaneous pedicle screw insertion, there is a concern for increased facet violation (FV) in minimally invasive fusion procedures. The purpose of this study was to analyze and compare the incidence of FV among patients undergoing minimally invasive transforaminal lumbar interbody fusion (MITLIF) and open transforaminal lumbar interbody fusion (TLIF). The impact of O-arm navigation compared with traditional fluoroscopy on FV in MITLIF is also assessed, as are risk factors for FV.
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A typical bilateral Toxoplasma retinochoroiditis in a bone marrow transplant patient with negative serum titers.
J Ophthalmic Inflamm Infect
PUBLISHED: 01-28-2013
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Toxoplasma retinochoroiditis can have an atypical presentation and be difficult to diagnose in immunocompromised patients. Accurate diagnosis and appropriate treatment is important since the disease can be aggressive in these patients. This paper is a case report with literature review, emphasizing on the diagnosis and treatment of Toxoplasma retinochoroiditis.
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The American Brachytherapy Society consensus statement for accelerated partial breast irradiation.
Brachytherapy
PUBLISHED: 01-21-2013
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To develop clinical guidelines for the quality practice of accelerated partial breast irradiation (APBI) as part of breast-conserving therapy for women with early-stage breast cancer.
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Impaired gastrointestinal transit and its associated morbidity in the intensive care unit.
J Crit Care
PUBLISHED: 01-16-2013
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To determine the proportion of critically ill adults developing impaired gastrointestinal transit (IGT) using a clinically pragmatic definition, its associated morbidity and risk factors.
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Investigation of antigenotoxic potential of Syzygium cumini extract (SCE) on cyclophosphamide-induced genotoxicity and oxidative stress in mice.
Drug Chem Toxicol
PUBLISHED: 01-09-2013
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The present study investigated the protective effects of Syzygium cumini extract (SCE; 100 and 200 mg/kg) against genotoxicity and oxidative stress (OS) induced by cyclophosphamide (CP) in mice. Animals were received 14 days pretreatment (oral) of SCE, followed by induction of genotoxicity by CP (40 mg/kg), 24 hours before sacrifice. Mice bone marrow chromosomal aberration assay, micronucleus assay, and sperm abnormality assay were employed for the study. Activities of hepatic antioxidant enzymes were also investigated. Phytochemical investigation was done to determine total phenolic and flavonoid content in SCE. Results showed that CP produced a significant increase in average percentage of aberrant metaphases and chromosomal aberrations (CAs) excluding gap, and micronuclei (MN) formation in polychromatic erythrocytes produced cytotoxicity in mouse bone marrow cells and induced abnormal sperms in a male germ line. CP also markedly inhibited the activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutahione (GSH) and increased malondialdehyde (MDA) content. Pretreatments with SCE significantly inhibited the frequencies of aberrant metaphases, CAs, MN formation, and cytotoxicity in mouse bone marrow cells induced by CP. SCE also produced a significant reduction of abnormal sperm and antagonized the reduction of CP-induced SOD, CAT, and GSH activities and inhibited increased MDA content in the liver. Total phenolic content present in SCE was 24.68%, whereas total flavonoids were calculated as 3.80%. SCE has a protective effect against genotoxicity and OS induced by CP.
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Role of the b93cys, ATP and adenosine in red cell dependent hypoxic vasorelaxation.
Int J Physiol Pathophysiol Pharmacol
PUBLISHED: 01-03-2013
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Two of the proposed mechanisms by which red blood cells (RBC) mediate hypoxic vasorelaxation by coupling hemoglobin deoxygenation to the activation of nitric oxide signaling involve ATP-release from RBC and S-nitrosohemoglobin (b93C(SNO)Hb) dependent bioactivity. However, different studies have reached opposite conclusions regarding the aforementioned mechanisms. Using isolated vessels, hypoxic vasorelaxation induced by human, C57BL/6 or mouse RBC which exclusively express either native human hemoglobin (HbC93) or human hemoglobin in which the conserved b93cys was replaced with Ala (HbC93A) were compared. All RBCs stimulated hypoxic vasodilation to similar extents suggesting the b93cys is not required for this RBC-mediated function. Hypoxic vasorelaxation was inhibited by co-incubation of ATP-pathway blockers including L-NAME (eNOS inhibitor) and Apyrase. Moreover, we tested if modulation of adenosine-dependent signaling affected RBC-dependent vasorelaxation using pan- or subtype specific adenosine receptor blockers, or adenosine deaminase (ADA). Interestingly, ADA and adenosine A2 receptor blockade, but not A1 receptor blockade, inhibited HbC93, HbC93A dependent hypoxic vasorelaxation. Equivalent results were obtained with human RBC. These data suggest that using isolated vessels, RBC do not require the presence of the b93cys to elicit hypoxic vasorelaxation and mediate this response via ATP- and a novel adenosine-dependent mechanism.
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Is methemoglobin an inert bystander, biomarker or a mediator of oxidative stress-The example of anemia?
Redox Biol
PUBLISHED: 01-01-2013
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Acute anemia increases the risk for perioperative morbidity and mortality in critically ill patients who experience blood loss and fluid resuscitation (hemodilution). Animal models of acute anemia suggest that neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) is adaptive and protects against anemia-induced mortality. During acute anemia, we have observed a small but consistent increase in methemoglobin (MetHb) levels that is inversely proportional to the acute reduction in Hb observed during hemodilution in animals and humans. We hypothesize that this increase in MetHb may be a biomarker of anemia-induced tissue hypoxia. The increase in MetHb may occur by at least two mechanisms: (1) direct hemoglobin oxidation by increased nNOS-derived NO within the perivascular tissue and (2) by increased deoxyhemoglobin (DeoxyHb) nitrite reductase activity within the vascular compartment. Both mechanisms reflect a potential increase in NO signaling from the tissue and vascular compartments during anemia. These responses are thought to be adaptive; as deletion of nNOS results in increased mortality in a model of acute anemia. Finally, it is possible that prolonged activation of these mechanisms may lead to maladaptive changes in redox signaling. We hypothesize, increased MetHb in the vascular compartment during acute anemia may reflect activation of adaptive mechanisms which augment NO signaling. Understanding the link between anemia, MetHb and its treatments (transfusion of stored blood) may help us to develop novel treatment strategies to reduce the risk of anemia-induced morbidity and mortality.
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Inhalation of nitric oxide prevents ischemic brain damage in experimental stroke by selective dilatation of collateral arterioles.
Circ. Res.
PUBLISHED: 12-29-2011
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Stroke is the third most common cause of death in industrialized countries. The main therapeutic target is the ischemic penumbra, potentially salvageable brain tissue that dies within the first few hours after blood flow cessation. Hence, strategies to keep the penumbra alive until reperfusion occurs are needed.
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Adenovirus E4orf3 targets transcriptional intermediary factor 1? for proteasome-dependent degradation during infection.
J. Virol.
PUBLISHED: 12-28-2011
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The ability of adenovirus early region proteins, E1B-55K and E4orf6, to usurp control of cellular ubiquitin ligases and target proteins for proteasome-dependent degradation during infection is well established. Here we show that the E4 gene product, E4orf3 can, independently of E1B-55K and E4orf6, target the transcriptional corepressor transcriptional intermediary factor 1? (TIF1?) for proteasome-mediated degradation during infection. Initial mass spectrometric studies identified TIF1 family members-TIF1?, TIF1?, and TIF1?-as E1B-55K-binding proteins in both transformed and infected cells, but analyses revealed that, akin to TIF1?, TIF1? is reorganized in an E4orf3-dependent manner to promyelocytic leukemia protein-containing nuclear tracks during infection. The use of a number of different adenovirus early region mutants identified the specific and sole requirement for E4orf3 in mediating TIF1? degradation. Further analyses revealed that TIF1? is targeted for degradation by a number of divergent human adenoviruses, suggesting that the ability of E4orf3 to regulate TIF1? expression is evolutionarily conserved. We also determined that E4orf3 does not utilize the Cullin-based ubiquitin ligases, CRL2 and CRL5, or the TIF1? ubiquitin ligase in order to promote TIF1? degradation. Further studies suggested that TIF1? possesses antiviral activity and limits adenovirus early and late gene product expression during infection. Indeed, TIF1? knockdown accelerates the adenovirus-mediated degradation of MRE11, while TIF1? overexpression delays the adenovirus-mediated degradation of MRE11. Taken together, these studies have identified novel adenovirus targets and have established a new role for the E4orf3 protein during infection.
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Synergistic antioxidant activity of green tea with some herbs.
J Adv Pharm Technol Res
PUBLISHED: 12-16-2011
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Cardiovascular diseases, cancer, arthritis, etc. are caused by free radicals that are byproducts of metabolic pathways. Selected plants namely Vitis vinifera, Phyllanthus emblica L., Punica granatum, Cinnamomum cassia, Ginkgo biloba L., and Camellia sinensis Linn. are reported to produce antioxidant property. This study is undertaken to support the hypothesis that formulation of a polyherbal combination of these plants shows a synergistic effect with green tea. The extracts of each drug were characterized by phytochemical studies and tests for phenolics and flavonoids. In vitro antioxidant activity for individual drug and its combination was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide, and nitric oxide free radical scavenging methods. Our results suggest that a combination of all these herbs with green tea can synergistically enhance antioxidant activity and thus lower doses of each herb with green tea may be used. Antioxidant potential of polyherbal combination was also comparable to that of standard ascorbic acid. Studies showed that selected individual plants contained abundant quantity of phenolics and flavonoids and their polyherbal combination with green tea was found to produce best antioxidant activity among all individual extracts. This will help in avoiding undesirable side effects due to higher doses of single herb.
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Pharmacognostic parameters for evaluation of the rhizomes of Curcuma caesia.
J Adv Pharm Technol Res
PUBLISHED: 12-16-2011
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In ethno medicinal practices, the traditional healers use the genus Curcuma for the treatment of various ailments but Curcuma caesia Roxb. is a very less known and almost untouched drug. The present work attempts to establish the necessary pharmocognostic standards for evaluating the plant material of C. caesia Roxb. Various parameters, such as morphology, microscopy, physicochemical constants, and phytochemical profiles of the entire parts of the plant were studied and the salient diagnostic features are documented. Major chemical constituents, extractive values, physicochemical constants, and other features are also been recorded.
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Role of interventional nephrology in dialysis access management.
Mo Med
PUBLISHED: 09-13-2011
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Interventional nephrology is an area of medicine under the subspecialty of nephrology that provides improved vascular access care for dialysis patients. Since vascular access issues are a major cause of hospitalization in dialysis patients, interventional nephrologists help reduce hospitalization rates and costs, providing focused and economical medical care. A case has been presented at the end that highlights some management principles of vascular accesses. We also present a comprehensive review of recent data regarding trends in dialysis access management.
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Endothelial surface N-glycans mediate monocyte adhesion and are targets for anti-inflammatory effects of peroxisome proliferator-activated receptor ? ligands.
J. Biol. Chem.
PUBLISHED: 09-12-2011
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Endothelial-monocyte interactions are regulated by adhesion molecules and key in the development of vascular inflammatory disease. Peroxisome proliferator-activated receptor (PPAR) ? activation in endothelial cells is recognized to mediate anti-inflammatory effects that inhibit monocyte rolling and adhesion. Herein, evidence is provided for a novel mechanism for the anti-inflammatory effects of PPAR? ligand action that involves inhibition of proinflammatory cytokine-dependent up-regulation of endothelial N-glycans. TNF? treatment of human umbilical vein endothelial cells increased surface expression of high mannose/hybrid N-glycans. A role for these sugars in mediating THP-1 or primary human monocyte rolling and adhesion was indicated by competition studies in which addition of ?-methylmannose, but not ?-methylglucose, inhibited monocyte rolling and adhesion during flow, but not under static conditions. This result supports the notion that adhesion molecules provide scaffolds for sugar epitopes to mediate adhesion with cognate receptors. A panel of structurally distinct PPAR? agonists all decreased TNF?-dependent expression of endothelial high mannose/hybrid N-glycans. Using rosiglitazone as a model PPAR? agonist, which decreased TNF?-induced high mannose N-glycan expression, we demonstrate a role for these carbohydrate residues in THP-1 rolling and adhesion that is independent of endothelial surface adhesion molecule expression (ICAM-1 and E-selectin). Data from N-glycan processing gene arrays identified ?-mannosidases (MAN1A2 and MAN1C1) as targets for down-regulation by TNF?, which was reversed by rosiglitazone, a result consistent with altered high mannose/hybrid N-glycan epitopes. Taken together we propose a novel anti-inflammatory mechanism of endothelial PPAR? activation that involves targeting protein post-translational modification of adhesion molecules, specifically N-glycosylation.
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Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole: A comparative assessment.
Saudi Pharm J
PUBLISHED: 07-07-2011
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THE OBJECTIVE OF WORK WAS TO FORMULATE, EVALUATE AND COMPARE THE TRANSDERMAL POTENTIAL OF NOVEL VESICULAR NANOCARRIERS: ethosomes and ultradeformable liposomes, containing clotrimazole (CLT), an anti-fungal bioactive. The ethosomal formulation (ET4) and ultradeformable liposomal (UL) formulation (TT3) showed highest entrapment 68.73 ± 1.4% and 55.51 ± 1.7%, optimal nanometric size range 132 ± 9.5 nm and 121 ± 9.7 nm, and smallest polydispersity index 0.027 ± 0.011 and 0.067 ± 0.009, respectively. The formulation ET4 provided enhanced transdermal flux 56.25 ± 5.49 ?g/cm(2)/h and decreased the lag time of 0.9 h in comparison to TT3 formulation (50.16 ± 3.84 ?g/cm(2)/h; 1.0 h). Skin interaction and FT-IR studies revealed greater penetration enhancing effect of ET4 than TT3 formulation. ET4 formulation also had the highest zone of inhibition (34.6 ± 0.57 mm), in contrast to TT3 formulation (29.6 ± 0.57 mm) and marketed cream formulation (19.0 ± 1.00 mm) against candidal species. Results suggested ethosomes to be the most proficient carrier system for dermal and transdermal delivery of clotrimazole.
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Bioequivalence of two tacrolimus formulations under fasting conditions in healthy male subjects.
Clin Ther
PUBLISHED: 06-09-2011
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Tacrolimus is a macrolide immunosuppressant indicated for prophylaxis of transplant rejection. The European regulatory authorities require comparative bioavailability studies with an innovator product to grant marketing authorization of generic products.
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Cervical spine trauma in children and adults: perioperative considerations.
J Am Acad Orthop Surg
PUBLISHED: 06-02-2011
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A wide spectrum of cervical spine injuries, including stable and unstable injuries with and without neurologic compromise, account for a large percentage of emergency department visits. Effective treatment of the polytrauma patient with cervical spine injury requires knowledge of cervical spine anatomy and the pathophysiology of spinal cord injury, as well as techniques for cervical spine stabilization, intraoperative positioning, and airway management. The orthopaedic surgeon must oversee patient care and coordinate treatment with emergency department physicians and anesthesia services in both the acute and subacute settings. Children are particularly susceptible to substantial destabilizing cervical injuries and must be treated with a high degree of caution. The surgeon must understand the unique anatomic and biomechanical properties associated with the pediatric cervical spine as well as injury patterns and stabilization techniques specific to this patient population.
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Facet violation with the placement of percutaneous pedicle screws.
Spine
PUBLISHED: 05-19-2011
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Independent review and classification of therapeutic procedures performed on cadavers by surgeons blinded to purpose of study.
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Red blood cell age and potentiation of transfusion-related pathology in trauma patients.
Transfusion
PUBLISHED: 04-19-2011
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The specific negative clinical manifestations associated with the transfusion of stored red blood cells (RBCs) and the corresponding mechanisms responsible for such phenomena remain poorly defined. Our recent studies document that leukoreduced older RBC units potentiate transfusion-related toxicity in trauma patients. It is our hypothesis that the transfusion of relatively older blood impedes microvascular perfusion. The central mechanisms proposed to mediate this microcirculatory alteration include: 1) the loss of RBC-dependent control of nitric oxide-mediated homeostasis concerning vasodilation and 2) immune cell and complement activation. In this review, we outline the background for our hypothesis and detail our current investigations toward the understanding of this pathophysiology.
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Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy.
Free Radic. Biol. Med.
PUBLISHED: 04-04-2011
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Beyond an inert oxidation product of nitric oxide (NO) metabolism, current thinking posits a key role for nitrite as a mediator of NO signaling, especially during hypoxia. This concept has been discussed in the context of nitrite serving a role as an endogenous modulator of NO homeostasis, but also from a novel clinical perspective whereby nitrite therapy may replenish NO signaling and prevent ischemic tissue injury. Indeed, the relatively rapid translation of studies delineating mechanisms of action to ongoing and planned clinical trials has been critical in fuelling interest in nitrite biology, and several excellent reviews have been written on this topic. In this article we limit our discussions to current concepts and what we feel are questions that remain unanswered within the paradigm of nitrite being a mediator of NO biology.
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Elevated levels of NO are localized to distal airways in asthma.
Free Radic. Biol. Med.
PUBLISHED: 03-03-2011
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The contribution of nitric oxide (NO) to the pathophysiology of asthma remains incompletely defined despite its established pro- and anti-inflammatory effects. Induction of the inducible nitric oxide synthase (iNOS), arginase, and superoxide pathways is correlated with increased airway hyperresponsiveness in asthmatic subjects. To determine the contributions of these pathways in proximal and distal airways, we compared bronchial wash (BW) to traditional bronchoalveolar lavage (BAL) for measurements of reactive nitrogen/oxygen species, arginase activation, and cytokine/chemokine levels in asthmatic and normal subjects. Levels of NO were preferentially elevated in the BAL, demonstrating higher level NOS activation in the distal airway compartment of asthmatic subjects. In contrast, DHE(+) cells, which have the potential to generate reactive oxygen species, were increased in both proximal and distal airway compartments of asthmatics compared to controls. Different patterns of cytokines and chemokines were observed, with a predominance of epithelial cell-associated mediators in the BW compared to macrophage/monocyte-derived mediators in the BAL of asthmatic subjects. Our study demonstrates differential production of reactive species and soluble mediators within the distal airways compared to the proximal airways in asthma. These results indicate that cellular mechanisms are activated in the distal airways of asthmatics and must be considered in the development of therapeutic strategies for this chronic inflammatory disorder.
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Effects of T- and R-state stabilization on deoxyhemoglobin-nitrite reactions and stimulation of nitric oxide signaling.
Nitric Oxide
PUBLISHED: 01-18-2011
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Recent data suggest that transitions between the relaxed (R) and tense (T) state of hemoglobin control the reduction of nitrite to nitric oxide (NO) by deoxyhemoglobin. This reaction may play a role in physiologic NO homeostasis and be a novel consideration for the development of the next generation of hemoglobin-based blood oxygen carriers (HBOCs, i.e. artificial blood substitutes). Herein we tested the effects of chemical stabilization of bovine hemoglobin in either the T- (THb) or R-state (RHb) on nitrite-reduction kinetics, NO-gas formation and ability to stimulate NO-dependent signaling. These studies were performed over a range of fractional saturations that is expected to mimic biological conditions. The initial rate for nitrite-reduction decreased in the following order RHb>bHb>THb, consistent with the hypothesis that the rate constant for nitrite reduction is faster with R-state Hb and slower with T-state Hb. Moreover, RHb produced more NO-gas and inhibited mitochondrial respiration more potently than both bHb and THb. Interestingly, at low oxygen fractional saturations, THb produced more NO and stimulated nitrite-dependent vasodilation more potently than bHb despite both derivatives having similar initial rates for nitrite reduction and a more negative reduction potential in THb versus bHb. These data suggest that cross-linking of bovine hemoglobin in the T-state conformation leads to a more effective coupling of nitrite reduction to NO-formation. Our results support the model of allosteric regulation of nitrite reduction by deoxyhemoglobin and show that cross-linking hemoglobins in distinct quaternary states can generate products with increased NO yields from nitrite reduction that could be harnessed to promote NO-signaling in vivo.
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Mitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 12-10-2010
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Nitrite (NO(2)(-)) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO(2)(-) in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO(2)(-) mitigate chlorine (Cl(2))-induced lung injury in rats. Rats were exposed to Cl(2) (400 ppm) for 30 min and returned to room air. NO(2)(-) (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL), and wet-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F(2)-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl(2) exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO(2)(-) resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F(2)-isoprostane levels increased at 6 and 24 h after Cl(2) exposure in NO(2)(-)- and saline-injected rats. This is the first demonstration that systemic NO(2)(-) administration mitigates airway and epithelial injury.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.